Systematic Review and Meta-Analysis of Psychological and Behavioral Symptoms in Alzheimer’s Disease and Their Impact on Professional Caregiver Burden

Systematic Review and Meta-Analysis of Psychological and Behavioral Symptoms in Alzheimer’s Disease and Their Impact on Professional Caregiver Burden | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Systematic Review and Meta-Analysis of Psychological and Behavioral Symptoms in Alzheimer’s Disease and Their Impact on Professional Caregiver Burden Aline Muhigwa, Sandrine Kalenzaga This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7199792/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Alzheimer's disease is a progressive neurodegenerative disorder associated with cognitive decline and psychological and behavioral symptoms (PBSA), which significantly impact both patients and professional caregivers. Despite their central role in managing PBSA, limited research has evaluated caregivers’ knowledge of these symptoms and the burden they experience. Understanding caregivers’ perceptions and the intensity of PBSA is essential to improving care quality and caregiver well-being. Methods A systematic review and meta-analysis were conducted following PRISMA guidelines. Databases searched included PubMed, PsycINFO, and Google Scholar up to December 2024. Of 918 identified records, 56 studies met inclusion criteria. Data extraction was conducted using CADIMA, and statistical analyses were performed with the “METAFOR” package in R. Pooled effect sizes of mean Neuropsychiatric Inventory (NPI) subdomain scores were calculated to assess symptom intensity. A mixed-effects meta-regression examined whether sample size influenced caregiver burden variability. Results Agitation (pooled mean = 2.90; 95% CI [0.64, 5.17]), depression (15.92; 95% CI [8.89, 22.96]), apathy (9.40; 95% CI [3.48, 22.28]), anosognosia (15.92; 95% CI [8.89, 22.96]), and anxiety (1.72; 95% CI [0.98, 2.46]) were the most intense symptoms. Formal caregivers’ knowledge varied across studies, with pooled means of 2.67 (95% CI [2.02, 3.31]) for symptom knowledge and 6.24 (95% CI [5.02, 7.31]) for treatment knowledge. Substantial heterogeneity was present (I² > 90%). Meta-regression revealed that sample size was not a significant moderator of caregiver burden (estimate = -0.017, p = 0.804), with residual heterogeneity remaining high (I² = 99.85%). Conclusion This review highlights the high prevalence and intensity of PBSA in Alzheimer’s care and underscores the variability in caregiver knowledge and burden. Sample size does not account for differences in reported burden, suggesting the influence of other contextual or organizational factors. These findings emphasize the urgent need for structured education and support programs tailored to formal caregivers to enhance symptom management and reduce burden. Alzheimer’s disease behavioral and psychological symptoms formal caregivers caregiver burden knowledge meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and significant psychological and behavioral symptoms (Psychological and Behavioral Symptoms of Alzheimers’ disease, PBSA)[11]. These symptoms, including agitation, aggression, depression, anxiety, and apathy, pose substantial challenges for both patients and caregivers[6]. According to a systematic review by Kwon and Lee in 2020[71], the pooled prevalence rates of PBSA among Alzheimer’s patients are as follows: agitation and aggression (31%), aberrant motor behavior (20%), eating disorders (21%), wandering (15%), sleep disturbances (13%), and disinhibition (8%). Managing PBSA is a crucial aspect of AD care, as these symptoms can exacerbate cognitive decline, reduce patients' quality of life, and increase caregivers’ burden[6]. Formal caregivers, including nurses, aides, and other healthcare professionals, play a critical role in managing PBSA in institutional and home-care settings[67]. Their perception and understanding of these symptoms can influence care strategies, patient outcomes, and the caregivers’ own psychological well-being[6]. Despite their professional expertise, caregivers often face difficulties in interpreting and responding to PBSA due to variations in training, experience, and personal coping mechanisms[18]. Understanding the extent of caregivers’ knowledge and the impact of PBSA is essential for designing effective interventions that enhance patient care and mitigate caregiver stress. Existing literature on caregiver burden and the management of PBSA highlights disparities in the recognition and handling of these symptoms[65]. While some caregivers demonstrate a high level of awareness and adaptability, others struggle due to inadequate training and emotional exhaustion[15]. The high heterogeneity of findings across studies underscores the need for a comprehensive review to consolidate knowledge and identify gaps in caregiver education and support systems. Given the crucial role of structured education and support for formal caregivers and individuals AD, this study presents a systematic review and meta-analysis of caregivers’ knowledge of PBSA and symptom severity. Formal caregivers’ knowledge of PBSA significantly influences AD management. Synthesizing evidence from multiple studies, this research aims to identify key areas for intervention and inform policies on training and support strategies. Purpose of the study The primary objective of this study is to assess formal caregivers’ knowledge of PBSA and their impact on caregivers’ burden. The present study provides estimated pooled values of PBSA, caregivers’ knowledge and burden scores. Specifically, the study aims to : - Identify the most commonly reported PBSA symptoms and assess their severity. -Evaluate the level of caregiver knowledge regarding PBSA and its influence on care quality. -Assess the effects of PBSA on caregiver burden. 2. Methods This systematic review and meta-analysis followed PRISMA guidelines [68]. The study systematically searched PubMed, PsycINFO, and Google Scholar for relevant literature published up to December 2024, using Mesh terms related to Alzheimer’s disease, behavioral troubles, knowledge and formal caregivers: -Alzheimer’s disease AND formal caregiver -Alzheimer disease’s AND formal caregiver AND behavioral symptoms - Alzheimer’s disease OR dementia AND behavioral disturbances OR behavioral problems OR neuropsychiatric symptoms AND formal caregiver AND burden OR quality of life We used the C ADIMA platform to facilitate study selection, quality assessment, and data extraction. The protocole of this study was registered in PROSPERO (number : CRD420250653427) and available on https://www.crd.york.ac.uk/PROSPERO2/view/CRD420250653427. Inclusion Criteria : -Studies examining formal caregivers (healthcare professionals) providing care for AD patients. -Studies reporting the impact of PBSA, including agitation, aggression, anxiety, and apathy, on caregivers’ burden -Quantitative and qualitative studies evaluating the impact of caregiver burden and knowledge on patient care. -Studies employing validated assessment tools for measuring PBSA and caregiver burden. Exclusion Criteria : -Studies focused solely on pharmacological interventions without caregiver involvement. -Studies on informal caregivers or family members. -Case reports, editorials, and theoretical studies without empirical data. Data extraction and analysis: -Data extraction was conducted using the CADIMA platform to ensure systematic collection and organization of the studies’s findings. We extracted means and standard deviations (SD) and sample sizes of PBSA(NPI Score), caregiver burden score (Zarit Burden Score) and knowledge scores(ADKS), which were then synthesized in forest plots to illustrate heterogeneity across studies. Statistical analysis was performed using the R package METAFOR, which allowed for precise estimation of pooled mean effects and confidence intervals. Publication bias was assessed using funnel plots, and heterogeneity among studies was evaluated using I² statistics. Additionally, a mixed-effects meta-regression was performed to evaluate the impact of sample size (N) on variability of the formal caregiver burden score. 3. Results We conducted a systematic review of the literature on professional caregivers' knowledge, impact, and burden related to PBSA. A total of 918 records were identified, of which 825 were excluded because they did not meet the selection criteria. We fully reviewed 65 articles and included 56 in the systematic review and meta-analysis [ Fig. 2 ] .Most of the studies were conducted in Europe and Asia [ Fig. 1 ] . The literature search was conducted from October 2024 to January 2025, and it covered studies up until December 2024. The table below [table.1] shows the characteristics of the 56 studies included in our systematic review, showing that they were diverse regarding their design, population, major findings, geographical and cultural factors, and the addressed themes. The studies are of various study designs, including cross-sectional studies, qualitative interviews, randomized controlled trials, integrative reviews, and provide a broad overview of caregivers' knowledge and impact of the PBSA. Although some of the included studies also involved both formal and informal caregivers, the current review was concentrated on formal caregivers to provide a more uniform comparison of knowledge levels, and burden. The geographic and cultural diversity of the studies (spanning North America, Europe, Asia, South America, and Africa), underscores the influence of healthcare systems, societal attitudes, and access to caregiver training on study outcomes. The following are the major themes explored: caregiver burden, emotional distress, knowledge gaps, PBSA intervention strategies, and safety concerns. Some studies [ 2 ] discussed the emotional and psychological burden of caregiving, and others [ 64 ] underlined the short fall of knowledge of who give the care, especially healthcare providers. Other studies have analyzed link between anosognosia and care-giver burden [ 44 , 15 ]. The strength of these studies lies in their contributions to understanding the challenges formal caregivers face and the effectiveness of training and intervention programs. Yet, limitations include cross-sectional designs for most of the articles, restricting causal interpretations, and varied sample sizes, influencing generalizability. Although limited by these factors, the table provides a useful synthesis of emerging research with a clear call for additional studies of culturally tailored interventions, long-term caregiver outcomes, and approaches to prepare formal caregivers to manage PBSA. Table 1 Characteristics of studies included in the systematic review Author Continent Country Locality Study design Population studied Key outcomes Yildizhan.,2018[ 3 ] North America United states Aurora, colorado Qualitative study: semi structured interviews Patients with AD related dementias,formal caregivers and informal caregivers Caregiver views on behavioral disturbances and impact on firearm safety. Impact on Caregivers: Caregiver stress, fear, conflict, managing dementia related safety issues. Caregiver emotional and practical responses to safety issues. Lorenzo-lopez et al.,2017[ 62 ] Europe Spain coruña Cross-sectional observational study Both formal and informal caregivers, ad patients Quantitative data on caregiver distress. Analyzes caregiver burden, symptom severity, and emotional responses. Campana, m. et al.,2016[ 63 ] Europe France Marseille Quantitative AD patients, general pratictioners and informal caregivers Behavioral disturbances and management by general practitioners. yalon et al.,2009[ 2 ] North America United states California Cross-sectional study usingquestionnaires AD patients and formal caregivers Behavioral Disturbances Management knowledge and attitudes Caregiver Stress and Emotional Impact Intervention: Nonpharmacological Pharmacological Florindo et al.,2015[ 61 ] South America Brazil Brasilia Quantitative and qualitative Dementia patients,formal caregivers Behavioral Disturbances Reduction. Caregiver Impact: Emotional and burden reduce Polzer et al.,2022[ 64 ] Europe Spain Madrid Cross-sectional study Pharmacist,employees of pharmaceutical compagny Knowledge Gaps Behavioral and Emotional Impact Garcia et al.,2020[ 65 ] Asia China Beijing, shanghai Ntegrative review of both qualitative and quantitative studies Healthcare professionals knowledge and attitude towards dementia Zhao et al.,2022[ 66 ] North America Canada Manitoba Cross-sectional study Professional caregivers Impact of Resident Behaviors on Caregiver Stress Chappell et al.,1994[ 1 ] North America United states New york Cross-sectional study Professional caregivers,ad patients and family caregivers how professional and family caregivers differ in assessing behaviors. Robert et al.,2009[ 9 ] Europe France Gironde and alpes-maritimes Randomized controlled trial Professional caregivers and ad patients focus on non pharmacological interventions to manage PBSA Lukovits et al.,1992[ 34 ] North America United states Mississippi Quasi-experimental pretest-posttest design Nurses,ad patients nursing staff perceptions regarding PBSA and impact on care. Bilal et al.,2016[ 10 ] North America United states Cross-sectional study Nurses,ad patients Identification and management Behavioral Disturbances Boyd ,et al.,2001[ 11 ] Europe Poland Warsaw Cross-sectional design Formal and informal caregivers, AD patients Mental Health Problems caregivers Soltys et al.,2020[ 12 ] North America United states Colorado Qualitative study,focus groups Formal and informal caregivers,ad patients Behavioral troubles,communication Richter et al.,1995[ 13 ] Asia Israel Across israel Cross-sectional study Individuals with severe dementia-related and formal caregivers Caregiver Burden and Mental Health during the COVID-19 pandemic Karni et al.,2022[ 14 ] Asia Malaysia Selangor Qualitaive study,semi-structured interviews Formal and informal caregivers Challenges in dementia care,behavioral troubles cited Goodson et al.,2021[ 15 ] Europe France Paris Cross-sectional design AD patients and formal caregivers Behavioral Problems and professional healthcare burden Al-aloucy et al.,2011[ 16 ] Europe Germany North rhine-westphalia Qualitative study AD patients and formal caregivers Emotional experience in AD patients Cornelia ,2018[ 17 ] Europe Spain Murcia Cross-sectional design AD patients and formal caregivers Neuropsychiatric symptoms, caregiving burden Maria et al.,2012[ 18 ] North America United states California Cross-sectional AD patients and nurses Behavioral Symptoms,caregiver's burden Wood et al.,1999[] North America Canada Cross-sectional Formal and informal caregivers Knowledge of AD among professional caregivers Smyth,2013[ 20 ] Australia Australia Queensland Cross-sectional Formal caregivers Knowledge of ad among professional caregivers Tiana et al.,2007[ 19 ] North America United states Missouri Cross-sectional Diverse backgrounds including formal caregivers Knowledge on ad Brian,2011[ 21 ] Europe Norway Bergen Cross-sectional Final year students in health fields Knowledge about AD among final-year students in health and social care Sundaran ,2015[ 22 ] South America Peru Tacna, piura, trujillo, san martin Cross-sectional Health professionals in peru Knowledge of dementia and AD among healthcare professionals in peru Malaga et al.,2024[ 23 ] Asia Qatar Doha Cross-sectional study. Physicians, nurses, students, and researchers in qatar (n = 229) Examines knowledge, awareness, and attitudes of healthcare professionals regarding alzheimer’s disease.discusses training and its impact on care practice. Also adress gaps in training; emotional and professional impact of caregiving; strategies to address knowledge gaps. Paul et al.,2023[ 24 ] Europe Spain Jaen, andalusia Cross-sectional Formal caregivers Knowledge regarding ad in nurses in spain Laura et al.,2019[ 25 ] Asia and north America United Sstates and china Alabama and hong kong Cross-sectional Formal caregivers Knowledge and biases about ad among nurses in the u.s. And china Christine et al.,1994[ 26 ] Africa Egypt Minia, beni-suif, assuit Cross-sectional Formal caregivers Knowledge levels of formal caregivers about alzheimer's disease in egypt Shimaa et al.,2022[ 27 ] North America Unites States Chicago Cross-sectional study Pharmacists Pharmacists’ knowledge of ad disease care Marketa ,2017[ 28 ] Asia Jordan North jordan Cross-sectional Nurses Knowledge levels about ad among nurses in jordanian hospitals Aljezawi et al.,2021[ 29 ] North America United States Florida Cross-sectional Medical and nurse students' Knowledge about ad before and after an interprofessional education program Mccaffrey, r.,et al.,2013[ 30 ] Asia Saudi Arabia Majmaah,l-jouf, hafer al-batin,taif Cross-sectional Nursing students Knowledge levels about ad Jazi ,2024[ 31 ] Asia China Jiangsu province Cross-sectional Nurse staff Evaluate alzheimer's disease knowledge Zuo et al.,2023[ 32 ] Europe Germany North rhine-westphalia. Qualitative study Professional caregivers and patient's families Examine the emotional experiences of patients with advanced alzheimer's disease Karger, 2018[ 17 ] Norway Northern norway Qualitative intervention study Formal caregivers and ad patients Evaluate caregivers’ interactions with patients Hansebo et al.,2002[ 60 ] Europe United kingdom North wales Observational validation study Awareness and responsiveness in individuals with severe dementia Clare et al.,2012[ 51 ] Europe Netherlands Nijmegen and eindhoven Descriptive qualitative study Formal caregivers and ad patients Identification and management of apathy in dementia patients Nijsten et al.,2023[ 35 ] Europe Turkey Instabul Cross-sectional design Formal caregivers of aD Burnout and burden Eren et al.,2018[ 36 ] Europe Turkey Istanbul Cross-sectional Professional caregivers and ad patients Caregiver burden, and burnout levels among professional caregivers of AD patients Hayajneh et al.,2014[ 37 ] Asia Jordan Aman Qualitative study: semi structured interviews and quantitative AD patients and formal caregivers Caregiver adaptation and empathy Bernardino et al.,2015[ 38 ] Europe Spain Salamanca Randomized controlled trial Individuals with mild AD Unawareness of deficits (anosognosia) Daniel et al.,2015[ 39 ] Asia,south America China, india, peru, mexico, cuba, dominican republic Beijing, chennai, havana, santo domingo, caracas, lima, mexico Cross-sectional population-based survey AD Patients Relationship between anosognosia and behavioral symptoms Stephen et al.,2023[ 47 ] North America United states California Cross-sectional AD Patients, physicians, care partners Perspectives of patients, care partners, and primary care physicians regarding the management of AD Shiri s. et al.,2016[ 52 ] Asia Israel Tel aviv Cross-sectional Formal caregivers Relationship between ad illness representations and burnout among social workers and nurses Sandra v. et al.,2013[ 53 ] Europe Germany Düsseldorf Cross-sectional AD Patients Relationship between anosognosia (impaired awareness of illness) and depression in patients with AD S. Stirati et al.,2008[ 54 ] Europe France Tours Cross-sectional AD Patients Evaluate anosognosia (unawareness of illness) in patients with AD Salmon et al.,2023[ 55 ] Europe Belgium, italy, united kingdom, germany Liege,milan,cologne,dresden,manchester Cross-sectional AD Patients Compare unawareness (anosognosia) across different domains (cognition, behavior, daily activities) in AD Thomas et al.,2023[ 40 ] Europe France Paris Cross-sectional AD Patients Detect anosognosia in ad from the prodromal stage using the healthy aging brain care monitor Kenji et al.,2020[ 41 ] Asia Japan Tokyo Cross-sectional AD Patients Explore neuropsychiatric symptoms associated with anosognosia in patients with AD Bora et al.,2017[ 42 ] Asia South korea Seaoul Cross-sectional AD Patients Investigate the prevalence, clinical characteristics, and behavioral symptoms of anosognosia in patients with AD early-onset Yukiko et al.,2005[ 43 ] Asia Japan Kobe Cross-sectional AD Patients Investigate the relationship between anosognosia and patient characteristics, psychiatric symptoms, and cognitive deficits in ad Yohko et al.,2013[ 44 ] Asia Japan Maebashi Cross-sectional AD Patients Prevalence of anosognosia in patients with ad dementia, its association with behavioral and psychological symptoms Vignolo et al.,2024[ 45 ] Europe France Toulouse Cross-sectional Formal caregivers Healthcare workers' knowledge and experiences in managing anosognosia and behavioral troubles in patients with AD Mak. et al.,2015[ 46 ] Asia Singapore Singapore Cross-sectional AD Patients Anosognosia and neuropsychiatric symptoms in AD Corina et al.,2013[ 48 ] South America Brazil Brasilia Cross-sectional AD Patients Anosognosia and neuropsychiatric symptoms in AD Agitation : Agitation showed the highest pooled mean NPI score of 2.90 (95% CI: 0.64–5.17), indicating a moderate intensity of symptoms as measured by the combined frequency and severity (score range 0–12). This reflects that agitation, while variable, tends to be a symptom of meaningful clinical impact in the studied populations. Substantial heterogeneity was observed (I² = 92.9%), reflecting differences in study populations,and methodologies (Fig. 2 ). Depression : Depression had a pooled mean intensity score of 15.92 (95% CI: 8.89–22.96), with very high heterogeneity (I² = 99.7%). Although this score exceeds the classic NPI subdomain maximum of 12, it likely reflects aggregated or modified scoring approaches used across studies, such as inclusion of caregiver distress ratings or summation of multiple related items under the depression domain. Therefore, this score should be interpreted as an elevated overall burden or intensity of depressive symptoms rather than a simple frequency × severity product, confirming depression as a frequently intense behavioral symptom in Alzheimer’s disease across studies. Apathy : The pooled mean NPI score for apathy was 9.40 (95% CI: 3.48–22.28), accompanied by high heterogeneity (I² = 98.1%). Despite variability, these results support apathy as a significant symptom affecting patients with AD. Anxiety : Anxiety had a pooled mean intensity score of 1.72 (95% CI: 0.98–2.46) with moderate heterogeneity (I² = 40.1%). Most studies report notable symptom intensity, indicating anxiety as a common behavioral feature in Alzheimer’s disease. Heterogeneity and Bias: Across symptoms, high heterogeneity (I² >75%) indicates substantial variability in study design, populations, and NPI assessment methods. Forest plots (Fig. 1 ) illustrate these variations in symptom intensity, while funnel plots (supplementary materials) Formal caregivers Burden due to PBSA Meta-Regression on Factors Influencing Zarit Burden Scores Table 2 Meta-Regression Results Predicting Zarit Burden Scores (Mixed-Effects Model) Parameter Estimate SE z-value p-value 95% CI (Lower) 95% CI (Upper) Intercept 20.83 14.25 1.46 0.144 -7.10 48.75 Sample Size (N) -0.017 0.067 -0.25 0.804 -0.149 0.115 A mixed-effects meta-regression model was conducted to explore whether the sample size (N) could explain the variability in mean Zarit scores across studies. The model included four studies (k = 4), and the restricted maximum-likelihood (REML) estimator was used to estimate between-study variance. The model showed the following fit statistics: log-likelihood = -8.83, AIC = 23.66, BIC = 19.74, and AICc = 47.66. These values provide a general indication of model adequacy but are primarily useful for comparison across competing models. Heterogeneity The estimated between-study variance (tau²) was 400.51 (SE = 401.22), with a corresponding tau (√tau²) of 20.01, indicating a substantial degree of residual heterogeneity. The I² value was 99.85%, suggesting that nearly all of the observed variability in effect sizes was due to differences between studies rather than sampling error. The H² value was 683.73, and the R² (the proportion of heterogeneity explained by the moderator) was 0.00%, meaning the moderator did not account for any of the observed heterogeneity. The test for residual heterogeneity was significant: QE(df = 2) = 1944.10, p < 0.0001, confirming considerable heterogeneity remained unexplained after accounting for the moderator. The test for the moderator (sample size N) was not significant: QM(df = 1) = 0.0614,p = 0.8043, indicating that sample size did not significantly influence the mean Zarit burden scores. The intercept of the model was estimated at 20.83 (SE = 14.25, p = 0.144), and the regression coefficient for sample size (N) was − 0.017 (SE = 0.067, p = 0.804). The 95% confidence interval for the N coefficient ranged from − 0.149 to 0.115, which includes zero, reinforcing the non-significance of the effect. The results suggest that sample size does not significantly predict differences in caregiver burden as measured by the Zarit scale across the included studies. Moreover, the presence of substantial unexplained heterogeneity implies that other study-level characteristics (e.g., type of intervention, caregiver population, cultural factors) should be considered in future analyses. Professional caregivers knowledge and experience in AD The forest plots present the pooled means of different scores and questionnaires on professional caregivers' knowledge and experience regarding Alzheimer's disease, showing notable variability across studies [Fig. 3 ]. The forest plot on treatment knowledge shows high heterogeneity (I² = 98.3%), indicating differing levels of understanding among caregivers (pooled mean = 4.21, 95% CI [3.45, 5.02]). Similarly, the forest plot on disease progression knowledge also displays significant variability (I² = 97.6%), with caregivers showing a range of understanding (pooled mean = 6.14, 95% CI [5.02, 7.31]). Concerning the impact of AD on daily life, the plot suggests that most caregivers have a solid grasp, though the high heterogeneity (I² = 95.2%) points to differences in their understanding (pooled mean = 5.98, 95% CI [4.87, 7.02]). The forest plot on caregiver knowledge in managing symptoms indicates significant effect sizes (pooled mean = 7.45, 95% CI [6.32, 8.59]), but high heterogeneity (I² = 96.8%) suggests that some professional caregivers are less informed about best practices, highlighting the need for more focused trainings. The plot on symptom knowledge shows a statistically significant global effect (pooled mean = 2.67, 95% CI [2.01, 3.35]), although there is considerable variability between studies (I² = 99.5%), suggesting a general but uneven understanding of AD symptoms. Funnel plots generally suggest publication bias, with studies showing better caregiver knowledge being more likely to be published. Regarding professional caregiver experience, those with less than five years of experience in AD patients care show high heterogeneity (I² = 99.6%), indicating diverse experiences, which are hard to generalize (pooled mean = 8.23, 95% CI [7.12, 9.47]). In contrast, caregivers with more than five years of experience report a significant experience (pooled mean = 15.76, 95% CI [14.03, 17.52]), but with a broad range of uncertainty and extreme heterogeneity (I² = 100%). These results indicate that caregiver knowledge and experience vary greatly, suggesting the need for targeted interventions to standardize training, particularly in areas with significant variability. Discussion Instruments for evaluating PBSA Multiple validated scores and questionnaires were employed in the studies included in our meta-analysis to assess various PBSA. Although different tools were cited or used, we focused solely on Neuropsychiatric Inventory (NPI) scores for the subdomains, as it is possibly the most frequently applied tool measuring a wide array of PBSA such as anxiety, depression, agitation, apathy, and irritability. Depression was also specifically investigated using the Geriatric Depression Scale (GDS) and the Patient Health Questionnaire-9 (PHQ-9) [ 6 ], while anxiety symptoms were assessed with the Generalized Anxiety Disorder-7 (GAD-7) [ 6 ] and the Goldberg Anxiety Questionnaire. Additionally, apathy was evaluated with the Apathy Evaluation Scale (AES), an 18-item instrument assessing apathy based on a person’s thoughts, motivation, and emotions over the previous four weeks, as well as the Apathy Inventory (AI) [ 35 ]. To assess professional caregivers’ knowledge on AD, the Alzheimer’s Disease Knowledge Scale (ADKS) was used in some studies [ 28 , 29 , 30 ]. This widely used 30-item true/false questionnaire assesses caregivers’ knowledge across seven domains: life impact, risk factors, symptoms, treatment and management, assessment and diagnosis, caregiving, and disease progression. Professional caregivers’ years of experience in AD care were commonly self-reported through demographic questionnaires, with some studies reporting means and SD, particularly in logistic regression analyses exploring how caregiver expertise influences patient care and mental health outcomes. Professional caregiver burden was predominantly evaluated using the Zarit Caregiver Burden Scale, which assesses perceived caregiving burden and is frequently used in studies measuring caregiver stress and well-being [ 14 , 16 , 36 , 37 , 45 ]. The Maslach Burnout Inventory (MBI), measuring burnout levels among professional caregivers, was also applied in several studies [ 18 , 69 ]. To address methodological heterogeneity, we used a random-effects model to normalize and pool mean scores, enabling us to extract meaningful patterns across studies Thus, despite heterogeneity in approaches, our meta-analysis strengthened the reliability of conclusions regarding PBSA and caregiver burden in AD. PBSA and Formal Caregivers’ Burden in Alzheimer’s Disease Psychological and Behavioral Symptoms in Alzheimer’s Disease represent substantial challenges for caregivers and healthcare systems. Agitation, apathy, and depression are often reported among the most burdensome symptoms due to their disruptive impact on patient functioning and caregiver stress. While anxiety and depression frequently appear across studies, inconsistencies in reported prevalence such as those observed by Song and Oh (2015) [ 6 ] can be attributed to variability in study populations and the use of diverse diagnostic tools and rating scales, highlighting the need for standardized assessment approaches. In our meta-analysis, we addressed this challenge by exclusively aggregating mean scores from the NPI subdomains, rather than symptom prevalence. This approach allows for a more nuanced understanding of symptom intensity, which incorporates both frequency and severity, and reflects the clinical burden more accurately from the caregiver's perspective. The NPI is considered one of the most robust and widely validated tools for quantifying PBSA across domains like agitation, depression, apathy, and delusions (Cummings et al., 1994) [ 2 ]. By focusing solely on NPI-derived scores, we ensured a more homogeneous and clinically meaningful synthesis of the data across studies, minimizing heterogeneity due to tool variability and enabling more direct comparisons of symptom impact. The importance of caregiver perception in this domain has been emphasized in recent studies. Florindo et al.[ 61 ], results indicated that clinicians frequently perceive PBSA differently than caregivers;. They noted that discrepancies between caregivers and clinicians over PBSA tend to be greater in mild dementia than in more moderate forms. The caregivers' tendency to overestimate agitation and anxiety and to underestimate apathy could be a reflection of their emotional distress or lack of training. This idea is reinforced by Lorenzo-López et al. (2017) [ 62 ], which found that agitation and aggression caused significantly more distress to formal caregivers. Besides these aspects, the research of Song and Oh (2015)[ 6 ] also addressed the burden created by PBSA for professional caregivers in nursing homes. They identified a significant correlation between caregiver distress and the presence of more severe PBSA symptoms, in particular agitation/aggression. Professional caregivers, who are more directly involved in the daily care of dementia patients, showed higher levels of distress than registered nurses although not significantly. This is especially true when it comes to formal care settings, where professional caregivers are faced with a dual expectation: cope with troublesome behaviors and still attend to everyone else's needs, creating additional emotional demands. Professional caregivers described their most distressing symptoms as agitation and aggression, which is consistent with other studies that have shown that these symptoms cause greatest distress for formal caregivers. The study by Allegri et al. (2006)[ 7 ], emphasizes that symptoms such as hallucinations, aggression, and sleep disturbances are significant predictors of caregiver burden in AD, which aligns with your review's finding that agitation and aggression are particularly distressing. Furthermore, Allegri's work highlights the gap between caregiver and clinician perceptions, noting that caregivers often report more functional impairment from these symptoms, even in mild to moderate levels of cognitive impairment. Allegri’s work also illustrated that caregiving is not only stressful but can cause negative psychological effects like increased use of psychotropic drugs among formal caregivers. Moreover, behavioral issues such as aggression and issues with sleep disturbances are often highlighted as contributing factors to patients’ institutionalization, further strengthening the notion that severe behavioral disturbances amplify caregiver distress and can directly contribute to initiating important decisions regarding patient management. The study by Wood et al. (1999)[ 49 ] also corroborated with the idea that agitation and apathy are the most stressful symptoms from the perspective of caregivers alongside family caregivers and professionals who care for those with dementia. These findings underscore the necessity for standardized assessment instruments to reduce inconsistency in symptom assessment and to ensure that appropriate interventions are initiated. Education on the emotional impact of severe PBSA, along with training and resources to manage these symptoms, has the capability to both assist caregivers in alleviating caregiver burden, as well as improve the quality of care provided to individuals with AD. The presence of PBSA, which create a significant burden on caregivers, significantly influences caregiver burden in Alzheimer's disease. The research we uploaded showed that agitation/aggression represents one of the most distressing symptoms first-line professionals, such as nurses and care workers, can face. This is in keeping with the findings of Lorenzo-López et al. (2017) [ 62 ] and Gomez-Gallego et al. (2012) [ 50 ], who noted that the management of these symptoms in formal care settings was associated with significantly greater levels of distress. It is important to highlight the positive correlation found between the severity of PBSA and caregiver distress, as agitation and aggression has been shown to be especially distressing, and thus, adds to the understanding of the burden experienced by caregivers demonstrated a positive correlation between PBSA severity and caregiver distress, with a mean burden score of 15.58 (95% CI [13.38, 44.55]). Funnel plots suggested a publication bias, where studies reporting high burden levels were more likely to be published, which might lead to an incomplete understanding of the caregiver experience. This bias highlights the need for a balanced approach when interpreting caregiver distress, as more benign findings may be underreported. Finally Ribas et al. (2020)[ 65 ] highlighted the significance of training caregivers, finding that many formal caregivers, including those with medical training, do not have access to adequate coping strategies for PBSA management. This is reflected in a Korean study[ 6 ], where care workers reported higher levels of distress than registered nurses. This difference also implies that disparities in professional training and direct patient care may lead to discrepancies in distress levels between different care providers. The results underscore the need for specialized training to enable caregivers to manage PBSA effectively. Goodson et al. (2021)[ 15 ] illustrated the cultural and structural barriers that perpetuate distress in caregivers, especially in the absence of appropriate systemic support. In the Korean study [ 6 ], caregiver workload and the number of residents managed by individual caregivers were found to have an immediate impact on distress levels, which is practically mirrored with the two issues noted previously. In nursing homes, care workers often have multiple residents to take care of, stressing them out even more. This adds to the growing body of literature that highlights the need for a more systematic approach to provide support and interventions to address the burden of caregiving, especially in the case of those caring for individuals with AD and PBSA. Providing adequate care for patients with AD can impose considerable mental health risks, especially depression and anxiety on caregivers, which may be heightened by PBSA. Sołtys and Tyburski (2020) [ 12 ] conducted a study of 100 caregivers and support provides to highlight those personal resources (for example self-efficacy, sense of coherence) are important factors in predicting mental health among caregivers. Caregivers who demonstrated low comprehensibility and self-efficacy were found to have greater distress, consistent with PBSA studies indicating that severe symptoms contribute to caregiver burden. Emotional support was also mentioned as a significant predictor of depressive symptoms among formal caregivers, which indicates the need for institutional support and training to improve coping mechanisms. The results of this study illustrate the role of societal support, self-efficacy, and trained caregivers in alleviating the emotional burden of caregiving responsibilities, especially in healthcare settings where formal caregivers are more susceptible to long-term stress and burnout. Integrating these insights into caregiver intervention strategies could help reduce the mental health burden due to both BPSA and AD care. There are only a few studies on PBSA and formal caregivers which are also generally cross-sectional studies or with bias, such as publication bias, an example of which can be found when studies with more extreme outcomes are more likely to be published. This calls for further rigorous and well-crafted studies that can be generalized to the wider formal caregiver population. Caregivers’ Knowledge of AD It appears there is a gap in the existing literature, particularly regarding formal caregivers' knowledge of PBSA. While only one study superficially addresses the subject, focusing solely on anosognosia, a precursor rather than a PBSA. This relates to the article by Vignolo (2024)[ 45 ] whose main findings are concerned with the knowledge of healthcare workers about anosognosia and its influence. Vignolo conducted a study exposing a moderate level of knowledge among healthcare professionals such as those employed in the field of AD, but significant limits in the identification, assessment and management of anosognosia. The study also noted that training in gerontology, AD and anosognosia improved caregivers’ competence and gave them the tools to cope with behavioral symptoms of patients considerably. This ties closely with findings from Grosclaude (2007)[ 33 ] and others, such as Zhao et al. (2022) [ 66 ]. and Ribas et al. (2020) [ 65 ], who noted that structured training interventions could bridge knowledge gaps and enhance caregiver preparedness, thereby reducing caregiver burden. The study suggests that targeted, experience-based training programs are crucial for improving caregivers' skills in handling complex behavioral symptoms of AD, including ,agitation, and apathy. In our met-analysis, forest plots indicated a wide variability in caregivers’ knowledge of AD. Conclusion This meta-analysis highlights the critical role of PBSA in professional caregivers’ burden. Our findings emphasize the need for standardized assessment tools and structured training programs to improve professional caregiver awareness and reduce the impact of PBSA on caregivers' burden. Increasing caregiver awareness of PBSA is crucial for reducing these symptoms in patients and alleviating professional caregiver’s stress. Due to the large heterogeneity revealed in our meta-analysis, it would be valuable to conduct a large national study on caregivers' knowledge of PBSA and their perceptions of these symptoms. Such a study would provide insights into how to develop tailored training programs aimed at improving caregiver preparedness and optimizing intervention strategies. While addressing some of the potential biases in the literature on professional caregivers burden, these data could be utilized to provide a clearer understanding of the issue. Further research is necessary to explore long-term outcomes of caregiver education programs and the efficacy of structured interventions in reducing caregiver burden and improving patient quality of life. Abbreviations PBSA(Psychological and Behavioral Symptoms of Alzheimer’s disease),AD(Alzheimer’s disease),NPI(neuropsychiatric inventory) Declarations Authors contribution SK contributed at the validation of the subject and the study, AM contributed to the drafting of the research protocol, literature review, meta-analysis and the preparation of the manuscript. This manuscript has been read and approved by all the authors. Ethical approval Not applicable Funding No Funding Acknowledgements To Adekunle Roseline who contributed in meta-analysis with metapackage R and Charles Murhula who helped registering the Protocol in PROSPERO. Competing interest All other authors declare that there is no conflict of interest related to the writing and publication of this article. Clinical trial number not applicable. Ethics, Consent to Participate, and Consent to Publish declarations not applicable. References Chappell NL, Novak M. Caring for institutionalized elders: stress among nursing assistants. 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Hum Resour Health. 2020;18(1):41. doi:10.1186/s12960-020-00469-9 Mak E, Chin R, Ng LT, Yeo D, Hameed S. Clinical associations of anosognosia in MCI and Alzheimer’s: anosognosia and dementia. Int J Geriatr Psychiatry. 2015;30:1207–1214. doi:10.1002/gps.4275 Kwon CY, Lee B. Prevalence of behavioral and psychological symptoms of dementia: a systematic review. Front Psychiatry. 2021;12:741059. doi:10.3389/fpsyt.2021.741059 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7199792","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":492707098,"identity":"96922257-f643-4eb7-8bf3-4395026449f3","order_by":0,"name":"Aline 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distribution of the included studies.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7199792/v1/ae396231728d99291607235d.png"},{"id":88005544,"identity":"88192e8d-2c88-4a71-af44-1e5a98a51fb4","added_by":"auto","created_at":"2025-07-31 10:44:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":158113,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of pooled mean scores for PBSA symptoms.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7199792/v1/feb960e4bb18362e466ae782.png"},{"id":88004338,"identity":"2b43f057-dc12-4602-98a0-06973f7f8aca","added_by":"auto","created_at":"2025-07-31 10:36:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":129154,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of pooled caregiver knowledge scores.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7199792/v1/46e21947fe241cc284b2ca2d.png"},{"id":88004353,"identity":"34a6c334-5c27-40cf-a409-b058d692c344","added_by":"auto","created_at":"2025-07-31 10:36:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":33344,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of caregiver burden (Zarit scores).\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7199792/v1/8bccd67115f549aa496856e3.png"},{"id":88004342,"identity":"3a76fb51-4c13-4093-9d98-f99855279111","added_by":"auto","created_at":"2025-07-31 10:36:16","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":36755,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-regression plot showing the effect of sample size on caregiver burden.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7199792/v1/1bf7a30840e82ba41ebad5f5.png"},{"id":92728728,"identity":"7e9982fe-2ba0-4fe6-8b29-5ce3d12603c7","added_by":"auto","created_at":"2025-10-03 15:10:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1475468,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7199792/v1/45cd4556-a7e2-48fb-9d99-1ee247d9a2b6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Systematic Review and Meta-Analysis of Psychological and Behavioral Symptoms in Alzheimer’s Disease and Their Impact on Professional Caregiver Burden","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAlzheimer\u0026rsquo;s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and significant psychological and behavioral symptoms (Psychological and Behavioral Symptoms of Alzheimers\u0026rsquo; disease, PBSA)[11]. These symptoms, including agitation, aggression, depression, anxiety, and apathy, pose substantial challenges for both patients and caregivers[6].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to a systematic review by Kwon and Lee in 2020[71], the pooled prevalence rates of PBSA among Alzheimer\u0026rsquo;s patients are as follows: agitation and aggression (31%), aberrant motor behavior (20%), eating disorders (21%), wandering (15%), sleep disturbances (13%), and disinhibition (8%). Managing PBSA is a crucial aspect of AD care, as these symptoms can exacerbate cognitive decline, reduce patients\u0026apos; quality of life, and increase caregivers\u0026rsquo; burden[6].\u003c/p\u003e\n\u003cp\u003eFormal caregivers, including nurses, aides, and other healthcare professionals, play a critical role in managing PBSA in institutional and home-care settings[67]. Their perception and understanding of these symptoms can influence care strategies, patient outcomes, and the caregivers\u0026rsquo; own psychological well-being[6]. Despite their professional expertise, caregivers often face difficulties in interpreting and responding to PBSA due to variations in training, experience, and personal coping mechanisms[18]. Understanding the extent of caregivers\u0026rsquo; knowledge and the impact of PBSA is essential for designing effective interventions that enhance patient care and mitigate caregiver stress.\u003c/p\u003e\n\u003cp\u003eExisting literature on caregiver burden and the management of PBSA highlights disparities in the recognition and handling of these symptoms[65]. While some caregivers demonstrate a high level of awareness and adaptability, others struggle due to inadequate training and emotional exhaustion[15]. The high heterogeneity of findings across studies underscores the need for \u0026nbsp;a comprehensive review to consolidate knowledge and identify gaps in caregiver education and support systems.\u003c/p\u003e\n\u003cp\u003eGiven the crucial role of structured education and support for formal caregivers and individuals AD, this study presents a systematic review and meta-analysis of caregivers\u0026rsquo; knowledge of PBSA and symptom severity. Formal caregivers\u0026rsquo; knowledge of PBSA significantly influences AD management. Synthesizing evidence from multiple studies, this research aims to identify key areas for intervention and inform policies on training and support strategies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePurpose of the study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary objective of this study is to assess formal caregivers\u0026rsquo; knowledge of PBSA and their impact on caregivers\u0026rsquo; burden. The present study provides estimated pooled values of \u0026nbsp;PBSA, caregivers\u0026rsquo; knowledge and burden scores. Specifically, the study aims to :\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;- Identify the most commonly reported PBSA symptoms and assess their severity.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; -Evaluate the level of caregiver knowledge regarding PBSA and its influence on care quality.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; -Assess the effects of PBSA on caregiver burden.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eThis systematic review and meta-analysis followed PRISMA guidelines [68]. The study systematically searched PubMed, PsycINFO, and Google Scholar for relevant literature published up to December 2024, using Mesh terms related to Alzheimer\u0026rsquo;s disease, behavioral troubles, knowledge and formal caregivers:\u003c/p\u003e\n\u003cp\u003e-Alzheimer\u0026rsquo;s disease AND formal caregiver\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;-Alzheimer disease\u0026rsquo;s AND formal caregiver AND behavioral symptoms\u003c/p\u003e\n\u003cp\u003e-\u0026nbsp;Alzheimer\u0026rsquo;s disease OR dementia AND behavioral disturbances OR behavioral problems OR neuropsychiatric symptoms AND formal caregiver AND burden OR quality of life\u003c/p\u003e\n\u003cp\u003eWe used the \u003cstrong\u003eC\u003c/strong\u003eADIMA platform to facilitate study selection, quality assessment, and data extraction.\u003c/p\u003e\n\u003cp\u003eThe protocole of this study was registered in PROSPERO (number : CRD420250653427) and available \u0026nbsp;on https://www.crd.york.ac.uk/PROSPERO2/view/CRD420250653427.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion Criteria :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e-Studies examining formal caregivers (healthcare professionals) providing care for AD patients.\u003c/p\u003e\n\u003cp\u003e-Studies reporting the impact of PBSA, including agitation, aggression, anxiety, and apathy, on caregivers\u0026rsquo; burden\u003c/p\u003e\n\u003cp\u003e-Quantitative and qualitative studies evaluating the impact of caregiver burden and knowledge on patient care.\u003c/p\u003e\n\u003cp\u003e-Studies employing validated assessment tools for measuring PBSA and caregiver burden.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion Criteria :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e-Studies focused solely on pharmacological interventions without caregiver involvement.\u003c/p\u003e\n\u003cp\u003e-Studies on informal caregivers or family members.\u003c/p\u003e\n\u003cp\u003e-Case reports, editorials, and theoretical studies without empirical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction and analysis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e-Data extraction was conducted using the CADIMA platform to ensure systematic collection and organization of the studies\u0026rsquo;s findings. We extracted means and standard deviations (SD) and sample sizes of PBSA(NPI Score), caregiver burden score (Zarit Burden Score) and knowledge scores(ADKS), which were then synthesized in forest plots to illustrate heterogeneity across studies. Statistical analysis was performed using the R package METAFOR, which allowed for precise estimation of pooled mean effects and confidence intervals. Publication bias was assessed using funnel plots, and heterogeneity among studies was evaluated using I\u0026sup2; statistics. Additionally, a mixed-effects meta-regression was performed to evaluate the impact of sample size (N) on variability of the formal caregiver burden score.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eWe conducted a systematic review of the literature on professional caregivers' knowledge, impact, and burden related to PBSA. A total of 918 records were identified, of which 825 were excluded because they did not meet the selection criteria. We fully reviewed 65 articles and included 56 in the systematic review and meta-analysis\u003cb\u003e[\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e]\u003c/b\u003e.Most of the studies were conducted in Europe and Asia\u003cb\u003e[\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e]\u003c/b\u003e. The literature search was conducted from October 2024 to January 2025, and it covered studies up until December 2024.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe table below \u003cb\u003e[table.1]\u003c/b\u003e shows the characteristics of the 56 studies included in our systematic review, showing that they\u0026ensp;were diverse regarding their design, population, major findings, geographical and cultural factors, and the addressed themes. The studies are of various study designs,\u0026ensp;including cross-sectional studies, qualitative interviews, randomized controlled trials, integrative reviews, and provide a broad overview of caregivers' knowledge and impact of the PBSA. Although some of the included studies also involved both formal and informal caregivers, the current\u0026ensp;review was concentrated on formal caregivers to provide a more uniform comparison of knowledge levels, and burden.\u003c/p\u003e\u003cp\u003eThe geographic and cultural diversity of the studies (spanning North America, Europe, Asia, South America, and Africa), underscores the influence of healthcare systems, societal attitudes, and access to caregiver training on study outcomes. The following are the major themes explored: caregiver burden, emotional distress, knowledge\u0026ensp;gaps, PBSA intervention strategies, and safety concerns. Some studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] discussed the emotional and psychological burden of caregiving, and others [\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e] underlined the short fall of knowledge of who\u0026ensp;give the care, especially healthcare providers. Other studies have analyzed link between anosognosia and care-giver burden [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe strength of these studies lies in their contributions to understanding the challenges formal caregivers face and the effectiveness of training and intervention programs. Yet, limitations include cross-sectional designs for\u0026ensp;most of the articles, restricting causal interpretations, and varied sample sizes, influencing generalizability. Although limited by these factors, the table provides a useful synthesis of emerging research with a clear call for additional studies of culturally tailored interventions, long-term caregiver outcomes, and approaches to prepare\u0026ensp;formal caregivers to manage PBSA.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of studies included in the systematic review\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eContinent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCountry\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLocality\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStudy design\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePopulation studied\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKey outcomes\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYildizhan.,2018[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAurora, colorado\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQualitative study: semi structured interviews\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePatients with AD related dementias,formal caregivers and informal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCaregiver views on behavioral disturbances and impact on firearm safety. Impact on Caregivers: Caregiver stress, fear, conflict, managing dementia related safety issues. Caregiver emotional and practical responses to safety issues.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLorenzo-lopez et al.,2017[\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSpain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ecoru\u0026ntilde;a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional observational study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBoth formal and informal caregivers, ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eQuantitative data on caregiver distress. Analyzes caregiver burden, symptom severity, and emotional responses.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCampana, m. et al.,2016[\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMarseille\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQuantitative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD patients, general pratictioners and informal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eBehavioral disturbances and management by general practitioners.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eyalon et al.,2009[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCalifornia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study usingquestionnaires\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD patients and formal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eBehavioral Disturbances\u003c/p\u003e\u003cp\u003eManagement knowledge and attitudes\u003c/p\u003e\u003cp\u003eCaregiver Stress and Emotional Impact\u003c/p\u003e\u003cp\u003eIntervention:\u003c/p\u003e\u003cp\u003eNonpharmacological\u003c/p\u003e\u003cp\u003ePharmacological\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFlorindo et al.,2015[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSouth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBrazil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBrasilia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQuantitative and qualitative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDementia patients,formal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eBehavioral Disturbances Reduction.\u003c/p\u003e\u003cp\u003eCaregiver Impact: Emotional and burden reduce\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePolzer et al.,2022[\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSpain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMadrid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePharmacist,employees of pharmaceutical compagny\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge Gaps Behavioral and Emotional Impact\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGarcia et al.,2020[\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeijing, shanghai\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNtegrative review of both qualitative and quantitative studies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHealthcare professionals\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eknowledge and attitude towards dementia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eZhao et al.,2022[\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCanada\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eManitoba\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eProfessional caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eImpact of Resident Behaviors on Caregiver Stress\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChappell et al.,1994[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNew york\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eProfessional caregivers,ad patients and family caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ehow professional and family caregivers differ in assessing behaviors.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobert et al.,2009[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGironde and alpes-maritimes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRandomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eProfessional caregivers and ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003efocus on non pharmacological interventions to manage PBSA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLukovits et al.,1992[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMississippi\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQuasi-experimental pretest-posttest design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNurses,ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003enursing staff perceptions regarding PBSA and impact on care.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBilal et al.,2016[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNurses,ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIdentification and management Behavioral Disturbances\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBoyd ,et al.,2001[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePoland\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWarsaw\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal and informal caregivers, AD patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMental Health Problems caregivers\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSoltys et al.,2020[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eColorado\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQualitative study,focus groups\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal and informal caregivers,ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eBehavioral troubles,communication\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRichter et al.,1995[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIsrael\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAcross israel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIndividuals with severe dementia-related and formal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCaregiver Burden and Mental Health during the COVID-19 pandemic\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKarni et al.,2022[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMalaysia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSelangor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQualitaive study,semi-structured interviews\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal and informal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eChallenges in dementia care,behavioral troubles cited\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" 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colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSpain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMurcia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional design\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD patients and formal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNeuropsychiatric symptoms, caregiving burden\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaria et al.,2012[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCalifornia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD patients and nurses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eBehavioral Symptoms,caregiver's burden\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWood et al.,1999[]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCanada\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal and informal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge of AD among professional caregivers\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmyth,2013[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAustralia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAustralia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eQueensland\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge of ad among professional caregivers\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTiana et al.,2007[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMissouri\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDiverse backgrounds including formal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge on ad\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBrian,2011[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNorway\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBergen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFinal year students in health fields\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge about AD among final-year students in health and social care\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSundaran ,2015[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSouth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePeru\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTacna, piura, trujillo, san martin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHealth professionals in peru\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge of dementia and AD among healthcare professionals in peru\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalaga et al.,2024[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eQatar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDoha\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePhysicians, nurses, students, and researchers in qatar (n\u0026thinsp;=\u0026thinsp;229)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eExamines knowledge, awareness, and attitudes of healthcare professionals regarding alzheimer\u0026rsquo;s disease.discusses training and its impact on care practice.\u003c/p\u003e\u003cp\u003eAlso adress gaps in training; emotional and professional impact of caregiving; strategies to address knowledge gaps.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePaul et al.,2023[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSpain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eJaen, andalusia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge regarding ad in nurses in spain\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLaura et al.,2019[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia and north America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited Sstates and china\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAlabama and hong kong\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge and biases about ad among nurses in the u.s. And china\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChristine et al.,1994[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfrica\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEgypt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMinia, beni-suif, assuit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge levels of formal caregivers about alzheimer's disease in egypt\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eShimaa et al.,2022[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnites States\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eChicago\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePharmacists\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePharmacists\u0026rsquo; knowledge of ad disease care\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMarketa ,2017[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eJordan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNorth jordan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNurses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge levels about ad among nurses in jordanian hospitals\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAljezawi et al.,2021[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited States\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eFlorida\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eMedical and nurse students'\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge about ad before and after an interprofessional education program\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMccaffrey, r.,et al.,2013[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSaudi Arabia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMajmaah,l-jouf,\u003c/p\u003e\u003cp\u003e hafer al-batin,taif\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNursing students\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eKnowledge levels about ad\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJazi ,2024[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eJiangsu province\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNurse staff\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eEvaluate alzheimer's disease knowledge\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eZuo et al.,2023[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGermany\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNorth rhine-westphalia.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQualitative study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eProfessional caregivers and patient's families\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eExamine the emotional experiences of patients with advanced alzheimer's disease\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKarger, 2018[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNorway\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNorthern norway\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQualitative intervention study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers and ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eEvaluate caregivers\u0026rsquo; interactions with patients\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHansebo et al.,2002[\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited kingdom\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNorth wales\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eObservational validation study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAwareness and responsiveness in individuals with severe dementia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClare et al.,2012[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNetherlands\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNijmegen and eindhoven\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDescriptive qualitative study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers and ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eIdentification and management of apathy in dementia patients\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNijsten et al.,2023[\u003cspan citationid=\"CR35\" 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colname=\"c3\"\u003e\u003cp\u003eTurkey\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIstanbul\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eProfessional caregivers and ad patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCaregiver burden, and burnout levels among professional caregivers of AD patients\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHayajneh et al.,2014[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eJordan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAman\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eQualitative study: semi structured interviews and quantitative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD patients and formal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCaregiver adaptation and empathy\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBernardino et al.,2015[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSpain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSalamanca\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRandomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIndividuals with mild AD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eUnawareness of deficits (anosognosia)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDaniel et al.,2015[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia,south America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eChina, india, peru, mexico, cuba, dominican republic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeijing, chennai, havana, santo domingo, caracas, lima, mexico\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional population-based survey\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRelationship between anosognosia and behavioral symptoms\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStephen et al.,2023[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUnited states\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCalifornia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients, physicians, care partners\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePerspectives of patients, care partners, and primary care physicians regarding the management of AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eShiri s. et al.,2016[\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIsrael\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTel aviv\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRelationship between ad illness representations and burnout among social workers and nurses\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSandra v. et al.,2013[\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGermany\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eD\u0026uuml;sseldorf\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRelationship between anosognosia (impaired awareness of illness) and depression in patients with AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eS. Stirati et al.,2008[\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eEvaluate anosognosia (unawareness of illness) in patients with AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSalmon et al.,2023[\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBelgium, italy, united kingdom, germany\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLiege,milan,cologne,dresden,manchester\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCompare unawareness (anosognosia) across different domains (cognition, behavior, daily activities) in AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThomas et al.,2023[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eParis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDetect anosognosia in ad from the prodromal stage using the healthy aging brain care monitor\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKenji et al.,2020[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eJapan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTokyo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eExplore neuropsychiatric symptoms associated with anosognosia in patients with AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBora et al.,2017[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSouth korea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSeaoul\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eInvestigate the prevalence, clinical characteristics, and behavioral symptoms of anosognosia in patients with AD early-onset\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYukiko et al.,2005[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eJapan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eKobe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eInvestigate the relationship between anosognosia and patient characteristics, psychiatric symptoms, and cognitive deficits in ad\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYohko et al.,2013[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eJapan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMaebashi\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePrevalence of anosognosia in patients with ad dementia, its association with behavioral and psychological symptoms\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVignolo et al.,2024[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEurope\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eToulouse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFormal caregivers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHealthcare workers' knowledge and experiences in managing anosognosia and behavioral troubles in patients with AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMak. et al.,2015[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSingapore\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSingapore\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAnosognosia and neuropsychiatric symptoms in AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCorina et al.,2013[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSouth America\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBrazil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBrasilia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAD Patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAnosognosia and neuropsychiatric symptoms in AD\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eAgitation\u003c/b\u003e: Agitation showed the highest pooled mean NPI score of 2.90 (95% CI: 0.64\u0026ndash;5.17), indicating a moderate intensity of symptoms as measured by the combined frequency and severity (score range 0\u0026ndash;12). This reflects that agitation, while variable, tends to be a symptom of meaningful clinical impact in the studied populations. Substantial heterogeneity was observed (I\u0026sup2; = 92.9%), reflecting differences in study populations,and methodologies (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eDepression\u003c/b\u003e: Depression had a pooled mean intensity score of 15.92 (95% CI: 8.89\u0026ndash;22.96), with very high heterogeneity (I\u0026sup2; = 99.7%). Although this score exceeds the classic NPI subdomain maximum of 12, it likely reflects aggregated or modified scoring approaches used across studies, such as inclusion of caregiver distress ratings or summation of multiple related items under the depression domain. Therefore, this score should be interpreted as an elevated overall burden or intensity of depressive symptoms rather than a simple frequency \u0026times; severity product, confirming depression as a frequently intense behavioral symptom in Alzheimer\u0026rsquo;s disease across studies.\u003c/p\u003e\u003cp\u003e\u003cb\u003eApathy\u003c/b\u003e: The pooled mean NPI score for apathy was 9.40 (95% CI: 3.48\u0026ndash;22.28), accompanied by high heterogeneity (I\u0026sup2; = 98.1%). Despite variability, these results support apathy as a significant symptom affecting patients with AD.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAnxiety\u003c/b\u003e: Anxiety had a pooled mean intensity score of 1.72 (95% CI: 0.98\u0026ndash;2.46) with moderate heterogeneity (I\u0026sup2; = 40.1%). Most studies report notable symptom intensity, indicating anxiety as a common behavioral feature in Alzheimer\u0026rsquo;s disease.\u003c/p\u003e\u003cp\u003eHeterogeneity and Bias: Across symptoms, high heterogeneity (I\u0026sup2; \u0026gt;75%) indicates substantial variability in study design, populations, and NPI assessment methods. Forest plots (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e) illustrate these variations in symptom intensity, while funnel plots (supplementary materials)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFormal caregivers Burden due to PBSA\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMeta-Regression on Factors Influencing Zarit Burden Scores\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMeta-Regression Results Predicting Zarit Burden Scores (Mixed-Effects Model)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEstimate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e95% CI (Lower)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95% CI (Upper)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntercept\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.144\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-7.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e48.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSample Size (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.804\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-0.149\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.115\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eA mixed-effects meta-regression model was conducted to explore whether the sample size (N) could explain the variability in mean Zarit scores across studies. The model included four studies (k\u0026thinsp;=\u0026thinsp;4), and the restricted maximum-likelihood (REML) estimator was used to estimate between-study variance.\u003c/p\u003e\u003cp\u003eThe model showed the following fit statistics: log-likelihood = -8.83, AIC\u0026thinsp;=\u0026thinsp;23.66, BIC\u0026thinsp;=\u0026thinsp;19.74, and AICc\u0026thinsp;=\u0026thinsp;47.66. These values provide a general indication of model adequacy but are primarily useful for comparison across competing models.\u003c/p\u003e\u003cp\u003eHeterogeneity\u003c/p\u003e\u003cp\u003eThe estimated between-study variance (tau\u0026sup2;) was 400.51 (SE\u0026thinsp;=\u0026thinsp;401.22), with a corresponding tau (\u0026radic;tau\u0026sup2;) of 20.01, indicating a substantial degree of residual heterogeneity. The I\u0026sup2; value was 99.85%, suggesting that nearly all of the observed variability in effect sizes was due to differences between studies rather than sampling error. The H\u0026sup2; value was 683.73, and the R\u0026sup2; (the proportion of heterogeneity explained by the moderator) was 0.00%, meaning the moderator did not account for any of the observed heterogeneity. The test for residual heterogeneity was significant: QE(df\u0026thinsp;=\u0026thinsp;2)\u0026thinsp;=\u0026thinsp;1944.10, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, confirming considerable heterogeneity remained unexplained after accounting for the moderator. The test for the moderator (sample size N) was not significant: QM(df\u0026thinsp;=\u0026thinsp;1)\u0026thinsp;=\u0026thinsp;0.0614,p\u0026thinsp;=\u0026thinsp;0.8043, indicating that sample size did not significantly influence the mean Zarit burden scores.\u003c/p\u003e\u003cp\u003eThe intercept of the model was estimated at 20.83 (SE\u0026thinsp;=\u0026thinsp;14.25, p\u0026thinsp;=\u0026thinsp;0.144), and the regression coefficient for sample size (N) was \u0026minus;\u0026thinsp;0.017 (SE\u0026thinsp;=\u0026thinsp;0.067, p\u0026thinsp;=\u0026thinsp;0.804). The 95% confidence interval for the N coefficient ranged from \u0026minus;\u0026thinsp;0.149 to 0.115, which includes zero, reinforcing the non-significance of the effect.\u003c/p\u003e\u003cp\u003eThe results suggest that sample size does not significantly predict differences in caregiver burden as measured by the Zarit scale across the included studies. Moreover, the presence of substantial unexplained heterogeneity implies that other study-level characteristics (e.g., type of intervention, caregiver population, cultural factors) should be considered in future analyses.\u003c/p\u003e\u003cp\u003e\u003cb\u003eProfessional caregivers knowledge and experience in AD\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe forest plots present the pooled means of different scores and questionnaires on professional caregivers' knowledge and experience regarding Alzheimer's disease, showing notable variability across studies [Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe forest plot on treatment knowledge shows high heterogeneity (I\u0026sup2; = 98.3%), indicating differing levels of understanding among caregivers (pooled mean\u0026thinsp;=\u0026thinsp;4.21, 95% CI [3.45, 5.02]). Similarly, the forest plot on disease progression knowledge also displays significant variability (I\u0026sup2; = 97.6%), with caregivers showing a range of understanding (pooled mean\u0026thinsp;=\u0026thinsp;6.14, 95% CI [5.02, 7.31]).\u003c/p\u003e\u003cp\u003eConcerning the impact of AD on daily life, the plot suggests that most caregivers have a solid grasp, though the high heterogeneity (I\u0026sup2; = 95.2%) points to differences in their understanding (pooled mean\u0026thinsp;=\u0026thinsp;5.98, 95% CI [4.87, 7.02]). The forest plot on caregiver knowledge in managing symptoms indicates significant effect sizes (pooled mean\u0026thinsp;=\u0026thinsp;7.45, 95% CI [6.32, 8.59]), but high heterogeneity (I\u0026sup2; = 96.8%) suggests that some professional caregivers are less informed about best practices, highlighting the need for more focused trainings.\u003c/p\u003e\u003cp\u003eThe plot on symptom knowledge shows a statistically significant global effect (pooled mean\u0026thinsp;=\u0026thinsp;2.67, 95% CI [2.01, 3.35]), although there is considerable variability between studies (I\u0026sup2; = 99.5%), suggesting a general but uneven understanding of AD symptoms. Funnel plots generally suggest publication bias, with studies showing better caregiver knowledge being more likely to be published.\u003c/p\u003e\u003cp\u003eRegarding professional caregiver experience, those with less than five years of experience in AD patients care show high heterogeneity (I\u0026sup2; = 99.6%), indicating diverse experiences, which are hard to generalize (pooled mean\u0026thinsp;=\u0026thinsp;8.23, 95% CI [7.12, 9.47]). In contrast, caregivers with more than five years of experience report a significant experience (pooled mean\u0026thinsp;=\u0026thinsp;15.76, 95% CI [14.03, 17.52]), but with a broad range of uncertainty and extreme heterogeneity (I\u0026sup2; = 100%). These results indicate that caregiver knowledge and experience vary greatly, suggesting the need for targeted interventions to standardize training, particularly in areas with significant variability.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cb\u003eInstruments for evaluating PBSA\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMultiple validated scores and questionnaires were employed in the studies included in our meta-analysis to assess various PBSA. Although different tools were cited or used, we focused solely on Neuropsychiatric Inventory (NPI) scores for the subdomains, as it is possibly the most frequently applied tool measuring a wide array of PBSA such as anxiety, depression, agitation, apathy, and irritability. Depression was also specifically investigated using the Geriatric Depression Scale (GDS) and the Patient Health Questionnaire-9 (PHQ-9) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], while anxiety symptoms were assessed with the Generalized Anxiety Disorder-7 (GAD-7) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and the Goldberg Anxiety Questionnaire. Additionally, apathy was evaluated with the Apathy Evaluation Scale (AES), an 18-item instrument assessing apathy based on a person\u0026rsquo;s thoughts, motivation, and emotions over the previous four weeks, as well as the Apathy Inventory (AI) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTo assess professional caregivers\u0026rsquo; knowledge on AD, the Alzheimer\u0026rsquo;s Disease Knowledge Scale (ADKS) was used in some studies [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This widely used 30-item true/false questionnaire assesses caregivers\u0026rsquo; knowledge across seven domains: life impact, risk factors, symptoms, treatment and management, assessment and diagnosis, caregiving, and disease progression. Professional caregivers\u0026rsquo; years of experience in AD care were commonly self-reported through demographic questionnaires, with some studies reporting means and SD, particularly in logistic regression analyses exploring how caregiver expertise influences patient care and mental health outcomes.\u003c/p\u003e\u003cp\u003eProfessional caregiver burden was predominantly evaluated using the Zarit Caregiver Burden Scale, which assesses perceived caregiving burden and is frequently used in studies measuring caregiver stress and well-being [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The Maslach Burnout Inventory (MBI), measuring burnout levels among professional caregivers, was also applied in several studies [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTo address methodological heterogeneity, we used a random-effects model to normalize and pool mean scores, enabling us to extract meaningful patterns across studies\u003c/p\u003e\u003cp\u003eThus, despite heterogeneity in approaches, our meta-analysis strengthened the reliability of conclusions regarding PBSA and caregiver burden in AD.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePBSA and Formal Caregivers\u0026rsquo; Burden in Alzheimer\u0026rsquo;s Disease\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePsychological and Behavioral Symptoms in Alzheimer\u0026rsquo;s Disease represent substantial challenges for caregivers and healthcare systems. Agitation, apathy, and depression are often reported among the most burdensome symptoms due to their disruptive impact on patient functioning and caregiver stress. While anxiety and depression frequently appear across studies, inconsistencies in reported prevalence such as those observed by Song and Oh (2015) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] can be attributed to variability in study populations and the use of diverse diagnostic tools and rating scales, highlighting the need for standardized assessment approaches.\u003c/p\u003e\u003cp\u003eIn our meta-analysis, we addressed this challenge by exclusively aggregating mean scores from the NPI subdomains, rather than symptom prevalence. This approach allows for a more nuanced understanding of symptom intensity, which incorporates both frequency and severity, and reflects the clinical burden more accurately from the caregiver's perspective. The NPI is considered one of the most robust and widely validated tools for quantifying PBSA across domains like agitation, depression, apathy, and delusions (Cummings et al., 1994) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. By focusing solely on NPI-derived scores, we ensured a more homogeneous and clinically meaningful synthesis of the data across studies, minimizing heterogeneity due to tool variability and enabling more direct comparisons of symptom impact.\u003c/p\u003e\u003cp\u003eThe importance\u0026ensp;of caregiver perception in this domain has been emphasized in recent studies. Florindo et al.[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e], results indicated that clinicians frequently perceive PBSA differently than caregivers;. They noted that discrepancies between caregivers and clinicians over PBSA\u0026ensp;tend to be greater in mild dementia than in more moderate forms. The caregivers' tendency to\u0026ensp;overestimate agitation and anxiety and to underestimate apathy could be a reflection of their emotional distress or lack of training. This idea is\u0026ensp;reinforced by Lorenzo-L\u0026oacute;pez et al. (2017) [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e], which found\u0026ensp;that agitation and aggression caused significantly more distress to formal caregivers.\u003c/p\u003e\u003cp\u003eBesides these aspects, the research of Song and Oh (2015)[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] also addressed the burden\u0026ensp;created by PBSA for professional caregivers in nursing homes. They\u0026ensp;identified a significant correlation between caregiver distress and the presence of more severe PBSA symptoms, in particular agitation/aggression. Professional caregivers, who are more directly involved in the daily care of dementia patients, showed higher levels of\u0026ensp;distress than registered nurses although not significantly. This is especially true\u0026ensp;when it comes to formal care settings, where professional caregivers are faced with a dual expectation: cope with troublesome behaviors and still attend to everyone else's needs, creating additional emotional demands. Professional caregivers described their most distressing symptoms as agitation and aggression, which\u0026ensp;is consistent with other studies that have shown that these symptoms cause greatest distress for formal caregivers.\u003c/p\u003e\u003cp\u003eThe study by Allegri et al. (2006)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], emphasizes that symptoms such as hallucinations, aggression, and sleep disturbances are significant predictors of caregiver burden in AD, which aligns with your review's finding that agitation and aggression are particularly distressing. Furthermore, Allegri's work\u0026ensp;highlights the gap between caregiver and clinician perceptions, noting that caregivers often report more functional impairment from these symptoms, even in mild to moderate levels of cognitive impairment.\u003c/p\u003e\u003cp\u003eAllegri\u0026rsquo;s work also illustrated that caregiving is\u0026ensp;not only stressful but can cause negative psychological effects like increased use of psychotropic drugs among formal caregivers. Moreover, behavioral issues such as aggression and issues with sleep\u0026ensp;disturbances are often highlighted as contributing factors to patients\u0026rsquo; institutionalization, further strengthening the notion that severe behavioral disturbances amplify caregiver distress and can directly contribute to initiating important decisions regarding patient management.\u003c/p\u003e\u003cp\u003eThe study by Wood et al. (1999)[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e] also corroborated with the\u0026ensp;idea that agitation and apathy are the most stressful symptoms from the perspective of caregivers alongside family caregivers and professionals who care for those with dementia. These findings underscore the necessity for standardized assessment instruments to reduce inconsistency\u0026ensp;in symptom assessment and to ensure that appropriate interventions are initiated. Education on the emotional impact of severe PBSA, along with training and resources to\u0026ensp;manage these symptoms, has the capability to both assist caregivers in alleviating caregiver burden, as well as improve the quality of care provided to individuals with AD.\u003c/p\u003e\u003cp\u003eThe presence of PBSA, which create a significant burden on caregivers, significantly influences caregiver burden in Alzheimer's disease. The research we uploaded showed that agitation/aggression represents one of the most distressing symptoms first-line professionals, such as nurses and care workers, can face. This is in keeping with the findings of Lorenzo-L\u0026oacute;pez et al. (2017) [\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e] and Gomez-Gallego et al. (2012) [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e], who noted that the management of these symptoms in formal care settings was associated with significantly greater levels of distress. It is important to highlight the positive correlation found between the severity of PBSA and caregiver distress, as agitation and aggression has been shown to be especially distressing, and thus, adds to the understanding of the burden experienced by caregivers demonstrated a positive correlation between PBSA severity and caregiver distress, with a mean burden score of 15.58 (95% CI [13.38, 44.55]). Funnel plots suggested a publication bias, where studies reporting high burden levels were more likely to be published, which might lead to an incomplete understanding of the caregiver experience. This bias highlights the need for a balanced approach when interpreting caregiver distress, as more benign findings may be underreported.\u003c/p\u003e\u003cp\u003eFinally Ribas et al. (2020)[\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e] highlighted the significance of training caregivers, finding that many formal caregivers, including those with medical training, do not have access to adequate coping strategies for PBSA management. This is reflected in a Korean study[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], where care workers reported higher levels of distress than registered nurses. This difference also implies that disparities in professional training and direct patient care may lead to discrepancies in distress levels between different care providers. The results underscore the need for specialized training to enable caregivers to manage PBSA effectively.\u003c/p\u003e\u003cp\u003eGoodson et al. (2021)[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] illustrated the cultural and structural barriers that perpetuate distress in caregivers, especially in the absence of appropriate systemic support. In the Korean study [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], caregiver workload and the number of residents managed by individual caregivers were found to have an immediate impact on distress levels, which is practically mirrored with the two issues noted previously. In nursing homes, care workers often have multiple residents to take care of, stressing them out even more. This adds to the growing body of literature that highlights the need for a more systematic approach to provide support and interventions to address the burden of caregiving, especially in the case of those caring for individuals with AD and PBSA.\u003c/p\u003e\u003cp\u003eProviding adequate care for patients with AD can impose considerable mental\u0026ensp;health risks, especially depression and anxiety on caregivers, which may be heightened by PBSA. Sołtys\u0026ensp;and Tyburski (2020) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] conducted a study of 100 caregivers and support provides to highlight those personal resources (for example self-efficacy, sense of coherence) are important factors in predicting mental health among caregivers. Caregivers who demonstrated low\u0026ensp;comprehensibility and self-efficacy were found to have greater distress, consistent with PBSA studies indicating that severe symptoms contribute to caregiver burden. Emotional support was also mentioned as a significant predictor of depressive symptoms among formal caregivers, which indicates the need for institutional support and training to improve coping mechanisms. The results of this study illustrate the role of societal support, self-efficacy, and trained caregivers in alleviating the emotional burden of caregiving responsibilities, especially in healthcare settings\u0026ensp;where formal caregivers are more susceptible to long-term stress and burnout. Integrating these insights into caregiver intervention strategies could help reduce the mental health burden due to both BPSA and AD care.\u003c/p\u003e\u003cp\u003eThere are only a few studies on PBSA and formal caregivers which are also generally cross-sectional\u0026ensp;studies or with bias, such as publication bias, an example of which can be found when studies with more extreme outcomes are more likely to be published. This calls\u0026ensp;for further rigorous and well-crafted studies that can be generalized to the wider formal caregiver population.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCaregivers\u0026rsquo; Knowledge of AD\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIt appears there is a gap in the existing literature, particularly regarding formal caregivers' knowledge of PBSA. While only one study superficially addresses the subject, focusing solely on anosognosia, a precursor rather than a PBSA.\u003c/p\u003e\u003cp\u003eThis relates to the article by Vignolo (2024)[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e] whose main findings are concerned with the knowledge of healthcare\u0026ensp;workers about anosognosia and its influence. Vignolo conducted a study exposing a moderate level of knowledge among healthcare professionals such as those employed in the field\u0026ensp;of AD, but significant limits in the identification, assessment and management of anosognosia. The study also noted that training in gerontology, AD\u0026ensp;and anosognosia improved caregivers\u0026rsquo; competence and gave them the tools to cope with behavioral symptoms of patients considerably.\u003c/p\u003e\u003cp\u003eThis ties closely with findings from Grosclaude (2007)[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and others, such as Zhao et al. (2022) [\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]. and Ribas et al. (2020) [\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e], who noted that structured training interventions could bridge knowledge gaps and enhance caregiver preparedness, thereby reducing caregiver burden. The study suggests that targeted, experience-based training programs are crucial for improving caregivers' skills in handling complex behavioral symptoms of AD, including ,agitation, and apathy. In our met-analysis, forest plots indicated a wide variability in caregivers\u0026rsquo; knowledge of AD.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis meta-analysis highlights the critical role of PBSA in professional caregivers\u0026rsquo; burden. Our findings emphasize the need for standardized assessment tools and structured training programs to improve professional caregiver awareness and reduce the impact of PBSA on caregivers' burden. Increasing caregiver awareness of PBSA is crucial for reducing these symptoms in patients and alleviating professional caregiver\u0026rsquo;s stress.\u003c/p\u003e\u003cp\u003eDue to the large heterogeneity revealed in our meta-analysis, it would be valuable to conduct a large national study on caregivers' knowledge of PBSA and their perceptions of these symptoms. Such a study would provide insights into how to develop tailored training programs aimed at improving caregiver preparedness and optimizing intervention strategies. While addressing some of the potential biases in the literature on professional caregivers burden, these data could be utilized to provide a clearer understanding of the issue.\u003c/p\u003e\u003cp\u003eFurther research is necessary to explore long-term outcomes of caregiver education programs and the efficacy of structured interventions in reducing caregiver burden and improving patient quality of life.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePBSA(Psychological and Behavioral Symptoms of Alzheimer’s disease),AD(Alzheimer’s disease),NPI(neuropsychiatric inventory)\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSK contributed at the validation of the subject and the study, AM \u0026nbsp;contributed to the drafting of the research protocol, literature review, meta-analysis and the preparation of the manuscript. This manuscript has been read and approved by all the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo Funding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo Adekunle Roseline who contributed in meta-analysis with metapackage R and Charles Murhula who helped registering the Protocol in PROSPERO.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll other authors declare that there is no conflict of interest related to the writing and publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics, Consent to Participate, and Consent to Publish declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eChappell NL, Novak M. 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Prevalence of behavioral and psychological symptoms of dementia: a systematic review. Front Psychiatry. 2021;12:741059. doi:10.3389/fpsyt.2021.741059\u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Alzheimer’s disease, behavioral and psychological symptoms, formal caregivers, caregiver burden, knowledge, meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-7199792/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7199792/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003cbr\u003e\nAlzheimer's disease is a progressive neurodegenerative disorder associated with cognitive decline and psychological and behavioral symptoms (PBSA), which significantly impact both patients and professional caregivers. Despite their central role in managing PBSA, limited research has evaluated caregivers’ knowledge of these symptoms and the burden they experience. Understanding caregivers’ perceptions and the intensity of PBSA is essential to improving care quality and caregiver well-being.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003cbr\u003e\nA systematic review and meta-analysis were conducted following PRISMA guidelines. Databases searched included PubMed, PsycINFO, and Google Scholar up to December 2024. Of 918 identified records, 56 studies met inclusion criteria. Data extraction was conducted using CADIMA, and statistical analyses were performed with the “METAFOR” package in R. Pooled effect sizes of mean Neuropsychiatric Inventory (NPI) subdomain scores were calculated to assess symptom intensity. A mixed-effects meta-regression examined whether sample size influenced caregiver burden variability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003cbr\u003e\nAgitation (pooled mean = 2.90; 95% CI [0.64, 5.17]), depression (15.92; 95% CI [8.89, 22.96]), apathy (9.40; 95% CI [3.48, 22.28]), anosognosia (15.92; 95% CI [8.89, 22.96]), and anxiety (1.72; 95% CI [0.98, 2.46]) were the most intense symptoms. Formal caregivers’ knowledge varied across studies, with pooled means of 2.67 (95% CI [2.02, 3.31]) for symptom knowledge and 6.24 (95% CI [5.02, 7.31]) for treatment knowledge. Substantial heterogeneity was present (I² \u0026gt; 90%). Meta-regression revealed that sample size was not a significant moderator of caregiver burden (estimate = -0.017, p = 0.804), with residual heterogeneity remaining high (I² = 99.85%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003cbr\u003e\nThis review highlights the high prevalence and intensity of PBSA in Alzheimer’s care and underscores the variability in caregiver knowledge and burden. Sample size does not account for differences in reported burden, suggesting the influence of other contextual or organizational factors. These findings emphasize the urgent need for structured education and support programs tailored to formal caregivers to enhance symptom management and reduce burden.\u003c/p\u003e","manuscriptTitle":"Systematic Review and Meta-Analysis of Psychological and Behavioral Symptoms in Alzheimer’s Disease and Their Impact on Professional Caregiver Burden","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-31 10:36:11","doi":"10.21203/rs.3.rs-7199792/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b9216639-5fa1-4bc8-bbb5-21600844c4f1","owner":[],"postedDate":"July 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-03T15:10:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-31 10:36:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7199792","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7199792","identity":"rs-7199792","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}