Nonpharmacological Multicomponent Intervention for Mild Cognitive Impairment with a Family-Patient Approach: Protocol for the Pilot Clinical Trial-INTERCOG Study

Nonpharmacological Multicomponent Intervention for Mild Cognitive Impairment with a Family-Patient Approach: Protocol for the Pilot Clinical Trial-INTERCOG Study | 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 Study protocol Nonpharmacological Multicomponent Intervention for Mild Cognitive Impairment with a Family-Patient Approach: Protocol for the Pilot Clinical Trial-INTERCOG Study Diana Carolina Tiga-Loza, William Armando Álvarez-Anaya, Raquel Rivera Carvajal, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8140713/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Given the absence of effective pharmacological treatments and the risk of progression to dementia ranging from 6–44.8% over approximately 4 years of follow-up, nonpharmacologicalmulticomponent interventions are emerging as promising strategies to improve or maintain cognitive function and quality of life in individuals with mild cognitive impairment (MCI). This pilot study aims to evaluate the potential efficacy and feasibility of a multicomponent and transdisciplinary intervention focused on the dyad of older adults with MCI-family caregivers to promote cognitive function in older adults. Methods A pilot, randomized, controlled, and double-blind clinical trial will be conducted with 102 dyads consisting of an older adult with MCI and their family caregiver. The participants will be randomly assigned to two groups: the intervention group (INTERCOG) and the control group. The INTERCOG group will receive a 12-week home-based intervention (two weekly sessions) with the support of a healthcare professional. The intervention components consist of cognitive training and stimulation, nutritional counseling, and physical exercises. Simultaneously, family members will participate in a training program on care and self-care. The control group will receive standard care and educational messages on infection prevention. Changes in global cognition (MMSE and MoCA) and in specific cognitive domains will be measured. The feasibility of the study will also be assessed through an analysis of recruitment, data collection, intervention acceptability, and implementation challenges. Secondary outcomes will include changes in health-related quality of life, caregiver burden, social support for family members, as well as changes in functional independence, frailty, physical capacity, family functioning, and nutritional status in patients, with follow-up at 3, 6, and 9 months. In a subsample of 40 participants, the diversity of the gut microbiota will be characterized, and the frequency of the APOE-ε4 allele will be determined. Discussion Multicomponent and transdisciplinary interventions focused on the caregiver–patient dyad have the potential to optimize cognitive outcomes and quality of life. This pilot study will allow us to identify key aspects of the feasibility and potential efficacy of INTERCOG intervention, crucial information for the design of future larger-scale studies. Trial registration : NCT06408103. December 6, 2024, atclinicaltrials.gov. In recruitment Cognitive dysfunction aged family caregivers clinical trial multicomponent feasibility Figures Figure 1 Introduction Population aging is expected to lead to an increase in chronic noncommunicable diseases, posing a challenge to health systems [1]. In the Americas, the global burden of dementia is projected to rise from 6.86 million cases in 2020 to 19.3 million in 2025, an escalation of more than threefold increase [2]. This projection underscores the need to implement comprehensive interventions that preserve cognitive function, prevent or slow the progression to dementia, and engage families, multiple sectors and public policy [3]. Interventions focusing on individuals with mild cognitive impairment (MCI) are crucial, given that progression to dementia can occur in 6% to 44.8% of cases, with an average follow-up of 3.7 years in low- and middle-income countries[4]. Preventing this progression is vital in countries such as Colombia, where the prevalence of MCI in the elderly population is 17.93% [5]. This risk of progression is significantly compounded by existing comorbidities, nearly tripling in uncontrolled diabetes (HR = 2.87, 95% CI 1.20–6.85) and doubling with cardiac comorbidities (HR = 2.27, 95% CI 1.21–4.25) [6]. These figures underline the necessity of developing culturally relevant interventions that optimize cognitive function and mitigate progression to dementia by linking the prevention and control of noncommunicable chronic diseases. Furthermore, it is essential to integrate caregivers and family members as active participants in the management process. This integration is decisive because of the high caregiver burden often experienced by those caring for individuals with cognitive disorders, which negatively impacts their quality of life and can exacerbate the patient's cognitive decline [7]. Multicomponent interventions have demonstrated efficacy in reducing the burden and increasing the social support of caregivers of patients with Alzheimer's disease (AD) [8,9]. Nonpharmacological multicomponent interventions (NPMIs) have been shown to be superior to single-domain interventions in improving cognition in patients with MCI. A meta-analysis of 28 studies published between 2011 and 2021 concluded that multidomain interventions had superior effects to single interventions in terms of global cognition (standardized mean difference SMD=0.41; 95% CI, 0.23–0.59; p<0.001) and other cognitive domains, such as executive functions, verbal fluency and memory; however, high variability was observed in terms of the combination of interventions, duration, and frequency [10]. Similarly, another meta-analysis of 8 clinical trials indicated a moderate effect of NPMIs on global cognition, with a moderate effect for the Mini-Mental State Examination (MMSE) (SMD=0.249; 95% CI, 0.067–0.431). Importantly, compared with cognitive-based interventions, studies that combine cognitive and physical interventions have shown superior effects on global cognition [11]. Given the lack of curative treatments for MCI, the identification of modifiable risk factors is crucial for intervention. Nutritional intake and diet are recognized lifestyle elements that are linked to the risk of MCI and AD [12]. Nutritional intervention has become a nonpharmacological approach, either through the intake of specific nutrients or dietary patterns that have protective effects [13,14]. This protective effect is likely mediated by various biological pathways involved in cognitive impairment, such as amyloid-beta deposition, inflammation, and oxidative stress, which justifies the inclusion of nutritional counseling as a key component in a multicomponent intervention aimed at the management of MCI [14]. Additionally, nutritional interventions could modulate the composition of the gut microbiota, as various studies have shown differences between individuals with MCI/AD and healthy older adults [15,16]. In line with the above, and despite the scientific support for NPMIs, the need to determine their optimal combination and dosage persists. This underscores the importance of comprehensive and multicomponent interventions that integrate physical activity, rehabilitation or cognitive stimulation, and nutritional counseling, also involving the family member as a potential caregiver and a key factor for adherence. Therefore, this study aims to evaluate the potential efficacy and feasibility of a multicomponent and transdisciplinary intervention directed at the caregiver–older adult dyad with MCI to optimize cognitive function. For this purpose, the efficacy of the NPMIs on global and domain-specific cognitive function in patients with MCI will be explored. Additionally, the feasibility, acceptability, and adherence to the intervention will be examined. Additionally, changes in the health-related quality of life of the dyad, social support, independence, frailty, physical capacity, family cohesion and adaptability, nutritional status, and, in a subgroup, potential changes in the composition of the gut microbiota will be evaluated. Methods Design We will conduct a randomized controlled pilot trial, parallel group, with an allocation ratio of 1:1, and investigator/evaluators will be blinded, following the SPIRIT guidelines and CONSORT extension for pilots [17,18]. Participants and eligibility criteria Dyads, consisting of a patient diagnosed with MCI and a family caregiver, who are both residents of four cities in the Metropolitan Area of Bucaramanga in Santander, Colombia, will be selected to participate in this study. Patients aged 55 years or older were required to have an MCI diagnosis made by a psychiatrist or neurologist and confirmed by neuropsychological evaluation. In addition, they needed to be functional for instrumental activities of daily living, have basic reading and writing skills, not present uncorrected sensory impairments (auditory or visual), have no limitations for physical activity or mobility, have a Barthel Index ≥ 80, a body mass index ≥ 18.5, have no history of surgical resection of the intestinal tract, tolerate oral intake, and be vaccinated against COVID-19. The exclusion criteria for patients in the study are: a clinical history of congenital intellectual disability or psychosis; the presence of central nervous system pathologies that affect cognitive function; a diagnosis of untreated psychiatric disorders; clinically significant systemic diseases, including chronic kidney disease, hepatopathies, and lung diseases requiring oxygen therapy; a diagnosis of Crohn's disease or colitis; active cancer treatment with chemotherapy; continuous administration in the last three months of probiotics, prebiotics, antibiotics, antifungals, or antivirals; problematic use of alcohol, tobacco, or psychoactive substances; use of steroids or immunosuppressants in the 30 days prior to the start of the study; the need for nutritional support via oral, enteral, or parenteral routes; and the identification of low exercise tolerance, vertigo, or medical restriction for performing moderate to vigorous intensity physical activity. The study elimination criteria include institutionalization of the participant for a period longer than one week during the intervention phase, death of the participant during the intervention phase, and nonattendance at 34% or more of the scheduled sessions with professional accompaniment. Setting The study will be conducted in Santander, Colombia, in four cities: Bucaramanga, Floridablanca, Girón and Piedecuesta (metropolitan area). The participants will be recruited through three main sources: 1) healthcare providing institutions (IPSs) that collaborate with the study, including hospitals and health centers; 2) private neurology clinics; and 3) the general community through dissemination strategies such as press, radio, television, and personal contact. The Biomedical and Biotechnological Research Laboratory (LIBB) of the Bacteriology and Clinical Laboratory program at Universidad de Santander (UDES) will be used for sample collection for microbiota evaluation and APOE genotype analysis. These samples will be analyzed at the Universidad de Málaga. The design and implementation of the intervention will be carried out through a strategic alliance between the Universidad de Santander (UDES), Universidad Manuela Beltrán (UMB), Universidad Autónoma de Bucaramanga (UNAB), La Universidad Santo Tomás (USTA), Universidad de Málaga, and Fundación Oftalmológica de Santander (FOSCAL). The intervention will be carried out in the patients' homes, and the family component will be provided through training at the UMB. Dyad involvement The call for participation in the study and the dissemination of inclusion criteria will be carried out in the three recruitment sources through informational posters, flyers, and announcements in radio and television media. Individuals who report amnestic cognitive complaints or have a diagnosis of MCI will be invited to participate, accompanied by a family caregiver, and their interest will be expressed via WhatsApp messages or emails. A telephone interview will be conducted for the preselection of candidates, inquiring about their cognitive manifestations and the fulfillment of preliminary inclusion criteria, such as the ability to perform physical activities, the level of independence, cognitive complaints, and the presence of anxious or depressive symptoms. Following this, participants will be formally invited to participate in the study through an informed consent process for both the patient and their family member. Then, comprehensive baseline evaluations for the patient will be carried out by professionals in neuropsychology, nursing, physiotherapy, neurology, and psychiatry in appropriately equipped offices to ensure privacy, the absence of sound interference, and the availability of necessary resources. Similarly, family members will be asked to complete questionnaires regarding social support, quality of life, and caregiver burden. Finally, an adjudication committee composed of a neurologist, a psychiatrist, a neuropsychologist, and an epidemiological nurse will analyze the collected information to confirm the diagnosis of MCI according to the DSM-5 criteria and verify compliance with the established inclusion criteria (see Figure 1). Intervention INTERCOG is a nonpharmacological, multicomponent and transdisciplinary intervention with a focus on the patient-family dyad. Its components include cognitive training and stimulation, physical training, nutritional counseling, and support for the family member/caregiver. Patients assigned to the intervention group will receive the NPMI INTERCOG for 12 weeks, with a frequency of two weekly home-based sessions and one weekly independent work session consisting of 10–30 minutes of daily walking and complete homework. The home-based sessions will include cognitive training/stimulation, physical training, and nutritional counseling. For their part, family caregivers will receive weekly training at a university institution for 12 weeks. The intervention plan for the dyad is described in Table 1. To facilitate the intervention process, two workbooks were developed (one for patients and another for family caregivers), as were video recordings to guide physical activity and nutritional recommendations. Table 1. The nonpharmacological, multicomponent Intervention INTERCOG for MCI focuses on the patient‒family dyad, Bucaramanga, and the metropolitan area, Santander, Colombia, 2025. Week DCL patients Family caregivers Sesion 1 Sesion 2 Trabajo independiente 1 Life Story- Orientation to person Avoid Added Sugars Aerobic Training Family Tree Sugar Withdrawal Syndrome Balance and Equilibrium Evidence of completeness of: Family tree, Reduction of added sugars 10-minute walk Welcome, group integration, component presentation 2 Cognitive training Reducing ultra-processed foods Strength training Healthy Snacks Double-Task Activity: Cognition and Physical Activity Evidence of completeness of: Preparing healthy snacks Attention-focused activity (selecting the letter "a" from a text) 15-minute walk Communication and expression Family reorganization 3 Cognitive training- Working and episodic memory Reducing consumption of wheat-based foods and including other grains Strength training Cooking workshop Quinoa preparation, combined with physical and cognitive activities (attention and concentration) Evidence of completeness of: Quinoa Preparation Audio narration of the cooking workshop experience 20-minute walk Support Network Promoting Healthy Living Habits 4 Cognitive training- attention and concentration Identification of whole grains and complex carbohydrates Balance and equilibrium Promoting traditional food Cognitive stimulation - Attention and concentration Strength training Evidence of completeness of: Trail making exercise Traditional food preparation. 20-minute walk Technological support for care Healthy eating through traditional foods 5 Importance and functions of fats in the body Cognitive stimulation-calculation Balance and equilibrium Importance of fats for brain function Cognitive training -calculation Strength training Evidence of completeness of: Math homework Healthy fat replacement list 25-minute walk Conflict resolution workshop, relaxation therapy 6 Cooking Techniques Cognitive Stimulation - Working and Sensory Memory Balance and Equilibrium Importance of the senses in nutrition Cognitive stimulation - memory Strength training Evidence of completeness of: Food description through the senses Healthy cooking preparation 25-minute walk Daily activities for cognitive stimulation, elements to promote memory, language and cognition 7 Promotion Omega 3 consumption Cognitive training - language Strength training Cooking workshop Preparation of a flaxseed-based drink Dual task: physical and cognitive activity (dyad) Evidence of completeness of: Flaxseed Preparation Proverb Worksheet 25-minute walk Cooking workshop Preparation of a flaxseed-based drink (dyad) 8 Sources of healthy fats Cognitive stimulation - visuoconstruction Balance and equilibrium Fat Classification Cognitive Training - visual construction Strength Training Evidence of completeness of: Meal preparations with added avocado, flax or nuts. Daily living activity log. 25-minute walk. Dance therapy, family and social relationships, building healthy relationships 9 Promoting the consumption of foods rich in antioxidants Dual-task activity: cognition and physical activity - Praxis and gnosis Promoting the consumption of foods rich in antioxidants Dual-task activity: cognition and physical activity - Praxis and gnosis Evidence of completeness of: Fruit consumption Activity with geometric pieces. 30-minute walk. Identification of free time and relaxation time activities 10 Benefits of green leafy vegetables Cognitive training- orientation to person Balance and equilibrium Vegetable consumption and its health benefits Cognitive stimulation - orientation Strength training Evidence of completeness of: Vegetable meal Homework about places visited in the past and present 30-minute walk. Importance of routines, skin self-care, ergonomics and physical activity 11 Implement two servings of vegetables a day Cognitive stimulation - executive functions Strength training Cooking workshop Preparation of salad recipes, alternating with physical and cognitive activity (dyad) Evidence of completeness of: Step-by-step planning for three (3) daily activities during the week. Preparation of a recipe of your choice from the provided recipe book. 30-minute walk. Cooking workshop Preparation of salad recipes, alternating with physical and cognitive activity (dyad) 12 Benefits of legumes Cognitive stimulation - working and episodic memory Balance and equilibrium Legume Recipe Book Cognitive Training - Memory Strength Training Evidence of completeness of: Preparation of the chosen recipe. Share three (3) old photographs with a description of the moment. 30-minute walk Interventions Completion Physical activity, capstone experiences, graduation The control group, in addition to usual care, will receive weekly information on the prevention of infectious diseases on their mobile devices. This material, similar to that available online, will be provided as an active control (Supplement 2). Once the study is completed, participants in the control group will receive an intensive one-week version of the NPMI INTERCOG, as well as the workbooks for the patient and the caregiver. Outcomes The potential efficacy of the NPMI INTERCOG will be evaluated as a primary outcome by measuring the change in global and cognitive domains: 1-Global cognition: change in the scores of the Montreal Cognitive Assessment (MoCA) [19,20] and the Mini-Mental State Examination (MMSE) [21,22]; 2-Verbal Learning and Memory: change in the scores of the Hopkins Verbal Learning Test (HVLT) [23,24]. 3- Processing speed and visual attention: change in scores on the Symbol Digit Modalities Test (SDMT) [24,25]. 4-Visual attention, processing speed, and visuospatial ability: change in the scores of the Trail Making Test (TMT-Forms A and B) [24,26]; 5-Executive function and selective attention: change in the scores of the Stroop Color and Word Test [27,28]; 6-Perceptual organization and visual memory: change in the scores of the Rey–Osterrieth Complex Figure Test [24,29]; 7-Verbal fluency and executive functions: change in the scores of the Semantic and Phonemic Verbal Fluency Test [24]. 8-Comprehension and expression levels: change in the scores of the Boston Naming Test [24,30]. 9-Verbal comprehension: change in the scores of the Token Test [31,32]. 10-Digit span: change in the scores of the digit span subtest of the WAIS-III (Wechsler Adult Intelligence Scale-Third Edition)[33]. Descriptions of the measures, scores, cutoff points, and interpretations are described in the trial registry [34]. To evaluate the feasibility, acceptability and adherence of the intervention as a primary outcome, several dimensions were proposed by Gadke et al. [35]. will be assessed. Table 2 presents the dimensions, questions, measurements and possible actions to be taken in the progress of the trial. Table 2. Evaluation of feasibility, acceptability and adherence of NPMI INTERCOG Dimension Questions Measurements Possible actions Recruitment and retention capability What are the difficulties or ease in recruiting dyads? Is it possible to recruit 102 dyads that meet the inclusion criteria? Number of collaborating institutions contacted, the number of interested individuals, the number of individuals preselected and evaluated, the participant rejection criteria, the number of people who decided not to continue in the trial, and the recruitment rate. Expanding the number of collaborating institutions and ways to disseminate the call for participation or extend it overtime, increasing recruitment staff, and strategies to prevent participants dropouts. Data Collection Procedures Are the measurements sensitive enough to determine change? Are the measurement procedures useful? Were any outcomes missing? What are the difficulties or ease in data collection? Difficulties in data collection, changes in questionnaire cutoff points, completeness of data collection, data collected unnecessarily. Supervision of instrument completion and data quality control. Alternative analysis of the variable without cutoff points, or as a continuous variable, or establishment of tertiles or quartiles. Social Validity Do participants perceive the intervention as appropriate, safe, and potentially effective? Are the frequency, intensity, and methods used in the interventions perceived as appropriate? What are the reasons for not participating in an intervention? Participant and caregiver surveys and interviews to obtain postintervention feedback data in person and by telephone Implement strategies to improve understanding of interventions. Evaluate the possibility of making any adjustments to the intervention methodology. Practicality Can interventions be implemented with time, training, available resources/materials? Interview participants and healthcare professionals to identify implementation challenges related to pacticality Availability to acquire materials and supplies for the intervention. Evaluate alternative materials or resources that are easier to acquire, reduce or recalculate intervention times, and retrain staff. Adherence Do participants comply with the proposed activities? Completion rate Activity completeness In the event of difficulties, interview the possible reasons to evaluate alternatives for compliance. Among the secondary outcomes, the variation in health-related quality of life will be estimated through the application of the 36-Item Short Form Health Survey (SF-36) to both the patient and the family member [36,37]. Similarly, the change in the Fried's criteria of frailty, which includes the assessment of weight loss (weight, body mass index and waist‒to-hip ratio), physical activity, exhaustion, and grip strength, will be evaluated [38,39]. The change in instrumental activities of daily living (IADL) will be measured through the Lawton and Brody scale [40,41], nutritional status with the Mini Nutritional Assessment (Long-MNA) [51], and the change in the risk of falls will be evaluated with the Tinetti balance scale [52]. Data collection procedures Data collection will be conducted at three time points: 1) during the preselection process, 2) at baseline, and 3) during follow-up (at 3, 6 and 9 months of the study). At each point, a team of professionals from various previously trained disciplines will administer multiple questionnaires and perform measurements. The detailed schedules of the instruments, measurement time points, and evaluators are presented in Table 1. Preselection To identify compliance with the inclusion criteria, the following instruments will be used in the preselection stage: Geriatric Depression Scale (GDS): Patients with a score below 10 points will be invited to participate [53]. Barthel Index of Activities of Daily Living (BI-ADL): Independence in performing activities of daily living will be evaluated, establishing a cutoff point of 80 or more points to confirm functional independence compatible with the diagnosis of MCI [54]. Physical Activity Readiness Questionnaire for Everyone (PAR-Q & YOU): This will be used to identify the absence of restrictions for physical activity, considering negative responses to 6 of the 7 questions as a participation criterion (the question about medication use will be excluded, considering it a precaution and not a restriction) [55]. International Physical Activity Questionnaire Short Form (IPAQ-SF): Participants who engage in intense physical activity will be identified, excluding those with an energy expenditure greater than 1500 METs per week [56]. Mini-Cog©: The memory component will be used as a screening tool for major neurocognitive disorders, excluding those who obtain a score of 0 [57]. Baseline and Postintervention Follow-up (0, 3, 6 and 9 months) Neuropsychological assessment: A neuropsychologist will administer tests to evaluate global cognition, and the cognitive domains will be defined as the primary outcome. Together, these tests provide a detailed profile of the key cognitive areas affected by MCI. Nursing assessment: Measurements of blood pressure and pulse will be taken with an OMROM model HEM-7130 automated monitor. In addition, the following instruments will be administered: the SF-36 Health Survey[42], Patient Characterization Form (basic information, family, pathological, pharmacological, and surgical history), Family APGAR [43], Family Adaptability Cohesion Evaluation Scale FACES III [44], Mini Nutritional Assessment (Long-MNA®) [45], Pittsburgh Sleep Quality Index (PSQI) [46] and Bristol Stool Form Scale (BSFS) [47] Physiotherapy Assessment: Dominant handgrip strength will be measured with a JAMAR 6386 hydraulic analog hand dynamometer. Weight and body composition will be assessed by bioimpedance with a Body Composition Monitor and Scale OMRON HBF 514C. Height and waist and hip circumferences will be recorded via a standardized method. Additionally, the gait speed test, Tinetti gait and balance assessment tool [48], Senior Fitness Test [49], Linda Fried Frailty Phenotype [50], and Lawton-Brody Instrumental Activities of Daily Living Scale [51] will be administered. Family Member Assessment: Nursing staff will apply the GCPC-UN-D© sociodemographic form for the characterization of the patient-family caregiver dyad[52]. Social support will also be assessed via the Medical Outcomes Study Social Support Survey (MOS) [53], quality of life with the SF-36 [42], and caregiver burden with the Zarit Caregiver Burden Interview [54,55]. Data management and monitoring Study data will initially be collected via paper forms and then double-entered into REDCap electronic data capture tools, which are hosted at the Universidad de Santander [55]. The captured information will be audited by a researcher exclusively dedicated to data quality review. This individual will supervise the completeness of the completed forms and review any discrepant data identified during the double-entry process. Healthcare professionals delivering the intervention will be specifically trained to recognize and report any potential Adverse Events (AEs), particularly those related to the physical activity component. All AEs will be immediately reported to the principal investigator and the study's insurance provider, as detailed in the protection policy. Sample size The required sample size was estimated to be 102 dyads, comprising 51 dyads per group (1:1 ratio), based on a repeated-measures design and two correlated means. The calculation was performed using an alpha level of 5% and a statistical power of 80%, adjusting for a 15% estimated attrition rate. The effect size data (MoCa: 0.7; MMSE 0.5) and the standard deviation of differences (MoCa: 1.8; MMSE 2.3) were derived from previous studies [56,57]. All sample size calculations were executed using STATA-13 statistical software. Secondary Subsample Analysis Additionally, a secondary analysis will be conducted on a subsample consisting of the first 40 older adults (20 per group) diagnosed with amnestic mild cognitive impairment (aMCI), for whom the gut microbiota will be analyzed. For the statistical analysis of the microbiota data, alpha diversity differences will be evaluated via the Wilcoxon random-sum test, beta diversity variations will be assessed via permutational multivariate analysis of variance, and bacterial differences between the comparison groups will be identified via linear discriminant analysis effect size. Randomization and Allocation Concealment A two-level stratified block randomization scheme will be employed to ensure balance across key demographic variables, given the characteristics of the screened population. The randomization sequence will be generated by a researcher independent of the core study team using the blockrand module (version 1.5) in R software (version 4.4.3). This individual will not participate in any study procedures. The stratification process will include the following: First-level (stratification) dyads will be stratified into four groups based on two factors: sex (male/female) and age (above/below 71 years). Second Level (Block Size): Within each stratum, a block size of 2 is used to ensure an automatic 1:1 allocation ratio between the intervention and control groups. The allocation sequence will be concealed, and the assignment will be executed in two phases: first, after the initial 52 dyads are completely identified and screened, and second, again for the remaining 50 dyads. This approach ensures that all participants maintain the same probability of assignment and helps maintain balance throughout the recruitment process. This entire procedure will be performed by personnel external to the core research team. Blinding Owing to the nature of the intervention, which cannot be masked with a placebo, it is not possible to blind the participants, their family members/caregivers, or the intervention team. However, efforts will be made to maintain blinding at other levels: the assessment team, data collectors, and the statistical analyst will remain blinded to the group assignment (intervention or control) throughout the study and during the statistical analysis. Statistical methods Continuous data will be described using means and standard deviations (SDs) or medians and interquartile ranges (IQRs), depending on their distribution as assessed by the Shapiro‒Wilk test. These data will be compared between the intervention and control groups via Student's t test or the Mann‒Whitney U test, respectively. Categorical data will be summarized using absolute and relative frequencies and compared between groups via the χ² test or Fisher's exact test, as appropriate. Primary and secondary outcomes will be analyzed across the baseline, 3-, 6-, and 9-month follow-up measurements via generalized linear mixed-effects models (GLMMs). These models will include fixed factors (intervention group, time, and the group × time interaction) and a random effect for participants to account for individual variability. The models utilize maximum likelihood estimation (MLE) methods to handle data that are missing at random (MAR). Potential confounding variables identified during the descriptive analysis were adjusted for. The results are reported as adjusted mean differences with their respective 95% confidence intervals (95% CIs). Imputation methods will not be used. The analysis will be performed on both intention-to-treat (ITT) and per-protocol (PP) basis. All the statistical analyses will be conducted via STATA 17 (Stata Corporation, College Station, USA), with the level of statistical significance set at α=0.05. Ethics and Dissemination The overarching INTERCOG study (which includes the review phase, intervention design, and clinical trial pilot study) was initially approved by the Institutional Bioethics Committee of Universidad de Santander (Acta No. 013, May 24, 2022). Specific ethical approval for the pilot clinical trial phase has been granted by the CEI – the FOSCAL Research Ethics Committee (Approval No. 11319/2025, June 25, 2025), the Hospital Universitario Los Comuneros Research Ethics Committee (February 20, 2025), and the Instituto de Salud de Bucaramanga ISABU (Registration No. 00004601, December 10, 2024). Permissions have also been secured from all the collaborating medical centers and hospitals involved in recruitment. Any necessary changes to the protocol will be promptly reported to the Research Committees of UDES and FOSCAL. The participants who were interested in the microbiota and ApoE substudy provided additional written informed consent. This extra consent was required because this specific component of the research was approved after the main study, following the acquisition of a second funding source, and necessitated independent ethical review. Ethical approval for this substudy was granted by the Institutional Bioethics Committee of Universidad de Santander (Acta No. 03 del 8 de abril del 2024). Written informed consent will be obtained from both the patients and their family caregivers. The consent process will involve a detailed explanation of the research objectives, the reason for the invitation to participate, the procedures, potential risks, and benefits (if any), and participants will be given ample opportunity to clarify any questions they may have. The information supplied by or obtained from participants will be treated as confidential. Data will be stored in a manner that preserves individuals' rights to privacy and intimacy. Access to the data, housed in REDCap, will be restricted to using authorized usernames and passwords managed by the study coordination, and access time will be limited. Participants assigned to the control group will receive the full NPMI intensively for one month (twice per week) at the conclusion of the study (after the 9-month follow-up), as compensation for their participation. No participant will receive monetary compensation. Discussion The management of cognitive decline represents a substantial challenge, particularly in Latin American countries with progressive and accelerated population aging [58]. NPMIs are promising targets for maintaining or improving global cognitive function [10,11], physical status, and quality of life in older adults with MCI and potentially preventing progression to dementia [59]. Given that better outcomes are associated with greater adherence [60], the primary focus of this study is the evaluation of the feasibility and implementation of the NPMI INTERCOG. Despite increasing evidence, challenges persist regarding the generalization and implementation of these interventions, due to the lack of standardization in their duration, intensity and frequency [59]. A key strength of the NPMI INTERCOG is its comprehensive scope, which addresses not only global cognition or specific cognitive domains but also critical health dimensions such as functional independence, physical frailty, quality of life and nutritional status. Furthermore, the inclusion of family members is fundamental for proactively mitigating future caregiver burden and increasing perceived social support. We anticipate that linking the family will also enhance adherence to multicomponent interventions. The execution of this pilot will provide critical information for future implementations or larger-scale clinical trials by estimating recruitment and adherence rates, dropout factors and specific implementation difficulties encountered by the intervention team. Additionally, this study offers a unique opportunity to explore the links between the gut–brain axis and variables related to the gut microbiota and evaluate the presence of ApoE risk genotypes. Although recruitment from specific geographical areas may restrict generalizability and the intervention duration and follow-up period were designed for a pilot, the results will be important for large-scale clinical trials. Abbreviations AD: Alzheimer's disease AEs: adverse events aMCI: amnestic mild cognitive impairment APGAR: Adaptability, partnership, growth, affect, and resolve -family functioning APOE: Apolipoprotein E BI-ADL: Barthel Index of Activities of Daily Living FACES: Family Adaptability Cohesion Evaluation Scale FACES III GCPC-UN-D: Guía de Caracterización del Paciente Crónico y su Cuidador en la Universidad Nacional de Colombia GDS: Geriatric Depression Scale GLMMs: Generalized linear mixed-effects models HR: Hazard ratio HVLT: Hopkins Verbal Learning Test IADL: instrumental activities of daily living IPAQ-SF: International Physical Activity Questionnaire Short Form IQR: interquartile range ITT: intention-to-treat MAR: Missing at random MCI: mild cognitive impairment METs: metabolic equivalents MLE: Likelihood estimation MMSE: Mental State Examination MNA: Mini Nutritional Assessment MoCA: Montreal Cognitive Assessment MOS: Medical outcomes study social support survey NPMI INTERCOG: Intervención no farmacológica multicomponente para la cognición del adulto mayor NPMI: Nonpharmacological Multicomponent Intervention PAR-Q & YOU: Physical Activity Readiness Questionnaire for Everyone PP: per-protocol SD: standard deviation SDMT: Symbol Digit Modalities Test SF-36: 36-Item Short Form Health Survey SMD: standardized mean difference TMT: Trail Making Test WAIS-III: Wechsler Adult Intelligence Scale-Third Edition 95% CI: 95% confidence interval Declarations Ethics approval and consent to participate All study methods and procedures, including the informed consent process, were reviewed and approved by the Bioethics Committee of the University of Santander, the Research Ethics Committee (CEI) – FOSCAL, the Research Ethics Committee of the Los Comuneros University Hospital, and the Ethics Committee of the Bucaramanga Health Institute. Consent for publication Not applicable. Availability of data and materials Since this manuscript is a protocol article, data sharing is not applicable. Competing interests The authors declare that they have no conflicts of interest. Funding The INTERCOG study is supported primarily by the Ministry of Science, Technology and Innovation (Minciencias, Colombia) under grant code 129989786963 (contract 652--21) for the project “Eficacia de una intervención multicomponente sobre la función cognitiva para la diada cuidador-paciente en el marco de la cohorte PURE Colombia y la red de apoyo social para cuidadores - Estudio INTERCOG. Co-funding was provided by Universidad de Santander, Universidad Manuela Beltrán and FOSCAL. The assessments related to the microbiota and ApoE analysis were supported by a substudy titled “Correlación entre microbiota y cambios neurocognitivos en adultos mayores con deterioro cognitivo leve posterior a una intervención multicomponente no farmacológico”, which received funds from Universidad Santo Tomás – USTA, Universidad Autónoma de Bucarmanga – UNAB, and Universidad de Santander- UDES (grant code: RED-001-24). Authors’ contributions All the authors contributed to the writing, reviewing, and revision of the final manuscript. The specific contributions of each author are as follows: D. Tiga-Loza conceived the study, and D. Tiga-Loza, W. Álvarez-Anaya, and A. Castañeda-Hernández were responsible for funding acquisition. A. Pabón-Moreno, K. Prado, and H. Acosta participated in the conceptualization of the study and the definition of the study outcomes. A. Calderón was responsible for the conception of the manuscript, and A. Calderón, J. Buitrago, E. Urrea-Vega, and L. Carreño-Parra were responsible for drafting the manuscript. R. Rivera, P. Camacho, D- Tiga-Loza and M. Reyes provided supervision and critically reviewed the final draft of the manuscript. Acknowledgments The authors express their gratitude to the participating institutions (ASOPORMEN, Hospital Universitario Los Comuneros e Instituto de Salud de Bucaramanga-ISABU) for their valuable collaboration and continued commitment to the development of the INTERCOG protocol and to the intervention team for their dedication and interdisciplinary efforts. References Hambleton IR, Caixeta R, Jeyaseelan SM, Luciani S, Hennis AJM. The rising burden of non-communicable diseases in the Americas and the impact of population aging: a secondary analysis of available data. The Lancet Regional Health - Americas 2023;21. https://doi.org/10.1016/j.lana.2023.100483. Bai W, Chen P, Cai H, Zhang Q, Su Z, Cheung T, et al. 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1","display":"","copyAsset":false,"role":"figure","size":51753,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of participant allocation\u003c/p\u003e","description":"","filename":"Screenshot20251128195149.png","url":"https://assets-eu.researchsquare.com/files/rs-8140713/v1/9bd3d469b0d055412b9bd43b.png"},{"id":97664985,"identity":"53ab52a7-d39c-4022-a22c-cea4d7d615f4","added_by":"auto","created_at":"2025-12-08 09:15:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":632816,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8140713/v1/fe4c170c-1a23-485e-863e-ab15663397dd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Nonpharmacological Multicomponent Intervention for Mild Cognitive Impairment with a Family-Patient Approach: Protocol for the Pilot Clinical Trial-INTERCOG Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePopulation aging is expected to lead to an increase in chronic noncommunicable diseases, posing a challenge to health systems [1]. In the Americas, the global burden of dementia is projected to rise from 6.86 million cases in 2020 to 19.3 million in 2025, an escalation of more than threefold increase [2]. This projection underscores the need to implement comprehensive interventions that preserve cognitive function, prevent or slow the progression to dementia, and engage families, multiple sectors and public policy [3].\u003c/p\u003e\n\u003cp\u003eInterventions focusing on individuals with mild cognitive impairment (MCI) are crucial, given that progression to dementia can occur in 6% to 44.8% of cases, with an average follow-up of 3.7 years in low- and middle-income countries[4]. Preventing this progression is vital in countries such as Colombia, where the prevalence of MCI in the elderly population is 17.93% [5]. This risk of progression is significantly compounded by existing comorbidities, nearly tripling in uncontrolled diabetes (HR = 2.87, 95% CI 1.20\u0026ndash;6.85) and doubling with cardiac comorbidities (HR = 2.27, 95% CI 1.21\u0026ndash;4.25) [6]. These figures underline the necessity of developing culturally relevant interventions that optimize cognitive function and mitigate progression to dementia by linking the prevention and control of noncommunicable chronic diseases. Furthermore, it is essential to integrate caregivers and family members as active participants in the management process. This integration is decisive because of the high caregiver burden often experienced by those caring for individuals with cognitive disorders, which negatively impacts their quality of life and can exacerbate the patient\u0026apos;s cognitive decline [7]. Multicomponent interventions have demonstrated efficacy in reducing the burden and increasing the social support of caregivers of patients with Alzheimer\u0026apos;s disease (AD) [8,9].\u003c/p\u003e\n\u003cp\u003eNonpharmacological multicomponent interventions (NPMIs) have been shown to be superior to single-domain interventions in improving cognition in patients with MCI. A meta-analysis of 28 studies published between 2011 and 2021 concluded that multidomain interventions had superior effects to single interventions in terms of global cognition (standardized mean difference SMD=0.41;\u0026nbsp;95% CI, 0.23\u0026ndash;0.59; p\u0026lt;0.001) and other cognitive domains,\u0026nbsp;such as executive functions, verbal fluency and memory; however, high variability was observed in terms of the combination of interventions, duration, and frequency [10].\u0026nbsp;Similarly, another meta-analysis of 8 clinical trials indicated a moderate effect of NPMIs on global cognition, with a moderate effect for the Mini-Mental State Examination (MMSE) (SMD=0.249; 95% CI, 0.067\u0026ndash;0.431).\u0026nbsp;Importantly, compared with cognitive-based interventions,\u0026nbsp;studies that combine cognitive and physical interventions\u0026nbsp;have shown\u0026nbsp;superior\u0026nbsp;effects\u0026nbsp;on global cognition [11].\u003c/p\u003e\n\u003cp\u003eGiven the lack of curative treatments for MCI, the identification of modifiable risk factors is crucial for intervention. Nutritional intake and diet are recognized lifestyle elements that are linked to the risk of MCI and AD [12]. Nutritional intervention has become a nonpharmacological approach, either through the intake of specific nutrients or dietary patterns that have protective effects [13,14]. This protective effect is likely mediated by various biological pathways involved in cognitive impairment, such as amyloid-beta deposition, inflammation, and oxidative stress, which justifies the inclusion of nutritional counseling as a key component in a multicomponent intervention aimed at the management of MCI [14]. Additionally, nutritional interventions could modulate the composition of the gut microbiota, as various studies have shown differences between individuals with MCI/AD and healthy older adults [15,16].\u003c/p\u003e\n\u003cp\u003eIn line with the above, and despite the scientific support for NPMIs, the need to determine their optimal combination and dosage persists. This underscores the importance of comprehensive and multicomponent interventions that integrate physical activity, rehabilitation or cognitive stimulation, and nutritional counseling, also involving the family member as a potential caregiver and a key factor for adherence. Therefore, this study aims to evaluate the potential efficacy and feasibility of a multicomponent and transdisciplinary intervention directed at the caregiver\u0026ndash;older adult dyad with MCI to optimize cognitive function. For this purpose, the efficacy of the NPMIs on global and domain-specific cognitive function in patients with MCI will be explored. Additionally, the feasibility, acceptability, and adherence to the intervention will be examined. Additionally, changes in the health-related quality of life of the dyad, social support, independence, frailty, physical capacity, family cohesion and adaptability, nutritional status, and, in a subgroup, potential changes in the composition of the gut microbiota will be evaluated.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eDesign\u003c/p\u003e\n\u003cp\u003eWe will conduct a randomized controlled pilot trial, parallel group, with an allocation ratio of 1:1, and investigator/evaluators will be blinded, following the SPIRIT guidelines and CONSORT extension for pilots [17,18].\u003c/p\u003e\n\u003cp\u003eParticipants and eligibility criteria\u003c/p\u003e\n\u003cp\u003eDyads, consisting of a patient diagnosed with MCI and a family caregiver, who are both residents of four cities in the Metropolitan Area of Bucaramanga in Santander, Colombia, will be selected to participate in this study. Patients aged 55 years or older were required to have an MCI diagnosis made by a psychiatrist or neurologist and confirmed by neuropsychological evaluation. In addition, they needed to be functional for instrumental activities of daily living, have basic reading and writing skills, not present uncorrected sensory impairments (auditory or visual), have no limitations for physical activity or mobility, have a Barthel Index \u0026ge; 80, a body mass index \u0026ge; 18.5, have no history of surgical resection of the intestinal tract, tolerate oral intake, and be vaccinated against COVID-19.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria for patients in the study are: a clinical history of congenital intellectual disability or \u0026nbsp;psychosis; the presence of central nervous system pathologies that affect cognitive function; a diagnosis of untreated psychiatric disorders; clinically significant systemic diseases, including chronic kidney disease, hepatopathies, and lung diseases requiring oxygen therapy; a diagnosis of Crohn\u0026apos;s disease or colitis; active cancer treatment with chemotherapy; continuous administration in the last three months of probiotics, prebiotics, antibiotics, antifungals, or antivirals; problematic use of alcohol, tobacco, or psychoactive substances; use of steroids or immunosuppressants in the 30 days prior to the start of the study; the need for nutritional support via oral, enteral, or parenteral routes; and the identification of low exercise tolerance, vertigo, or medical restriction for performing moderate to vigorous intensity physical activity. The study elimination criteria include institutionalization of the participant for a period longer than one week during the intervention phase, death of the participant during the intervention phase, and nonattendance at 34% or more of the scheduled sessions with professional accompaniment.\u003c/p\u003e\n\u003cp\u003eSetting\u003c/p\u003e\n\u003cp\u003eThe study will be conducted in Santander, Colombia, in four cities: Bucaramanga, Floridablanca, Gir\u0026oacute;n and Piedecuesta (metropolitan area).\u0026nbsp;The participants will be recruited through three main sources: 1) healthcare providing institutions (IPSs) that collaborate with the study, including hospitals and health centers; 2) private neurology clinics; and 3) the general community through dissemination strategies such as press, radio, television, and personal contact. The Biomedical and Biotechnological Research Laboratory (LIBB) of the Bacteriology and Clinical Laboratory program at Universidad de Santander (UDES) will be used for sample collection for microbiota evaluation and APOE\u0026nbsp;genotype analysis.\u0026nbsp;These\u0026nbsp;samples will be analyzed at the Universidad de M\u0026aacute;laga. The design and implementation of the intervention will be carried out through a strategic alliance between the Universidad de Santander (UDES), Universidad Manuela Beltr\u0026aacute;n (UMB), Universidad Aut\u0026oacute;noma de Bucaramanga (UNAB), La Universidad Santo Tom\u0026aacute;s (USTA), Universidad de M\u0026aacute;laga, and Fundaci\u0026oacute;n Oftalmol\u0026oacute;gica de Santander (FOSCAL). The intervention will be carried out in the patients\u0026apos; homes, and the family component will be provided through training at the UMB.\u003c/p\u003e\n\u003cp\u003eDyad involvement\u003c/p\u003e\n\u003cp\u003eThe call for participation in the study and the dissemination of inclusion criteria will be carried out in the three recruitment sources through informational posters, flyers, and announcements in radio and television media. Individuals who report amnestic cognitive complaints or have a diagnosis of MCI will be invited to participate, accompanied by a family caregiver, and their interest will be expressed via WhatsApp messages or emails. A telephone interview will be conducted for the preselection of candidates, inquiring about their cognitive manifestations and the fulfillment of preliminary inclusion criteria, such as the ability to perform physical activities, the level of independence, cognitive complaints, and the presence of anxious or depressive symptoms. Following this, participants will be formally invited to participate in the study through an informed consent process for both the patient and their family member. Then, comprehensive baseline evaluations for the patient will be carried out by professionals in neuropsychology, nursing, physiotherapy, neurology, and psychiatry in appropriately equipped offices to ensure privacy, the absence of sound interference, and the availability of necessary resources. Similarly, family members will be asked to complete questionnaires regarding social support, quality of life, and caregiver burden. Finally, an adjudication committee composed of a neurologist, a psychiatrist, a neuropsychologist, and an epidemiological nurse will analyze the collected information to confirm the diagnosis of MCI according to the DSM-5 criteria and verify compliance with the established inclusion criteria (see Figure 1).\u003c/p\u003e\n\u003cp\u003eIntervention\u003c/p\u003e\n\u003cp\u003eINTERCOG is a nonpharmacological, multicomponent and transdisciplinary intervention with a focus on the patient-family dyad. Its components include cognitive training and stimulation, physical training, nutritional counseling, and support for the family member/caregiver. Patients assigned to the intervention group will receive the NPMI INTERCOG for 12 weeks, with a frequency of two weekly home-based sessions and one weekly independent work session consisting of 10\u0026ndash;30 minutes of daily walking and complete homework.\u003c/p\u003e\n\u003cp\u003eThe home-based sessions will include cognitive training/stimulation, physical training, and nutritional counseling. For their part, family caregivers will receive weekly training at a university institution for 12 weeks. The intervention plan for the dyad is described in Table 1. To facilitate the intervention process, two workbooks were developed (one for patients and another for family caregivers), as were video recordings to guide physical activity and nutritional recommendations.\u003c/p\u003e\n\u003cp\u003eTable 1. The nonpharmacological, multicomponent Intervention INTERCOG for MCI focuses on the patient‒family dyad, Bucaramanga, and the metropolitan area, Santander, Colombia, 2025.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"608\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 45px;\"\u003e\n \u003cp\u003eWeek\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 386px;\"\u003e\n \u003cp\u003eDCL patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 177px;\"\u003e\n \u003cp\u003eFamily caregivers\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eSesion 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eSesion 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eTrabajo independiente\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eLife Story- Orientation to person\u003c/p\u003e\n \u003cp\u003eAvoid Added Sugars\u003c/p\u003e\n \u003cp\u003eAerobic Training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eFamily Tree\u003c/p\u003e\n \u003cp\u003eSugar Withdrawal Syndrome\u003c/p\u003e\n \u003cp\u003eBalance and Equilibrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eFamily tree,\u003c/p\u003e\n \u003cp\u003eReduction of added sugars\u003c/p\u003e\n \u003cp\u003e10-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eWelcome, group integration, component presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eCognitive training\u003c/p\u003e\n \u003cp\u003eReducing ultra-processed foods\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eHealthy Snacks\u003c/p\u003e\n \u003cp\u003eDouble-Task Activity: Cognition and Physical Activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003ePreparing healthy snacks\u003c/p\u003e\n \u003cp\u003eAttention-focused activity (selecting the letter \u0026quot;a\u0026quot; from a text)\u003c/p\u003e\n \u003cp\u003e15-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eCommunication and expression\u003c/p\u003e\n \u003cp\u003eFamily reorganization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eCognitive training- Working and episodic memory\u003c/p\u003e\n \u003cp\u003eReducing consumption of wheat-based foods and including other grains\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eCooking workshop\u003c/p\u003e\n \u003cp\u003eQuinoa preparation, combined with physical and cognitive activities (attention and concentration)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eQuinoa Preparation\u003c/p\u003e\n \u003cp\u003eAudio narration of the cooking workshop experience\u003c/p\u003e\n \u003cp\u003e20-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eSupport Network\u003c/p\u003e\n \u003cp\u003ePromoting Healthy Living Habits\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eCognitive training- attention and concentration\u003c/p\u003e\n \u003cp\u003eIdentification of whole grains and complex carbohydrates\u003c/p\u003e\n \u003cp\u003eBalance and equilibrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003ePromoting traditional food\u003c/p\u003e\n \u003cp\u003eCognitive stimulation - Attention and concentration\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eTrail making exercise\u003c/p\u003e\n \u003cp\u003eTraditional food preparation.\u003c/p\u003e\n \u003cp\u003e20-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eTechnological support for care\u003c/p\u003e\n \u003cp\u003eHealthy eating through traditional foods\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eImportance and functions of fats in the body\u003c/p\u003e\n \u003cp\u003eCognitive stimulation-calculation\u003c/p\u003e\n \u003cp\u003eBalance and equilibrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eImportance of fats for brain function\u003c/p\u003e\n \u003cp\u003eCognitive training -calculation\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eMath homework\u003c/p\u003e\n \u003cp\u003eHealthy fat replacement list\u003c/p\u003e\n \u003cp\u003e25-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eConflict resolution workshop, relaxation therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eCooking Techniques\u003c/p\u003e\n \u003cp\u003eCognitive Stimulation - Working and Sensory Memory\u003c/p\u003e\n \u003cp\u003eBalance and Equilibrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eImportance of the senses in nutrition\u003c/p\u003e\n \u003cp\u003eCognitive stimulation - memory\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eFood description through the senses\u003c/p\u003e\n \u003cp\u003eHealthy cooking preparation\u003c/p\u003e\n \u003cp\u003e25-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eDaily activities for cognitive stimulation, elements to promote memory, language and cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003ePromotion Omega 3 consumption\u003c/p\u003e\n \u003cp\u003eCognitive training - language\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eCooking workshop\u003c/p\u003e\n \u003cp\u003ePreparation of a flaxseed-based drink\u003c/p\u003e\n \u003cp\u003eDual task: physical and cognitive activity (dyad)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eFlaxseed Preparation\u003c/p\u003e\n \u003cp\u003eProverb Worksheet\u003c/p\u003e\n \u003cp\u003e25-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eCooking workshop\u003c/p\u003e\n \u003cp\u003ePreparation of a flaxseed-based drink (dyad)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eSources of healthy fats\u003c/p\u003e\n \u003cp\u003eCognitive stimulation - visuoconstruction\u003c/p\u003e\n \u003cp\u003eBalance and equilibrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eFat Classification\u003c/p\u003e\n \u003cp\u003eCognitive Training - visual construction\u003c/p\u003e\n \u003cp\u003eStrength Training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eMeal preparations with added avocado, flax or nuts. Daily living activity log.\u003c/p\u003e\n \u003cp\u003e25-minute walk.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eDance therapy, family and social relationships, building healthy relationships\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003ePromoting the consumption of foods rich in antioxidants Dual-task activity: cognition and physical activity - Praxis and gnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003ePromoting the consumption of foods rich in antioxidants Dual-task activity: cognition and physical activity - Praxis and gnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eFruit consumption\u003c/p\u003e\n \u003cp\u003eActivity with geometric pieces.\u003c/p\u003e\n \u003cp\u003e30-minute walk.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eIdentification of free time and relaxation time activities\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eBenefits of green leafy vegetables\u003c/p\u003e\n \u003cp\u003eCognitive training- orientation to person\u003c/p\u003e\n \u003cp\u003eBalance and equilibrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eVegetable consumption and its health benefits\u003c/p\u003e\n \u003cp\u003eCognitive stimulation - orientation\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eVegetable meal\u003c/p\u003e\n \u003cp\u003eHomework about places visited in the past and present\u003c/p\u003e\n \u003cp\u003e30-minute walk.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eImportance of routines, skin self-care, ergonomics and physical activity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eImplement two servings of vegetables a day\u003c/p\u003e\n \u003cp\u003eCognitive stimulation - executive functions\u003c/p\u003e\n \u003cp\u003eStrength training\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eCooking workshop\u003c/p\u003e\n \u003cp\u003ePreparation of salad recipes, alternating with physical and cognitive activity (dyad)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003eStep-by-step planning for three (3) daily activities during the week.\u003c/p\u003e\n \u003cp\u003ePreparation of a recipe of your choice from the provided recipe book.\u003c/p\u003e\n \u003cp\u003e30-minute walk.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eCooking workshop\u003c/p\u003e\n \u003cp\u003ePreparation of salad recipes, alternating with physical and cognitive activity (dyad)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eBenefits of legumes\u003c/p\u003e\n \u003cp\u003eCognitive stimulation - working and episodic memory\u003c/p\u003e\n \u003cp\u003eBalance and equilibrium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 107px;\"\u003e\n \u003cp\u003eLegume Recipe Book Cognitive Training - Memory Strength Training\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003eEvidence of completeness of:\u003c/p\u003e\n \u003cp\u003ePreparation of the chosen recipe.\u003c/p\u003e\n \u003cp\u003eShare three (3) old photographs with a description of the moment.\u003c/p\u003e\n \u003cp\u003e30-minute walk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eInterventions Completion\u003c/p\u003e\n \u003cp\u003ePhysical activity, capstone experiences, graduation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe control group, in addition to usual care, will receive weekly information on the prevention of infectious diseases on their mobile devices. This material, similar to that available online, will be provided as an active control (Supplement 2). Once the study is completed, participants in the control group will receive an intensive one-week version of the NPMI INTERCOG, as well as the workbooks for the patient and the caregiver.\u003c/p\u003e\n\u003cp\u003eOutcomes\u003c/p\u003e\n\u003cp\u003eThe potential efficacy of the NPMI INTERCOG will be evaluated as a primary outcome by measuring the change in global and cognitive domains: 1-Global cognition:\u0026nbsp;change in the scores of the Montreal Cognitive Assessment (MoCA) [19,20] and the Mini-Mental State Examination (MMSE) [21,22];\u0026nbsp;2-Verbal\u0026nbsp;Learning and Memory: change in the scores of the Hopkins Verbal Learning Test (HVLT) [23,24]. 3- Processing speed and visual attention:\u0026nbsp;change in scores on the Symbol Digit Modalities Test (SDMT) [24,25]. 4-Visual attention, processing speed, and visuospatial ability:\u0026nbsp;change in the scores of the Trail Making Test (TMT-Forms A and B) [24,26];\u0026nbsp;5-Executive function and selective attention: change in the scores of the Stroop Color and Word Test [27,28];\u0026nbsp;6-Perceptual organization and visual memory: change in the scores of the\u0026nbsp;Rey\u0026ndash;Osterrieth\u0026nbsp;Complex Figure Test [24,29];\u0026nbsp;7-Verbal fluency and executive functions:\u0026nbsp;change\u0026nbsp;in the scores of the Semantic and Phonemic Verbal Fluency Test [24]. 8-Comprehension and expression levels: change in the scores of the Boston Naming Test [24,30].\u0026nbsp;9-Verbal comprehension: change in the scores of the Token Test [31,32].\u0026nbsp;10-Digit span: change in the scores of the\u0026nbsp;digit span subtest of the WAIS-III (Wechsler Adult Intelligence Scale-Third Edition)[33]. Descriptions of the measures, scores,\u0026nbsp;cutoff\u0026nbsp;points, and interpretations are described in the trial registry [34].\u003c/p\u003e\n\u003cp\u003eTo evaluate the feasibility, acceptability and adherence of the intervention as a primary outcome, several dimensions were proposed by Gadke et al. [35]. will be assessed. Table 2 presents the dimensions, questions, measurements and possible actions to be taken in the progress of the trial.\u003c/p\u003e\n\u003cp\u003eTable 2. Evaluation of feasibility, acceptability and adherence of\u0026nbsp;NPMI\u0026nbsp;INTERCOG\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"668\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eDimension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eQuestions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eMeasurements\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003ePossible actions\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eRecruitment and retention capability\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eWhat are the difficulties or ease in recruiting dyads?\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eIs it possible to recruit 102 dyads that meet the inclusion criteria?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNumber of collaborating institutions contacted, the number of interested individuals, the number of individuals preselected and evaluated, the participant rejection criteria, the number of people who decided not to continue in the trial, and the recruitment rate.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eExpanding the number of collaborating institutions and ways to disseminate the call for participation or extend it overtime, increasing recruitment staff, and strategies to prevent participants dropouts.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eData Collection Procedures\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eAre the measurements sensitive enough to determine change?\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAre the measurement procedures useful?\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eWere any outcomes missing?\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eWhat are the difficulties or ease in data collection?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eDifficulties in data collection, changes in questionnaire cutoff points, completeness of data collection, data collected unnecessarily.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSupervision of instrument completion and data quality control.\u003c/p\u003e\n \u003cp\u003eAlternative analysis of the variable without cutoff points, or as a continuous variable, or establishment of tertiles or quartiles.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eSocial Validity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eDo participants perceive the intervention as appropriate, safe, and potentially effective?\u003c/p\u003e\n \u003cp\u003eAre the frequency, intensity, and methods used in the interventions perceived as appropriate?\u003c/p\u003e\n \u003cp\u003eWhat are the reasons for not participating in an intervention?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eParticipant and caregiver surveys and interviews to obtain postintervention feedback data in person and by telephone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eImplement strategies to improve understanding of interventions.\u003c/p\u003e\n \u003cp\u003eEvaluate the possibility of making any adjustments to the intervention methodology.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003ePracticality\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eCan interventions be implemented with time, training, available resources/materials?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eInterview participants and healthcare professionals to identify implementation challenges related to pacticality\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAvailability to acquire materials and supplies for the intervention.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eEvaluate alternative materials or resources that are easier to acquire, reduce or recalculate intervention times, and retrain staff.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eAdherence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eDo participants comply with the proposed activities?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eCompletion rate\u003c/p\u003e\n \u003cp\u003eActivity completeness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eIn the event of difficulties, interview the possible reasons to evaluate alternatives for compliance.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eAmong the secondary outcomes, the variation in health-related quality of life will be estimated through the application of the 36-Item Short Form Health Survey (SF-36) to both the patient and the family member [36,37]. Similarly, the change in the Fried\u0026apos;s criteria of frailty, which includes the assessment of weight loss (weight, body mass index and waist‒to-hip ratio), physical activity, exhaustion, and grip strength, will be evaluated [38,39]. The change in instrumental activities of daily living (IADL) will be measured through the Lawton and Brody scale [40,41], nutritional status with the Mini Nutritional Assessment (Long-MNA) [51], and the change in the risk of falls will be evaluated with the Tinetti balance scale [52].\u003c/p\u003e\n\u003cp\u003eData collection procedures\u003c/p\u003e\n\u003cp\u003eData collection will be conducted at three time points: 1) during the preselection process, 2) at baseline, and 3) during follow-up (at 3, 6 and 9 months of the study). At each point, a team of professionals from various previously trained disciplines will administer multiple questionnaires and perform measurements. The detailed schedules of the instruments, measurement time points, and evaluators are presented in Table 1.\u003c/p\u003e\n\u003cp\u003ePreselection\u003c/p\u003e\n\u003cp\u003eTo identify compliance with the inclusion criteria, the following instruments will be used in the preselection stage: Geriatric Depression Scale (GDS): Patients with a score below 10 points will be invited to participate [53]. Barthel Index of Activities of Daily Living (BI-ADL): Independence in performing activities of daily living will be evaluated, establishing a cutoff point of 80 or more points to confirm functional independence compatible with the diagnosis of MCI [54]. Physical Activity Readiness Questionnaire for Everyone (PAR-Q \u0026amp; YOU): This will be used to identify the absence of restrictions for physical activity, considering negative responses to 6 of the 7 questions as a participation criterion (the question about medication use will be excluded, considering it a precaution and not a restriction) [55]. International Physical Activity Questionnaire Short Form (IPAQ-SF): Participants who engage in intense physical activity will be identified, excluding those with an energy expenditure greater than 1500 METs per week [56]. Mini-Cog\u0026copy;: The memory component will be used as a screening tool for major neurocognitive disorders, excluding those who obtain a score of 0 [57].\u003c/p\u003e\n\u003cp\u003eBaseline and Postintervention Follow-up (0, 3, 6 and 9 months)\u003c/p\u003e\n\u003cp\u003eNeuropsychological assessment: A neuropsychologist will administer tests to evaluate global cognition, and the cognitive domains will be defined as the primary outcome. Together, these tests provide a detailed profile of the key cognitive areas affected by MCI.\u003c/p\u003e\n\u003cp\u003eNursing assessment: Measurements of blood pressure and pulse will be taken with an OMROM model HEM-7130 automated monitor. In addition, the following instruments will be administered: the SF-36 Health Survey[42], Patient Characterization Form (basic information, family, pathological, pharmacological, and surgical history), Family APGAR [43], Family Adaptability Cohesion Evaluation Scale FACES III [44], Mini Nutritional Assessment (Long-MNA\u0026reg;) [45], Pittsburgh Sleep Quality Index (PSQI) [46] and Bristol Stool Form Scale (BSFS) [47]\u003c/p\u003e\n\u003cp\u003ePhysiotherapy Assessment: Dominant handgrip strength will be measured with a JAMAR 6386 hydraulic analog hand dynamometer. Weight and body composition will be assessed by bioimpedance with a Body Composition Monitor and Scale OMRON HBF 514C. Height and waist and hip circumferences will be recorded via a standardized method. Additionally, the gait speed test, Tinetti gait and balance assessment tool [48], Senior Fitness Test [49], Linda Fried Frailty Phenotype [50], and Lawton-Brody Instrumental Activities of Daily Living Scale [51] will be administered.\u003c/p\u003e\n\u003cp\u003eFamily Member Assessment: Nursing staff will apply the GCPC-UN-D\u0026copy; sociodemographic form for the characterization of the patient-family caregiver dyad[52]. Social support will also be assessed via the Medical Outcomes Study Social Support Survey (MOS) [53], quality of life with the SF-36 [42], and caregiver burden with the Zarit Caregiver Burden Interview [54,55].\u003c/p\u003e\n\u003cp\u003eData management and monitoring\u003c/p\u003e\n\u003cp\u003eStudy data will initially be collected via paper forms and then double-entered into REDCap electronic data capture tools, which are hosted at the Universidad de Santander [55]. The captured information will be audited by a researcher exclusively dedicated to data quality review. This individual will supervise the completeness of the completed forms and review any discrepant data identified during the double-entry process.\u003c/p\u003e\n\u003cp\u003eHealthcare professionals delivering the intervention will be specifically trained to recognize and report any potential Adverse Events (AEs), particularly those related to the physical activity component. All AEs will be immediately reported to the principal investigator and the study\u0026apos;s insurance provider, as detailed in the protection policy.\u003c/p\u003e\n\u003cp\u003eSample size\u003c/p\u003e\n\u003cp\u003eThe required sample size was estimated to be 102 dyads, comprising 51 dyads per group (1:1 ratio), based on a repeated-measures design and two correlated means. The calculation was performed using an alpha level of 5% and a statistical power of 80%, adjusting for a 15% estimated attrition rate. The effect size data (MoCa: 0.7; MMSE 0.5) and the standard deviation of differences (MoCa: 1.8; MMSE 2.3) were derived from previous studies [56,57]. All sample size calculations were executed using STATA-13 statistical software.\u003c/p\u003e\n\u003cp\u003eSecondary Subsample Analysis\u003c/p\u003e\n\u003cp\u003eAdditionally, a secondary analysis will be conducted on a subsample consisting of the first 40 older adults (20 per group) diagnosed with amnestic mild cognitive impairment (aMCI), for whom the gut microbiota will be analyzed. For the statistical analysis of the microbiota data, alpha diversity differences will be evaluated via the Wilcoxon random-sum test, beta diversity variations will be assessed via permutational multivariate analysis of variance, and bacterial differences between the comparison groups will be identified via linear discriminant analysis effect size.\u003c/p\u003e\n\u003cp\u003eRandomization and Allocation Concealment\u003c/p\u003e\n\u003cp\u003eA two-level stratified block randomization scheme will be employed to ensure balance across key demographic variables, given the characteristics of the screened population. The randomization sequence will be generated by a researcher independent of the core study team using the blockrand module (version 1.5) in R software (version 4.4.3). This individual will not participate in any study procedures.\u003c/p\u003e\n\u003cp\u003eThe stratification process will include the following: First-level (stratification) dyads will be stratified into four groups based on two factors: sex (male/female) and age (above/below 71 years). Second Level (Block Size): Within each stratum, a block size of 2 is used to ensure an automatic 1:1 allocation ratio between the intervention and control groups.\u003c/p\u003e\n\u003cp\u003eThe allocation sequence will be concealed, and the assignment will be executed in two phases: first, after the initial 52 dyads are completely identified and screened, and second, again for the remaining 50 dyads. This approach ensures that all participants maintain the same probability of assignment and helps maintain balance throughout the recruitment process. This entire procedure will be performed by personnel external to the core research team.\u003c/p\u003e\n\u003cp\u003eBlinding\u003c/p\u003e\n\u003cp\u003eOwing to the nature of the intervention, which cannot be masked with a placebo, it is not possible to blind the participants, their family members/caregivers, or the intervention team. However, efforts will be made to maintain blinding at other levels: the assessment team, data collectors, and the statistical analyst will remain blinded to the group assignment (intervention or control) throughout the study and during the statistical analysis.\u003c/p\u003e\n\u003cp\u003eStatistical methods\u003c/p\u003e\n\u003cp\u003eContinuous data will be described using means and standard deviations (SDs) or medians and interquartile ranges (IQRs), depending on their distribution as assessed by the Shapiro‒Wilk test. These data will be compared between the intervention and control groups via Student\u0026apos;s t test or the Mann‒Whitney U test, respectively. Categorical data will be summarized using absolute and relative frequencies and compared between groups via the \u0026chi;\u0026sup2; test or Fisher\u0026apos;s exact test, as appropriate.\u003c/p\u003e\n\u003cp\u003ePrimary and secondary outcomes will be analyzed across the baseline, 3-, 6-, and 9-month follow-up measurements via generalized linear mixed-effects models (GLMMs). These models will include fixed factors (intervention group, time, and the group \u0026times; time interaction) and a random effect for participants to account for individual variability. The models utilize maximum likelihood estimation (MLE) methods to handle data that are missing at random (MAR). Potential confounding variables identified during the descriptive analysis were adjusted for. The results are reported as adjusted mean differences with their respective 95% confidence intervals (95% CIs). Imputation methods will not be used.\u003c/p\u003e\n\u003cp\u003eThe analysis will be performed on both intention-to-treat (ITT) and per-protocol (PP) basis. All the statistical analyses will be conducted via STATA 17 (Stata Corporation, College Station, USA), with the level of statistical significance set at \u0026alpha;=0.05.\u003c/p\u003e\n\u003cp\u003eEthics and Dissemination\u003c/p\u003e\n\u003cp\u003eThe overarching INTERCOG study (which includes the review phase, intervention design, and clinical trial pilot study) was initially approved by the Institutional Bioethics Committee of Universidad de Santander (Acta No. 013, May 24, 2022). Specific ethical approval for the pilot clinical trial phase has been granted by the CEI \u0026ndash; the FOSCAL Research Ethics Committee (Approval No. 11319/2025, June 25, 2025), the Hospital Universitario Los Comuneros Research Ethics Committee (February 20, 2025), and the Instituto de Salud de Bucaramanga ISABU (Registration No. 00004601, December 10, 2024). Permissions have also been secured from all the collaborating medical centers and hospitals involved in recruitment. Any necessary changes to the protocol will be promptly reported to the Research Committees of UDES and FOSCAL.\u003c/p\u003e\n\u003cp\u003eThe participants who were interested in the microbiota and ApoE substudy provided additional written informed consent. This extra consent was required because this specific component of the research was approved after the main study, following the acquisition of a second funding source, and necessitated independent ethical review. Ethical approval for this substudy was granted by the Institutional Bioethics Committee of Universidad de Santander (Acta No. 03 del 8 de abril del 2024).\u003c/p\u003e\n\u003cp\u003eWritten informed consent will be obtained from both the patients and their family caregivers. The consent process will involve a detailed explanation of the research objectives, the reason for the invitation to participate, the procedures, potential risks, and benefits (if any), and participants will be given ample opportunity to clarify any questions they may have. The information supplied by or obtained from participants will be treated as confidential. Data will be stored in a manner that preserves individuals\u0026apos; rights to privacy and intimacy. Access to the data, housed in REDCap, will be restricted to using authorized usernames and passwords managed by the study coordination, and access time will be limited. Participants assigned to the control group will receive the full NPMI intensively for one month (twice per week) at the conclusion of the study (after the 9-month follow-up), as compensation for their participation. No participant will receive monetary compensation.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe management of cognitive decline represents a substantial challenge, particularly in Latin American countries with progressive and accelerated population aging [58]. NPMIs are promising targets for maintaining or improving global cognitive function [10,11], physical status, and quality of life in older adults with MCI and potentially preventing progression to dementia [59]. Given that better outcomes are associated with greater adherence [60], the primary focus of this study is the evaluation of the feasibility and implementation of the NPMI INTERCOG. Despite increasing evidence, challenges persist regarding the generalization and implementation of these interventions, due to the lack of standardization in their duration, intensity and frequency [59]. A key strength of the NPMI INTERCOG is its comprehensive scope, which addresses not only global cognition or specific cognitive domains but also critical health dimensions such as functional independence, physical frailty, quality of life and nutritional status.\u003c/p\u003e\n\u003cp\u003eFurthermore, the inclusion of family members is fundamental for proactively mitigating future caregiver burden and increasing perceived social support. We anticipate that linking the family will also enhance adherence to multicomponent interventions. The execution of this pilot will provide critical information for future implementations or larger-scale clinical trials by estimating recruitment and adherence rates, dropout factors and specific implementation difficulties encountered by the intervention team. Additionally, this study offers a unique opportunity to explore the links between the gut\u0026ndash;brain axis and variables related to the gut microbiota and evaluate the presence of ApoE risk genotypes.\u003c/p\u003e\n\u003cp\u003eAlthough recruitment from specific geographical areas may restrict generalizability and the intervention duration and follow-up period were designed for a pilot, the results will be important for large-scale clinical trials.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAD: Alzheimer\u0026apos;s disease\u003c/p\u003e\n\u003cp\u003eAEs: adverse events\u003c/p\u003e\n\u003cp\u003eaMCI: amnestic mild cognitive impairment\u003c/p\u003e\n\u003cp\u003eAPGAR: Adaptability, partnership, growth, affect, and resolve -family functioning\u003c/p\u003e\n\u003cp\u003eAPOE: Apolipoprotein E\u003c/p\u003e\n\u003cp\u003eBI-ADL: Barthel Index of Activities of Daily Living\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFACES: Family Adaptability Cohesion Evaluation Scale FACES III\u003c/p\u003e\n\u003cp\u003eGCPC-UN-D: Gu\u0026iacute;a de Caracterizaci\u0026oacute;n del Paciente Cr\u0026oacute;nico y su Cuidador en la Universidad Nacional de Colombia\u003c/p\u003e\n\u003cp\u003eGDS: Geriatric Depression Scale\u003c/p\u003e\n\u003cp\u003eGLMMs: Generalized linear mixed-effects models\u003c/p\u003e\n\u003cp\u003eHR: Hazard ratio\u003c/p\u003e\n\u003cp\u003eHVLT: Hopkins Verbal Learning Test\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIADL: instrumental activities of daily living\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIPAQ-SF: International Physical Activity Questionnaire Short Form\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIQR: interquartile range\u003c/p\u003e\n\u003cp\u003eITT: intention-to-treat\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMAR: Missing at random\u003c/p\u003e\n\u003cp\u003eMCI: mild cognitive impairment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMETs: metabolic equivalents\u003c/p\u003e\n\u003cp\u003eMLE: Likelihood estimation\u003c/p\u003e\n\u003cp\u003eMMSE: Mental State Examination\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMNA: Mini Nutritional Assessment\u003c/p\u003e\n\u003cp\u003eMoCA: Montreal Cognitive Assessment\u003c/p\u003e\n\u003cp\u003eMOS: Medical outcomes study social support survey\u003c/p\u003e\n\u003cp\u003eNPMI INTERCOG: Intervenci\u0026oacute;n no farmacol\u0026oacute;gica multicomponente para la cognici\u0026oacute;n del adulto mayor\u003c/p\u003e\n\u003cp\u003eNPMI: Nonpharmacological Multicomponent Intervention\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePAR-Q \u0026amp; YOU: Physical Activity Readiness Questionnaire for Everyone\u003c/p\u003e\n\u003cp\u003ePP: per-protocol\u003c/p\u003e\n\u003cp\u003eSD: standard deviation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSDMT: Symbol Digit Modalities Test\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSF-36: 36-Item Short Form Health Survey\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSMD: standardized mean difference\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTMT: Trail Making Test\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWAIS-III: Wechsler Adult Intelligence Scale-Third Edition\u003c/p\u003e\n\u003cp\u003e95% CI: 95% confidence interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eAll study methods and procedures, including the informed consent process, were reviewed and approved by the Bioethics Committee of the University of Santander, the Research Ethics Committee (CEI) – FOSCAL, the Research Ethics Committee of the Los Comuneros University Hospital, and the Ethics Committee of the Bucaramanga Health Institute.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eSince this manuscript is a protocol article, data sharing is not applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe INTERCOG study is supported primarily by the Ministry of Science, Technology and Innovation (Minciencias, Colombia) under grant code 129989786963 (contract\u0026nbsp;652--21) for the project “Eficacia de una intervención multicomponente sobre la función cognitiva para la diada cuidador-paciente en el marco de la cohorte PURE Colombia y la red de apoyo social para cuidadores - Estudio INTERCOG. Co-funding was provided by Universidad de Santander, Universidad Manuela Beltrán and FOSCAL.\u003c/p\u003e\n\u003cp\u003eThe assessments related to the microbiota and ApoE analysis were supported by a substudy titled “Correlación entre microbiota y cambios neurocognitivos en adultos mayores con deterioro cognitivo leve posterior a una intervención multicomponente no farmacológico”, which received funds from Universidad Santo Tomás – USTA, Universidad Autónoma de Bucarmanga – UNAB, and Universidad de Santander- UDES (grant code: RED-001-24).\u003c/p\u003e\n\u003cp\u003eAuthors’ contributions\u003c/p\u003e\n\u003cp\u003eAll the authors contributed to the writing, reviewing, and revision of the final manuscript. The specific contributions of each author are as follows:\u003c/p\u003e\n\u003cp\u003eD. Tiga-Loza conceived the study, and D. Tiga-Loza, W. Álvarez-Anaya, and A. Castañeda-Hernández were responsible for funding acquisition. A. Pabón-Moreno, K. Prado, and H. Acosta participated in the conceptualization of the study and the definition of the study outcomes. A. Calderón was responsible for the conception of the manuscript, and A. Calderón, J. Buitrago, E. Urrea-Vega, and L. Carreño-Parra were responsible for drafting the manuscript. R. Rivera, P. Camacho, D- Tiga-Loza and M. Reyes provided supervision and critically reviewed the final draft of the manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThe authors express their gratitude to the participating institutions (ASOPORMEN, Hospital Universitario Los Comuneros e Instituto de Salud de Bucaramanga-ISABU) for their valuable collaboration and continued commitment to the development of the INTERCOG protocol and to the intervention team for their dedication and interdisciplinary efforts.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHambleton IR, Caixeta R, Jeyaseelan SM, Luciani S, Hennis AJM. 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Br Med J 1993;306:1437\u0026ndash;40. https://doi.org/10.1136/BMJ.306.6890.1437.\u003c/li\u003e\n\u003cli\u003eLugo LH, Garc\u0026iacute;a HI, G\u0026oacute;mez C. Reliability of sf-36 quality of life in health questionnaire in Medell\u0026iacute;n, Colombia. Revista Facultad Nacional de Salud P\u0026uacute;blica 2006;24:27\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eFried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in Older Adults: Evidence for a Phenotype. The Journals of Gerontology: Series A 2001;56:M146\u0026ndash;57. https://doi.org/10.1093/GERONA/56.3.M146.\u003c/li\u003e\n\u003cli\u003eRam\u0026iacute;rez Ram\u0026iacute;rez JU, Cadena Sanabria MO, Ochoa ME. Aplicaci\u0026oacute;n de la Escala de fragilidad de Edmonton en poblaci\u0026oacute;n colombiana. Comparaci\u0026oacute;n con los criterios de Fried. Rev Esp Geriatr Gerontol 2017;52:322\u0026ndash;5. https://doi.org/10.1016/J.REGG.2017.04.001.\u003c/li\u003e\n\u003cli\u003eD\u0026iacute;az AA, Serna GPM, Garc\u0026iacute;a LFR, Marulanda NLS, Molina JHV, Rueda LV. Dise\u0026ntilde;o de un sistema de informaci\u0026oacute;n para determinar la autonom\u0026iacute;a de los adultos mayores de acuerdo con la normatividad colombiana. Ciencia, Tecnolog\u0026iacute;a e Innovaci\u0026oacute;n En Salud 2019;4:13\u0026ndash;22. https://doi.org/10.23850/25393871.2873.\u003c/li\u003e\n\u003cli\u003eLawton MP, Brody EM. Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living. Gerontologist 1969;9:179\u0026ndash;86. https://doi.org/10.1093/GERONT/9.3_PART_1.179.\u003c/li\u003e\n\u003cli\u003eWare Jr JE. SF-36 health survey update. Spine (Phila Pa 1976) 2000;25:3130\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eSmilkstein G. The family APGAR: a proposal for a family function test and its use by physicians. J Fam Pract 1978;6:1231\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eVilca LW, D\u0026iacute;az-Narv\u0026aacute;ez V, Hidalgo WP, Niekerk Bakit N Van, Reyes PM, Herazo-Beltr\u0026aacute;n Y, et al. Evaluation of the psychometric properties of the family adaptability and cohesion scale (FACES III) through item response theory models in students from Chile and Colombia. BMC Psychol 2024;12:1\u0026ndash;11. https://doi.org/10.1186/S40359-024-01526-X/FIGURES/4.\u003c/li\u003e\n\u003cli\u003eGuigoz Y, Lauque S, Vellas BJ. Identifying the elderly at risk for malnutrition: The Mini Nutritional Assessment. Clin Geriatr Med 2002;18:737\u0026ndash;57. https://doi.org/10.1016/S0749-0690(02)00059-9.\u003c/li\u003e\n\u003cli\u003eSmyth C. The Pittsburgh Sleep Quality Index (PSQI). J Gerontol Nurs 1999;25:10\u0026ndash;1. https://doi.org/10.3928/0098-9134-19991201-10.\u003c/li\u003e\n\u003cli\u003eMartinez AP, De Azevedo GR. The Bristol Stool Form Scale: its translation to Portuguese, cultural adaptation and validation. Rev Lat Am Enfermagem 2012;20:583\u0026ndash;9. https://doi.org/10.1590/S0104-11692012000300021.\u003c/li\u003e\n\u003cli\u003eTinetti ME, Franklin Williams T, Mayewski R. Fall risk index for elderly patients based on number of chronic disabilities. Am J Med 1986;80:429\u0026ndash;34. https://doi.org/10.1016/0002-9343(86)90717-5.\u003c/li\u003e\n\u003cli\u003eLanghammer B, Stanghelle JK. The Senior Fitness Test. J Physiother 2015;61:163. https://doi.org/10.1016/j.jphys.2015.04.001.\u003c/li\u003e\n\u003cli\u003eFried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in Older Adults: Evidence for a Phenotype. The Journals of Gerontology: Series A 2001;56:M146\u0026ndash;57. https://doi.org/10.1093/GERONA/56.3.M146.\u003c/li\u003e\n\u003cli\u003eLawton MP, Brody EM. Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living. Gerontologist 1969;9:179\u0026ndash;86. https://doi.org/10.1093/GERONT/9.3_PART_1.179.\u003c/li\u003e\n\u003cli\u003eBarrera Ortiz L, Vargas Rosero E, Cendales PA. Characterization Survey to Define the Care of a Person with Chronic Disease. Investigaci\u0026oacute;n En Enfermer\u0026iacute;a: Imagen y Desarrollo 2014;17. https://doi.org/10.11144/javeriana.ie17-1.eccp.\u003c/li\u003e\n\u003cli\u003eSherbourne CD, Stewart AL. The MOS social support survey. Soc Sci Med 1991;32:705\u0026ndash;14. https://doi.org/https://doi.org/10.1016/0277-9536(91)90150-B.\u003c/li\u003e\n\u003cli\u003eMart\u0026iacute;n-Carrasco M, Otermin P, Perez Camo V, Pujol J, Ag\u0026uuml;era L, Mart\u0026iacute;n MJ, et al. EDUCA study: Psychometric properties of the Spanish version of the Zarit Caregiver Burden Scale. Aging Ment Health 2010;14:705\u0026ndash;11. https://doi.org/10.1080/13607860903586094.\u003c/li\u003e\n\u003cli\u003eZarit SH, Reever KE, Bach-Peterson J. Relatives of the Impaired Elderly: Correlates of Feelings of Burden. Gerontologist 1980;20:649\u0026ndash;55. https://doi.org/10.1093/GERONT/20.6.649.\u003c/li\u003e\n\u003cli\u003eHan JW, Lee H, Hong JW, Kim K, Kim T, Byun HJ, et al. Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial. Journal of Alzheimer\u0026rsquo;s Disease 2017;55:787\u0026ndash;96. https://doi.org/10.3233/JAD-160619.\u003c/li\u003e\n\u003cli\u003eChen LK, Hwang AC, Lee WJ, Peng LN, Lin MH, Neil DL, et al. Efficacy of multidomain interventions to improve physical frailty, depression and cognition: data from cluster-randomized controlled trials. J Cachexia Sarcopenia Muscle 2020;11:650\u0026ndash;62. https://doi.org/10.1002/jcsm.12534.\u003c/li\u003e\n\u003cli\u003eAmarante V, Colacce M, Manzi P. Aging and Productivity in Latin America. Lat Am Res Rev 2021;56:844\u0026ndash;63. https://doi.org/10.25222/LARR.924.\u003c/li\u003e\n\u003cli\u003eYang Q hong, Lyu X, Lin Q ran, Wang Z wen, Tang L, Zhao Y, et al. Effects of a multicomponent intervention to slow mild cognitive impairment progression: A randomized controlled trial. Int J Nurs Stud 2022;125:104110. https://doi.org/10.1016/J.IJNURSTU.2021.104110.\u003c/li\u003e\n\u003cli\u003eLevy SA, Smith G, De Wit L, DeFeis B, Ying G, Amofa P, et al. Behavioral Interventions in Mild Cognitive Impairment (MCI): Lessons from a Multicomponent Program. Neurotherapeutics 2022;19:117\u0026ndash;31. https://doi.org/10.1007/S13311-022-01225-8.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"pilot-and-feasibility-studies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pafs","sideBox":"Learn more about [Pilot and Feasibility Studies](http://pilotfeasibilitystudies.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/PAFS/default.aspx","title":"Pilot and Feasibility Studies","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cognitive dysfunction, aged, family caregivers, clinical trial, multicomponent, feasibility","lastPublishedDoi":"10.21203/rs.3.rs-8140713/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8140713/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the absence of effective pharmacological treatments and the risk of progression to dementia ranging from 6–44.8% over approximately 4 years of follow-up, nonpharmacologicalmulticomponent interventions are emerging as promising strategies to improve or maintain cognitive function and quality of life in individuals with mild cognitive impairment (MCI). This pilot study aims to evaluate the potential efficacy and feasibility of a multicomponent and transdisciplinary intervention focused on the dyad of older adults with MCI-family caregivers to promote cognitive function in older adults.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA pilot, randomized, controlled, and double-blind clinical trial will be conducted with 102 dyads consisting of an older adult with MCI and their family caregiver. The participants will be randomly assigned to two groups: the intervention group (INTERCOG) and the control group. The INTERCOG group will receive a 12-week home-based intervention (two weekly sessions) with the support of a healthcare professional.\u003c/p\u003e\n\u003cp\u003eThe intervention components consist of cognitive training and stimulation, nutritional counseling, and physical exercises. Simultaneously, family members will participate in a training program on care and self-care. The control group will receive standard care and educational messages on infection prevention. Changes in global cognition (MMSE and MoCA) and in specific cognitive domains will be measured. The feasibility of the study will also be assessed through an analysis of recruitment, data collection, intervention acceptability, and implementation challenges. Secondary outcomes will include changes in health-related quality of life, caregiver burden, social support for family members, as well as changes in functional independence, frailty, physical capacity, family functioning, and nutritional status in patients, with follow-up at 3, 6, and 9 months. In a subsample of 40 participants, the diversity of the gut microbiota will be characterized, and the frequency of the APOE-ε4 allele will be determined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMulticomponent and transdisciplinary interventions focused on the caregiver–patient dyad have the potential to optimize cognitive outcomes and quality of life. This pilot study will allow us to identify key aspects of the feasibility and potential efficacy of INTERCOG intervention, crucial information for the design of future larger-scale studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNCT06408103. December 6, 2024, atclinicaltrials.gov. 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