Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol

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This may progress to dementia. Dementia risk reduction is often misconceived as a strategy associated with later life. However, the newer term ‘brain health’ resonates with people of all ages. Individuals at midlife with mNCD face challenges in maintaining cognitive function while managing work and social responsibilities. Midlife provides a critical window for preventive interventions which begin to exert a significant influence on brain health trajectories. However, available evidence on how middle-aged individuals with mNCD maintain brain health remains fragmented. This protocol addresses the main question: How do middle-aged individuals with mild neurocognitive disorder maintain brain health? This will systematically map the existing literature on brain health strategies and interventions used by this group to provide a more nuanced understanding of barriers and facilitators to maintaining brain health. Methods This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and Arksey and O'Malley’s (2005) methodology framework. A systematic search will be conducted across five electronic databases [PubMed, Embase, CINAHL, PsycINFO and Cochrane], grey literature sources and specific websites of professional and healthcare organisations. Studies will be selected according to a set of inclusion and exclusion criteria by independent reviewers, with conflicts resolved by a third reviewer. Screening and data extraction will be managed using Covidence software. Equity mapping will be undertaken using the Cochrane Progress Plus tool. Conclusion This scoping review will provide a comprehensive synthesis of strategies employed by middle aged individuals with mild neurocognitive disorder to maintain brain health. By mapping the existing evidence, the review will offer insights into commonly used interventions by people themselves and identify areas requiring further research. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://hrbopenresearch.org/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://hrbopenresearch.org/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://hrbopenresearch.org/articles/8-63", "name": "Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults..." } } ] } Home Browse Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Dookhy J, Stokes D, Kroll T and Frazer K. Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.12688/hrbopenres.14161.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Revised Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] Joshi Dookhy https://orcid.org/0000-0001-7271-2021 1 , Diarmuid Stokes https://orcid.org/0000-0003-4319-8048 2 , Thilo Kroll https://orcid.org/0000-0003-2082-5117 1 , Kate Frazer https://orcid.org/0000-0002-6703-266X 1 Joshi Dookhy https://orcid.org/0000-0001-7271-2021 1 , Diarmuid Stokes https://orcid.org/0000-0003-4319-8048 2 , Thilo Kroll https://orcid.org/0000-0003-2082-5117 1 , Kate Frazer https://orcid.org/0000-0002-6703-266X 1 PUBLISHED 18 Jan 2026 Author details Author details 1 University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Leinster, Ireland 2 Library, University College Dublin, Dublin, Leinster, Ireland Joshi Dookhy Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Diarmuid Stokes Roles: Methodology Thilo Kroll Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Kate Frazer Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Dementia Trials Ireland (DTI) and Dementia Research Network Ireland (DRNI) gateway. Abstract Introduction Mild neurocognitive disorder (mNCD) is characterised by a slight and noticeable decline in cognitive abilities that does not significantly interfere with an individual’s daily functioning. This may progress to dementia. Dementia risk reduction is often misconceived as a strategy associated with later life. However, the newer term ‘brain health’ resonates with people of all ages. Individuals at midlife with mNCD face challenges in maintaining cognitive function while managing work and social responsibilities. Midlife provides a critical window for preventive interventions which begin to exert a significant influence on brain health trajectories. However, available evidence on how middle-aged individuals with mNCD maintain brain health remains fragmented. This protocol addresses the main question: How do middle-aged individuals with mild neurocognitive disorder maintain brain health? This will systematically map the existing literature on brain health strategies and interventions used by this group to provide a more nuanced understanding of barriers and facilitators to maintaining brain health. Methods This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and Arksey and O'Malley’s (2005) methodology framework. A systematic search will be conducted across five electronic databases [PubMed, Embase, CINAHL, PsycINFO and Cochrane], grey literature sources and specific websites of professional and healthcare organisations. Studies will be selected according to a set of inclusion and exclusion criteria by independent reviewers, with conflicts resolved by a third reviewer. Screening and data extraction will be managed using Covidence software. Equity mapping will be undertaken using the Cochrane Progress Plus tool. Conclusion This scoping review will provide a comprehensive synthesis of strategies employed by middle aged individuals with mild neurocognitive disorder to maintain brain health. By mapping the existing evidence, the review will offer insights into commonly used interventions by people themselves and identify areas requiring further research. READ ALL READ LESS Keywords brain health, mild neurocognitive disorder, scoping review, middle-aged, dementia prevention Corresponding Author(s) Joshi Dookhy ( [email protected] ) Close Corresponding author: Joshi Dookhy Competing interests: No competing interests were disclosed. Grant information: No funding was sought or received for this scoping review proposal. The primary author is currently a recipient of a PhD scholarship from their affiliated university (University College Dublin). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Copyright: © 2026 Dookhy J et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Dookhy J, Stokes D, Kroll T and Frazer K. Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.12688/hrbopenres.14161.3 ) First published: 05 Jun 2025, 8 :63 ( https://doi.org/10.12688/hrbopenres.14161.1 ) Latest published: 18 Jan 2026, 8 :63 ( https://doi.org/10.12688/hrbopenres.14161.3 ) Revised Amendments from Version 2 The authors have now addressed the reviewers' comments and made changes to the manuscript accordingly- specifically in the introduction, brain health and rationale for scoping review sections. The authors have now addressed the reviewers' comments and made changes to the manuscript accordingly- specifically in the introduction, brain health and rationale for scoping review sections. See the authors' detailed response to the review by Timothy Daly See the authors' detailed response to the review by Sarah Kremen READ REVIEWER RESPONSES Introduction Mild neurocognitive disorder (mNCD) is characterised by a slight but noticeable decline in cognitive abilities, which does not significantly interfere with an individual’s daily functioning ( American Psychiatric Association [APA], 2013 ). Although individuals with mNCD maintain relative independence, they may experience difficulties with memory, executive function, and other cognitive domains, affecting their quality of life ( Sachdev et al. , 2014 ). This condition often serves as an intermediate stage between normal cognitive aging and major neurocognitive disorder, such as dementia ( Irwin et al. , 2018 ). The terms ‘mNCD’ and ‘mild cognitive impairment’ (MCI) have often been used interchangeably in research and clinical settings ( Levada et al. , 2017 ; Sachs-Ericsson & Blazer, 2015 ). Historically, MCI emerged in close connection with Alzheimer’s disease, particularly in the context of amnestic presentations; however, the DSM-5 category of mild neurocognitive disorder (mNCD) ( APA, 2013 ) was created to account for a broader range of aetiologies, including traumatic brain injury or substance use. Both terms are intended as aetiologically inclusive descriptors of mild, non-dementia cognitive impairment. The annual progression rate from cognitive impairment to dementia varies significantly ( McGrattan et al. , 2022 ; Mitchell et al. , 2014 ), however, it is widely recognised that the prodromal phase of dementia often begins at midlife, commonly defined as individuals aged 45 years and older, and at least two decades before clinical symptoms emerge ( Bransby et al. , 2023 ; Schubert et al. , 2019 ). Dementia can significantly impact an individual's ability to perform daily activities and leads to substantial personal, healthcare, financial and societal burdens ( Irwin et al. , 2018 ; Livingston et al. , 2020 ). Historically, reducing the risk of dementia has been viewed as a concern only for older populations by the general population ( Curran et al. , 2021 ; Heger et al. , 2020 ; van Asbroeck et al. , 2021 ). However, emerging research suggests that a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia ( Licher et al. , 2019 ; Walsh et al. , 2022 ). Brain health The concept of ‘brain health’ has gained increasing recognition as a lifespan approach to cognitive well-being ( Baumgart et al. , 2015 ; Brain Health Scotland, 2022 ). Unlike ‘dementia risk-reduction’, which is often perceived as relevant only in later life, brain health resonates with individuals across different age groups and fosters engagement in long-term preventive strategies and resilience ( Alzheimer’s Research UK, 2021 ; Arenaza-Urquijo & Vemuri, 2020 ). A concept analysis by Chen et al. (2022) framed brain health as an ongoing state encompassing both typical ageing processes and pathological conditions. This definition was further enhanced by the World Health Organisation (WHO), who described brain health as “functioning across cognitive, sensory, social-emotional, behavioural and motor domains, allowing a person to realize their full potential over the life course, irrespective of the presence or absence of disorders” ( WHO, 2022 , P. 17). Beyond this definitional shift, recent works emphasise that brain health is shaped by multiple, interconnected determinants across the life course, namely environments, safety and security, opportunities for learning and social connection, and access to quality services. Addressing brain health, therefore, requires action not only on individual behaviours but also on social, economic and environmental conditions that can promote or undermine brain health. Brain health research gaps in midlife Midlife offers a critical window for preventive interventions to optimise brain health, such as addressing modifiable risk factors that begin to exert a significant influence on brain health trajectories ( Livingston et al. , 2020 ). Some of these modifiable risk factors include physical activity, mental stimulation, sleep quality and stress management, while non-modifiable factors include genetics and biological ageing ( Alzheimer’s Research UK, 2021 ; Won et al. , 2025 ). Despite recent global efforts to integrate brain health into healthcare frameworks, disparities persist, particularly for individuals at midlife with mNCD who encounter unique challenges in maintaining cognitive function while managing occupational and social responsibilities ( Irwin et al. , 2018 ). Research on non-pharmacological strategies to improve and maintain brain health, including cognitive training, physical exercise, dietary modifications, and social engagement, has predominantly focused on older adults ( Rosenberg et al. , 2018 ; Treacy et al. , 2023 ; Yaffe et al. , 2024 ). In addition, while research in other health domains, such as cardiovascular disease and diabetes prevention, suggests that middle-aged individuals often struggle to sustain preventive behaviours due to time constraints, financial pressures, and limited health literacy, this has not been explored in the context of dementia prevention ( Sun et al. , 2020 ). There is growing recognition that dementia prevention strategies which focus solely on high-risk individuals and lifestyle modification risk may exacerbate health and cultural inequalities, such as accessibility to services, ethnicity and education ( Giebel et al. , 2024 ; Gove et al. , 2021 ). Walsh et al. (2022) argue that individually targeted interventions must be complemented by whole-population, structural approaches that change environments to make healthy choices easier. However, this impact of health inequalities and disparities on brain health interventions in midlife has not been explored. There is also some conflicting evidence that suggests individuals with greater awareness of dementia risks are more likely to engage in brain health activities ( Ngandu et al. , 2015 ), while others indicate that awareness alone is insufficient ( van Asbroeck et al. , 2021 ). Rationale for scoping review Our focus on individuals at midlife with mNCD reflects the need to understand how people who are already at higher risk of dementia, and who often face substantial responsibilities, attempt to maintain brain health in real-world contexts. This high-risk focus is not intended to imply that responsibility for brain health rests solely with individuals. Instead, by mapping engagement and the barriers and facilitators they encounter, we aim to generate evidence to inform both person-centred support, structural, and policy responses aligned with international calls for equitable, population-level dementia prevention. To ensure a comprehensive and inclusive approach to evidence synthesis, this scoping review will be informed by the Cochrane Equity Framework ( Welch et al. , 2024 ), which emphasises the importance of identifying and addressing health inequities across populations. Mapping evidence through an equity lens will help identify gaps in intervention reach, relevance, and adaptability across diverse populations. This aligns with the WHO’s call to prioritise equity in brain health initiatives as part of achieving universal health coverage and reducing health disparities globally ( WHO, 2022 ) and the WHO’s Global Action Plan on the public health response to dementia 2017–2025 ( WHO, 2017 ), by promoting tailored public health responses at both national and local levels. Research aim & objectives This study aims to systematically review the existing literature to provide a comprehensive understanding of the various brain health strategies used by this population. It seeks to evaluate the effectiveness of these approaches, identify patterns and gaps and highlight opportunities for future research and practice advancement of evidence-based interventions in brain health in published evidence. The objectives are to: 1. Identify and map the depth and breadth of strategies used by individuals with mNCD to maintain brain health. 2. Examine the decision-making processes underlying individuals' selection of strategies to maintain brain health. 3. Examine the facilitators and barriers experienced by individuals using strategies to maintain brain health. Methods Design This proposed systematic scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews ( Hadie, 2024 ; Peters et al. , 2020 ) and recommendations from ( Levac et al. , 2010 ), which was built on previous the existing theoretical framework of Arksey and O’Malley (2005) . This methodology was chosen due to its transparency, through publication of a pre-defined protocol and explicit data extraction and analysis, as well as its alignment with international reporting standards. A five-stage process will be employed throughout the review process and has been used in the development of this scoping review protocol. Below is an overview of each stage, with section headings adapted from Levac et al. (2010) . Reporting will be guided by the Preferred Reporting Items for Systematic Reviews and Meta Analyses Scoping Review extension (PRISMA-ScR) checklist, to ensure compliance with up-to-date PRISMA reporting guidance ( Tricco et al. , 2018 ). The researchers have already engaged with stages 1 to 3 of this protocol. Stage 1 Identifying the research question The Population, Concept, Context (PCC) model ( Peters et al. , 2020 ), widely recommended for scoping reviews, was used to determine the focus of the research question and to formulate inclusion and exclusion criteria. The primary research question is: "How do middle-aged individuals with mild neurocognitive disorder maintain brain health?” The review will also address other secondary questions: 1. What types of strategies do these individuals use to maintain or enhance their brain health? 2. How do individuals identify, evaluate and choose brain health strategies? 3. “What individual, social and structural factors enable or prevent equitable access to, and uptake of, strategies to maintain brain health?” Population : Adults aged 40 to 65 years of all genders, ethnicities, and socioeconomic backgrounds who have been explicitly diagnosed with a mild neurocognitive disorder will be included. Individuals in this age group represent a distinct subgroup often described as having early-onset cognitive impairment, encompassing people in early or midlife adulthood, whose life circumstances, responsibilities, and coping strategies differ substantially from older individuals with late-onset cognitive disorders. Studies involving individuals with advanced or major neurocognitive disorders, such as dementia, will be excluded. Concept : This review will focus on identifying and exploring specific strategies actively undertaken or adopted by individuals with mNCD to maintain or improve their brain health. These strategies will include individual, family, organisational, and population-level practices, approaches, activities, or interventions, such as lifestyle modifications, cognitive stimulation, social engagement, psychological approaches, using technological tools, and non-pharmacological methods. Studies involving strategies solely administered by health care professionals or researchers without active participant engagement or purely diagnostic measures will be excluded. The aim is to understand what people actively do in daily life contexts, reflecting choices and behaviours that can realistically support brain health. Context: This review will include studies conducted globally in real-life settings, such as home-based, residential care, clinical and community to capture approaches realistically implemented by individuals with mNCD in their daily lives. Studies conducted exclusively in controlled laboratory environments will be excluded, as these interventions may not reflect the practical behaviours that individuals typically adopt to maintain brain health. Stage 2 Identifying relevant studies The scoping review follows the three-step search strategy recommended by the JBI methodology ( Hadie, 2024 ; Peters et al. , 2020 ): 1. Beginning with a preliminary search in at least two pertinent online databases and analysing keywords and MeSH. 2. Analysing keywords and index terms used in the initial findings to refine the search strategy for a more comprehensive search across the five databases. 3. Reviewing the reference lists of all selected sources for additional relevant studies. Five electronic databases were searched: PubMed, Embase via Elsevier, CINAHL via EBSCOhost, PsycINFO and Cochrane Library. PubMed, Embase and CINHAL were used as they index a number of medical and health science journals. PsycINFO was used because it includes international literature on psychology which may provide important articles on the emotional processes and behavioural research. Grey literature sources such as publications from WHO, Lenus (the Irish Health Repository), National Institute for Health and Care Excellence (NICE) and Guideline Central will also be included. 2.1 Eligibility criteria The inclusion and exclusion criteria for this scoping review is provided in Table 1 below. Table 1. Inclusion and Exclusion criteria for studies. Inclusion criteria Rationale Individuals aged between 40–65 years To target the midlife age group ( Infurna et al. , 2020 ), which is the focus of this review Studies based on individuals diagnosed and living with mNCD To maintain the review’s focus on individuals with mNCD Exclusion criteria Rationale Articles that do not include an abstract in English language 1. To ensure accurate screening of abstracts based on the review team's language capabilities, translation resource constraints and the need to ensure consistent data extraction and synthesis. 2. To mitigate possible omissions, we searched extensively across multiple English-language databases, grey literature sources and screened reference lists of included studies for additional relevant works. Articles published after 2014 The search was limited to studies published from January 2015 onwards to ensure the evidence reflects contemporary definitions, methodologies and technological advances in brain health research. ‘Brain health’ was recognised as a concept at the 2015 International Association of Gerontology and Geriatrics (IAGG) and its Global Aging Research Network (GARN) consensus panel ( Morley et al. , 2015 ). The past 10 years captures the shift toward standardised outcome measures, multi-domain prevention strategies and alignment with global policy initiatives for this new concept of 'brain health'. Studies based solely on individuals with major neurocognitive disorders (e.g., dementia) To maintain the review’s focus on individuals with mNCD Studies conducted exclusively in controlled laboratory environments To focus on practical strategies that individuals typically adopt to maintain brain health. Conference abstracts, protocol papers, position papers and editorials To map peer-reviewed original research that provides completed and validated findings relevant to brain health 2.1 Search strategy The researchers worked with a librarian to refine the search strategy to ensure that relevant and key articles are found. The search strategy, including all identified keywords and index terms, were adapted for each included database. The search strategy for PubMed is included in Table 2 . Table 2. Search Strategy for PubMed (conducted 31st July 2025). Search Query Records retrieved #1 Population "Cognition Disorders"[Mesh] OR "Amnesia"[Mesh] OR "Delirium"[Mesh] OR "Cognitive Impairment"[Title/Abstract] OR "Mild Neurocognitive Disorder"[Title/Abstract] OR "MCI"[Title/Abstract] OR "Memory Deficit*"[Title/Abstract] OR "neurocognitive dysfunction*"[Title/Abstract] OR “Cognit* Disorder*"[Title/Abstract] OR "Amnesia"[Title/Abstract] OR "Delirium"[Title/Abstract] 245,045 #2 Concept "Cognitive Health"[Title/Abstract] OR "cognitive preservation*"[Title/Abstract] OR "cognitive enhancement*"[Title/Abstract] OR "brain reserve*"[Title/Abstract] OR "brain health"[Title/Abstract] OR "dementia risk* reduction*"[Title/Abstract] OR "Preventive Health"[Title/Abstract] OR "neuroprotecti*"[Title/Abstract] OR "Healthy Aging"[Title/Abstract] OR "Health Status"[Title/Abstract] OR “Cognitive Reserve"[Title/Abstract] OR "Cognitive Reserve"[Mesh] OR "Preventive Health Services"[Mesh] OR "neuroprotection"[Mesh] OR "Healthy Aging"[Mesh] OR "Health Status"[Mesh] 1,382,116 #3 Concept "health strategy"[Title/Abstract] OR "Cognitive Dissonance"[Mesh] OR "Cognitive Flexibility"[Mesh] OR "Health Promotion"[Mesh] OR "Metacognition"[Mesh] OR "resilience, psychological"[Mesh] OR "Human Activities"[Mesh] OR "Psychotherapy"[Mesh] OR "Health Services"[Mesh] OR "Psychological Phenomena"[Mesh] OR "Life Style"[Mesh] OR "Cognitive Dissonance"[Title/Abstract] OR "Cognitive Flexibility"[Title/Abstract] OR "Health Promotion"[Title/Abstract] OR "Metacognition"[Title/Abstract] OR "resilience"[Title/Abstract] OR "Human Activities"[Title/Abstract] OR "Psychotherapy"[Title/Abstract] OR "Health Services"[Title/Abstract] OR "Psychological Phenomena"[Mesh] OR "Life Style"[Title/Abstract] OR "health aware*"[Title/Abstract] OR "health improvement*"[Title/Abstract] OR "health intervention"[Title/Abstract] OR "health-related intervention"[Title/Abstract] OR "preventive intervention"[Title/Abstract] OR "public health intervention"[Title/Abstract] OR "health promotion"[Title/Abstract] OR "behavi*ral intervention"[Title/Abstract] OR "lifestyle intervention"[Title/Abstract] OR "wellness program*"[Title/Abstract] OR "disease prevention"[Title/Abstract] OR "clinical intervention"[Title/Abstract] OR "modifiable risks factors"[Text Word] OR "brain health behavi*rs"[All Fields] 5,347,022 #4 Concept #2 AND #3 960,971 #5 #1 AND #4 [** No filters or exclusion criteria applied] 17,761 #6 #1 AND #4 [**Filters applied from 2004] 15,967 #7 #1 AND #4 [**Filters applied: from 2004, English & French language] 15,387 #8 Article type filter applied: Bibliography, Case Reports, Classical Article, Comparative Study, English Abstract, Evaluation Study, Introductory Journal Article, Meta-Analysis, Multileft Study, Network Meta-Analysis, Observational Study, Patient Education Handout, Personal Narrative, Preprint, Randomized Controlled Trial, Review, Scientific Integrity Review, Scoping Review, Systematic Review, Technical Report, Twin Study, Validation Study 5300 Filters applied: Abstract, Classical Article, Clinical Study, Interview, Meta-Analysis, Multileft Study, Observational Study, Scoping Review, Systematic Review, English, Humans, Adult: 19–44 years, Middle Aged: 45–64 years, from 2004 - 2025 1190 Stage 3 Study selection Following the search, all identified citations were collated and uploaded into Endnote 21 and uploaded into Covidence. EndNote 21 was chosen as citations can be efficiently uploaded into it from database searches, full texts can be attached to their citations and stored within it. Covidence is a software tool that streamlines the review process by enabling collaborative screening, data extraction, and quality assessment, while automatically identifying and removing duplicates ( Babineau, 2014 ). It is available online ( https://www.covidence.org ). Covidence was chosen because it is compatible with EndNote. The study selection has been carried out in four stages: 1. Article Management: All articles (n= 6842) obtained from the database searches were imported into Covidence, and the platform was used to detect and remove duplicates (n= 493). 2. Title/Abstract Screening: Two Independent reviewers screened titles and abstracts of all articles against inclusion and exclusion criteria. Any abstract where it was clear whether they met the inclusion criteria was forwarded to the full-text screening stage. 3. Full-Text Screening: Eligible full texts (n= 247) were reviewed independently against the inclusion/exclusion criteria. Reasons for exclusion were recorded and will be reported in the published review. 3. Disagreements: Discrepancies at each stage in the process was resolved through discussion and overseen by an independent reviewer. The results of the search will be presented in a PRISMA flow diagram in the published review. Stage 4 Data extraction Data extraction is currently being conducted iteratively by combining inductive and deductive methods. Data extraction will be completed for each included full text article using a data extraction form via Microsoft Excel platform. The form will be developed using expertise within the team and pilot tested for applicability and usability (first five studies) and will be modified as necessary. Independent data extraction of 50% of included studies will be proposed to reduce errors in reporting. Variables to be extracted may be updated at this stage, if other salient data becomes apparent, and the data extraction form will be finalised. Data will be extracted on: Author(s) Year of publication Country of origin Setting Study design Sample size Participants age Description of strategy used Duration or frequency of strategy Decision Making Construct The evidence from included studies will be mapped for equity reporting, using the Cochrane PROGRESS-Plus tool, which identifies characteristics that stratify health opportunities and outcomes. PROGRESS-Plus is an acronym used to identify social, economic, and cultural characteristics that may influence health opportunities and outcomes ( O’Neill et al. , 2014 ). It refers to place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, social capital, personal characteristics, features of relationships and time-dependent relationships. It is available online ( https://methods.cochrane.org/equity/projects/evidence-equity/progress-plus ). Stage 5 Summarising & reporting results All data extracted will be mapped into tabular format, based on descriptive headings in the data extraction form, and accompanied by a narrative summary of the results in line with the review objectives. A comparison of strategies and outcomes from mapping to equity tool will be included in the discussion. Discussion This review and findings will contribute to the understanding of people with mNCD and will provide a comprehensive foundation upon which to design a robust main study for the primary author. Ultimately, this scoping review will ensure that studies are grounded in current evidence, address relevant gaps through a novel lens and align with both clinical and research needs. Ethics and dissemination As this review involves publicly available studies, ethical approval is not required. Findings from the scoping review will be published in a peer-reviewed journal publication and conference presentation. Dissemination plan The intended audiences for this study will be researchers, health care professionals and policymakers who are involved in the management of care for people with mNCD as well as individuals diagnosed. This study will be submitted for publication in a peer-reviewed scientific journal and for scientific conference presentation. A plain English summary of the review findings will be co-developed with people with mNCD to support dissemination. Conclusions This scoping review will provide a comprehensive synthesis of strategies employed by middle aged individuals with mNCD to maintain brain health. By mapping the existing evidence, the review will offer insights into commonly used interventions by people themselves and identify areas requiring further research. Data availability No data are associated with this article. 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PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 05 Jun 2025 ADD YOUR COMMENT Comment Author details Author details 1 University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Leinster, Ireland 2 Library, University College Dublin, Dublin, Leinster, Ireland Joshi Dookhy Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Diarmuid Stokes Roles: Methodology Thilo Kroll Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Kate Frazer Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information No funding was sought or received for this scoping review proposal. The primary author is currently a recipient of a PhD scholarship from their affiliated university (University College Dublin). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Article Versions (3) version 3 Revised Published: 18 Jan 2026, 8:63 https://doi.org/10.12688/hrbopenres.14161.3 version 2 Revised Published: 15 Oct 2025, 8:63 https://doi.org/10.12688/hrbopenres.14161.2 version 1 Published: 05 Jun 2025, 8:63 https://doi.org/10.12688/hrbopenres.14161.1 Copyright © 2026 Dookhy J et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics VIEWS $counts.viewCount downloads Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Dookhy J, Stokes D, Kroll T and Frazer K. Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.12688/hrbopenres.14161.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 3 VERSION 3 PUBLISHED 18 Jan 2026 Revised Views 0 Cite How to cite this report: Kremen S. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15782.r52948 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v3#referee-response-52948 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 10 Feb 2026 Sarah Kremen , Cedars-Sinai Medical Center, Los Angeles, California, USA Approved VIEWS 0 https://doi.org/10.21956/hrbopenres.15782.r52948 I have re-reviewed the article and the comments and have no further comments except that Livingston et al 2020 has been updated and is more detailed now in the more recent paper Livingston et al 2024. Why not reference that? ... Continue reading READ ALL I have re-reviewed the article and the comments and have no further comments except that Livingston et al 2020 has been updated and is more detailed now in the more recent paper Livingston et al 2024. Why not reference that? References 1. Livingston G, Huntley J, Liu K, Costafreda S, et al.: Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. The Lancet . 2024; 404 (10452): 572-628 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: clinical translation in behavioral neurology (AD, DLB, FTLD, LATE) I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kremen S. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15782.r52948 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v3#referee-response-52948 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Daly T. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15782.r52947 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v3#referee-response-52947 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 30 Jan 2026 Timothy Daly , Bioethics Program, FLACSO Argentina, Buenos Aires, Argentina Approved with Reservations VIEWS 0 https://doi.org/10.21956/hrbopenres.15782.r52947 The authors' response to my initial review contained three sections. I am satisfied with sections one and two. However, the third part of my comment read as follows: I just want to see some actual arguments in ... Continue reading READ ALL The authors' response to my initial review contained three sections. I am satisfied with sections one and two. However, the third part of my comment read as follows: I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667 The authors respond that they ' have revised secondary question 3 and clarified the ‘Rationale for scoping review ’. I appreciate that this is a scoping review protocol and not a philosophical discussion, however, I do believe that they should cite some literature containing ethical arguments. That includes Walsh et al. 2022, but there are other papers that the authors should read and cite, in my opinion, to make this "high-risk" approach more grounded in a balanced of structural factors that increase dementia risk. I include some here below. For example, the general problem of individual vs. structural changes in health promotion, beyond dementia: Refer to reference no. 1, 2 & 3 The problems this creates for the risk conceptualisation of dementia: https://cdn.who.int/media/docs/default-source/bulletin/online-first/blt.25.293220.pdf?sfvrsn=2a6e265d_3 "Accounting for inequality in dementia prevention programmes" Refer to reference no.4, 5, & 6 The more specific problem of healthism: Refer to reference no. 7 And the question of responsibility vs. rights-based approaches: Refer to reference no. 8 References 1. Chater N, Loewenstein G: The i-frame and the s-frame: How focusing on individual-level solutions has led behavioral public policy astray. Behavioral and Brain Sciences . 2023; 46 . Publisher Full Text 2. Tubeuf S, Valdivia A, Tavoschi L, Empana J, et al.: The responsibility of health: shifting the focus from individuals to systems. The Lancet Public Health . 2025; 10 (3). Publisher Full Text 3. Carey G, Malbon E, Crammond B, Pescud M, et al.: Can the sociology of social problems help us to understand and manage ‘lifestyle drift’?. Health Promotion International . 2016. Publisher Full Text 4. Horstkötter D, Deckers K, Köhler S: Primary Prevention of Dementia: An Ethical Review. Journal of Alzheimer's Disease . 2021; 79 (2): 467-476 Publisher Full Text 5. Knaggs G, Siette J: The ethical allocation of dementia prevention responsibility. The Lancet Healthy Longevity . 2025; 6 (5). Publisher Full Text 6. Petersen N, Andreoletti M, Blasimme A, Lazzaroni C, et al.: Disentangling Responsibility: Perspectives on Dementia Prevention From Stakeholders in Canada, Germany and Switzerland. Sociology of Health & Illness . 2026; 48 (1). Publisher Full Text 7. Slocombe F, Peel E, Pilnick A, Albert S: Providing Hope or Assigning Blame? Healthism in Print Media Portrayals of Dementia Risk and Responsibility. Sociology of Health & Illness . 2025; 47 (8). Publisher Full Text 8. Daly T: Brain health is a human right: Implications for policy and research. Neuroscience . 2025; 569 : 147-154 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Brain health promotion. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Daly T. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15782.r52947 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v3#referee-response-52947 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 15 Oct 2025 Revised Views 0 Cite How to cite this report: Daly T. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15699.r51213 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v2#referee-response-51213 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 11 Dec 2025 Timothy Daly , Bioethics Program, FLACSO Argentina, Buenos Aires, Argentina Approved with Reservations VIEWS 0 https://doi.org/10.21956/hrbopenres.15699.r51213 This report is set to provide a comprehensive account of strategies of middle-aged people with mild cognitive impairment to maintain their brain health. From a technical point of view, I see no problem with the manuscript. But ... Continue reading READ ALL This report is set to provide a comprehensive account of strategies of middle-aged people with mild cognitive impairment to maintain their brain health. From a technical point of view, I see no problem with the manuscript. But it fails to really ask an important question at the heart of the concerns around brain health and highlight the tension to be found in brain health conceptualisation. For example, the authors quote Walsh et al. 2022 as suggesting that "a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia." This is a very superficial citation. Walsh et al. specifically set out many of the weaknesses of the "high-risk" [PMID 36098322] approach defended by the authors here—that is, the idea that high-risk individuals are those who "maintain brain health." What about a public health approach? The authors only offer a very superficial citation of WHO's 2022 Optimizing brain health — why not mention determinants, those found in the very definition? ("Different determinants related to..."); see also Section 3 of Livingston et al. 2024: PMID 39096926, and a Blueprint for dementia research: https://www.who.int/publications/i/item/9789240058248. This doesn't mean the authors aren't doing a legitimate study. I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Brain health promotion. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Daly T. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15699.r51213 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v2#referee-response-51213 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 19 Jan 2026 Joshi Dookhy , University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Ireland 19 Jan 2026 Author Response Dear Dr Timothy Daly, Thank you for your thoughtful and constructive comments, particularly regarding the conceptualisation of brain health and the balance between high-risk and population-level approaches to dementia ... Continue reading Dear Dr Timothy Daly, Thank you for your thoughtful and constructive comments, particularly regarding the conceptualisation of brain health and the balance between high-risk and population-level approaches to dementia prevention. These have been helpful in interpreting the findings of the actual scoping review. Regarding this protocol, we have now clarified our original framing and revised the manuscript accordingly. “The authors only offer a very superficial citation of WHO's 2022 Optimizing brain health — why not mention determinants, those found in the very definition? ("Different determinants related to..."); see also Section 3 of Livingston et al. 2024: PMID 39096926, and a Blueprint for dementia research” We agree that our initial use of WHO (2022) focused on definitional aspects of brain health and did not sufficiently reflect that brain health is shaped by interconnected determinants. In response, we have expanded the “Brain health” subsection to briefly summarise the WHO determinant framework and to explicitly state that our use of the concept of brain health aligns with this multi-determinant, life-course view rather than with purely behavioural or lifestyle framings. “The authors quote Walsh et al. 2022 as suggesting that "a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia." This is a very superficial citation. Walsh et al. specifically set out many of the weaknesses of the "high-risk" [PMID 36098322] approach defended by the authors here—that is, the idea that high-risk individuals are those who "maintain brain health." What about a public health approach?” We are grateful for this observation and agree that our original citation of Walsh et al. did not adequately reflect the core argument of that paper. Our intention is not to defend high-risk approach as a stand-alone solution. Rather, our scoping review focuses on one high-risk group, middle-aged adults living with mNCD, precisely because this group is at elevated risk of progression and currently under-represented in the literature. We see this as complementary to, not in competition with, the development of population-level interventions. “I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667” We appreciate this reminder to engage with the emerging ethics and public-health literature and agree that lifestyle-focused narratives can be ethically problematic when determinants shape risks and behaviour change. Our population focus on adults at midlife with mNCD reflects clinical and epidemiological considerations. We see this as a critical and currently under-researched component of a broader dementia prevention agenda. That said, it is essential not to imply that responsibility for brain health rests solely with individuals, especially when structural constraints and policy decisions shape what is possible. Rather than expanding this protocol into a full scoping review of policy responses (which would require a separate, differently scoped review!), we have revised secondary question 3 and clarified the ‘Rationale for scoping review’. The new wording makes clear that we will extract and report information on how broader social determinants support or hinder the interventions described in the included studies. Dear Dr Timothy Daly, Thank you for your thoughtful and constructive comments, particularly regarding the conceptualisation of brain health and the balance between high-risk and population-level approaches to dementia prevention. These have been helpful in interpreting the findings of the actual scoping review. Regarding this protocol, we have now clarified our original framing and revised the manuscript accordingly. “The authors only offer a very superficial citation of WHO's 2022 Optimizing brain health — why not mention determinants, those found in the very definition? ("Different determinants related to..."); see also Section 3 of Livingston et al. 2024: PMID 39096926, and a Blueprint for dementia research” We agree that our initial use of WHO (2022) focused on definitional aspects of brain health and did not sufficiently reflect that brain health is shaped by interconnected determinants. In response, we have expanded the “Brain health” subsection to briefly summarise the WHO determinant framework and to explicitly state that our use of the concept of brain health aligns with this multi-determinant, life-course view rather than with purely behavioural or lifestyle framings. “The authors quote Walsh et al. 2022 as suggesting that "a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia." This is a very superficial citation. Walsh et al. specifically set out many of the weaknesses of the "high-risk" [PMID 36098322] approach defended by the authors here—that is, the idea that high-risk individuals are those who "maintain brain health." What about a public health approach?” We are grateful for this observation and agree that our original citation of Walsh et al. did not adequately reflect the core argument of that paper. Our intention is not to defend high-risk approach as a stand-alone solution. Rather, our scoping review focuses on one high-risk group, middle-aged adults living with mNCD, precisely because this group is at elevated risk of progression and currently under-represented in the literature. We see this as complementary to, not in competition with, the development of population-level interventions. “I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667” We appreciate this reminder to engage with the emerging ethics and public-health literature and agree that lifestyle-focused narratives can be ethically problematic when determinants shape risks and behaviour change. Our population focus on adults at midlife with mNCD reflects clinical and epidemiological considerations. We see this as a critical and currently under-researched component of a broader dementia prevention agenda. That said, it is essential not to imply that responsibility for brain health rests solely with individuals, especially when structural constraints and policy decisions shape what is possible. Rather than expanding this protocol into a full scoping review of policy responses (which would require a separate, differently scoped review!), we have revised secondary question 3 and clarified the ‘Rationale for scoping review’. The new wording makes clear that we will extract and report information on how broader social determinants support or hinder the interventions described in the included studies. Competing Interests: Not applicable. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 19 Jan 2026 Joshi Dookhy , University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Ireland 19 Jan 2026 Author Response Dear Dr Timothy Daly, Thank you for your thoughtful and constructive comments, particularly regarding the conceptualisation of brain health and the balance between high-risk and population-level approaches to dementia ... Continue reading Dear Dr Timothy Daly, Thank you for your thoughtful and constructive comments, particularly regarding the conceptualisation of brain health and the balance between high-risk and population-level approaches to dementia prevention. These have been helpful in interpreting the findings of the actual scoping review. Regarding this protocol, we have now clarified our original framing and revised the manuscript accordingly. “The authors only offer a very superficial citation of WHO's 2022 Optimizing brain health — why not mention determinants, those found in the very definition? ("Different determinants related to..."); see also Section 3 of Livingston et al. 2024: PMID 39096926, and a Blueprint for dementia research” We agree that our initial use of WHO (2022) focused on definitional aspects of brain health and did not sufficiently reflect that brain health is shaped by interconnected determinants. In response, we have expanded the “Brain health” subsection to briefly summarise the WHO determinant framework and to explicitly state that our use of the concept of brain health aligns with this multi-determinant, life-course view rather than with purely behavioural or lifestyle framings. “The authors quote Walsh et al. 2022 as suggesting that "a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia." This is a very superficial citation. Walsh et al. specifically set out many of the weaknesses of the "high-risk" [PMID 36098322] approach defended by the authors here—that is, the idea that high-risk individuals are those who "maintain brain health." What about a public health approach?” We are grateful for this observation and agree that our original citation of Walsh et al. did not adequately reflect the core argument of that paper. Our intention is not to defend high-risk approach as a stand-alone solution. Rather, our scoping review focuses on one high-risk group, middle-aged adults living with mNCD, precisely because this group is at elevated risk of progression and currently under-represented in the literature. We see this as complementary to, not in competition with, the development of population-level interventions. “I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667” We appreciate this reminder to engage with the emerging ethics and public-health literature and agree that lifestyle-focused narratives can be ethically problematic when determinants shape risks and behaviour change. Our population focus on adults at midlife with mNCD reflects clinical and epidemiological considerations. We see this as a critical and currently under-researched component of a broader dementia prevention agenda. That said, it is essential not to imply that responsibility for brain health rests solely with individuals, especially when structural constraints and policy decisions shape what is possible. Rather than expanding this protocol into a full scoping review of policy responses (which would require a separate, differently scoped review!), we have revised secondary question 3 and clarified the ‘Rationale for scoping review’. The new wording makes clear that we will extract and report information on how broader social determinants support or hinder the interventions described in the included studies. Dear Dr Timothy Daly, Thank you for your thoughtful and constructive comments, particularly regarding the conceptualisation of brain health and the balance between high-risk and population-level approaches to dementia prevention. These have been helpful in interpreting the findings of the actual scoping review. Regarding this protocol, we have now clarified our original framing and revised the manuscript accordingly. “The authors only offer a very superficial citation of WHO's 2022 Optimizing brain health — why not mention determinants, those found in the very definition? ("Different determinants related to..."); see also Section 3 of Livingston et al. 2024: PMID 39096926, and a Blueprint for dementia research” We agree that our initial use of WHO (2022) focused on definitional aspects of brain health and did not sufficiently reflect that brain health is shaped by interconnected determinants. In response, we have expanded the “Brain health” subsection to briefly summarise the WHO determinant framework and to explicitly state that our use of the concept of brain health aligns with this multi-determinant, life-course view rather than with purely behavioural or lifestyle framings. “The authors quote Walsh et al. 2022 as suggesting that "a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia." This is a very superficial citation. Walsh et al. specifically set out many of the weaknesses of the "high-risk" [PMID 36098322] approach defended by the authors here—that is, the idea that high-risk individuals are those who "maintain brain health." What about a public health approach?” We are grateful for this observation and agree that our original citation of Walsh et al. did not adequately reflect the core argument of that paper. Our intention is not to defend high-risk approach as a stand-alone solution. Rather, our scoping review focuses on one high-risk group, middle-aged adults living with mNCD, precisely because this group is at elevated risk of progression and currently under-represented in the literature. We see this as complementary to, not in competition with, the development of population-level interventions. “I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667” We appreciate this reminder to engage with the emerging ethics and public-health literature and agree that lifestyle-focused narratives can be ethically problematic when determinants shape risks and behaviour change. Our population focus on adults at midlife with mNCD reflects clinical and epidemiological considerations. We see this as a critical and currently under-researched component of a broader dementia prevention agenda. That said, it is essential not to imply that responsibility for brain health rests solely with individuals, especially when structural constraints and policy decisions shape what is possible. Rather than expanding this protocol into a full scoping review of policy responses (which would require a separate, differently scoped review!), we have revised secondary question 3 and clarified the ‘Rationale for scoping review’. The new wording makes clear that we will extract and report information on how broader social determinants support or hinder the interventions described in the included studies. Competing Interests: Not applicable. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Kremen S. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15699.r50846 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v2#referee-response-50846 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Nov 2025 Sarah Kremen , Cedars-Sinai Medical Center, Los Angeles, California, USA Approved with Reservations VIEWS 0 https://doi.org/10.21956/hrbopenres.15699.r50846 The authors of this article entitled, " Brain Health Strategies to Reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol" present the rationale with our current knowledge that many risk factors for dementia begin in midlife, ... Continue reading READ ALL The authors of this article entitled, " Brain Health Strategies to Reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol" present the rationale with our current knowledge that many risk factors for dementia begin in midlife, it is important to understand how people in midlife approach brain health and ways to maintain it. The manuscript describes a framework based upon best practices for conducting systematic searches, and designing and carrying out scoping reviews. In regard to the appropriateness of the study design to the research question, I am still unclear if the authors aim to use the term mild neurocognitive disorder or mild cognitive impairment, or both terms in order to conduct the search of the literature. They make a point that MCI has been associated tightly with Alzheimer's disease specifically but that is not uniformly true, and to not utilize a common term such as MCI and to use only the DSM definition of mild neurocognitive disorder may exclude important sources. A separate question is whether there will be sufficient sources to evaluate for mNCD/MCI in people ages 40-55. This population may not be coming in for cognitive evaluation. Perhaps the scoping review will shed light on whether this is true or not, but I do wonder how much will be found outside of literature attached to early onset, autosomal dominant AD groups, or people at risk for dementia in general, who are concerned about their health. Smaller issues for this manuscript in regard to ease of reading - could be tightened: 1) it goes back and forth between present test and past tense, making the reader a bit confused. It sounds like the work to be done is in the future and then a following paragraph is in the past tense stating a particular analysis was carried out. 2) review grammar - missing a period at the end of the first paragraph of Research aim & objectives. - repetitive wording - Population: This population of interest in this review... Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes References 1. Livingston G, Huntley J, Liu K, Costafreda S, et al.: Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. The Lancet . 2024; 404 (10452): 572-628 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: clinical translation in behavioral neurology (AD, DLB, FTLD, LATE) I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kremen S. Reviewer Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15699.r50846 ) The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v2#referee-response-50846 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 19 Jan 2026 Joshi Dookhy , University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Ireland 19 Jan 2026 Author Response Dear Dr Sarah Kremen, Thank you for your thoughtful comments and careful reading of our protocol. We address each point in turn below and have revised the manuscript accordingly. ... Continue reading Dear Dr Sarah Kremen, Thank you for your thoughtful comments and careful reading of our protocol. We address each point in turn below and have revised the manuscript accordingly. “I am still unclear if the authors aim to use the term mild neurocognitive disorder or mild cognitive impairment, or both terms in order to conduct the search of the literature. They make a point that MCI has been associated tightly with Alzheimer's disease specifically but that is not uniformly true, and to not utilize a common term such as MCI and to use only the DSM definition of mild neurocognitive disorder may exclude important sources.” We agree that MCI is a widely used clinical and research term, and that it is not uniformly restricted to Alzheimer’s disease. We did not intend to exclude MCI-based literature, and we appreciate the opportunity to clarify this more explicitly. As shown in the revised PubMed strategy (Table 2), the Population block already includes both “Mild Neurocognitive Disorder” and “MCI” and broader terms such as “Cognitive Impairment”, “neurocognitive dysfunction*” and “Cognit* Disorder*”. Our searches therefore capture studies using either MCI or mNCD terminology, irrespective of aetiology. We have modified the introduction to replace the previous statement about MCI and AD. “A separate question is whether there will be sufficient sources to evaluate for mNCD/MCI in people ages 40-55. This population may not be coming in for cognitive evaluation. Perhaps the scoping review will shed light on whether this is true or not, but I do wonder how much will be found outside of literature attached to early onset, autosomal dominant AD groups, or people at risk for dementia in general, who are concerned about their health” We share the reviewer’s concern that younger and midlife adults with mild cognitive impairment are under-represented in the literature, which is precisely one of the reasons we considered a scoping review necessary. To address the concern about representativeness, we have added to the data extraction plan that we will record, for each included study, the aetiological classification of impairment and the type of sample. This will allow us to comment explicitly on how far the existing literature extends beyond early-onset autosomal dominant AD or highly selected at-risk groups. “ 1) it goes back and forth between present test and past tense, making the reader a bit confused. It sounds like the work to be done is in the future and then a following paragraph is in the past tense stating a particular analysis was carried out. 2) review grammar - missing a period at the end of the first paragraph of Research aim & objectives. - repetitive wording - Population: This population of interest in this review..” Thank you for flagging these issues, which we have now addressed. We have inserted the missing period at the end of the first paragraph under “Research aim & objectives” and re-checked that section for punctuation and clarity. We have revised the repetitive wording in the “Population” subsection. As for the tenses, the future tense was used for planned steps (e.g., “will be conducted,” “will be extracted”), and the present perfect/past tense was used for elements that had already occurred regarding the actual scoping review. Dear Dr Sarah Kremen, Thank you for your thoughtful comments and careful reading of our protocol. We address each point in turn below and have revised the manuscript accordingly. “I am still unclear if the authors aim to use the term mild neurocognitive disorder or mild cognitive impairment, or both terms in order to conduct the search of the literature. They make a point that MCI has been associated tightly with Alzheimer's disease specifically but that is not uniformly true, and to not utilize a common term such as MCI and to use only the DSM definition of mild neurocognitive disorder may exclude important sources.” We agree that MCI is a widely used clinical and research term, and that it is not uniformly restricted to Alzheimer’s disease. We did not intend to exclude MCI-based literature, and we appreciate the opportunity to clarify this more explicitly. As shown in the revised PubMed strategy (Table 2), the Population block already includes both “Mild Neurocognitive Disorder” and “MCI” and broader terms such as “Cognitive Impairment”, “neurocognitive dysfunction*” and “Cognit* Disorder*”. Our searches therefore capture studies using either MCI or mNCD terminology, irrespective of aetiology. We have modified the introduction to replace the previous statement about MCI and AD. “A separate question is whether there will be sufficient sources to evaluate for mNCD/MCI in people ages 40-55. This population may not be coming in for cognitive evaluation. Perhaps the scoping review will shed light on whether this is true or not, but I do wonder how much will be found outside of literature attached to early onset, autosomal dominant AD groups, or people at risk for dementia in general, who are concerned about their health” We share the reviewer’s concern that younger and midlife adults with mild cognitive impairment are under-represented in the literature, which is precisely one of the reasons we considered a scoping review necessary. To address the concern about representativeness, we have added to the data extraction plan that we will record, for each included study, the aetiological classification of impairment and the type of sample. This will allow us to comment explicitly on how far the existing literature extends beyond early-onset autosomal dominant AD or highly selected at-risk groups. “ 1) it goes back and forth between present test and past tense, making the reader a bit confused. It sounds like the work to be done is in the future and then a following paragraph is in the past tense stating a particular analysis was carried out. 2) review grammar - missing a period at the end of the first paragraph of Research aim & objectives. - repetitive wording - Population: This population of interest in this review..” Thank you for flagging these issues, which we have now addressed. We have inserted the missing period at the end of the first paragraph under “Research aim & objectives” and re-checked that section for punctuation and clarity. We have revised the repetitive wording in the “Population” subsection. As for the tenses, the future tense was used for planned steps (e.g., “will be conducted,” “will be extracted”), and the present perfect/past tense was used for elements that had already occurred regarding the actual scoping review. Competing Interests: Not applicable Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 19 Jan 2026 Joshi Dookhy , University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Ireland 19 Jan 2026 Author Response Dear Dr Sarah Kremen, Thank you for your thoughtful comments and careful reading of our protocol. We address each point in turn below and have revised the manuscript accordingly. ... Continue reading Dear Dr Sarah Kremen, Thank you for your thoughtful comments and careful reading of our protocol. We address each point in turn below and have revised the manuscript accordingly. “I am still unclear if the authors aim to use the term mild neurocognitive disorder or mild cognitive impairment, or both terms in order to conduct the search of the literature. They make a point that MCI has been associated tightly with Alzheimer's disease specifically but that is not uniformly true, and to not utilize a common term such as MCI and to use only the DSM definition of mild neurocognitive disorder may exclude important sources.” We agree that MCI is a widely used clinical and research term, and that it is not uniformly restricted to Alzheimer’s disease. We did not intend to exclude MCI-based literature, and we appreciate the opportunity to clarify this more explicitly. As shown in the revised PubMed strategy (Table 2), the Population block already includes both “Mild Neurocognitive Disorder” and “MCI” and broader terms such as “Cognitive Impairment”, “neurocognitive dysfunction*” and “Cognit* Disorder*”. Our searches therefore capture studies using either MCI or mNCD terminology, irrespective of aetiology. We have modified the introduction to replace the previous statement about MCI and AD. “A separate question is whether there will be sufficient sources to evaluate for mNCD/MCI in people ages 40-55. This population may not be coming in for cognitive evaluation. Perhaps the scoping review will shed light on whether this is true or not, but I do wonder how much will be found outside of literature attached to early onset, autosomal dominant AD groups, or people at risk for dementia in general, who are concerned about their health” We share the reviewer’s concern that younger and midlife adults with mild cognitive impairment are under-represented in the literature, which is precisely one of the reasons we considered a scoping review necessary. To address the concern about representativeness, we have added to the data extraction plan that we will record, for each included study, the aetiological classification of impairment and the type of sample. This will allow us to comment explicitly on how far the existing literature extends beyond early-onset autosomal dominant AD or highly selected at-risk groups. “ 1) it goes back and forth between present test and past tense, making the reader a bit confused. It sounds like the work to be done is in the future and then a following paragraph is in the past tense stating a particular analysis was carried out. 2) review grammar - missing a period at the end of the first paragraph of Research aim & objectives. - repetitive wording - Population: This population of interest in this review..” Thank you for flagging these issues, which we have now addressed. We have inserted the missing period at the end of the first paragraph under “Research aim & objectives” and re-checked that section for punctuation and clarity. We have revised the repetitive wording in the “Population” subsection. As for the tenses, the future tense was used for planned steps (e.g., “will be conducted,” “will be extracted”), and the present perfect/past tense was used for elements that had already occurred regarding the actual scoping review. Dear Dr Sarah Kremen, Thank you for your thoughtful comments and careful reading of our protocol. We address each point in turn below and have revised the manuscript accordingly. “I am still unclear if the authors aim to use the term mild neurocognitive disorder or mild cognitive impairment, or both terms in order to conduct the search of the literature. They make a point that MCI has been associated tightly with Alzheimer's disease specifically but that is not uniformly true, and to not utilize a common term such as MCI and to use only the DSM definition of mild neurocognitive disorder may exclude important sources.” We agree that MCI is a widely used clinical and research term, and that it is not uniformly restricted to Alzheimer’s disease. We did not intend to exclude MCI-based literature, and we appreciate the opportunity to clarify this more explicitly. As shown in the revised PubMed strategy (Table 2), the Population block already includes both “Mild Neurocognitive Disorder” and “MCI” and broader terms such as “Cognitive Impairment”, “neurocognitive dysfunction*” and “Cognit* Disorder*”. Our searches therefore capture studies using either MCI or mNCD terminology, irrespective of aetiology. We have modified the introduction to replace the previous statement about MCI and AD. “A separate question is whether there will be sufficient sources to evaluate for mNCD/MCI in people ages 40-55. This population may not be coming in for cognitive evaluation. Perhaps the scoping review will shed light on whether this is true or not, but I do wonder how much will be found outside of literature attached to early onset, autosomal dominant AD groups, or people at risk for dementia in general, who are concerned about their health” We share the reviewer’s concern that younger and midlife adults with mild cognitive impairment are under-represented in the literature, which is precisely one of the reasons we considered a scoping review necessary. To address the concern about representativeness, we have added to the data extraction plan that we will record, for each included study, the aetiological classification of impairment and the type of sample. This will allow us to comment explicitly on how far the existing literature extends beyond early-onset autosomal dominant AD or highly selected at-risk groups. “ 1) it goes back and forth between present test and past tense, making the reader a bit confused. It sounds like the work to be done is in the future and then a following paragraph is in the past tense stating a particular analysis was carried out. 2) review grammar - missing a period at the end of the first paragraph of Research aim & objectives. - repetitive wording - Population: This population of interest in this review..” Thank you for flagging these issues, which we have now addressed. We have inserted the missing period at the end of the first paragraph under “Research aim & objectives” and re-checked that section for punctuation and clarity. We have revised the repetitive wording in the “Population” subsection. As for the tenses, the future tense was used for planned steps (e.g., “will be conducted,” “will be extracted”), and the present perfect/past tense was used for elements that had already occurred regarding the actual scoping review. Competing Interests: Not applicable Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 05 Jun 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 3 (revision) 18 Jan 26 read read Version 2 (revision) 15 Oct 25 read read Version 1 05 Jun 25 Sarah Kremen , Cedars-Sinai Medical Center, Los Angeles, USA Timothy Daly , Bioethics Program, FLACSO Argentina, Buenos Aires, Argentina Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Kremen S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10 Feb 2026 | for Version 3 Sarah Kremen , Cedars-Sinai Medical Center, Los Angeles, California, USA 0 Views copyright © 2026 Kremen S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I have re-reviewed the article and the comments and have no further comments except that Livingston et al 2020 has been updated and is more detailed now in the more recent paper Livingston et al 2024. Why not reference that? References 1. Livingston G, Huntley J, Liu K, Costafreda S, et al.: Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. The Lancet . 2024; 404 (10452): 572-628 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise clinical translation in behavioral neurology (AD, DLB, FTLD, LATE) I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Kremen S. Peer Review Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15782.r52948) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v3#referee-response-52948 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Daly T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Jan 2026 | for Version 3 Timothy Daly , Bioethics Program, FLACSO Argentina, Buenos Aires, Argentina 0 Views copyright © 2026 Daly T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors' response to my initial review contained three sections. I am satisfied with sections one and two. However, the third part of my comment read as follows: I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667 The authors respond that they ' have revised secondary question 3 and clarified the ‘Rationale for scoping review ’. I appreciate that this is a scoping review protocol and not a philosophical discussion, however, I do believe that they should cite some literature containing ethical arguments. That includes Walsh et al. 2022, but there are other papers that the authors should read and cite, in my opinion, to make this "high-risk" approach more grounded in a balanced of structural factors that increase dementia risk. I include some here below. For example, the general problem of individual vs. structural changes in health promotion, beyond dementia: Refer to reference no. 1, 2 & 3 The problems this creates for the risk conceptualisation of dementia: https://cdn.who.int/media/docs/default-source/bulletin/online-first/blt.25.293220.pdf?sfvrsn=2a6e265d_3 "Accounting for inequality in dementia prevention programmes" Refer to reference no.4, 5, & 6 The more specific problem of healthism: Refer to reference no. 7 And the question of responsibility vs. rights-based approaches: Refer to reference no. 8 References 1. Chater N, Loewenstein G: The i-frame and the s-frame: How focusing on individual-level solutions has led behavioral public policy astray. Behavioral and Brain Sciences . 2023; 46 . Publisher Full Text 2. Tubeuf S, Valdivia A, Tavoschi L, Empana J, et al.: The responsibility of health: shifting the focus from individuals to systems. The Lancet Public Health . 2025; 10 (3). Publisher Full Text 3. Carey G, Malbon E, Crammond B, Pescud M, et al.: Can the sociology of social problems help us to understand and manage ‘lifestyle drift’?. Health Promotion International . 2016. Publisher Full Text 4. Horstkötter D, Deckers K, Köhler S: Primary Prevention of Dementia: An Ethical Review. Journal of Alzheimer's Disease . 2021; 79 (2): 467-476 Publisher Full Text 5. Knaggs G, Siette J: The ethical allocation of dementia prevention responsibility. The Lancet Healthy Longevity . 2025; 6 (5). Publisher Full Text 6. Petersen N, Andreoletti M, Blasimme A, Lazzaroni C, et al.: Disentangling Responsibility: Perspectives on Dementia Prevention From Stakeholders in Canada, Germany and Switzerland. Sociology of Health & Illness . 2026; 48 (1). Publisher Full Text 7. Slocombe F, Peel E, Pilnick A, Albert S: Providing Hope or Assigning Blame? Healthism in Print Media Portrayals of Dementia Risk and Responsibility. Sociology of Health & Illness . 2025; 47 (8). Publisher Full Text 8. Daly T: Brain health is a human right: Implications for policy and research. Neuroscience . 2025; 569 : 147-154 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Brain health promotion. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Daly T. Peer Review Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15782.r52947) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v3#referee-response-52947 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Daly T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 11 Dec 2025 | for Version 2 Timothy Daly , Bioethics Program, FLACSO Argentina, Buenos Aires, Argentina 0 Views copyright © 2025 Daly T. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This report is set to provide a comprehensive account of strategies of middle-aged people with mild cognitive impairment to maintain their brain health. From a technical point of view, I see no problem with the manuscript. But it fails to really ask an important question at the heart of the concerns around brain health and highlight the tension to be found in brain health conceptualisation. For example, the authors quote Walsh et al. 2022 as suggesting that "a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia." This is a very superficial citation. Walsh et al. specifically set out many of the weaknesses of the "high-risk" [PMID 36098322] approach defended by the authors here—that is, the idea that high-risk individuals are those who "maintain brain health." What about a public health approach? The authors only offer a very superficial citation of WHO's 2022 Optimizing brain health — why not mention determinants, those found in the very definition? ("Different determinants related to..."); see also Section 3 of Livingston et al. 2024: PMID 39096926, and a Blueprint for dementia research: https://www.who.int/publications/i/item/9789240058248. This doesn't mean the authors aren't doing a legitimate study. I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Brain health promotion. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 19 Jan 2026 Joshi Dookhy, University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Ireland Dear Dr Timothy Daly, Thank you for your thoughtful and constructive comments, particularly regarding the conceptualisation of brain health and the balance between high-risk and population-level approaches to dementia prevention. These have been helpful in interpreting the findings of the actual scoping review. Regarding this protocol, we have now clarified our original framing and revised the manuscript accordingly. “The authors only offer a very superficial citation of WHO's 2022 Optimizing brain health — why not mention determinants, those found in the very definition? ("Different determinants related to..."); see also Section 3 of Livingston et al. 2024: PMID 39096926, and a Blueprint for dementia research” We agree that our initial use of WHO (2022) focused on definitional aspects of brain health and did not sufficiently reflect that brain health is shaped by interconnected determinants. In response, we have expanded the “Brain health” subsection to briefly summarise the WHO determinant framework and to explicitly state that our use of the concept of brain health aligns with this multi-determinant, life-course view rather than with purely behavioural or lifestyle framings. “The authors quote Walsh et al. 2022 as suggesting that "a whole-population approach, with a specific focus in midlife, on preventive interventions can significantly alter brain health trajectories and delay or prevent the onset of dementia." This is a very superficial citation. Walsh et al. specifically set out many of the weaknesses of the "high-risk" [PMID 36098322] approach defended by the authors here—that is, the idea that high-risk individuals are those who "maintain brain health." What about a public health approach?” We are grateful for this observation and agree that our original citation of Walsh et al. did not adequately reflect the core argument of that paper. Our intention is not to defend high-risk approach as a stand-alone solution. Rather, our scoping review focuses on one high-risk group, middle-aged adults living with mNCD, precisely because this group is at elevated risk of progression and currently under-represented in the literature. We see this as complementary to, not in competition with, the development of population-level interventions. “I just want to see some actual arguments in favour of maintaining the status quo here, as opposed to a more ambitious move towards collective responsibility: see PMID 39071741. So: Why do the authors continue to focus on the high-risk approach? Why not ask a question like: What are governments and policy makers doing to support high-risk midlife individuals? See PMID: 37379079, 41151667” We appreciate this reminder to engage with the emerging ethics and public-health literature and agree that lifestyle-focused narratives can be ethically problematic when determinants shape risks and behaviour change. Our population focus on adults at midlife with mNCD reflects clinical and epidemiological considerations. We see this as a critical and currently under-researched component of a broader dementia prevention agenda. That said, it is essential not to imply that responsibility for brain health rests solely with individuals, especially when structural constraints and policy decisions shape what is possible. Rather than expanding this protocol into a full scoping review of policy responses (which would require a separate, differently scoped review!), we have revised secondary question 3 and clarified the ‘Rationale for scoping review’. The new wording makes clear that we will extract and report information on how broader social determinants support or hinder the interventions described in the included studies. View more View less Competing Interests Not applicable. reply Respond Report a concern Daly T. Peer Review Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15699.r51213) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://hrbopenresearch.org/articles/8-63/v2#referee-response-51213 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Kremen S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Nov 2025 | for Version 2 Sarah Kremen , Cedars-Sinai Medical Center, Los Angeles, California, USA 0 Views copyright © 2025 Kremen S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors of this article entitled, " Brain Health Strategies to Reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol" present the rationale with our current knowledge that many risk factors for dementia begin in midlife, it is important to understand how people in midlife approach brain health and ways to maintain it. The manuscript describes a framework based upon best practices for conducting systematic searches, and designing and carrying out scoping reviews. In regard to the appropriateness of the study design to the research question, I am still unclear if the authors aim to use the term mild neurocognitive disorder or mild cognitive impairment, or both terms in order to conduct the search of the literature. They make a point that MCI has been associated tightly with Alzheimer's disease specifically but that is not uniformly true, and to not utilize a common term such as MCI and to use only the DSM definition of mild neurocognitive disorder may exclude important sources. A separate question is whether there will be sufficient sources to evaluate for mNCD/MCI in people ages 40-55. This population may not be coming in for cognitive evaluation. Perhaps the scoping review will shed light on whether this is true or not, but I do wonder how much will be found outside of literature attached to early onset, autosomal dominant AD groups, or people at risk for dementia in general, who are concerned about their health. Smaller issues for this manuscript in regard to ease of reading - could be tightened: 1) it goes back and forth between present test and past tense, making the reader a bit confused. It sounds like the work to be done is in the future and then a following paragraph is in the past tense stating a particular analysis was carried out. 2) review grammar - missing a period at the end of the first paragraph of Research aim & objectives. - repetitive wording - Population: This population of interest in this review... Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes References 1. Livingston G, Huntley J, Liu K, Costafreda S, et al.: Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. The Lancet . 2024; 404 (10452): 572-628 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise clinical translation in behavioral neurology (AD, DLB, FTLD, LATE) I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 19 Jan 2026 Joshi Dookhy, University College Dublin School of Nursing Midwifery and Health Systems, Dublin, Ireland Dear Dr Sarah Kremen, Thank you for your thoughtful comments and careful reading of our protocol. We address each point in turn below and have revised the manuscript accordingly. “I am still unclear if the authors aim to use the term mild neurocognitive disorder or mild cognitive impairment, or both terms in order to conduct the search of the literature. They make a point that MCI has been associated tightly with Alzheimer's disease specifically but that is not uniformly true, and to not utilize a common term such as MCI and to use only the DSM definition of mild neurocognitive disorder may exclude important sources.” We agree that MCI is a widely used clinical and research term, and that it is not uniformly restricted to Alzheimer’s disease. We did not intend to exclude MCI-based literature, and we appreciate the opportunity to clarify this more explicitly. As shown in the revised PubMed strategy (Table 2), the Population block already includes both “Mild Neurocognitive Disorder” and “MCI” and broader terms such as “Cognitive Impairment”, “neurocognitive dysfunction*” and “Cognit* Disorder*”. Our searches therefore capture studies using either MCI or mNCD terminology, irrespective of aetiology. We have modified the introduction to replace the previous statement about MCI and AD. “A separate question is whether there will be sufficient sources to evaluate for mNCD/MCI in people ages 40-55. This population may not be coming in for cognitive evaluation. Perhaps the scoping review will shed light on whether this is true or not, but I do wonder how much will be found outside of literature attached to early onset, autosomal dominant AD groups, or people at risk for dementia in general, who are concerned about their health” We share the reviewer’s concern that younger and midlife adults with mild cognitive impairment are under-represented in the literature, which is precisely one of the reasons we considered a scoping review necessary. To address the concern about representativeness, we have added to the data extraction plan that we will record, for each included study, the aetiological classification of impairment and the type of sample. This will allow us to comment explicitly on how far the existing literature extends beyond early-onset autosomal dominant AD or highly selected at-risk groups. “ 1) it goes back and forth between present test and past tense, making the reader a bit confused. It sounds like the work to be done is in the future and then a following paragraph is in the past tense stating a particular analysis was carried out. 2) review grammar - missing a period at the end of the first paragraph of Research aim & objectives. - repetitive wording - Population: This population of interest in this review..” Thank you for flagging these issues, which we have now addressed. We have inserted the missing period at the end of the first paragraph under “Research aim & objectives” and re-checked that section for punctuation and clarity. We have revised the repetitive wording in the “Population” subsection. As for the tenses, the future tense was used for planned steps (e.g., “will be conducted,” “will be extracted”), and the present perfect/past tense was used for elements that had already occurred regarding the actual scoping review. View more View less Competing Interests Not applicable reply Respond Report a concern Kremen S. Peer Review Report For: Brain Health Strategies to reduce Dementia Risk in Middle-Aged Adults with Cognitive Decline: A Scoping Review Protocol [version 3; peer review: 1 approved, 1 approved with reservations] . HRB Open Res 2026, 8 :63 ( https://doi.org/10.21956/hrbopenres.15699.r50846) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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