Understanding exogenous factors and biological mechanisms for cognitive frailty: a multidisciplinary scoping review

Cognitive frailty (CF) is the conjunction of cognitive impairment without dementia and physical frailty. While predictors of each element are well-researched, mechanisms of their co-occurrence have not been integrated, particularly in terms of relationships between social, psychological, and biological factors. This interdisciplinary scoping review set out to categorise a heterogenous multidisciplinary literature to identify potential pathways and mechanisms of CF, and research gaps. Studies were included if they used the definition of CF OR focused on conjunction of cognitive impairment and frailty, AND excluded studies on specific disease populations, interventions, epidemiology or prediction of mortality. Searches used Web of Science, PubMed and Science Direct. Search terms included "cognitive frailty" OR (("cognitive decline" OR "cognitive impairment") AND (frail*)), with terms to elicit mechanisms, predictors, causes, pathways and risk factors. To ensure inclusion of animal and cell models, keywords such as "behavioural" or "cognitive decline" or "senescence", were added. 206 papers were included. Descriptive analysis provided high-level categorisation of determinants from social and environmental through psychological to biological. Patterns distinguishing CF from Alzheimer's disease were identified and social and psychological moderators and mediators of underlying biological and physiological changes and of trajectories of CF development were suggested as foci for further research. ### Competing Interest Statement Carol Holland reports financial support was provided by UKRI BBSRC & MRC BB/W018322/1, which support was relevant for all authors. Carol Holland reports a relationship with Brocher Foundation that includes: travel reimbursement. Carol Holland reports a relationship with CONGRESO INTERNACIONAL DE PSICOLOGIA Y EDUCACION, Spain that includes: speaking and lecture fees and. travel reimbursement. Alexandre Benedetto reports further financial support from the UKRI BBSRC BB/S017127/1. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ### Funding Statement This work was supported by interdisciplinary funding from the UKRI BBSRC and MRC, grant number: BB/W018322/1. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The study reports a scoping review; data associated with individuals studies are not archived as part of the review.