Abstract
Subjective Cognitive Decline (SCD) in older adults has been identified as a risk factor for dementia, although the literature is inconsistent, and it is unclear which factors moderate progression from SCD to dementia. Through separate meta-analyses, we aimed to determine if SCD increased the risk of developing dementia or mild cognitive impairment (MCI). Furthermore, we examined several possible moderators. Longitudinal studies of participants with SCD at baseline, with data regarding incident dementia or MCI, were extracted from MEDLINE and PsycINFO. Articles were excluded if SCD occurred solely in the context of dementia, MCI, or as part of a specific disease. Pooled estimates were calculated using a random-effects model, with moderator analyses examining whether risk varied according to SCD definition, demographics, genetics, recruitment source, and follow-up duration. Risk of study bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. 46 studies with more than 74,000 unique participants were included. SCD was associated with increased risk of developing dementia (HR = 1.90, 95% CI 1.52–2.36; OR = 2.48, 95% CI 1.97–3.14) and MCI (HR = 1.73, 95% CI 1.18–2.52; OR = 1.83, 95% CI 1.56–2.16). None of the potential moderating factors examined influenced the HR or OR of developing dementia. In contrast, including worry in the definition of SCD, younger age, and recruitment source impacted the OR of developing MCI, with clinic samples demonstrating highest risk. SCD thus represents an at-risk phase, ideal for early intervention, with further research required to identify effective interventions for risk reduction, and cognitive-behavioural interventions for cognitive management. PROSPERO, protocol number: CRD42016037993
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Funding
This work was supported by a National Health and Medical Research Council of Australia Clinical Research Training Fellowship (Grant Number 602543; Kerryn Pike), and a Tracey Banivanua Mar Fellowship through La Trobe University (Kerryn Pike). This work was conducted during the tenure of an Alzheimer’s Australia Dementia Research Foundation (now Dementia Australia Research Foundation) PhD Scholarship (Marina Cavuoto).
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KP had the idea for the review. Literature search, data-extraction, and quality analysis were performed by KP and MC. Data analysis was performed by KP and BW. The first draft of the manuscript was written by KP and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Appendices
Appendix A: MEDLINE and PsychINFO Search Strategies
Ovid MEDLINE (R) 1946 to Present, including In-Process & Other Non-Indexed Citations | ||||
|---|---|---|---|---|
Subjective | Cognitive/ Memory | Decline | Ageing | Longitudinal studies |
exp Self Report/ OR exp Diagnostic Self Evaluation/ OR exp Self-Assessment OR subjective.mp OR self report.mp OR self rated.mp | exp Memory/ OR exp Cognition/ OR cognit*.mp. OR memory.mp | exp Memory Disorders/ OR exp Cognition Disorders/ OR change*.mp. OR impairment*.mp. OR complaint*.mp. OR disorder*.mp. OR decline.mp. OR concern*.mp. OR difficult*.mp | exp Aging/ OR exp Aged/ OR OR aging.mp. OR ageing.mp. OR aged.mp. OR elderly.mp OR older.mp | exp Longitudinal Studies/OR exp Prospective Studies/ OR exp Followup Studies/ OR follow up.mp. OR prospective.mp. OR longitudinal.mp |
With limits: English language, Human | ||||
(((exp Self Report/ OR exp Diagnostic Self Evaluation/ OR exp Self-Assessment OR subjective.mp. OR self rated.mp. OR self report.mp.)
AND (exp Memory/ OR exp Cognition/ OR exp OR cognit*.mp. OR memory.mp.)
AND (exp Memory Disorders/ OR exp Cognition Disorders/ OR change*.mp. OR impairment*.mp. OR complaint*.mp. OR disorder*.mp. OR decline.mp. OR concern*.mp. OR difficult*.mp.)).
OR ((exp Memory/ OR exp Cognition/ OR cognit*.mp. OR memory.mp.) AND complaint*.mp.)).
AND (exp Aging/ OR exp Aged/ OR aging.mp. OR ageing.mp. OR aged.mp. OR elderly.mp OR older.mp).
AND (exp Longitudinal Studies/OR exp Prospective Studies/ OR exp Followup Studies/ OR follow up.mp. OR prospective.mp. OR longitudinal.mp.)
PsycINFO (1987 – present) | ||||
|---|---|---|---|---|
Subjective | Cognitive/ Memory | Decline | Ageing | Longitudinal studies |
exp Self Report/ OR exp Self Evaluation/ OR subjective.mp. OR self rated.mp. OR self report.mp | exp Memory/ OR exp Cognition/ OR exp Cognitive Ability/ OR exp Cognitive Impairment/ OR cognit*.mp. OR memory.mp | exp Memory Disorders/ OR exp Brain Disorders/ OR change*.mp. OR impairment*.mp. OR complaint*.mp. OR disorder*.mp. OR decline.mp. OR concern*.mp. OR difficult*.mp | exp Aging/ OR aging.mp. OR ageing.mp. OR aged.mp. OR elderly.mp OR older.mp | exp Longitudinal Studies/OR exp Prospective Studies/ OR exp Followup Studies/ OR follow up.mp. OR prospective.mp. OR longitudinal.mp |
With limits: English language, Human | ||||
(((exp Self Report/ OR exp Self Evaluation/ OR subjective.mp. OR self rated.mp. OR self report.mp.)
AND (exp Memory/ OR exp Cognition/ OR exp Cognitive Ability/ OR exp Cognitive Impairment/ OR cognit*.mp. OR memory.mp.)
AND (exp Memory Disorders/ OR exp Brain Disorders/ OR change*.mp. OR impairment*.mp. OR complaint*.mp. OR disorder*.mp. OR decline.mp. OR concern*.mp. OR difficult*.mp.)).
OR ((exp Memory/ OR exp Cognition/ OR exp Cognitive Ability/ OR exp Cognitive Impairment/ OR cognit*.mp. OR memory.mp.) AND complaint*.mp.)).
AND (exp Aging/ OR aging.mp. OR ageing.mp. OR aged.mp. OR elderly.mp OR older.mp).
AND (exp Longitudinal Studies/OR exp Prospective Studies/ OR exp Followup Studies/ OR follow up.mp. OR prospective.mp. OR longitudinal.mp.)
Appendix B: Retrieved Studies from the Same Cohort and Decisions Made re Inclusion
Appendix C: Signalling Questions Used to Assess Risk of Bias in each QUADAS-2 Tool Domain
Domain | Signalling question(s) |
|---|---|
Patient selection | 1. Are the baseline demographics of controls and SCD well matched? 2. Was the same recruitment source used for controls and SCD? 3. Was the same screening process applied to controls and SCD? |
Index test (SCD) | 1. Does the definition of SCD capture the group of interest? 2. Was there sufficient screen of cognitive impairment at baseline? |
Reference standard (outcome) | 1. Was a valid outcome measure used? 2. Were those making the outcome diagnoses blind to SCD status? 3. Was there no selectivity in reporting of outcomes? |
Patient flow and timing | 1. Was attrition similar across SCD and controls? |
Appendix D: Funnel Plots Assessing Publication Bias
Funnel plot of publication bias for incident dementia hazard ratio studies
Funnel plot of publication bias for incident dementia odds ratio studies
Funnel plot of publication bias for incident mild cognitive impairment hazard ratio studies
Funnel plot of publication bias for incident mild cognitive impairment odds ratio studies
Appendix E: Moderation analyses
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Pike, K.E., Cavuoto, M.G., Li, L. et al. Subjective Cognitive Decline: Level of Risk for Future Dementia and Mild Cognitive Impairment, a Meta-Analysis of Longitudinal Studies. Neuropsychol Rev 32, 703–735 (2022). https://doi.org/10.1007/s11065-021-09522-3
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DOI: https://doi.org/10.1007/s11065-021-09522-3