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Subjective Cognitive Decline: Level of Risk for Future Dementia and Mild Cognitive Impairment, a Meta-Analysis of Longitudinal Studies

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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 develo** 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 develo** 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 develo** dementia. In contrast, including worry in the definition of SCD, younger age, and recruitment source impacted the OR of develo** 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).

Author information

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Kerryn E. Pike.

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Conflict of Interest

None. The funding source had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Data Availability

Data is available from Kerryn Pike on reasonable request.

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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

Table.7 Decisions made re studies retrieved from the same cohort

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

Fig. 7
figure 7

Funnel plot of publication bias for incident dementia hazard ratio studies

Fig. 8
figure 8

Funnel plot of publication bias for incident dementia odds ratio studies

Fig. 9
figure 9

Funnel plot of publication bias for incident mild cognitive impairment hazard ratio studies

Fig. 10
figure 10

Funnel plot of publication bias for incident mild cognitive impairment odds ratio studies

Appendix E: Moderation analyses

Table.8 Subgroup moderator analyses: definition and recruitment source
Table 9 Meta-regression moderator analyses: Demographics, genetics, and duration of follow-up

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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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