Predictors of progression from subjective cognitive decline to objective cognitive impairment: A systematic review and meta-analysis of longitudinal studies

Abstract

Background: Subjective cognitive decline is one of the first symptoms of dementia. With increasing awareness of brain health and a rising prevalence of dementia, a growing number of individuals seek medical assistance for purely subjective cognitive decline. However, only individuals with specific characteristics tend to experience clinical progression.

Objectives: This study aims to summarize the predictors of objective cognitive impairment in individuals with subjective cognitive decline and to identify those at higher risk of clinical progression.

Design: Systematic review and meta-analysis.

Methods: We systematically searched 11 electronic databases from inception to February 1, 2023, for longitudinal studies investigating factors associated with the clinical progression of subjective cognitive decline. Effect sizes were pooled using fixed-effects and random-effects models. Leveraging the results of the meta-analysis, we developed two risk prediction models for objective cognitive impairment.

Results: Forty-six cohort studies were included in the systematic review, of which 28 met the meta-analysis criteria. Fifteen predictors were identified, including 4 biomarkers (amyloid β deposition, lower Hulstaert Formula scores, apolipoprotein e4, and hippocampus atrophy), four epidemiological factors (older age at baseline, impaired instrumental activity of daily living, depression, and anxiety), and seven neuropsychological factors (participants in clinical settings, older age at onset, stable symptom, concerns, cognitive decline confirmed by informant, severe symptoms, and poor performance on Trail Making Test B). Based on the meta-analysis results, we developed two risk prediction models. The first model (Model₁) incorporates epidemiological and neuropsychological factors, distinguishing individuals with low and medium risk. The second model (Model₂) includes additional biomarkers to enhance predictive performance and identify individuals at high risk.

Conclusions: This study provides a comprehensive characterization of individuals undergoing clinical progression from subjective cognitive decline to mild cognitive impairment or dementia. The developed models support the prediction of progression risk in both memory clinic and community settings, aiding in the early identification of individuals at risk of disease conversion and facilitating the translation of evidence into clinical practice.

Registration: The systematic review and meta-analysis have been registered in PROSPERO (CRD 42023392476).

Tweetable abstract: Factors for predicting progression from subjective cognitive decline to objective cognitive impairment: evidence from longitudinal studies.

Keywords: Cognitive dysfunction; Dementia; Prediction model; Predictors; Systematic review.