Predictors of cognitive deterioration in subjective cognitive decline: evidence from longitudinal studies and implications for SCD-plus criteria

Background Subjective cognitive decline (SCD) is an early manifestation of cognitive deterioration (CD) in some individuals. Therefore, it is worthwhile to conduct a systematic review and meta-analysis to summarise predictors of CD among individuals with SCD. Method PubMed, Embase, and Cochrane Library were searched until May 2022. Longitudinal studies that assessed factors associated with CD in SCD population were included. Multivariable-adjusted effect estimates were pooled using random-effects models. The credibility of evidence was assessed. The study protocol was registered with PROSPERO. Results A total of 69 longitudinal studies were identified for systematic review, of which 37 were included for the meta-analysis. The mean conversion rate of SCD to any CD was 19.8%, including all-cause dementia (7.3%) and Alzheimer’s disease (4.9%). Sixteen factors (66.67%) were found as predictors, including 5 SCD features (older age at onset, stable SCD, both self- and informant-reported SCD, worry and SCD in the memory clinic), 4 biomarkers (cerebral amyloid β-protein deposition, lower scores of Hulstaert formula, higher total tau in the cerebrospinal fluid and hippocampus atrophy), 4 modifiable factors (lower education, depression, anxiety and current smoking), 2 unmodifiable factors (apolipoprotein E4 and older age) and worse performance on Trail Making Test B. The robustness of overall evidence was impaired by risk of bias and heterogeneity. Conclusion This study constructed a risk factor profile for SCD to CD conversion, supporting and supplementing the existing list of features for identifying SCD populations at high risk of objective cognitive decline or dementia. These findings could promote early identification and management of high-risk populations to delay dementia onset. PROSPERO registration number CRD42021281757.