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Systematic review
Predictors of cognitive deterioration in subjective cognitive decline: evidence from longitudinal studies and implications for SCD-plus criteria
  1. Han Li1,2,
  2. Chen-Chen Tan1,
  3. Lan Tan1,
  4. Wei Xu1
  1. 1Neurology department, Qingdao Municipal Hospital Group, Qingdao University, Qingdao, Shandong, China
  2. 2Medical College, Qingdao University, Qingdao, China
  1. Correspondence to Dr Wei Xu, Neurology department, Qingdao Municipal Hospital Group, Qingdao, Shandong, China; dr_xuwei{at}


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.

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Contributors WX: conceptualisation and design of the study, drafting and revision of the manuscript and the figures, and acting as guarantor for the overall content. HL: collection and analysis of the data, drafting and revision of the manuscript, and preparation of all the figures. C-CT: collection of the data and revision of the manuscript. LT: revision of the manuscript.

  • Funding This work was supported by grants from the National Natural Science Foundation of China (82001136 and 81901121) and the Taishan Scholar Project.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.