Association of Subjective Cognitive Decline with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Longitudinal Studies

Background: Subjective cognitive decline (SCD) as an early pathological manifestation of brain aging has become more prevalent among older adults. Objectives: We aimed to investigate the associations of subjective cognitive decline (SCD) with the combined risk of cognitive impairment and dementia. Design: We performed a systematic review and meta-analysis via searching Embase, PubMed and Cochrane electronic databases from January 1 st 1970 to June 4th, 2020. Setting: Prospective cohort studies Participants: Healthy individuals were recruited from community, clinics and population. Measurements: Healthy individuals with SCD were classified into exposure groups, while those without were considered as the reference group. Adjusted relative risks (RR) were estimated in a random-effects model. Both primary and subgroup analyses were conducted. Results: Of 28,895 identified studies, 21 studies containing 22 cohorts were eligible for inclusion in the meta-analysis. SCD increased the risk of subsequent cognitive disorders (RR=2.12, 95% confidence intervals [CI] =1.75-2.58, I2=87%, P<0.01). To be specific, SCD conferred a 2.29-fold excess risk for cognitive impairment (RR=2.29, 95% CI=1.66-3.17, I2=83%, P<0.01) and a 2.16-fold excess risk for dementia (RR=2.16, 95% CI=1.63-2.86, I2=81%, P<0.01). In subgroup analyses, participants with SCD in the subgroup of 65-75 years old, long-education (>15 years) subgroup and subgroup of clinics showed a higher risk of developing objective cognitive disorders. Conclusions: SCD is associated with an increased combined risk of cognitive impairment and incident dementia and should be considered a risk factor for objective cognitive disorders.