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.