Subjective Cognitive Decline and APOE ɛ4: A Systematic Review

Individuals with subjective cognitive decline (SCD) report self-perceived declines in cognitive function but perform within normal limits on standardized tests. However, for some, these self-perceived changes may herald eventual decline to Alzheimer's disease (AD). In light of this, the relationship between SCD and APOE ɛ4, a known genetic risk factor for AD, has garnered interest; however, no systematic review of this literature exists. The current review (n = 36 articles) examined the prevalence of APOE ɛ4 in SCD samples relative to healthy and objectively impaired samples, and summarized APOE ɛ4-related risk of conversion from SCD to AD. Univariate ANOVA indicated that APOE ɛ4 frequency was comparable between healthy control and SCD samples, yet significantly higher in objectively impaired samples (i.e., MCI, AD) relative to either of these groups. Narrative review provided mixed evidence linking coincident APOE ɛ4-positive genotype and SCD to structural neuropathology. Though there was little evidence to suggest that APOE ɛ4 predisposes individuals to developing SCD, both APOE ɛ4 and SCD were found to confer individual and multiplicative risk of conversion to objective cognitive impairment. Combined, it is likely that a relationship between APOE ɛ4, SCD, and AD exists, though its exact nature remains undetermined. A clearer understanding of these relationships is hindered by a lack of standardization in SCD classification and a dearth of longitudinal outcome research. Wide-scale adoption of genetic screening for dementia risk in persons with SCD is considered premature at this time. Ethical considerations and clinical implications of genetic testing for dementia risk are discussed.