Subjective Cognitive Decline and Genetic Propensity for Dementia beyond Apolipoprotein ε4: A Systematic Review

Subjective cognitive decline (SCD) has been described as a probable early stage of dementia, as it has consistently appeared to precede the onset of objective cognitive impairment. SCD is related to many risk factors, including genetic predisposition for dementia. The Apolipoprotein (APOE) epsilon 4 allele, which has been thoroughly studied, seems to explain genetic risk for SCD only partially. Therefore, we aimed to summarize existing data regarding genetic factors related to SCD, beyond APOE epsilon 4, in order to improve our current understanding of SCD. We conducted a PRISMA systematic search in PubMed/MEDLINE and Embase databases using the keywords "subjective cognitive decline" and "genetic predisposition" with specific inclusion and exclusion criteria. From the 270 articles identified, 16 were finally included for the qualitative analysis. Family history of Alzheimer's disease (AD) in regard to SCD was explored in eight studies, with conflicting results. Other genes implicated in SCD, beyond APOE epsilon 4, were investigated in six studies, which were not strong enough to provide clear conclusions. Very few data have been published regarding the association of polygenic risk for AD and SCD. Thus, many more genes related to AD must be studied, with polygenic risk scores appearing to be really promising for future investigation.