Subjective Cognitive Decline is a Better Marker for Future Cognitive Decline in Females than in Males

Abstract

AbstractBackgroundThe identification of biomarkers and other mechanisms for early detection of Alzheimer’s disease is critical to the development and further advancement of therapies and interventions targeted at managing symptoms and tracking the pathophysiology of disease. The endorsement of subjective cognitive decline (SCD) has emerged as a potential indicator of early change in cognitive status that may be predictive of future impairment at a time when measurable declines in neuropsychological performance cannot be detected. While there are numerous findings revealing sex differences in the prevalence of Alzheimer’s disease, there is a paucity of research examining sex differences in SCD. Therefore, the goal of this project is to determine if the relationship between the endorsement of SCD and future cognitive changes differ as a function of biological sex.MethodsA sample of 3019 male and female healthy older adults (2188 without SCD, 831 with SCD), with a mean follow-up time of 5.7 years, were included from the Rush Alzheimer’s Disease Center Research Sharing Hub. Linear regressions were performed to determine group differences in baseline cognitive scores, while linear mixed effects models were computed to determine group differences in the rate of cognitive change over time.ResultsIndividuals endorsing SCD had significantly lower baseline cognitive scores and increased rates of decline in all cognitive domains compared to those without SCD. Males exhibited significantly lower scores in baseline performance in global cognition, episodic memory, semantic memory, and perceptual speed regardless of SCD classification. Females with SCD were found to decline at significantly faster rates than both males with SCD and males and females without SCD in all cognitive domains over 15-year follow-up.ConclusionsSCD is related to lower baseline cognitive performance and faster cognitive decline compared to those who do not endorse SCD. Females with SCD have the fastest rate of decline suggesting that SCD may be more predictive of future decline in females than in males. Therapeutic interventions targeting SCD in females may aid in the mitigation of sex disparities in AD prevalence.