Subjective cognitive decline is a better marker for future cognitive decline in females than in males

Abstract

Background The identification of biomarkers for early detection of Alzheimer’s disease (AD) is critical to the development of therapies and interventions targeted at symptom management 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 AD, there is a paucity of research examining sex differences in SCD. Therefore, the goal of this project was to determine if the relationship between the endorsement of SCD and future cognitive changes differ as a function of biological sex. Methods A 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 completed to determine group differences in the rate of cognitive change over time. Results Individuals 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, 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 a maximum 15-year follow-up period. Conclusions SCD 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. Targeted assessments of SCD may allow for the identification of individuals for inclusion in intervention trials, and other research studies, aiming to attenuate casual disease processes, which may ultimately aid in the mitigation of sex disparities in AD.

Neuroimaging Insights into Subjective Cognitive Decline: Differential Sensitivity of Cognitive Change Index and Everyday Cognition Scale

“…Given that entorhinal cortex is consistently reported as one of the first brain regions to show abnormal changes in AD (Igarashi, 2023), these findings suggest that female with SCD may be on the trajectory for AD-related brain changes. This finding is consistent with previous reports showing that SCD is more strongly associated with cognitive decline in females than males over 15 years (Oliver et al, 2022) and that females with SCD are more likely to convert to dementia (Heser et al, 2019). Even when females exhibit the same amount of age- and dementia-related brain changes as males they experience more cognitive decline and worse dementia outcomes (Barnes et al, 2005; Ferretti et al, 2018).…”

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship

“…Our findings for subjective cognition are clinically meaningful: Subjective cognitive impairment may be even more important than neuropsychological test results [9]. There is some evidence that subjective cognitive impairment predicts future objective decline particularly well among women [64]. Moreover, compared to neuropsychological testing, self-report measures may capture more subtle impairment.…”

Clinical predictors of Alzheimer's disease‐like brain atrophy in individuals with memory complaints

“…Sex : Studies have previously suggested that women with SCD are at a higher risk of cognitive decline and dementia (Heser et al., 2019 ; Oliver et al., 2022 ). Interestingly, in our study, men with SCD had smaller hippocampal volumes.…”