Sex/gender differences in subjective cognitive decline’s association to cognition and depression

Abstract

AbstractBackgroundDespite the fact that women are more likely to develop Alzheimer’s disease (AD) than men, and develop pathological changes at an earlier age, women often receive diagnoses later. This disparity is possibly due to women’s verbal memory advantage, and the fact that verbal memory tests are often the gold‐standard for diagnostics. Further, a recent meta‐analysis found that female sex/gender was associated with greater depression which is often a differential diagnosis for dementia (Eikelboom 2022). Understanding sex/gender differences in Subjective Cognitive Decline (SCD) is critical to closing the care gap, as SCD is thought to be a preclinical stage of AD where intervention may be most effective. Integration of challenging cognitive testing, including non‐verbal memory tests, along with measurement of depression, is key for defining this preclinical stage. In this study, we compare SCD’s associations with non‐verbal and verbal list‐learning and depression as a function of sex/gender.Method97 cognitively unimpaired older adults were recruited for this study. Participants completed surveys regarding SCD and depression (Geriatric Depression Scale [GDS]) and cognitive testing. Non‐verbal memory was assessed with the Biber Figure Learning Test – Extended (BFLT‐E), a challenging non‐verbal figure‐learning test. Verbal memory was assessed with the Loewenstein‐Acevedo Scales for Semantic Interference and Learning (LASSI‐L). Both tests are associated with early AD changes. Linear regressions were conducted and stratified by sex/gender to assess the relationships of cognition and mood with SCD. Models of cognitive performance included age and education as covariates.ResultVerbal list‐learning (LASSI‐L) predicted SCD in men (R2= .416, β = ‐.390, p = .017), but not in women (R2 = .217, β = ‐.173, p = .167). Non‐verbal figure‐learning, as measured by the BFLT‐E, predicted SCD in women (R2 = .267, β = ‐.342, p = .006), but not in men (R2 = .175, β = ‐.334, p = .078). Similarly, depression predicted SCD in women (R2 = .109, β = .330, p = .007), but not in men (R2 = .003, β = .055, p = .763).ConclusionResults demonstrate that in AD risk states such as SCD, cognitive dysfunction may manifest differently for women than men. Clinical care settings should consider integration of non‐verbal memory tests such as BFLT‐E along with regular screening of depression in order to address the inequities in diagnostics for women.