Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

Abstract

Objective: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance. Methods: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Results: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Conclusions: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

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

“…These findings suggest that waning cognitive abilities may have the potential to be captured early, particularly in females, with SCD+ individuals detecting subtle cognitive changes prior to objective testing. Previous studies have observed that females tend to self-report cognitive changes more than males (Martinez et al, 2021).…”

“…These findings suggest that waning cognitive abilities may have the potential to be captured early, particularly in females, with SCD+ individuals detecting subtle cognitive changes prior to objective testing. Previous studies have observed that females tend to self-report cognitive changes more than males (Martinez et al, 2021). Combining with our findings with the increased reports in females relative to males may be indicative of either greater changes, or better perception of cognitive changes in females.…”

Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective

“…US‐based studies found that, compared to males, SMC is more strongly associated with objective memory performance among females with amnestic MCI 224 and with incident dementia among non‐demented older adults followed over 15 years 221 . Similarly, in a Colombian cohort of cognitively unimpaired individuals with autosomal dominant AD and non‐carrier family members, women had greater self‐reported SCD than men 225 . Study partner‐reported SCD was also a stronger indicator of memory decline in women versus men.…”

“…221 Similarly, in a Colombian cohort of cognitively unimpaired individuals with autosomal dominant AD and non-carrier family members, women had greater self-reported SCD than men. 225 Study partner-reported SCD was also a stronger indicator of memory decline in women versus men.…”

Associations Among Loneliness, Purpose in Life and Subjective Cognitive Decline in Ethnoracially Diverse Older Adults Living in the United States

“…Studies including Latinos (i.e., with origins in Latin American countries; Jaimes et al, 2013 ) is sparse overall. Some studies investigated SCD in members of a Colombian kindred with early-onset autosomal dominant AD, where Presenilin-1 mutation carriers showed greater subjective concerns than non-carriers ( Norton et al, 2017 ), and female carriers more than males ( Martinez et al, 2021 ). Though prior research suggests protective benefits of PiL ( Wingo et al, 2020 ) and increased risk of loneliness ( Montejo et al, 2020 ) for SCD, there is a paucity of research investigating these relationships, and differences in these ratings, in ethnoracially diverse samples.…”