Sex differentiated and domain specific patterns of longitudinal cognitive decline across subjective cognitive decline and amyloid positivity groups

Structured AbstractO_ST_ABSBackgroundC_ST_ABSSubjective cognitive decline (SCD) is associated with increased cognitive impairment and dementia. However, limited research has explored how amyloid (A) pathology contributes to these cognitive changes over time and whether these changes differ by sex. Methods1185 cognitively normal older adults (955 A-, 230 A+; 959 SCD-, 226 SCD+) from the National Alzheimers Coordinating Center dataset were included. Linear mixed effects examined the interactions between SCD, sex, and amyloid positivity in predicting cognitive decline. ResultsSCD+ and A+ individuals exhibited increased global cognition declines (p<.05), and A+SCD+ individuals showed the steepest decline in global cognition and function status (p<.05). A+ males exhibited increased functional deficits (p<.05), while A+SCD+ females exhibited increased language deficits (p<.05). DiscussionOur findings suggest that SCD and amyloid-positivity differentially impact global cognition, functional status, and language in males versus females, with important implications for clinical trials and therapeutic interventions. Highlights- Few studies have explored the independent and joint effects of amyloid and sex in SCD - SCD is associated with increased rates of global cognitive decline - Amyloid positive females with SCD exhibit increased language declines - Amyloid positive males exhibit increased functional status declines Research in ContextO_ST_ABSSystematic reviewC_ST_ABSWe reviewed the literature using traditional sources (e.g., PsycInfo, PubMed) and found that there are limited findings exploring longitudinal cognitive trajectories in people who are amyloid positive with SCD and whether these trajectories differ by sex. InterpretationOur findings suggest that SCD and amyloid positivity jointly interact to influence global cognitive and functional declines. Females experience language deficits when they have both SCD and amyloid positivity whereas males with amyloid positivity exhibit increased functional deficits. Together these findings suggest that SCD status and amyloid positivity differentially impact females and males. Future directionsMore research is needed using grouping amyloid, tau, neurodegeneration, and vascular pathologies together to explore the joint impact on cognitive change and conversion in people with SCD.