Effects of Sex, APOE4, and Lifestyle Activities on Cognitive Reserve in Older Adults

Abstract

Background and Objectives:Lifestyle activities, such as physical activity and cognitive stimulation, may mitigate age-associated cognitive decline, delay dementia onset, and increase cognitive reserve. Whether the association between lifestyle activities and cognitive reserve differs by sex and APOE4 status is an understudied yet critical component for informing targeted prevention strategies. The current study examined interactions between sex and physical or cognitive activities on cognitive reserve for speed and memory in older adults.Methods:Research participants with unimpaired cognition, mild cognitive impairment, or dementia from the Washington Heights-Inwood Columbia Aging Cohort were included in this study. Cognitive reserve scores for speed and memory were calculated by regressing out hippocampal volume, total gray matter volume, and white matter hyperintensity volume from composite cognitive scores for speed and memory, respectively. Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire, converted to metabolic equivalents (METS). Self-reported cognitive activity (COGACT) was calculated as the sum of three yes/no questions. Sex by activity interactions and sex-stratified analyses were conducted using multivariable linear regression models, including a secondary analysis with APOE4 as a moderating factor.Results: 758 participants (mean age=76.11+6.31 years, 62% women) were included in this study. Higher METS was associated with greater speed reserve in women (β=0.04, CI: (0,0.08)), but not in men (β=0.004, CI: (-0.04,0.05)). METS was not associated with memory reserve in women or men. More COGACT was associated with greater speed reserve in the cohort (β=0.13, CI: (0.05,0.21)). More COGACT had a trend for greater memory reserve in women (β=0.06, CI: (-0.02,0.14)), but not in men (β=-0.04, CI: (-0.16,0.08)). Among women only, APOE4 carrier status attenuated relationships between METS and speed reserve (β=-0.09, CI: (-0.22,0.04)), and between COGACT and both speed (β=-0.26, CI: (-0.63,0.11)) and memory reserves (β=-0.20, CI: (-0.50,0.093)).Discussion:The associations of self-reported physical and cognitive activities with cognitive reserve are more pronounced in women, although APOE4 attenuates these associations. Future studies are needed to understand the causal relationship among sex, lifestyle activities, and genetic factors on cognitive reserve in older adults to best understand which lifestyle activities may be most beneficial and for whom.

Moderating effect of cognitive reserve on brain integrity and cognitive performance

“…Since the relationship between depressive symptoms and cognitive performance is complex ( Butters et al, 2008 ) (e.g., depression could be a risk factor for, consequence of, or reaction to cognitive impairment), we also conducted analyses not controlling for depressive symptoms to determine the stability of effects. Additionally, as sex has been shown to influence reserve or resilience effects ( Sundermann et al, 2016 ; Ewers, 2020 ; Subramaniapillai et al, 2021 ; Pa et al, 2022 ), we also conducted analyses stratified by sex.…”

Structural white matter properties and cognitive resilience to tau pathology

“…Increasing evidence suggests that protective lifestyle factors may play a role in cognitive resilience. [11][12][13] Leveraging a longitudinal cohort of cognitively unimpaired older adults at increased risk of AD, we investigated whether macro-/microstructural white matter properties influence cognitive resilience to AD pathology in vivo. More specifically, we tested whether global efficiency of the limbic network and the DMN, or diffusion metrics within Given that AD pathology also influenced white matter properties, as a last step, we examined the association between white matter characteristics of both networks and health/risk factors with the aim to identify factors that could influence white matter integrity.…”

“…9,10 Various lifestyle and health factors, such as higher education, increased physical activity, and lower vascular risk factors, have been consistently linked to cognitive resilience in AD. 11,12 Those modifiable risk factors have been suggested to enhance tolerance to AD pathology through functional and structural coping mechanisms. 13 Advanced imaging techniques, including positron emission tomography (PET)…”

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

“…An association between the ApoE genotype and synaptic loss in AD was widely demonstrated [60,61]. However, results regarding the relationship between ApoE and CSF Ng are contrasting [54,56,62]. Fan and colleagues found higher levels of CSF Ng in ApoE 4(+), suggesting a role for the relationship between ApoE and Ng in the pathophysiology of AD [54].…”