APOE4 Status is Related to Differences in Memory-Related Brain Function in Asymptomatic Older Adults with Family History of Alzheimer’s Disease: Baseline Analysis of the PREVENT-AD Task Functional MRI Dataset

Abstract

Background: Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's disease (AD). Older adults with the apolipoprotein E 4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. Objective: Here we report the baseline episodic memory task functional MRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease cohort in Montreal, Canada, in which 327 healthy older adults were scanned within 15 years of their parent's conversion to AD.

Dedifferentiation of memory-related brain function as a potential early biomarker of Alzheimer’s disease in asymptomatic older women: Results from the PREVENT-AD Cohort

“…The data-driven mean-centered T-PLS analysis identified general patterns of objectonly and object-location associative encoding and retrieval activity that were common to both sexes (LV1, LV2) and supported the task-related brain activation patterns we previously found in this cohort (Rabipour et al, 2020). Women and men exhibited similar patterns of event- are consistent with those previously reported for the encoding and retrieval of associative information in older adults (Maillet & Rajah, 2014;Salami, Eriksson, & Nyberg, 2012).…”

“…Enrolment criteria for the PREVENT-AD trial (Breitner et al, 2016) as well as a description of the baseline task (Rabipour et al, 2020) are described elsewhere. Briefly, all participants had at least one parent or multiple siblings diagnosed with sporadic AD or a condition suggesting Alzheimer's-like dementia within 15 years (Tschanz, Norton, Zandi, & Lyketsos, 2013).…”

“…As previously described (Rabipour et al, 2020), for both T-PLS and B-PLS we averaged the event-related data for each participant across the entire time series. PLS fMRI data were stacked into a between group data matrix wherein participants were nested within event/task condition; conditions were nested within group; and data for the group of Men were stacked above data for the group of Women.…”

“…carrier status, circulating tau and Aβ levels (Brookmeyer, Abdalla, Kawas, & Corrada, 2018;Kern et al, 2018;Leoutsakos, Gross, Jones, Albert, & Breitner, 2016;Molinuevo et al, 2016;Rabipour et al, 2020;Weiner & Veitch, 2015) -may exert different influences on neural processes in men and women (Buckley et al, 2020;Caldwell, Berg, Cummings, & Banks, 2017). For example, female APOE4 carriers show greater brain hypometabolism and cortical thinning than male carriers, suggesting that women may be more susceptible to the metabolic effects of APOE4 (Sampedro et al, 2015).…”

“…To elucidate neural and behavioural processes underlying episodic memory changes related to healthy vs. pathological aging, studies increasingly focus on examining asymptomatic adults at higher risk of developing AD (Frankish & Horton, 2017). Such work suggests that early neural biomarkers or cognitive indices of AD development – e.g., APOE4 carrier status, circulating tau and Aβ levels (Brookmeyer, Abdalla, Kawas, & Corrada, 2018; Kern et al, 2018; Leoutsakos, Gross, Jones, Albert, & Breitner, 2016; Molinuevo et al, 2016; Rabipour et al, 2020; Weiner & Veitch, 2015) – may exert different influences on neural processes in men and women (Buckley et al, 2020; Caldwell, Berg, Cummings, & Banks, 2017). For example, female APOE4 carriers show greater brain hypometabolism and cortical thinning than male carriers, suggesting that women may be more susceptible to the metabolic effects of APOE4 (Sampedro et al, 2015).…”