Sex Differences in the Neural Correlates of Spatial Context Memory Decline in Healthy Aging

Pasvanis

et al. 2020

Preprint

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Late-onset Alzheimer's disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether there are sex differences in episodic memory-related brain function in cognitively intact older adults at risk of developing AD. In the current study, we used task fMRI to test for sex differences in episodic memory-related brain activity and brain activity-behavior correlations in cognitively intact older adults with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage=63.03 ± 3.78; Meducation=15.41 ± 3.40). Importantly, we tested women and men who were matched in age, body mass index, years of education, and proximity to the age of parental AD onset. We used data-driven task-based multivariate partial least squares (PLS) analysis to identify sex differences in brain activity during the successful encoding and retrieval of objects and their associated spatial context. We used behavior PLS to examine sex differences in the correlations between brain activity and memory performance at encoding and retrieval. Our results suggested no significant sex differences in behavioral performance on the memory task. Yet, we observed sex differences in task-related brain activity and in brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Specifically, subsequent object-location associative retrieval associated with encoding related activation of caudate, cingulate, and middle occipital cortex in women and, additionally, of temporo-parietal regions in men. We also found male-specific activations in ventrolateral prefrontal cortex (PFC) and insula during associated with the encoding and retrieval of object-only information. Moreover, whereas activity in ventrolateral PFC, posterior cingulate, and inferior parietal regions during encoding supported subsequent performance in women, activity in these regions during retrieval supported object-location associative memory in men. Similarly, we found that activity in ventrolateral PFC, precuneus, parahippocampal, anterior cingulate, and occipital regions during retrieval supported general memory performance in women but object-only retrieval in men. Our findings suggest functional dedifferentiation of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development.

Section: Discussionsupporting

confidence: 89%

Section: Few Sex Differences In Behavior and Brain Activity Related Tsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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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

Pasvanis

et al. 2020

Preprint

Self Cite

“…We performed behavioral data analyses on neuropsychological tests and episodic memory task performance using SPSS version 24 with a significance threshold of p = 0.05, Greenhouse-Geisser corrections for sphericity, and Bonferroni corrections for multiple comparisons, where applicable. Because evidence suggests meaningful sex/gender differences in the neural and behavioral correlates of episodic memory and cognition in aging [47][48][49], we also investigated self-reported sex as a factor in our analyses.…”

Section: Behavioral Analysesmentioning

confidence: 99%

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

et al. 2020

JAD

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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.

“…We performed behavioral data analyses on neuropsychological tests and episodic memory task performance using SPSS version 24 with a significance threshold of p=.05, Greenhouse-Geisser corrections for sphericity, and Bonferroni corrections for multiple comparisons, where applicable. Because evidence suggests meaningful sex/gender differences in the neural and behavioral correlates of episodic memory and cognition in aging (Gur & Gur, 2002;McCarrey, An, Kitner-Triolo, Ferrucci, & Resnick, 2016;Subramaniapillai et al, 2019), we also investigated self-reported sex as a factor in our analyses.…”

Section: Behavioral Analysesmentioning

confidence: 99%

APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset

et al. 2019

Preprint

Self Cite

Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's Disease (AD) and older adults with the apolipoprotein E e4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. In the current study we report the baseline episodic memory task fMRI results from the PResymptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) study in Montreal, Canada, in which 327 healthy older adults, within 15 years of the parent's conversion to AD, were scanned. During the task fMRI protocol volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to successful spatial source recollection and failures in spatial source recollection, with memory for only item (object) memory.Multivariate task-related partial least squares (task PLS) was used to test the hypothesis that +APOE4 adults with a family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also tested for group differences in the correlation between event-related brain activity and memory performance in +APOE4 compared to -APOE4 adults using behavioral-PLS (B-PLS). We found group similarities in memory performance and in task-related brain activity in the recollection network.However, the B-PLS results indicated there were group differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with parental history of AD. Future research should further investigate the potential to distinguish risk of AD development based on memory performance and associated patterns of brain activity.