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Aging is associated with episodic memory decline and changes in functional brain connectivity. Understanding whether and how biological sex influences age- and memory performance-related functional connectivity has important theoretical and clinical implications for our understanding of brain and cognitive aging. Yet, little is known about the effect of sex on neurocognitive aging. Here, we scanned 161 healthy adults between 19-76 yrs of age in an event-related functional magnetic resonance imaging (fMRI) study of face-location spatial context memory. Adults were scanned while performing easy and difficult versions of the task at both encoding and retrieval. We used multivariate whole-brain partial least squares (PLS) connectivity to test the hypothesis that there are sex differences in age- and episodic memory performance-related functional connectivity. We examined how individual differences in age and retrieval accuracy correlated with task-related connectivity. We then repeated this analysis after disaggregating the data by self-reported sex. We found that increased encoding and retrieval-related connectivity within the dorsal attention network (DAN), and between DAN and frontoparietal network (FPN) and visual networks, was positively correlated to retrieval accuracy and negatively correlated with age in both sexes. We also observed sex differences in age- and performance-related functional connectivity: i) greater between-network integration was apparent at both levels of task difficulty in women only, and ii) increased DAN-DMN connectivity with age was observed in men and was correlated with poorer memory performance. Therefore, the neural correlates of age-related episodic memory decline differ in women and men and has important theoretical and clinical implications for the cognitive neuroscience of memory, aging and dementia prevention.

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 sex influences episodic memory-related brain function in cognitively intact older adults at risk of developing AD. Here we used task-based multivariate partial least squares analysis to examine sex differences in episodic memory-related brain activity and brain activity-behavior correlations in a matched sample of cognitively intact older women and men 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). We observed sex differences in task-related brain activity and 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. Our findings suggest a generalization 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. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP .

Background Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's disease (AD). Older adults with the apolipoprotein E ɛ4 (+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. Methods Volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to spatial source recollection and object-only (recognition) memory. We used multivariate partial least squares (PLS) to test the hypothesis that +APOE4 adults with 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 examined group differences in the correlation between event-related brain activity and memory performance. Results We found group similarities in memory performance and in task-related brain activity in the recollection network, but differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. Conclusion 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 first-degree family history of AD.

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 PRe-symptomatic 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 encodedandretrieved 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.

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, we tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face–location associations (spatial context memory). Forty-one women and 41 men between the ages of 21 and 76 years participated in this study. Between-group multivariate partial least squares analysis of the fMRI data was conducted to directly test for sex differences and similarities in age-related and performance-related patterns of brain activity. Our behavioral analysis indicated no significant sex differences in retrieval accuracy on the fMRI tasks. In relation to performance effects, we observed similarities and differences in how retrieval accuracy related to brain activity in women and men. Both sexes activated dorsal and lateral PFC, inferior parietal cortex, and left parahippocampal gyrus at encoding, and this supported subsequent memory performance. However, there were sex differences in retrieval activity in these same regions and in lateral occipital-temporal and ventrolateral PFC. In relation to age effects, we observed sex differences in the effect of age on memory-related activity within PFC, inferior parietal cortex, parahippocampal gyrus, and lateral occipital-temporal cortices. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared with men.

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, we tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face-location associations (spatial context memory). Forty-one women and 41 men between the ages of 21 to 76 years participated in this study. Between-group multivariate partial least squares (PLS) analysis of the fMRI data was conducted to directly test for sex-group differences and similarities in age-related and performance-related patterns of brain activity. Our behavioural analysis indicated no significant sex differences in retrieval accuracy on the fMRI tasks. In relation to performance effects, we observed similarities and differences in how retrieval accuracy related to brain activity in women and men. Both sexes activated dorsal and lateral prefrontal cortex (PFC), inferior parietal cortex (IPC) and left parahippocampal gyrus (PHG) at encoding and this supported subsequent memory performance. However, there were sex differences in retrieval activity in these same regions and in lateral occipital-temporal and ventrolateral PFC. In relation to age effects, we observed sex differences in the effect of age on memory-related activity within PFC, IPC, PHG and lateral occipital-temporal cortices. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared to men.

Remembering associations between encoded items and their contextual setting is a feature of episodic memory. Although this ability generally deteriorates with age, there is substantial variability in how older individuals perform on episodic memory tasks. This variability may stem from genetic and/or environmental factors related to reserve, allowing some individuals to compensate for age-related decline through differential recruitment of brain regions. In this fMRI study spanning a large adult lifespan sample (N=154), we used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of reserve (i.e., a composite of years of education and premorbid I.Q.), impacted brain activity patterns during spatial and temporal context encoding and retrieval. We also conducted a secondary B-PLS to explore whether higher cognitive ability was associated with additional compensatory patterns capturing other aspects of reserve not accounted for by our composite measure of education and I.Q. Our results showed that higher reserve did not moderate the effect of age on cognitive ability or context memory, but higher cognitive ability was associated with better context memory performance and with task-specific compensatory responses in ventral visual, temporal, and fronto-parietal regions in advanced age. Additionally, higher reserve was associated with task-general responses in superior temporal, occipital, and inferior frontal regions. These findings suggest that task-specific compensatory responses in the aging brain are modulated by differences in general cognitive ability, which may be related to accumulated reserve, but not by proxy measures of reserve based on premorbid I.Q. and years of education.

Highlights • +APOE4 women with family history of AD had greater brain aging than men. • Non-modifiable risk factors interact with modifiable ones to decrease brain aging. • Higher BMI was associated with less brain aging in +APOE4 women. • Sex differences in APOE status on brain aging were found in physical activity. • Greater physical activity was associated with less brain aging in +APOE4 men., Emerging evidence suggests that Alzheimer’s Disease (AD) risk factors may differentially contribute to disease trajectory in women than men. Determining the effect of AD risk factors on brain aging in women, compared to men, is critical for understanding whether there are sex differences in the pathways towards AD in cognitively intact but at-risk adults. Brain Age Gap (BAG) is a concept used increasingly as a measure of brain health; BAG is defined as the difference between predicted age (based on structural MRI) and chronological age, with negative values reflecting preserved brain health with age. Using BAG, we investigated whether there were sex differences in the brain effects of AD risk factors (i.e., family history of AD, and carrying an apolipoprotein E ε4 allele [+APOE4]) in cognitively intact adults, and if this relationship was moderated by modifiable factors (i.e. body mass index [BMI], blood pressure and physical activity). We undertook a cross-sectional study of structural MRIs from 1067 cognitively normal adults across four neuroimaging datasets. An elastic net regression model found that women with a family history of AD and +APOE4 genotype had more advanced brain aging than their male counterparts. In a sub-cohort of women with those risk factors, higher BMI was associated with less brain aging whereas lower BMI was not. In a sub-cohort of women and men with +APOE4, engaging in physical activity was more beneficial to men’s brain aging than women’s. Our results demonstrate that AD risk factors are associated with greater brain aging in women than men, although there may be more unexplored modifiable factors that influence this relationship. These findings suggest that the complex interplay between unmodifiable and modifiable AD risk factors can potentially protect against brain aging in women and men.

We consider the problem of scanning and modelling small objects using easily available RGBD sensors such as the Kinect. These sensors allow for the acquisition of view-based registered depth and color data. We register the point clouds by recovering the rigid transformation between successive pairs in a sequence of views, and then demonstrate the utility of surface evolution for shrink wrapping the result using geometric flow based approaches for surface modelling. In our experiments we use a PrimeSense Carmine 1.09, which is a high resolution short range RGBD sensor suited to capture small objects. We obtain high quality surface and appearance models of small objects that are competitive with commercial software packages while better capturing surface detail.