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Recent work suggests that the relationship between age and memory-related brain activity are different for men and women. We sought to extend this work by examining sex differences in the association between age, memory performance, and brain signal variability during context memory tasks in neurotypical adults (aged 19-76 years; N = 128, 87 women). We measured blood oxygen level-dependent standard deviation (BOLD SD) during encoding and retrieval in easy and difficult spatial context memory tasks and investigated sex-specific, age- and performance-associated BOLD SD patterns. Behavioral analysis revealed age-related decreases in memory retrieval, but no sex differences nor an age-by-sex interaction. Imaging results indicated that both sexes showed a negative correlation between BOLD SD and retrieval accuracy in memory-related regions. We also identified significant sex differences: women exhibited age-associated increases in BOLD SD which were negatively associated with performance. Men exhibited both age-associated decreases and increases, which were not related to performance. Our results revealed sex differences in the relationship between age and BOLD SD during high-demand episodic memory tasks.

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.

A functional gradient has been proposed across the medial temporal lobes (MTL) such that the anterior MTL is thought to support processing of individual items (e.g., item memory and complex object perception), whereas the posterior MTL is thought to support item-context retrieval (e.g., source memory). Whereas functional imaging studies have provided evidence supporting this anatomical organization, results from structural analyses remain inconclusive. The current study examined the relationship between volume of MTL regions of interest (ROIs), and performance on a source memory task and a fine-grain complex object perception task, in healthy young adults (mean age = 21.5, range = 18-29). Using a semiautomated procedure, we segmented the parahippocampal and perirhinal cortices (PHC, PRC), posteromedial and anterolateral entorhinal cortices (pmERC, alERC), and posterior and anterior hippocampus (postHC, antHC) on high-resolution T2-weighted MRIs. Regional volumes were computed as proportions of intracranial volume, and as posterior-anterior volumetric ratios (PHC:PRC, pmERC:alERC, postHC:antHC). Partial-least squares regressions were applied to predict source and item memory, and perceptual discrimination accuracy, based on ROI and ratio volumes. In our ROI regressions, we found that postHC volume was positively correlated with a latent factor predicting source memory, and PRC and antHC volumes were negatively correlated to this latent factor. In our ratio regressions, we observed an effect relating the posterior-anterior distribution of gray matter across the MTL with source memory. Our results demonstrate differential associations between anterior and posterior MTL and source memory performance. Findings from this study highlight the importance of considering patterns of structure-behavior associations in the neurobiology of episodic memory.

Cardiometabolic risk factors (CMRs) are associated with accelerated brain aging and increased risk for sex-dimorphic illnesses such as Alzheimer’s Disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E-ε4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi-shell diffusion-weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied i) between males and females, ii) according to age at menopause in females, and iii) across different age groups in males and females. We report sex differences in associations between BAG and all three CMRs, with stronger positive associations among males com- pared to females. Higher BAG (older brain age relative to chronological age) was associated with greater BMI, WHR, and BF% in males, whereas in females, higher BAG was associated with greater WHR, but not BMI and BF%. These divergent associations were most prominent within the oldest group of females (66-81yrs), where higher BF% was linked to lower BAG (younger brain age relative to chronological age). Earlier menopause transition was associated with higher BAG, but no interactions were found with CMRs. APOE4 status was not significantly associated with BAG, and no significant interactions with CMRs were found. In conclusion, the findings point to sex- and age-specific associations between body fat composition and brain age. Incorporating sex as a factor of interest in studies addressing cardiometabolic risk may promote sex-specific precision medicine, consequently improving health care for both males and females.

Women represent (2)/(3) of the cases of Alzheimers disease (AD). Current research has focused on differential risks to explain higher rates of AD in women. However, factors that reduce risk for AD, like cognitive/brain reserve, are less well explored. We asked: what is known about sex and gender differences in how reserve mitigates risk for AD? We conducted a narrative review of the literature, with keywords: "sex/gender differences", "cognitive/brain reserve", "Alzheimers Disease", and the following cognitive reserve contributors: "education", "IQ", "occupation", "cognitive stimulation", "bilingualism", "socioeconomic status", "physical activity", "social support". Sixteen papers disaggregated their data by sex. Those papers observed sex and gender differences in reserve contributors. There is also evidence that greater reserve may be more beneficial in lowering AD risk in women, although more research is needed. We discuss how traditional reserve contributors are gendered and may not capture factors that support cognition in aging women. Funding Agencies|Canadian Consortium on Neurodegeneration and Aging; Wilfred and Joyce Posluns Chair in Womens Brain Health and Aging (the Womens Brain Health Initiative, Ontario Brain Institute); Wilfred and Joyce Posluns Chair in Womens Brain Health and Aging (Canadian Institutes of Health Research)Canadian Institutes of Health Research (CIHR); Canadian Institute of Health ResearchCanadian Institutes of Health Research (CIHR) [PJT 201610-153321, GS9-171369]; Natural Science and Engineering Research CouncilNatural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2018-05761]; Alzheimers Society; Natural Science and Engineering Research CouncilNatural Sciences and Engineering Research Council of Canada (NSERC)

The menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of cardiometabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause. Using the UK Biobank sample, we investigated associations between brain characteristics and visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) in 10,251 post-menopausal females, and assessed whether the relationships varied depending on length of reproductive span (age at menarche to age at menopause). To parse the effects of common genetic variation, we computed polygenic scores for reproductive span. The results showed that higher VAT and ASAT were both associated with higher grey and white matter brain age, and greater white matter hyperintensity load. The associations varied positively with reproductive span, indicating more prominent associations between adipose tissue and brain measures in females with a longer reproductive span. The effects were in general small, but could not be fully explained by genetic variation or relevant confounders. Our findings indicate that associations between abdominal adipose tissue and brain health post-menopause may partly depend on individual differences in cumulative oestrogen exposure during reproductive years, emphasising the complexity of neural and endocrine ageing processes in females. Funding Agencies|Swiss National Science Foundation [PZ00P3_193658]; NCCR Synapsy [32003B_135679, 32003B_159780, 324730_192755, CRSK-3_190185]; Leenaards Foundation; Natural Sciences and Engineering Research Council of Canada; Research Council of Norway [276082, 323961, 273345, 249795, 298646, 300768, 250358, 223273, 283799, 283798]; South-Eastern Norway Regional Health Authority [2018076, 2019101, 2017112, 2022080]; European Research Council under the European Union [802998, 732592, 847776]; HDH Wills 1965 Charitable Trust [1117747]; Alzheimers Society [441]; Academy of Medical Sciences; Wellcome Trust [203139/Z/16/Z]; Government Department of Business, Energy and Industrial Strategy; British Heart Foundation; Diabetes UK Springboard Award [SBF006/1078]

Abstract. Neurobiological research indicates that altered reward processing is among the most promising risk mechanisms in alcohol use disorder and depression. To elucidate differences and similarities between both disorders, we investigated clinical patients and at-risk individuals in two studies using a functional magnetic resonance imaging (fMRI) monetary reward paradigm. In the first study, alcohol use disorder patients compared to depressed and healthy individuals showed increased activation of the ventral striatum during reward anticipation. In contrast, both patient groups showed reduced frontostriatal connectivity compared to controls. In the second study, at-risk comorbid individuals showed decreased activation in the dorsal striatum along with decreased frontostriatal connectivity. While the connectivity results replicate the common pattern found for the patient groups, the activation results indicate a more depression-related pattern in individuals prone to developing both disorders. In conclusion, frontostriatal connectivity might be a promising transdiagnostic marker for depression, alcohol use disorder, and their comorbidity.

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.

Purpose: To investigate whether significant differences exist in everyday memory between youth with Fetal Alcohol Spectrum (FASD) compared with a nonexposed (NE) control group, while controlling fo...

Background. Theatre-based interventions use artistic media to facilitate social and emotional awareness and have therapeutic benefits for persons with developmental disabilities and mental health problems. The role of these interventions with Indigenous youth who have emotional, behavioural, and cognitive sequelae related to fetal alcohol spectrum disorder (FASD) has not been explored. Purpose. The purpose of this study was to explore the experiences and acceptability of a theatre-based approach for facilitating social communication and engagement in youth with FASD. Method. Participants were three Indigenous youth with FASD. A qualitative exploration of the experiences and acceptability of the intervention was conducted via focus groups held 2 weeks post–program participation with the participants, their caregivers, and program facilitators. The transcripts were analyzed using an inductive thematic approach. Findings. Our results identified perceived postintervention improvements in participants’ development of self-esteem, social skills, and emotional awareness. Implications. A theatre-based arts intervention has the potential to support improvements in social skills for youth with FASD.

Supplemental Material, Agnihotri_Appendix_A_FINAL for Investigating a theatre-based intervention for Indigenous youth with fetal alcohol spectrum disorder by Michelle Keightley, Sabrina Agnihotri, Sivaniya Subramaniapillai, Julia Gray, Jennifer Keresztesi, Angela Colantonio, Helene J. Polatajko, Debra Cameron, and Catherine Wiseman-Hakes in Canadian Journal of Occupational Therapy

Acute intracerebral hemorrhage (ICH) heterogeneity on NCCT, characterized by qualitative and quantitative methods, is predictive of hematoma expansion and mortality however association with the spot sign is not well-described. We sought to validate and determine the association between qualitative and quantitative hematoma heterogeneity with expansion and the spot sign, respectively. We retrospectively studied 71 ICH patients presenting