Language diversity across home and work contexts differentially impacts age- and menopause-related declines in cognitive control in healthy females.

Menopause is associated with declines in cognitive control. However, there is individual variability in the slope of this decline. Recent work suggests that indices of cognitive control are mediated by communicative demands of the language environment. However, little is known about how the impact of bilingual experience generalizes across the lifespan, particularly in females who exhibit steeper cognitive decline due to increasing age and menopausal transition. Thus, we investigated whether diversity of language use in distinct communicative contexts modulated the effects of aging and menopause on cognitive control in an adult lifespan sample of healthy females. We performed robust linear regressions on a sample of 120 females (age range 20-65 years) to characterize age- (n = 120) and menopause-related (n = 59) declines in cognitive control (as assessed by the Wisconsin Card Sorting Test) and to determine whether they are modulated by different facets of bilingual language experience, including the diversity of language use (i.e., language entropy) in home and workplace environments. Workplace but not home language diversity modulated age- and menopause-related declines in cognitive control, suggesting that females may compensate for decline by virtue of adapting to the externally imposed demands of the language environment. These findings have implications for identifying which aspects of bilingual experience may contribute to cognitive reserve in healthy aging. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure.

BACKGROUND: Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease-related brain structural changes. METHODS: We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes. RESULTS: Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age. CONCLUSIONS: Our study demonstrates that the effect of hypertension on cerebral small vessel disease-related brain structure differs by sex and by age at hypertension diagnosis.

Sex differences in longitudinal changes of episodic memory-related brain activity and cognition in cognitively unimpaired older adults with a family history of Alzheimer's disease.

Episodic memory decline is an early symptom of Alzheimer's disease (AD) - a neurodegenerative disease that has a higher prevalence rate in older females compared to older males. However, little is known about why these sex differences in prevalence rate exist. In the current longitudinal task fMRI study, we explored whether there were sex differences in the patterns of memory decline and brain activity during object-location (spatial context) encoding and retrieval in a large sample of cognitively unimpaired older adults from the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer's Disease (PREVENT-AD) program who are at heightened risk of developing AD due to having a family history (+FH) of the disease. The goal of the study was to gain insight into whether there are sex differences in the neural correlates of episodic memory decline, which may advance knowledge about sex-specific patterns in the natural progression to AD. Our results indicate that +FH females performed better than +FH males at both baseline and follow-up on neuropsychological and task fMRI measures of episodic memory. Moreover, multivariate data-driven task fMRI analysis identified generalized patterns of longitudinal decline in medial temporal lobe activity that was paralleled by longitudinal increases in lateral prefrontal cortex, caudate and midline cortical activity during successful episodic retrieval and novelty detection in +FH males, but not females. Post-hoc analyses indicated that higher education had a stronger effect on +FH females neuropsychological scores compared to +FH males. We conclude that higher educational attainment may have a greater neuroprotective effect in older +FH females compared to +FH males.

Menopause Status and Within-Group Differences in Chronological Age Affect the Functional Neural Correlates of Spatial Context Memory in Middle-Aged Females.

Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife-a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged premenopausal and postmenopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal females (age range, 39.55-53.30 years; mean age, 44.28 years; SD age, 3.12 years) and 41 postmenopausal females (age range, 46.70-65.14 years; mean age, 57.56 years; SD age, 3.93 years). We found that postmenopausal status, and advanced age within postmenopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal cortices during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife.SIGNIFICANCE STATEMENT This is the first fMRI study to examine how premenopause and postmenopause status affect the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age-related and performance-related correlations with brain activity in inferior parietal, parahippocampal, and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at premenopause compared with postmenopause.

Disturbed sleep is associated with reduced verbal episodic memory and entorhinal cortex volume in younger middle-aged women with risk-reducing early ovarian removal.

Introduction: Women with early ovarian removal (<48 years) have an elevated risk for both late-life Alzheimer's disease (AD) and insomnia, a modifiable risk factor. In early midlife, they also show reduced verbal episodic memory and hippocampal volume. Whether these reductions correlate with a sleep phenotype consistent with insomnia risk remains unexplored. Methods: We recruited thirty-one younger middleaged women with risk-reducing early bilateral salpingo-oophorectomy (BSO), fifteen of whom were taking estradiol-based hormone replacement therapy (BSO+ERT) and sixteen who were not (BSO). Fourteen age-matched premenopausal (AMC) and seventeen spontaneously peri-postmenopausal (SM) women who were ~10y older and not taking ERT were also enrolled. Overnight polysomnography recordings were collected at participants' home across multiple nights (M=2.38 SEM=0.19), along with subjective sleep quality and hot flash ratings. In addition to group comparisons on sleep measures, associations with verbal episodic memory and medial temporal lobe volume were assessed. Results: Increased sleep latency and decreased sleep efficiency were observed on polysomnography recordings of those not taking ERT, consistent with insomnia symptoms. This phenotype was also observed in the older women in SM, implicating ovarian hormone loss. Further, sleep latency was associated with more forgetting on the paragraph recall task, previously shown to be altered in women with early BSO. Both increased sleep latency and reduced sleep efficiency were associated with smaller anterolateral entorhinal cortex volume. Discussion: Together, these findings confirm an association between ovarian hormone loss and insomnia symptoms, and importantly, identify an younger onset age in women with early ovarian removal, which may contribute to poorer cognitive and brain outcomes in these women.

Women's Brain Health: Midlife Ovarian Removal Affects Associative Memory.

Women with early bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes) have greater Alzheimer's disease (AD) risk than women in spontaneous/natural menopause (SM), but early biomarkers of this risk are not well-characterized. Considering associative memory deficits may presage preclinical AD, we wondered if one of the earliest changes might be in associative memory and whether younger women with BSO had changes similar to those observed in SM. Women with BSO (with and without 17ß-estradiol replacement therapy (ERT)), their age-matched premenopausal controls (AMC), and older women in SM completed a functional magnetic resonance imaging face-name associative memory task shown to predict early AD. Brain activation during encoding was compared between groups: AMC (n=25), BSO no ERT (BSO; n=15), BSO+ERT (n=16), and SM without hormone therapy (n=16). Region-of-interest analyses revealed AMC did not contribute to functional group differences. BSO+ERT had higher hippocampal activation than BSO and SM. This hippocampal activation correlated positively with urinary metabolite levels of 17ß-estradiol. Multivariate partial least squares analyses showed BSO+ERT had a different network-level activation pattern than BSO and SM. Thus, despite being approximately 10 years younger, women with BSO without ERT had similar brain function to those with SM, suggesting early 17ß-estradiol loss may lead to an altered functional brain phenotype which could influence late-life AD risk, making face-name encoding a potential biomarker for midlife women with increased AD risk. Despite similarities in activation, BSO and SM groups showed opposite within-hippocampus connectivity, suggesting menopause type is an important consideration when assessing brain function.

Scene memory and hippocampal volume in middle-aged women with early hormone loss.

The present study explored whether early midlife bilateral salpingo-oophorectomy (BSO), a female-specific risk factor for dementia, is associated with reduced medial temporal lobe structure and function. Younger middle-aged women with the BRCA1/2 mutation and a BSO prior to spontaneous menopause (SM) were recruited. We determined the performance of women with BSO not taking estradiol-based hormone therapy (n = 18) on a task measuring object and scene recognition and quantified medial temporal lobe subregion volumes using manually segmented high-resolution T2-weighted MRI scans. Comparisons were made to those with BSO taking estradiol-based hormone therapy (n = 20), age-matched premenopausal controls (n = 28), and older women in SM not taking hormone therapy matched for duration of hormone deprivation (n = 17). Reduced hippocampal integrity specific to the BSO group not taking hormone therapy was observed, reflected by significantly smaller dentate gyrus/CA2/CA3 volumes and lower scene recognition memory performance. These findings show that hippocampal subfield volume may be useful for identifying early midlife changes in women at elevated risk for dementia.

Age- and Episodic Memory-related Differences in Task-based Functional Connectivity in Women and Men.

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 implications for the cognitive neuroscience of memory and aging. Here, we scanned 161 healthy adults between 19 and 76 years of age in an event-related 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 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 and visual networks, were 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: (a) Greater between-networks integration was apparent at both levels of task difficulty in women only, and (b) increased DAN-default mode network 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 have important theoretical and clinical implications for the cognitive neuroscience of memory, aging, and dementia prevention.

Volume of the posterior hippocampus mediates age-related differences in spatial context memory and is correlated with increased activity in lateral frontal, parietal and occipital regions in healthy aging.

Healthy aging is associated with episodic memory decline, particularly in the ability to encode and retrieve object-context associations (context memory). Neuropsychological and neuroimaging studies have highlighted the importance of the medial temporal lobes (MTL) in supporting episodic memory across the lifespan. However, given the functional heterogeneity of the MTL, volumetric declines in distinct regions may impact performance on specific episodic memory tasks, and affect the function of the large-scale neurocognitive networks supporting episodic memory encoding and retrieval. In the current study, we investigated how MTL structure may mediate age-related differences in performance on spatial and temporal context memory tasks, in a sample of 125 healthy adults aged 19-76 years old. Standard T1-weighted MRIs were segmented into the perirhinal, entorhinal and parahippocampal cortices, as well as the anterior and posterior hippocampal subregions. We observed negative linear and quadratic associations between age and volume of the parahippocampal cortex, and anterior and posterior hippocampal subregions. We also found that volume of the posterior hippocampus fully mediated the association between age and spatial, but not temporal context memory performance. Further, we employed a multivariate behavior partial-least-squares analysis to assess how age and regional MTL volumes correlated with brain activity during the encoding and retrieval of spatial context memories. We found that greater activity within lateral prefrontal, parietal, and occipital regions, as well as within the anterior MTL was related to older age and smaller volume of the posterior hippocampus. Our results highlight the heterogeneity of MTL contributions to episodic memory across the lifespan and provide support for the posterior-anterior shift in aging, and scaffolding theory of aging and cognition.

The impact of the Siemens Tim Trio to Prisma upgrade and the addition of volumetric navigators on cortical thickness, structure volume, and 1H-MRS indices: An MRI reliability study with implications for longitudinal study designs.

Many magnetic resonance imaging (MRI) measures are being studied longitudinally to explore topics such as biomarker detection and clinical staging. A pertinent concern to longitudinal work is MRI scanner upgrades. When upgrades occur during the course of a longitudinal MRI neuroimaging investigation, there may be an impact on the compatibility of pre- and post-upgrade measures. Similarly, subject motion is another issue that may be detrimental to MRI work and embedding volumetric navigators (vNavs) within acquisition sequences has emerged as a technique that allows for prospective motion correction. Our research group recently underwent an upgrade from a Siemens MAGNETOM 3T Tim Trio system to a Siemens MAGNETOM 3T Prisma Fit system. The goals of the current work were to: 1) investigate the impact of this upgrade on commonly used structural imaging measures and proton magnetic resonance spectroscopy indices ("Prisma Upgrade protocol") and 2) examine structural imaging measures in a sequence with vNavs alongside a standard acquisition sequence ("vNav protocol"). While high reliability was observed for most of the investigated MRI outputs, suboptimal reliability was observed for certain indices. Across the scanner upgrade, increases in frontal, temporal, and cingulate cortical thickness (CT) and thalamus volume, along with decreases in parietal CT and amygdala, globus pallidus, hippocampus, and striatum volumes, were observed. No significant impact of the upgrade was found in 1H-MRS analyses. Further, CT estimates were found to be larger in MPRAGE acquisitions compared to vNav-MPRAGE acquisitions mainly within temporal areas, while the opposite was found mostly in parietal brain regions. The results from this work should be considered in longitudinal study designs and comparable prospective motion correction investigations are warranted in cases of marked head movement.

Generalization of memory-related brain function in asymptomatic older women with a family history of late onset Alzheimer's Disease: Results from the PREVENT-AD Cohort.

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.

Sex differences in brain aging among adults with family history of Alzheimer's disease and APOE4 genetic risk.

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.

Latent patterns of task-related functional connectivity in relation to regions of hyperactivation in individuals at risk of Alzheimer's disease.

The goal of this study was to assess how task-related hyperactivation relates to brain network dysfunction and memory performance in individuals at risk of Alzheimer's disease (AD). Eighty participants from the CIMA-Q cohort were included, of which 28 had subjective cognitive decline plus (SCD+), as they had memory complaints and worries in addition to a smaller hippocampal volume and/or an APOE4 allele, 26 had amnestic mild cognitive impairment (MCI) and 26 were healthy controls without memory complaints. Functional magnetic resonance imaging (fMRI) activation was measured during an object-location memory task. Seed-partial least square analyses (seed-PLS) were conducted in controls and in the SCD+/MCI groups to yield sets of orthogonal latent variables (LVs) assessing the triple association between: i) seed activity in brain regions found to be hyperactive in individuals at risk of AD (left hippocampus, left superior parietal lobule, right inferior temporal lobe), ii) latent patterns of whole-brain task-related activation, and iii) associative memory performance. Three LVs in the SCD+ and MCI groups (67.88% of total covariance explained) and two LVs in the controls (77.85% of total covariance explained) were significant. While controls and SCD+/MCI groups shared a common pattern of memory-related connectivity, patterns of hyperactivation-networks interactions were unique to the clinical groups. Interestingly, higher hippocampal connectivity was associated with poorer memory performance whereas higher neocortical connectivity predicted better memory performance in SCD+ and MCI groups. Our data provides empirical evidence that early dysfunction in brain activation and connectivity is present in the very early stages of AD and offers new insights on the relationship between functional brain alterations and memory performance.

The association between cognitive reserve and performance-related brain activity during episodic encoding and retrieval across the adult lifespan.

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. A current topic of debate in the cognitive neuroscience of aging literature revolves around whether 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 tested whether higher cognitive reserve was associated with better task-fMRI context memory performance, and functional compensatory activity patterns in the aging brain. We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of cognitive reserve [i.e., a composite score consisting of years of education (EDU) and crystallized IQ], impacted brain activity during the encoding and retrieval of spatial and temporal contextual details. The results indicated that age-related increases in encoding activity within anterior and lateral frontal, inferior parietal, occipito-temporal and medial temporal cortices, was correlated with better subsequent memory performance; and may be indicative of age-related functional compensation at encoding. Interestingly this compensatory pattern was not correlated with our proxy measure of cognitive reserve but was associated with total brain volume (a measure of brain reserve). However, cognitive reserve was associated with age-invariant and task-general activity in superior temporal, occipital, and left inferior frontal regions. We conclude that the relationship between cognitive reserve, brain reserve and age-related functional compensation is complex, and that EDU and IQ may not fully account for individual differences in cognitive reserve when studying well educated, healthy aging cohorts.

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.

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.

Preparing for the Worst: Evidence that Older Adults Proactively Downregulate Negative Affect.

Previous studies have only investigated age-related differences in emotional processing and encoding in response to, not in anticipation of, emotional stimuli. In the current study, we investigated age-related differences in the impact of emotional anticipation on affective responses and episodic memory for emotional images. Young and older adults were scanned while encoding negative and neutral images preceded by cues that were either valid or invalid predictors of image valence. Participants were asked to rate the emotional intensity of the images and to complete a recognition task. Using multivariate behavioral partial least squares (PLS) analysis, we found that greater anticipatory recruitment of the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus in older adults predicted reduced memory for negative than neutral images and the opposite for young adults. Seed PLS analysis further showed that following negative cues older adults, but not young adults, exhibited greater activation of vmPFC, reduced activation of amygdala, and worse memory for negative compared with neutral images. To the best of our knowledge, this is the first study to provide evidence that the "positivity effect" seen in older adults' memory performance may be related to the spontaneous emotional suppression of negative affect in anticipation of, not just in response to, negative stimuli.

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

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.

Multielement Episodic Encoding in Young and Older Adults.

Previous research on age-related associative memory deficits has generally focused on memory for single associations. However, our real-world experiences contain a multitude of details that must be effectively integrated and encoded into coherent representations to facilitate subsequent retrieval of the event as a whole. How aging interferes with the processes necessary for multielement encoding is still unknown. We investigated this issue in the current fMRI study. While undergoing scanning, young and older adults were presented with an occupation and an object and were asked to judge how likely the two were to interact, either in general or within the context of a given scene. After scanning, participants completed recognition tasks for the occupation-object pairs and the sources/contexts with which the pairs were studied. Using multivariate behavioral partial least squares analyses, we identified a set of regions including anterior pFC and medial-temporal lobes whose activity was beneficial to subsequent memory for the pairs and sources in young adults but detrimental in older adults. An additional behavioral partial least squares analysis found that, although both groups recruited anterior pFC areas to support context memory performance, only in the young did this activity appear to reflect integration of the occupation, object, and scene features. This was also consistent with behavioral results, which found that young adults showed greater conditional dependence between pair and context memory compared with older adults. Together, these findings suggest that binding and/or retrieving multiple details as an integrated whole becomes increasingly difficult with age.

Age-related differences in prefrontal-hippocampal connectivity are associated with reduced spatial context memory.

Altered functional connectivity between dorsolateral prefrontal cortex (DLPFC), posterior hippocampus (HC) and other brain regions with advanced age may contribute to age-related differences in episodic memory. In the current fMRI study of spatial context memory, we used seed connectivity analysis to test for age-related differences in the correlations between activity in DLPFC and HC seeds, and the rest of the brain, in an adult life span sample. In young adults, we found that connectivity between right DLPFC and other prefrontal cortex regions, parietal cortex, precuneus, and ventral visual cortices during encoding was positively related to performance. Positive seed connectivity among these regions, and negative connectivity with posterior HC at retrieval was also positively correlated with retrieval accuracy in young adults. In older adults, activity in right DLPFC was positively correlated with activity in this same set of brain regions, and with posterior HC during encoding and retrieval. Interestingly, this pattern of seed connectivity in older adults was negatively correlated with retrieval accuracy. Thus, age-related differences in context memory may be related to altered frontal-parietal and visual cortical interactions with posterior HC. (PsycINFO Database Record (c) 2019 APA, all rights reserved).