The formation of an event memory relies on integrating conceptual knowledge with encoded episodic content. Aging comes with an increased reliance on conceptual knowledge when forming event memories, which could contribute to the formation of gist-based memories. Alternatively, conceptual knowledge could serve as a scaffold, enhancing the ability to encode specific memories. To address how conceptual knowledge impacts episodic memory in aging, we conducted two preregistered experiments, where young and older adults encoded events tailored to include concepts with which they had a high or low degree of knowledge. Memory was tested 24 hr later using two recognition tasks, assessing memory for narrative and perceptual information. Results from Experiment 1 suggested that young adults generally benefited from conceptual knowledge, whereas the impact of knowledge on memory performance in older adults was mixed. However, conceptual knowledge differences across conditions were not equated between age groups: Older adults were more familiar with the concepts presented in their low knowledge condition, compared to young adults. In Experiment 2, we revised the stimuli to maximize differences in conceptual knowledge across conditions in both age groups. Following this modification, we found that both young and older adults displayed enhanced memory for specific details and reduced gist-based errors in their high compared to low conceptual knowledge conditions. Although results suggested that conceptual knowledge had a greater benefit on memory for narrative compared to perceptual content in older adults, differences in baseline performance on these tasks may have influenced this effect. Together, our findings suggest that when conceptual information within an event is aligned with knowledge, it can bolster episodic memory. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Abstract Background A priority in aging and dementia research is to integrate sex (biological attribute) and gender (sociocultural/behavioural characteristics) in theories, designs, analyses, and intervention protocols. We recently reported a data-mining procedure for operationalizing empirically-derived composite gender variables in archival databases. The present study extends the prior cross-sectional approach by examining sex and gender as separate and interactive predictors of longitudinal data-driven memory trajectory classes. Methods Participants (N = 746) contributed baseline data for binary sex (female/male), education (years), and empirically-derived composite variables representing complementary gender facets. These facets included Manual Tasks and Physical Activities; Social and Household Management; Leisure, Socializing, and Travel; Cognitive Activity and Brain Games; Health Perceptions and Practices; and Subjective Memory Beliefs. We integrated these into a longitudinal episodic memory trajectory distribution spanning 42 years (53–95) of aging. Data-driven latent class growth analysis (LCGA) on the trajectory distribution identified discriminable classes. Using the R3STEP approach, we separately tested sex, gender facets, and education as predictors of membership in the higher (healthier) trajectory classes relative to the lowest (benchmark) class. We then included interaction terms to test for sex moderation of gender effects. Finally, we identified all genotyped participants and tested whether sex and gender effects were moderated by Apolipoprotein E (APOE). Results LCGA revealed three memory classes: High-Stable (highest level/relatively stable), Moderate/Normal-Declining (average level/moderate decline), and Low-Declining (lowest level/steepest decline). Several variables separately predicted High-Stable membership. For sex, females were more likely than males to belong to this class. For gender, (a) higher scores for Social and Household Management, Cognitive Activity and Brain Games, and Subjective Memory Beliefs predicted High-Stable membership; and (b) higher scores for Manual Tasks and Physical Activities and Health Perceptions and Practices decreased the likelihood of High-Stable membership (relative to Low-Declining). Moderate/Normal-Declining membership was predicted by Social and Household Management (higher). For education, more years predicted High-Stable membership. Moderation analyses indicated that gender effects were consistent across both sexes and APOE carrier status. Conclusions Data-driven analyses show that biological sex and measurable facets of gender differentially contribute to memory trajectory patterns over a 42-year span of cognitively unimpaired aging.

Background Social and structural determinants of health (SSDH) are key drivers of disparities in cognitive aging and dementia risk, yet their collection in aging and dementia research remains inconsistent. We examined SSDH data collection practices across Canadian longitudinal cohorts of aging and dementia, aiming to identify which SSDH are collected and how they are operationalized. Methods We conducted an environmental scan using three sources: (1) literature databases (Cochrane, Embase, Medline, PubMed, and Web of Science), 2) grey literature (e.g., Alzheimer Society of Canada’s website), and 3) key informants. We included Canadian longitudinal cohorts of community-dwelling older adults that assessed at least one cognitive or dementia-related outcome, including seven key cohorts previously identified by our group. For each study, we extracted information from data collection instruments on whether specific SSDH were assessed, and which tools were used. Results From 1043 non-duplicated articles identified through database searches, fourteen unique cohorts met inclusion criteria, eleven of which provided data collection instruments. Five additional cohorts were identified from other sources, and together with 7 pre-identified key cohorts, yielded 23 included cohorts. Disability-related measures and ethnicity- and culture-related constructs were among the most comprehensively assessed domains, whereas literacy, environmental context, and economic conditions were among the least frequently assessed. Conclusion SSDH that shape dementia risk and brain resilience, many modifiable at the community and policy levels, remain unevenly collected in Canadian aging and dementia cohorts. Strengthening and harmonizing SSDH measurement is a critical step toward equitable dementia prevention and reducing health disparities.

The variability in cognitive and brain ageing trajectories may be influenced by inter-individual and community-level differences in resilience that result from differential exposures to social and structural determinants of health and be affected by an individual’s sex and gender. However, no clear guidance exists on how to best integrate these diversity-related factors (that is, sex, gender and social and structural determinants of health) into clinical and cognitive neuroscience research on resilience in ageing and dementia. The international Brain Resilience and Diversity in Aging and Dementia (BReDAD) Collaboratory was established in 2024 with the goals of synthesizing knowledge, identifying knowledge gaps and developing recommendations for conducting more inclusive research on resilience in this area. On the basis of a focused review of the literature, and discussions held and recommendations made by the Collaboratory, in this Roadmap article, we present a way forward for integrating diversity in future resilience research. This proposal comprises: (i) developing trust and meaningful long-term relationships with communities historically excluded from research; (ii) diversifying who is engaged in all aspects of the research process; (iii) adopting a life-course perspective; (iv) improving and expanding research designs and measurement tools; and (v) using sensitive computational analytics and mixed methods for testing complex, intersectional models. We conclude by recommending a transdisciplinary approach in resilience research to better reflect the complexities inherent in studying diversity and developing precision medicine outcomes. Guidance is lacking on how to best integrate sex, gender and social and structural determinants of health into neuroscience research on brain resilience in ageing and dementia. In this Roadmap article, Rajah et al. propose a way forward for conducting more inclusive research in this field.

The precuneus is a site of early amyloid-beta (Aβ) accumulation. Previous cross-sectional studies reported increased precuneus fMRI activity in older adults with mild cognitive deficits or elevated Aβ. However, longitudinal studies in early Alzheimer's disease (AD) are lacking and the relationship to the Apolipoprotein-E (APOE) genotype is unclear. Investigating the PREVENT-AD dataset, we assessed how baseline and longitudinal precuneus activity during successful memory retrieval relates to future Aβ and tau burden and change in memory performance. We further studied the moderation by APOE4 genotype. We included 165 older adults (age, 62.8 ± 4.4 years; 113 female; 66 APOE4 carriers) who were cognitively normal at baseline with a family history of AD. All participants performed task-fMRI at baseline and underwent 18F-flortaucipir-PET and 18F-NAV4694-Aβ-PET on average 5 years later. We found that higher baseline activity and greater longitudinal increase in precuneus activity were associated with higher Aβ burden in APOE4 carriers but not noncarriers. We observed no effects of precuneus activity on tau burden. Finally, APOE4 noncarriers with low baseline precuneus activity exhibited better longitudinal performance in an independent memory test compared with (1) noncarriers with higher baseline activity and (2) APOE4 carriers. Our findings suggest that higher task-related precuneus activity during memory retrieval at baseline and over time are associated with greater Aβ burden in cognitively normal APOE4 carriers. Our results further indicate that the absence of "hyperactivation" and the absence of the APOE4 allele is related with better future cognitive outcomes in cognitively normal older adults at risk for AD.

Individuals vary widely in their ability to encode and retrieve past personal experiences in rich contextual detail (episodic memory). However, it remains unclear how within-subject variations in attention, measured on a trial-by-trial basis at encoding, and between-subject variation in attention and executive function abilities affect encoding-related brain activity and subsequent episodic retrieval. In the present study, 38 healthy young adults (mean age = 26.5 ± 4.4, 21 females) completed a task fMRI study in which they were instructed to encode colored photographs of everyday objects and their left/right spatial location. In addition, participants were asked to respond as quickly as possible to a central fixation cross that expanded in size at a variable duration after each encoding trial. RTs to the fixation cross preceding and following the object were hypothesized to reflect attentional variations pre- and postencoding stimulus, respectively. A mixed-effects logistic regression was performed to predict source memory success from pre- and poststimulus RT. Slower poststimulus RT, but not prestimulus RT, predicted poorer subsequent source memory within-subject. In addition, between-subject variation in task-switching ability, self-reported cognitive failures, and self-reported attentional abilities affected the association between poststimulus RT and subsequent memory. In addition, trial-by-trial task fMRI analysis indicated that increased encoding activity within default mode network regions was associated with slower poststimulus RT and with subsequent source retrieval failures. These results shed light onto the cognitive and neural factors that contribute to within-subject and between-subject variations in source memory ability.

The cognitive neuroscience of human aging seeks to identify neural mechanisms behind the commonalities and individual differences in age-related behavioral changes. This goal has been pursued predominantly through structural or “task-free” resting-state functional neuroimaging. The former has elucidated the material foundations of behavioral decline, and the latter has provided key insight into how functional brain networks change with age. Crucially, however, neither is able to capture brain activity representing specific cognitive processes as they occur. In contrast, task-based functional imaging allows a direct probe into how aging affects real-time brain-behavior associations in any cognitive domain, from perception to higher-order cognition. Here, we outline why task-based functional neuroimaging must move center stage to better understand the neural bases of cognitive aging. In turn, we sketch a multi-modal, behavior-first research framework that is built upon cognitive experimentation and emphasizes the importance of theory and longitudinal design.

There is growing evidence that postmenopause is associated with episodic memory decline in some females. Although midlife vascular risk factors are established predictors of brain health, it is unclear whether episodic memory decline at postmenopause is related to vascular risk, and whether such effects affect specific mnemonic functions (e.g. recollective processing vs. novelty detection). This study investigated whether vascular risk, measured by the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, predicts episodic memory in middle-aged females at pre- and post-menopause. Eighty-five cognitively unimpaired females (42 premenopausal, 43 postmenopausal) aged 39.5 to 65.1 years completed easy (low encoding load) and hard (high encoding load) versions of a face-location episodic memory task. Outcome measures were spatial source retrieval (correct source accuracy; CS) and detection of novel stimuli (correct rejections; CR). Linear-mixed models (LMMs) tested menopause group effects on CS and CR, while separate LMMs stratified by menopause status assessed whether CAIDE score predicted memory performance in each group. Results indicated that postmenopausal females performed worse than premenopausal females in both CS (β = 0.08, p < 0.001) and CR (β = 0.05, p = 0.011), with postmenopausal females more sensitive to task difficulty in CS. Higher CAIDE scores were associated with poorer CS accuracy in postmenopausal females only (β = -0.14, p = 0.009), with no effect on CR. These findings highlight the significance of vascular risk in episodic memory decline and emphasize the role of reproductive status in midlife cognition.

Changes in functional connectivity (FC) strength involving the medial temporal lobe (MTL) and posteromedial cortex (PMC) are related to early Alzheimer’s pathology and alterations in episodic memory performance in cognitively unimpaired older adults, but their dynamics remain unclear. We examined how longitudinal changes in FC involving MTL and PMC during resting-state, episodic memory encoding, and retrieval relate to subsequent amyloid- and tau-PET burden, longitudinal episodic memory performance, and the APOE4 genotype in 152 cognitively unimpaired older adults from the PREVENT-AD cohort. We found APOE4- and fMRI paradigm-dependent associations of change in FC strength with pathology burden and change in episodic memory performance. Decreasing FC over time, or “hypoconnectivity”, within PMC during rest in APOE4 carriers and during retrieval in APOE4 non-carriers was related to more amyloid and tau, respectively. Conversely, increasing FC over time, or “hyperconnectivity”, within MTL during encoding in APOE4 carriers and between MTL and PMC during retrieval independent of APOE4 status was related to more tau. Further, increasing FC between MTL and PMC during rest, unlike during encoding, was beneficial for episodic memory. Our study highlights that pathology-related episodic memory network changes manifest differently during rest and task and have differential implications for episodic memory trajectories.

Emotional events are known to be prioritized during episodic encoding, leading to more detailed recollections compared to neutral events. Encoding an emotional event can influence the mnemonic fate of preceding or subsequent neutral events. Studies examining the impact of emotion on memory for neighboring neutral events have produced inconsistent results, which could be due to differences in the conceptual association between emotional and neutral stimuli. To test this idea, we conducted two behavioural experiments in which participants viewed one neutral and one emotional video clip from the same television series (Bates Motel) or from two different sources (emotional video from Bates Motel, neutral video from An Education). In both experiments, we manipulated the order in which participants viewed the videos - one group viewed the neutral video before the emotional video and the other group viewed the neutral video after the emotional video - and tested memory for all videos using free recall. We found that encoding a neutral video before, but not after an emotional video impaired recall, illustrating a retrograde impairment. Critically, this impairment only occurred when the videos were conceptually related, as in Experiment 1. In contrast, there was no indication of a retrograde impairment when the videos were not related, as in Experiment 2. Thus, a conceptual relationship is crucial for emotional events to imbue a retrograde impairment on neutral event memory.

BACKGROUND:The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for late-onset Alzheimer's disease (AD), yet there is little consensus about how and when the allele exerts its influence on the brain. METHODS:In this scoping review, we synthesized research examining APOE ε4-related differences on MRI-derived measures of brain structure, function, and connectivity in cognitively unimpaired, middle-aged adults (aged 40-65 years). Four online databases (Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Scopus) were searched on July 11, 2024, and forward/backward reference searching was conducted on identified studies. We extracted data on sample characteristics, methods, and key APOE ε4-related results. RESULTS:Our pre-registered search strategy identified 30 relevant studies. Overall, we found little evidence of robust, consistent differences between APOE ε4 carriers and non-carriers at midlife, especially in relation to brain structure. However, among the studies identified, small samples were common, and limited consideration was afforded to factors such as sex and ethnocultural diversity. CONCLUSION:Overall, the existing literature indicates that APOE ε4 exerts little, if any, influence on brain structure at midlife, while differences in brain function and connectivity remain poorly characterized.

Early midlife bilateral salpingo-oophorectomy (BSO) is associated with greater Alzheimer's disease risk compared to spontaneous/natural menopause. Previously, we found that participants with BSO had lower volume in the hippocampal dentate gyrus and cornu ammonis 2/3 composite subfield (DG-CA2/3). We sought to extend those hippocampal subfield findings by assessing whether BSO affected volumes along the anteroposterior hippocampal axis, anterolateral entorhinal cortex, and perirhinal cortex subregions (Brodmann area (BA) 35 and 36). We also correlated volumes with key demographic and wellbeing-related factors (age, depressive mood, education), hormone therapy characteristics, and recognition memory performance. Early midlife participants with BSO (with and without 17β-estradiol therapy (ET)) and age-matched control participants with intact ovaries (AMC) completed high-resolution T2-weighted structural magnetic resonance imaging (MRI). Medial temporal lobe volumes and Remember-Know task recognition memory performance were compared between groups-BSO (n = 23), BSO + ET (n = 28), AMC (n = 34) using univariate analyses. Multivariate Partial Least Squares (PLS) analyses were used to examine how volumes related to demographic and wellbeing-related factors, as well as hormone therapy characteristics. Relative to BSO + ET, BSO had lower posterior hippocampal and DG-CA2/3 volumes but greater perirhinal BA 36 volumes. Compared to age, depressive mood, and education, ET was the strongest positive predictor of hippocampal volumes and negative predictor of perirhinal BA 36 volumes. For BSO + ET, hippocampal volumes were negatively related to ET duration and positively related to concurrent progestogen therapy. Relative to AMC, BSO had greater anterolateral entorhinal cortex and perirhinal BA 35 and BA 36 volumes. BSO groups (with and without ET) relied more on familiarity than recollection for successful recognition memory. BSO and ET may have distinct effects on medial temporal lobe volumes, with potential implications for memory processes affected by Alzheimer's disease risk.

Decline in spatial context memory emerges in midlife, the time when most females transition from pre- to post-menopause. Recent evidence suggests that, among post-menopausal females, advanced age is associated with functional brain alterations and lower spatial context memory. However, it is unknown whether similar effects are evident for white matter (WM) and, moreover, whether such effects contribute to sex differences at midlife. To address this, we conducted a study on 96 cognitively unimpaired middle-aged adults (30 males, 32 pre-menopausal females, 34 post-menopausal females). Spatial context memory was assessed using a face-location memory paradigm, while WM microstructure was assessed using diffusion tensor imaging. Behaviorally, advanced age was associated with lower spatial context memory in post-menopausal females but not pre-menopausal females or males. Additionally, advanced age was associated with microstructural variability in predominantly frontal WM (e.g., anterior corona radiata, genu of corpus callosum), which was related to lower spatial context memory among post-menopausal females. Our findings suggest that post-menopausal status enhances vulnerability to age effects on the brain’s WM and episodic memory.

Study Objectives Although short sleep could promote neurodegeneration, long sleep may be a marker of ongoing neurodegeneration, potentially as a result of neuroinflammation. The objective was to evaluate sleep patterns with age of expected Alzheimer's disease (AD) onset and neuroinflammation.Methods We tested 203 dementia-free participants (68.5 +/- 5.4 years old, 78M). The PREVENT-AD cohort includes older persons with a parental history of AD whose age was nearing their expected AD onset. We estimated expected years to AD onset by subtracting the participants' age from their parent's at AD dementia onset. We extracted actigraphy sleep variables of interest (times of sleep onset and morning awakening, time in bed, sleep efficiency, and sleep duration) and general profiles (sleep fragmentation, phase delay, and hypersomnia). Cerebrospinal fluid (CSF) inflammatory biomarkers were assessed with OLINK multiplex technology.Results Proximity to, or exceeding, expected age of onset was associated with a sleep profile suggestive of hypersomnia (longer sleep and later morning awakening time). This hypersomnia sleep profile was associated with higher CSF neuroinflammatory biomarkers (IL-6, MCP-1, and global score). Interaction analyses revealed that some of these sleep-neuroinflammation associations were present mostly in those closer/exceeding the age of expected AD onset, APOE4 carriers, and those with better memory performance.Conclusions Proximity to, or exceeding, parental AD dementia onset was associated with a longer sleep pattern, which was related to elevated proinflammatory CSF biomarkers. We speculate that longer sleep may serve a compensatory purpose potentially triggered by neuroinflammation as individuals are approaching AD onset. Further studies should investigate whether neuroinflammatory-triggered long sleep duration could mitigate cognitive deficits. Graphical Abstract

Background and Objectives: Sex and gender are important topics of increasing interest in aging and dementia research. Few studies have jointly examined sex (as a biological attribute) and gender (as a sociocultural and behavioral characteristic) within a single study. We explored a novel data mining approach to include both sex and gender as potentially related influences in memory aging research. Research Design and Methods: Participants were 746 cognitively normal older adults from the Victoria Longitudinal Study. First, we adapted the Gender Outcomes INternational Group: To Further Well-being Development (GOING-FWD) framework-which is informed by gender dimensions of the Women's Health Research Network-to identify, extract, and operationalize gender-related variables in the database. Second, we applied principal component analysis (PCA) to a pool of potential gender variables for creating empirically derived gender-related components. Third, we verified the expected pattern of sex differences in memory performance and evaluated each gender-related component as a potential mediator of the observed sex-memory association. Results: Systematic data mining produced a roster of potential gender-related variables, 56 of which corresponded to gender dimensions represented in the GOING-FWD framework. The PCA revealed 6 gender-related components (n indicators = 37): Manual Non-Routine Household Tasks, Subjective Memory Beliefs, Leisure Free Time, Social and Routine Household Management, Health Perceptions and Practices, and Brain Games. We observed sex differences in latent memory performance whereby females outperformed males. Sex differences in memory performance were mediated by Manual Non-Routine Household Tasks, Social and Routine Household Management, and Brain Games. Follow-up analyses showed that education also mediated the sex-memory association. Discussion and Implications: We show that (i) data mining can identify and operationalize gender-related variables in archival aging and dementia databases, (ii) these variables can be examined for associations with sex, and (iii) sex differences in memory performance are mediated by selected facets of gender.

Bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes) prior to age 48 is associated with elevated risk for both Alzheimer's disease (AD) and sleep disorders such as insomnia and sleep apnea. In early midlife, individuals with BSO show reduced hippocampal volume, function, and hippocampal-dependent verbal episodic memory performance associated with changes in sleep. It is unknown whether BSO affects fine-grained sleep measurements (sleep microarchitecture) and how these changes might relate to hippocampal-dependent memory. We recruited thirty-six early midlife participants with BSO. Seventeen of these participants were taking 17β-estradiol therapy (BSO+ET) and 19 had never taken ET (BSO). Twenty age-matched control participants with intact ovaries (AMC) were also included. Overnight at-home polysomnography recordings were collected, along with subjective sleep quality and hot flash frequency. Multivariate Partial Least Squares (PLS) analysis was used to assess how sleep varied between groups. Compared to AMC, BSO without ET was associated with significantly decreased time spent in non-rapid eye movement (NREM) stage 2 sleep as well as increased NREM stage 2 and 3 beta power, NREM stage 2 delta power, and spindle power and maximum amplitude. Increased spindle maximum amplitude was negatively correlated with verbal episodic memory performance. Decreased sleep latency, increased sleep efficiency, and increased time spent in rapid eye movement sleep were observed for BSO+ET. Findings suggest there is an association between ovarian hormone loss and sleep microarchitecture, which may contribute to poorer cognitive outcomes and be ameliorated by ET.