Memory Performance In Older Adults Research Articles

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study

ABSTRACT Objective Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. Methods We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. Results Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. Conclusion As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Protective effects of physical activity on episodic memory during aging are explained by executive functioning

Aging is marked by a memory decline related to an executive function decline. Physical activity (PA) has beneficial effects on both executive functions and memory, especially in aging. The protective effects of PA on these two cognitive abilities have always been studied separately, despite the well-established relationship between memory and executive functions. Our objective was to explore whether the benefits of PA on memory could be explained by reduced age-related changes in executive functions.Nineteen young adults (27.16 years old) and 25 older adults (69.64 years old) performed a resource-dependent memory task, three executive tasks and completed a PA questionnaire (measuring sports and leisure PA). Age group and PA effects on memory and executive performance were analyzed with generalized linear models. Mediation analyses were calculated using method of causal steps approach with a non-parametric bootstrapping procedure.The results confirmed the effects of age and PA on memory and executive performance. A significant interaction confirmed the protective effect of PA on age-related cognitive performance. PA was positively correlated with performance in both memory and executive tasks, but only in the older adults. Although each predictor alone (age, executive functions and PA) significantly explained memory performance in older adults, only the effect of PA on memory performance remained significant when all the predictors were introduced in the analyses.PA mediates the effects of age and executive functions on memory performance. This suggests that PA protects older adults against memory decline by reducing the decline in executive functioning.

Acoustic stimulation during slow wave sleep shows delayed effects on memory performance in older adults

IntroductionIn young healthy adults, phase-locked acoustic stimulation (PLAS) during slow wave sleep (SWS) can boost over-night episodic memory consolidation. In older adults, evidence is scarce and available results are inconsistent, pointing toward reduced PLAS-effectiveness. We argue that multiple stimulation nights are required for effects to unfold in older individuals to compensate for age-related reductions in both SWS and memory performance. We test this assumption in a longitudinal within-subject design.MethodsIn a larger previous project, older adults participated in a three-night intervention receiving either real-PLAS (STIM group) or sham-PLAS (SHAM group). Encoding and immediate recall of face-occupation pairs was administered on the evening of the first intervention night (session one), with feedback-based retrievals ensuing on all following mornings and evenings across the intervention. To test for the benefit of the real-PLAS over sham-PLAS intervention within participants, 16 older adults [agemean: 68.9 (SD: 3.7)] were re-invited receiving the real-PLAS intervention exclusively. This resulted in a SHAMSTIM group (n = 9; T1: sham-PLAS intervention, T2: real-PLAS intervention) and a STIMSTIM group (n = 7; T1 and T2: real-PLAS intervention).ResultsWhile the STIMSTIM group exhibited highly similar responses during T1 and T2, the SHAMSTIM group exhibited a significantly higher increase in memory performance at T2 (real-PLAS) compared to T1 (sham-PLAS). These gains can be attributed to the late stages of the experiment, after three nights of real-PLAS, and remained stable when correcting for changes in baseline sleep quality (PSQI) and baseline cognitive ability (Montreal Cognitive Assessment) between T1 and T2.ConclusionsWe show that in older adults, PLAS-induced memory effects are delayed and manifest over the course of a three-night-PLAS intervention. Our results might explain the lack of effects in previous PLAS studies, where memory performance was solely assessed after a single night of PLAS.

Predicted gene expression identifies novel tissue‐specific gene predictors of memory performance in older adults

AbstractBackgroundMemory performance can serve as a strong endophenotype for Alzheimer’s disease (AD) that changes early and continues to decline with disease progression. Yet, the genetic architecture of memory is not well characterized in older adults. Here, we build on existing memory GWAS studies by performing predicted gene expression analysis (PrediXcan) among older (60+) individuals from four cohorts of aging and investigate specific gene‐tissue drivers of genetically regulated gene expression associated with memory performance.MethodTissue‐specific (49 tissues, 5455 genes) PrediXcan models were built following the method described in Gamazon et al. (Nature Genetics 2015) leveraging model weights derived in GTEx (v8 release, build 38). Baseline and longitudinal memory scores were harmonized leveraging cognitive item‐level data on 19,707 non‐Hispanic White participants from four cohort studies of aging and AD (mean age 75.6±7.7, 55% female) using confirmatory factor analyses models. PrediXcan analyses were run adjusting for age at baseline, sex, and 5 population PCs and then meta‐analyzed using a fixed effects model. Correction for multiple comparisons accounting for all gene‐tissue combinations (267,267) was completed with the false discovery rate procedure (fdr‐p&lt;0.05). Sensitivity analyses excluded all non‐AD dementia and other comorbid conditions (N = 16,373; 57% females).ResultAs expected, several signals emerged from chromosome 19, including 48 gene‐tissue combinations near the APOE locus. Outside of APOE, we identified 20 gene‐tissue combinations from 17 known AD loci and three novel loci: higher predicted PUS7 expression in the caudate (β = ‐0.018, p = 0.034) and higher RP11‐18C3.1 expression in colon (β = ‐0.0165, fdr‐p = 0.034) related to faster cognitive decline, while higher predicted LRRC25 in the nucleus accumbens related to slower cognitive decline (β = 0.009, fdr‐p = 0.015). These signals remain comparable in sensitivity analysis.ConclusionWe identified multiple candidates for future mechanistic analysis. LRRC25 is a particularly interesting candidate that is differentially expressed in the AD brain, regulates autophagy in myeloid cells, and is in a co‐expression network with other known AD genes in the immune pathway like MS4A4A (https://agora.adknowledgeportal.org/). Future work will test for replication of these effects and deconvolve genetically‐regulated versus measured gene expression effects in the AD brain.

Do non-traumatic stressful life events and ageing negatively impact working memory performance and do they interact to further impair working memory performance?

Stress and normal ageing produce allostatic load, which may lead to difficulties with cognition thereby degrading quality of life. The current study's objective was to assess whether ageing and cumulative stress interact to accelerate cognitive decline. With 60 participants, Marshall et al. found that ageing and cumulative stress interact significantly to impair working memory performance in older adults, suggesting vulnerability to the cumulative effects of life events beyond 60 years old. To replicate and extend this finding, we increased the sample size by conducting 3 independent studies with 156 participants and improved the statistical methods by conducting an iterative Bayesian meta-analysis with Bayes factors. Bayes factors deliver a more comprehensive result because they provide evidence for either the null hypothesis (H0), the alternative hypothesis (H1) or for neither hypothesis due to evidence not being sufficiently sensitive. Young (18-35 yrs) and older (60-85 yrs) healthy adults were categorised as high or low stress based on their life events score derived from the Life Events Scale for Students or Social Readjustment Rating Scale, respectively. We measured accuracy and reaction time on a 2-back working memory task to provide: a) Bayes factors and b) Bayesian meta-analysis, which iteratively added each study's effect sizes to evaluate the overall strength of evidence that ageing, cumulative stress and/or the combination of the two detrimentally affect working memory performance. Using a larger sample (N = 156 vs. N = 60) and a more powerful statistical approach, we did not replicate the robust age by cumulative stress interaction effect found by Marshall et al.. The effects of ageing and cumulative stress also fell within the anecdotal range (⅓<BF<3). We therefore conclude that there was inconclusive statistical evidence, as measured with a life events scale, that ageing and cumulative life stress interact to accelerate cognitive decline.

13 The Relationship Between Body Mass Index (BMI) and Cognitive Performance Among Overweight Adults

Objective:While previous research has repeatedly indicated that greater BMI was associated with reduced cognitive performance, emerging literature on BMI and cognition in late life (age 65 and above) shows conflicting results. Recent studies (Luchsinger et al., 2013; Arvanitakis, Capuano, Bennett, &amp; Barnes, 2018) have found that high BMI was associated with improved processing speed and verbal memory performance in older adults, but further research is needed to examine this relationship across additional aspects of cognition. The current study aims to build upon recent literature by exploring the relationship between BMI and four cognitive domains across the adult age span.Participants and Methods:Adults between the ages of 25-84 (n=217) were recruited for the Loma Linda University Healthy Avocado Trial study. Participants had a mean age of 49.61 (SD=13.13), mean education of 14.66 years (SD=2.44), and a mean BMI of 33.87 (SD=5.48). Cognition was measured using a two-hour neurocognitive battery divided into four discrete domains: attention/working memory (Digit Span, Auditory Consonant Trigrams), processing speed (Trail Making Test Part A, Stroop Color, Stroop Word, Symbol Digit Modalities Test), executive function (FAS/Phonemic Fluency, Stroop Word-Color, Trail Making Test Part B), and learning/memory (Rey Auditory Verbal Learning Test [RAVLT], Brief Visuospatial Memory Test-Revised [BVMT-R]). Individual test scores were standardized around the sample means and standard deviations, and cognitive domain scores were calculated as an average of the relevant standardized scores; a global cognition score represents the average of tests across all four domains. Participants were divided into three age groups (25-40, 41-60, and 61-84). Correlational analyses were performed between BMI and cognitive domain scores within each age group, while controlling for age, sex, and education.Results:No significant correlations were observed between BMI and any of the cognitive domains among adults aged 25-40 and 41-60. Among adults aged 61-84, a significant association was found between BMI and learning and memory (r=0.390, p=0.011). An examination of individual subtests within the domain revealed significant positive correlations between BMI and RAVLT short delay recall (r=0.338, p=0.029) and long delay recall (r=0.353, p=0.022), and between BMI and BVMT-R immediate- (r=0.351, p=0.023) and delayed recall (r=0.332, p=0.032). A trend for the association between BMI on global cognition was also observed in the oldest age group (r=0.275, p=0.078). No significant associations were observed between BMI and the domains of attention/working memory, processing speed, or executive function.Conclusions:No significant associations were observed between BMI and cognitive performance among young- and middle-aged adults. However, among older adults aged 6184, higher BMI was associated with higher scores on both verbal and nonverbal learning &amp; memory. These findings support the 'obesity paradox,' suggesting that increased BMI may be protective for elderly adults. Multiple explanations for this relationship have been proposed, including the role of BMI in the body’s inflammatory response system, as well as observations of dementia-related weight loss. Further research is needed to determine whether BMI has a protective benefit, or if it is simply a clinical marker of underlying disease.

7 P-Tau and Education as Moderators of the Relation between APOE4 and Memory Performance in Older Adults with Varying Cognitive Status

Objective:White matter microstructure (WMM) potentially mediates the relation between APOE4 and memory performance. This study’s purpose was to understand whether p-tau effects this mediation model and whether education level differentially impacts the relations between these genetic and biological biomarkers’ influence on memory.Participants and Methods:Participants included 161 older adults (M=74 years, 40.4% female, 92% White, 74 e4 non-carriers, 87 e4 carriers) with subjective and objective cognitive impairment from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A composite memory score created by ADNI was used as the outcome variable. Mean fractional anisotropy (FA) and radial diffusivity (RD) values of white matter tracts within regions of interest (i.e., fornix (FX), hippocampal cingulum (CGH)) were individually used as the measures of WMM. A moderated mediation was run to examine whether p-tau was a moderator of the mediation between APOE4, white matter microstructure, and memory. An exploratory dual moderated mediation analysis examined education as a moderator of the moderated mediation. Indirect effects were tested using bootstrapping procedures.Results:In the FA moderated mediation model, APOE4 was significantly related to FA of the fornix and memory performance. FA of the CGH and FX were also related to memory performance. With FA of the fornix as the mediator, the conditional indirect effect was not significant (95% CI[-.0009, .0070]). There was a trend suggesting at low (95% CI[-.2421, -.0140]) and average (95% CI[-.1658, -.0083]) levels of p-tau, FA of the fornix was a significant mediator but was non-significant at high levels of p-tau (95% CI [-.1322, .0341]). The RD moderated mediation model was non-significant. The FA and RD exploratory dual moderated mediation models were non-significant. However, the APOE4 x p-tau interaction with FA of the fornix as the mediator suggested a trend. At low levels of p-tau, increased education was related to a significant moderated mediation.Conclusions:Results suggest that FA of the fornix is a significant mediator between the relation of APOE4 and memory, and this may be dependent upon p-tau levels. When p-tau burden load was high, the path by which APOE4 impacts memory performance was not through white matter microstructure degradation. Additionally, the potential buffering effects of education may be most robust at lower levels of p-tau burden.

53 2-Back Performance Does Not Differ Between Cognitive Training Groups in Older Adults Without Dementia

Objective:Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.Participants and Methods:48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.Results:Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).Conclusions:After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.

6 Posterior cerebral artery-defined white matter hyperintensities are associated with object domain memory and transentorhinal volume independently of global beta-amyloid burden

Objective:White matter hyperintensities (WMH) are a radiological marker of small vessel cerebrovascular disease that are related to cognition and memory decline in aging and Alzheimer’s disease (AD). However, the mechanisms that link WMH to memory impairment and whether they interact with or act independently of AD pathophysiology are unclear. The transentorhinal cortex (BA35) is among the earliest anatomical regions to show tau deposition and subsequent atrophy, and baseline posterior WMH is related to longitudinal cortical thinning of the entorhinal cortex. However, it is unclear whether regional WMH are related to BA35 volume specifically, and whether this relationship is influenced by amyloid-β (Aβ) burden. We hypothesized that WMH in the vascular territory of the posterior cerebral artery (PCA), which perfuses both posterior and medial temporal lobe regions, would be associated with reduced BA35 volume and with lower memory in older adults independently of Aβ.Participants and Methods:114 older adults without dementia, aged 60 to 98 years (mean (SD) = 78.31 (11.02), 71 (62.8%) women), were included. Regional WMH volumes were derived from T2-FLAIR images using ANTs, a vascular territory atlas and manual editing. Global Aβ was assessed with 18F-florbetapir PET, using SUVR of a cortical composite region (FBP mean SUVR) with a cerebellar reference region. Total transentorhinal (BA35) volume was derived using T1 and T2-weighted images using ASHS. To assess hippocampal pattern separation ability, an index of episodic memory, participants completed both object (MDT-O) and spatial (MDT-S) versions of a mnemonic discrimination task, with the lure discrimination index as the outcome. Using linear regressions, we first tested for associations among PCA-defined WMH, Aβ, BA35 volume, and MDT-S and MDT-O scores. We then tested whether the relationship between PCA-defined WMH and MDT-O performance was mediated by BA35 volume and whether this mediation was moderated by Aβ. All models adjusted for age, sex, and education.Results:PCA-defined WMH were related to higher FBP mean SUVR (b=0.287, p=0.042) and lower BA35 volume (b=-0.222, p=0.038). PCA-defined WMH were also negatively related to MDT-O performance (b=-0.229, p=0.044), but not to MDT-S (b=-0.171, p=0.118). FBP mean SUVR was not related to BA35 volume (b=-0.131, p=0.344) or MDT performance (MDT-S: b=-0.138, p=0.348; MDT-O: b=0.059, p=0.690). Furthermore, FBP mean SUVR did not interact with PCA-defined WMH to predict memory performance (interaction b=-0.039, p=0.973), nor BA35 volume (interaction b=-0.140, p=0.894). The association of PCA-defined WMH to MDT-O was fully mediated by BA35 volume (indirect effect b=-0.0005, 95% CI (-0.0014, -0.0003)). This mediation was not moderated by FBP mean SUVR (indirect effect b=-0.00001, 95% CI (-0.001, 0.001)).Conclusions:We found that PCA-defined WMH were related to memory performance in older adults, and this association is fully mediated by transentorhinal volume. While PCA-defined WMH are related to higher global Aβ burden, there is no interaction between PCA-defined WMH and Aβ on BA35 volume. These findings point to an amyloid-independent vascular pathway towards memory decline in aging and AD. Future work should examine whether the pathway linking PCA-defined WMH to transentorhinal cortex atrophy and subsequent memory decline is mediated by regional tau pathology.

59 The Impact of Anxiety on Memory Performance in Older Adults with Depression

Objective:Late life depression (LLD) refers to a diagnosis of major depressive disorder in people older than 60, and has been linked to significant cognitive impairment and increased risk of Alzheimer's disease. Although anxiety and depression are highly comorbid, the impact of anxiety on cognition in LLD is far less researched. This is important given that over 20% of middle aged and older adults endorse clinically significant chronic worry. Generalized anxiety disorder in older adults with major depression is associated with poorer cognition and worse treatment outcomes compared with those without anxiety. Therefore, the purpose of the study is to examine the role of anxiety on memory in LLD. We hypothesized that presence of anxiety among older depressed adults would be associated with worse cognitive performance over time.Participants and Methods:Participants included 124 individuals (69.4% female, 90.3% Caucasian) aged 60 or above (M = 71.5, SD = 7.4) who met criteria for major depression, single episode or recurrent. They completed the State Trait Anxiety Inventory, Montgomery Asberg Depression Rating Scale, and a measure of verbal episodic memory (WMS-IV Logical Memory) as part of a larger neuropsychological battery. Data were collected from baseline to three years as part of a larger NIMH-supported longitudinal study. Two-level linear mixed-effect models were fitted to predict memory. State and trait anxiety were used as time-varying predictors. The between-person (level 2) and within-person (level 1) effects of anxiety on memory were assessed controlling for the time trend, age, education, gender, race, and change in depression over time.Results:Plot trajectories across variables revealed a negative correlation such that as anxiety decreased, memory improved over time. Hierarchical linear mixed-effect models revealed that average state anxiety was a marginally significant between-person (level2) predictor for memory [B=-0.041, t(128)=-1.8, p=0.083]. Individuals with greater average state anxiety were more likely to experience memory decline compared to those with lower average state anxiety. In addition, the within-person effect (level 1) of state anxiety was significant [B=-0.096, t(253)=-2.7, p=0.007]. As an individual's anxiety increased over time, their memory declined. Trait anxiety showed a significant within-person effect on memory [B=-0.087, t(254)=-2.0, p=0.048], but a non-significant between-person effect [B=-0.005, t(124)=-0.06, p=0.95].Conclusions:Anxiety appears to increase the risk of memory decline in older adults with major depression, a cohort who are already at risk of cognitive decline. Changes in anxiety increased risk of memory decline even when accounting for changes in depression over time. Although the causal link between anxiety and cognitive impairment remains unclear, it is possible that anxiety and worry may compete for cognitive resources necessary for demanding tasks and situations, detracting from abilities, such as attention and working memory. Older adults with depression may also have difficulty coping adaptively with anxiety, which may negatively affect cognition. Finally, presence of anxiety may represent a form of mild behavioral impairment, a prodrome of cognitive decline leading to dementia. Overall, the present study highlights the negative impact of anxiety on memory performance, indicating that treatment interventions targeting anxiety in older adults are essential to help prevent cognitive decline.

Inhibitory temporo-parietal effective connectivity is associated with explicit memory performance in older adults

Successful explicit memory encoding is associated with inferior temporal activations and medial parietal deactivations, which are attenuated in aging. Here we used dynamic causal modeling (DCM) of functional magnetic resonance imaging data to elucidate effective connectivity patterns between hippocampus, parahippocampal place area (PPA), and precuneus during encoding of novel visual scenes. In 117 young adults, DCM revealed pronounced activating input from the PPA to the hippocampus and inhibitory connectivity from the PPA to the precuneus during novelty processing, with both being enhanced during successful encoding. This pattern could be replicated in two cohorts (N= 141 and 148) of young and older adults. In both cohorts, older adults selectively exhibited attenuated inhibitory PPA-precuneus connectivity, which correlated negatively with memory performance. Our results provide insight into the network dynamics underlying explicit memory encoding and suggest that age-related differences in memory-related network activity are, at least partly, attributable to altered temporo-parietal neocortical connectivity.

Openness to Experience is associated with neural andperformance measures ofmemory inolder adults.

Age-related decline in episodic memory performance is a well-replicated finding across numerous studies. Recent studies focusing on aging and individual differences found that the Big Five personality trait Openness to Experience (hereafter: Openness) is associated with better episodic memory performance in older adults, but the associated neural mechanisms are largely unclear. Here, we investigated the relationship between Openness and memory network function in a sample of 352 participants (143 older adults, 50-80 years; 209 young adults, 18-35 years). Participants underwent functional magnetic resonance imaging (fMRI) during a visual memory encoding task. Functional memory brain-network integrity was assessed using the similarity of activations during memory encoding (SAME) scores, which reflect the similarity of a participant's memory network activity compared to prototypical fMRI activity patterns of young adults. Openness was assessed using the NEO Five-Factor Inventory. Older vs young adults showed lower memory performance and higher deviation of fMRI activity patterns (i.e.lower SAME scores). Specifically in older adults, high Openness was associated with better memory performance, and mediation analysis showed that this relationship was partially mediated by higher SAME scores. Our results suggest that trait Openness may constitute a protective factor in cognitive aging by better preservation of the brain's memory network.

Association of perceived stress with memory decline in older Chinese: The Guangzhou Biobank Cohort Study

BackgroundPrevious studies on associations of perceived stress with poor memory performance in older adults showed inconsistent results. We examined the prospective associations of perceived stress with memory decline using data from Guangzhou Biobank Cohort Study (GBCS). MethodsPerceived stress was measured by the Perceived Stress Scale (PSS) at baseline (2003–2006), with greater scores indicating greater stress. Memory function was measured by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT), with greater scores indicating better performance, at baseline and follow-up (2008–2012) examinations, analyzed as mean annual change in scores. Results9656 participants (72 % women) with mean age 61.6 (standard deviation = 6.4) years were included. During an average of 4.4 years of follow-up, after adjusting for confounders, each one-point greater PSS score was associated with mean annual decline in DWRT scores (β (95 % CI) = −0.005 (−0.008 to −0.002)). Greater Perceived Helplessness (PH) scores, but not Perceived Self-efficacy scores, was associated with greater mean annual decline in DWRT and IWRT scores (β (95 % CI) = −0.005 (−0.009 to −0.001) and − 0.012 (−0.018 to −0.005), respectively), and similar patterns were observed in five out of seven PH items (βs from −0.02 to −0.07). Interaction analysis showed that the association of greater PSS with greater decline in DWRT scores was observed only in those with low family income (β (95 % CI) = −0.08 (−0.13 to −0.04), P for interaction = 0.03). ConclusionsGreater perceived stress was associated with a greater decline in delayed recall memory, especially in those with low family income.

Plasma concentrations of anti-inflammatory cytokine TGF-β are associated with hippocampal structure related to explicit memory performance in older adults

Human cognitive abilities, and particularly hippocampus-dependent memory performance typically decline with increasing age. Immunosenescence, the age-related disintegration of the immune system, is increasingly coming into the focus of research as a considerable factor contributing to cognitive decline. In the present study, we investigated potential associations between plasma levels of pro- and anti-inflammatory cytokines and learning and memory performance as well as hippocampal anatomy in young and older adults. Plasma concentrations of the inflammation marker CRP as well as the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine TGF-β1 were measured in 142 healthy adults (57 young, 24.47 ± 4.48 years; 85 older, 63.66 ± 7.32 years) who performed tests of explicit memory (Verbal Learning and Memory Test, VLMT; Wechsler Memory Scale, Logical Memory, WMS) with an additional delayed recall test after 24 h. Hippocampal volumetry and hippocampal subfield segmentation were performed using FreeSurfer, based on T1-weighted and high-resolution T2-weighted MR images. When investigating the relationship between memory performance, hippocampal structure, and plasma cytokine levels, we found that TGF-β1 concentrations were positively correlated with the volumes of the hippocampal CA4–dentate gyrus region in older adults. These volumes were in turn positively associated with better performance in the WMS, particularly in the delayed memory test. Our results support the notion that endogenous anti-inflammatory mechanisms may act as protective factors in neurocognitive aging.

Mechanisms of Healthy Aging: An Integrated Neurobiological Perspective on Mood and Cognitive Function

Neurobiological approaches to healthy aging can protect against declines in cognitive function and mood disturbances in older adults. This symposium will focus on health-based mechanisms associated with mood and cognition in late life using an integrated micro- and macro-level perspective. Mechanistic pathways and predictors of healthy aging will be discussed across multiple levels of analysis (genetic, molecular, systems-level neurocircuitry, and behavioral). We will discuss these mechanisms of aging and late-life depression cross-sectionally and in the context of non-pharmacological interventions to identify potential pathways for more personalized treatments.This symposium will take a unique approach to classifying the neurobiology of healthy aging. Dr. Swathi Gujral will present a large study of 108 community-dwelling older adults who completed an exercise intervention and discuss differences in stress and emotional health as a function of exercise condition and APOE e4 carrier status. Dr. Julie Dumas will discuss functioning of the nicotinic cholinergic system in older adults and will present effects of nicotinic stimulation and blockade on brain activation and working memory performance in older adults with and without subjective cognitive decline. Dr. Lauren Oberlin will present neuroimaging features of small vessel disease (SVD) in older adults with and without depression and discuss the association between white matter abnormalities and cognitive decline in late life. Dr. Lindsay Victoria will present neural correlates of negative cognitive bias in late-life depression and their impact on treatment response to psychotherapy in depressed older adults.The unifying goal of these presentations is to characterize mechanistic pathways to precisely target cognitive deficits, improve mood, and promote healthy aging. With an emphasis on individual differences, we will examine predictors of change across a range of domains impacted in aging and late-life depression, including stress, working memory, and executive function. This mechanistic approach has important implications for the development of personalized interventions that emphasize health-based approaches to mood and cognitive function in older adults.

The role of metamemory and personality in episodic memory performance in older adults

This study newly investigated the joint contribution of metamemory and personality (traits and facets) in explaining episodic memory (EM) performance in typically aging older adults. Forty-eight participants (age range: 64–75 years) completed a self-paced word list (SPWL) recall task, a metamemory questionnaire assessing perceived control and potential improvement (PCPI) and self-efficacy and satisfaction (SESA) regarding one’s mental abilities (e.g., memory), and the Big-Five Questionnaire. Based on the SPWL encoding strategies reported, participants were then classified as effective (N = 20) or ineffective (N = 28) memory strategy users. Hierarchical regression analyses showed that a better SPWL performance was predicted by higher levels of PCPI, Scrupulousness and Dominance personality facets. Effective memory strategy users, then, showed higher SPWL performance and Dominance (Energy facet) than ineffective ones. These findings suggest that both specific metamemory processes and personality facets predict better EM performance in older adults. Moreover, personality dispositions relating to Dominance seem to characterize individuals adopting effective memory strategies to support EM performance. These results represent first evidence of the role of both metamemory and personality—facets—in explaining older adults’ EM performance, which should thus be considered when assessing or training EM in old age.

Hippocampal CA1 volume is associated with higher p‐tau and diminished memory performance in normal older adults

AbstractBackgroundPrior work has demonstrated that elevated CSF biomarkers in older adults are associated with diminished performance across several hippocampally‐dependent memory tasks. It is unknown whether early structural changes in medial temporal lobe subfields (1) may be impacted by elevated p‐tau181, and (2) mediate the effect of p‐tau181 on memory performance in older adults.MethodThe current study draws on a cohort of 147 cognitively unimpaired older adults (Stanford Aging and Memory Study) that completed both 3T MRI and lumbar punctures. To examine memory performance, participants completed two hippocampally dependent tasks: a paired associate cued recall task and a mnemonic discrimination task (MST) that examined discrimination between previously studied “old” objects, novel “foil” objects and perceptually similar “lure” objects. Lure trials were binned in five difficulty levels, ranging from low to high similarity compared to previously presented stimuli. Hippocampal subregions (CA1, CA3/DG, subiculum) were manually delineated on T2*weighted images following Carr et al., (2017). CSF was processed with Lumipulse to measure Ab42:Ab40 ratio and p‐tau181. Multiple regression was used to assess the associative memory d’ from the paired associate task. Given the repeated measures design of the MST task, linear mixed models were conducted to understand the association between hippocampal subfields and p‐tau181 on performance as a function of similarity strength (Trelle et al., 2021). Age, sex, and education were controlled in all models.ResultP‐tau181 was correlated with reduced left CA1 volume (partial r2=0.043, p = 0.01), but not with volume in other hippocampal subfields. Increased CA1 volume was positively associated with better memory performance, including higher associative memory recall and old‐lure discrimination. After controlling for p‐tau181, CA1 volume was no longer associated with performance on the associative memory task but remained significantly correlated with old/lure discrimination. Notably, increased CA1 volume improved overall discrimination for old/lure trials, independent of the difficulty level, while the association between p‐tau181 and performance was strongest at the lower similarity level.ConclusionReduced CA1 volume and p‐tau explain unique variance in memory performance in older adults. This combination of biofluid biomarkers and high‐resolution MRI has the potential to understand mechanisms underlying age‐related memory decline.

Physiological responsiveness to phase-locked auditory stimulation during slow wave sleep predicts increases in episodic memory performance in older adults

Physiological responsiveness to phase-locked auditory stimulation during slow wave sleep predicts increases in episodic memory performance in older adults

Hippocampal dentate gyrus integrity revealed with ultrahigh resolution diffusion imaging predicts memory performance in older adults.

Medial temporal lobe (MTL) atrophy is a core feature of age-related cognitive decline and Alzheimer's disease (AD). While regional volumes and thickness are often used as a proxy for neurodegeneration, they lack the sensitivity to serve as an accurate diagnostic test and indicate advanced neurodegeneration. Here, we used a submillimeter resolution diffusion weighted MRI sequence (ZOOMit) to quantify microstructural properties of hippocampal subfields in older adults (63-98 years old) using tensor derived measures: fractional anisotropy (FA) and mean diffusivity (MD). We demonstrate that the high-resolution sequence, and not a standard resolution sequence, identifies dissociable profiles for CA1, dentate gyrus (DG), and the collateral sulcus. Using ZOOMit, we show that advanced age is associated with increased MD of the CA1 and DG as well as decreased FA of the DG. Increased MD of the DG, reflecting decreased cellular density, mediated the relationship between age and word list recall. Further, increased MD in the DG, but not DG volume, was linked to worse spatial pattern separation. Our results demonstrate that ultrahigh-resolution diffusion imaging enables the detection of microstructural differences in hippocampal subfield integrity and will lead to novel insights into the mechanisms of age-related memory loss.

Structural and Functional Brain Connectivity Uniquely Contribute to Episodic Memory Performance in Older Adults.

In this study, we examined the independent contributions of structural and functional connectivity markers to individual differences in episodic memory performance in 107 cognitively normal older adults from the BIOCARD study. Structural connectivity, defined by the diffusion tensor imaging (DTI) measure of radial diffusivity (RD), was obtained from two medial temporal lobe white matter tracts: the fornix and hippocampal cingulum, while functional connectivity markers were derived from network-based resting state functional magnetic resonance imaging (rsfMRI) of five large-scale brain networks: the control, default, limbic, dorsal attention, and salience/ventral attention networks. Hierarchical and stepwise linear regression methods were utilized to directly compare the relative contributions of the connectivity modalities to individual variability in a composite delayed episodic memory score, while also accounting for age, sex, cerebrospinal fluid (CSF) biomarkers of amyloid and tau pathology (i.e., Aβ42/Aβ40 and p-tau181), and gray matter volumes of the entorhinal cortex and hippocampus. Results revealed that fornix RD, hippocampal cingulum RD, and salience network functional connectivity were each significant independent predictors of memory performance, while CSF markers and gray matter volumes were not. Moreover, in the stepwise model, the addition of sex, fornix RD, hippocampal cingulum RD, and salience network functional connectivity each significantly improved the overall predictive value of the model. These findings demonstrate that both DTI and rsfMRI connectivity measures uniquely contributed to the model and that the combination of structural and functional connectivity markers best accounted for individual variability in episodic memory function in cognitively normal older adults.