Memory Performance In Older Adults Research Articles

Improving Memory Through Better Sleep in Community-Dwelling Older Adults: A Tai Chi Intervention Study.

The relationship between sleep and memory has been well documented. However, it remains unclear whether a mind-body exercise, that is, Tai Chi exercise, can improve memory performance in older adults by improving their subjective and objective sleep. A randomized controlled trial was conducted with participants (M = 67.36, 56-79 years) randomly assigned to Tai Chi and control groups. The primary outcomes were sleep, both subjectively reported and objectively assessed by actigraphy, and memory performance, as well as the mediating role of sleep in memory improvement with Tai Chi practice. Tai Chi exercise led to improvements in subjective sleep, as indicated by Insomnia Severity Index (ISI) (p < .001, Cohen's d = 0.62) and daytime dysfunction of the Pittsburgh sleep quality index (PSQI) (p = .02, Cohen's d = 0.80), and in actigraphy-assessed sleep onset latency (p < .01, Cohen's d = 0.61), as well as improved memory performance on digit span forward (p < .001, Cohen's d = 1.20) and visual spatial memory tasks (p < .01, Cohen's d = 0.83) compared to the control group. Importantly, Tai Chi practice improved digit span forward memory performance through parallel mediation of both subjective sleep (i.e., daytime dysfunction of the PSQI) and objective sleep (i.e., sleep onset latency; b = 0.29, p < .01). Our findings uncovered the potential benefits of Tai Chi exercise in relation to both subjective and objective sleep in older adults, in turn, how sleep changes played a role in the link between Tai Chi exercise and memory changes in older adults.

Noninvasive neurostimulation promotes working memory performance in older adults: a systematic review

Working memory is a core component of high-level cognitive functions. A key feature of cognitive decline in older adults is the impairment of working memory capacity, which is also observed in many clinical conditions. In recent years, noninvasive neurostimulation techniques have garnered extensive research attention for their potential to enhance human cognitive function, particularly in older adults. This review focuses on several advanced noninvasive neurostimulation techniques for working memory in older adults. A systematic search of the PubMed and Google Scholar literature databases was conducted, covering research papers published from 2013 to 2023. This review identified 19 articles on transcranial electrical stimulation, 6 on transcranial magnetic stimulation, and 2 on transcranial photobiomodulation techniques that met the inclusion criteria. These results suggest that transcranial electrical stimulation, especially transcranial alternating current stimulation and transcranial direct current stimulation, can improve working memory performance in healthy older adults. Transcranial direct current stimulation combined with cognitive training improves functional connectivity between relevant brain regions in addition to performance gains. Transcranial random noise stimulation, transcranial magnetic stimulation, and transcranial photobiomodulation also have the potential to improve working memory. Further research is needed to understand the neural mechanisms involved and optimize stimulation parameters. In addition, emerging techniques such as transcranial focused ultrasound may offer promising solutions for future studies on working memory enhancement in older adults.

Beta-band neural variability reveals age-related dissociations in human working memory maintenance and deletion.

Maintaining and removing information in mind are 2 fundamental cognitive processes that decline sharply with age. Using a combination of beta-band neural oscillations, which have been implicated in the regulation of working memory contents, and cross-trial neural variability, an undervalued property of brain dynamics theorized to govern adaptive cognitive processes, we demonstrate an age-related dissociation between distinct working memory functions-information maintenance and post-response deletion. Load-dependent decreases in beta variability during maintenance predicted memory performance of younger, but not older adults. Surprisingly, the post-response phase emerged as the predictive locus of working memory performance for older adults, with post-response beta variability correlated with memory performance of older, but not younger adults. Single-trial analysis identified post-response beta power elevation as a frequency-specific signature indexing memory deletion. Our findings demonstrate the nuanced interplay between age, beta dynamics, and working memory, offering valuable insights into the neural mechanisms of cognitive decline in agreement with the inhibition deficit theory of aging.

The Mixed Role of Sleep and Time of Day in Working Memory Performance of Older Adults with Mild Cognitive Impairment.

The importance of night sleep for maintaining good physical and cognitive health is well documented as well as its negative changes during aging. Since Mild Cognitive Impairment (MCI) patients bear additional disturbances in their sleep, this study aimed at examining whether there are potential mixed effects of sleep and afternoon time of day (ToD) on the storage, processing, and updating components of working memory (WM) capacity in older adults with MCI. In particular, the study compared patients' performance in the three working memory components, in two-time conditions: "early in the morning and after night sleep", and "in the afternoon and after many hours since night sleep". The Working Memory Capacity & Updating Task from the R4Alz battery was administered twice to 50 older adults diagnosed with MCI. The repeated measures analysis showed statistically significant higher performance in the morning condition for the working memory updating component (p < 0.001). Based on the findings, it seems that the afternoon ToD condition negatively affects tasks with high cognitive demands such as the WM updating task in MCI patients. These findings could determine the optimal timing for cognitive rehabilitation programs for MCI patients and the necessary sleep duration when they are engaged in cognitively demanding daily activities.

Dendritic spine head diameter predicts episodic memory performance in older adults.

Episodic memory in older adults is varied and perceived to rely on numbers of synapses or dendritic spines. We analyzed 2157 neurons among 128 older individuals from the Religious Orders Study and Rush Memory and Aging Project. Analysis of 55,521 individual dendritic spines by least absolute shrinkage and selection operator regression and nested model cross-validation revealed that the dendritic spine head diameter in the temporal cortex, but not the premotor cortex, improved the prediction of episodic memory performance in models containing β amyloid plaque scores, neurofibrillary tangle pathology, and sex. These findings support the emerging hypothesis that, in the temporal cortex, synapse strength is more critical than quantity for memory in old age.

Synergistic effects of GFAP and Aβ42: Implications for white matter integrity and verbal memory across the cognitive spectrum

BackgroundPlasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer's disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory. MethodsIn a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-β42 (Aβ42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter. ResultsIn individuals in the low plasma amyloid-β42 (Aβ42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p = 0.007), higher mean diffusivity (MD; p < 0.001), higher radial diffusivity (RD; p < 0.001), and higher axial diffusivity (DA; p = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aβ42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance. DiscussionHigher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aβ42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aβ42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways.

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.