Episodic Memory Composite Scores Research Articles

Effect of cognitive reserve on the association between slow wave sleep and cognition in community-dwelling older adults.

Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances might have greater behavioral consequences. Polysomnography and neuropsychological assessments were performed in 135 cognitively intact older adults (mean age ± SD: 69.4 ± 3.8y) from the Age-Well randomized controlled trial (baseline data). Two measures of cognitive engagement throughout life were used as CR proxies. Linear regression analyses were performed between the proportion of SWS, and executive function and episodic memory composite scores. Then, interaction analyses between SWS and CR proxies on cognition were conducted to assess the possible impact of CR on these links. SWS was positively associated with episodic memory, but not with executive function. CR proxies modulated the associations between SWS and both executive and episodic memory performance. Specifically, individuals with higher CR were able to maintain cognitive performance despite low amounts of SWS. This study provides the first evidence that CR may protect against the deleterious effects of age-related sleep changes on cognition.

Polygenic hazard score modified the relationship between hippocampal subfield atrophy and episodic memory in older adults

Understanding genetic influences on Alzheimer's disease (AD) may improve early identification. Polygenic hazard score (PHS) is associated with the age of AD onset and cognitive decline. It interacts with other risk factors, but the nature of such combined effects remains poorly understood. We examined the effect of genetic risk and hippocampal atrophy pattern on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD using structural MRI. Participants included 51 memory unimpaired normal control (NC), 69 mild cognitive impairment (MCI), and 43 AD adults enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Hierarchical linear regression analyses examined the main and interaction effects of hippocampal subfield volumes and PHS, indicating genetic risk for AD, on a validated episodic memory composite score. Diagnosis-stratified models further assessed the role of PHS. Polygenic hazard score moderated the relationship between right fimbria/hippocampus volume ratio and episodic memory, such that patients with high PHS and lower volume ratio had lower episodic memory composite scores [ΔF = 6.730, p = 0.011, ΔR 2 = 0.059]. This effect was also found among individuals with MCI [ΔF = 4.519, p = 0.038, ΔR 2 = 0.050]. In contrast, no interaction effects were present for those NC or AD individuals. A follow-up mediation analysis also indicated that the right fimbria/hippocampus volume ratio might mediate the link between PHS and episodic memory performance in the MCI group, whereas no mediation effects were present for those NC or AD individuals. These findings suggest that the interaction between AD genetic risk and hippocampal subfield volume ratio increases memory impairment among older adults. Also, the results highlighted a potential pathway in which genetic risk affects memory by degrading hippocampal subfield volume ratio in cognitive decline subjects.

Longitudinal change in serial position scores in older adults with entorhinal and hippocampal neuropathologies.

Serial position scores on verbal memory tests are sensitive to early Alzheimer's disease (AD)-related neuropathological changes that occur in the entorhinal cortex and hippocampus. The current study examines longitudinal change in serial position scores as markers of subtle cognitive decline in older adults who may be in preclinical or at-risk states for AD. This study uses longitudinal data from the Religious Orders Study and the Rush Memory and Aging Project. Participants (n = 141) were included if they did not have dementia at enrollment, completed follow-up assessments, and died and were classified as Braak stage I or II. Memory tests were used to calculate serial position (primacy, recency), total recall, and episodic memory composite scores. A neuropathological evaluation quantified AD, vascular, and Lewy body pathologies. Mixed effects models were used to examine change in memory scores. Neuropathologies and covariates (age, sex, education, APOE e4) were examined as moderators. Primacy scores declined (β = -.032, p < .001), whereas recency scores increased (β = .021, p = .012). No change was observed in standard memory measures. Greater neurofibrillary tangle density and atherosclerosis explained 10.4% of the variance in primacy decline. Neuropathologies were not associated with recency change. In older adults with hippocampal neuropathologies, primacy score decline may be a sensitive marker of early AD-related changes. Tangle density and atherosclerosis had additive effects on decline. Recency improvement may reflect a compensatory mechanism. Monitoring for changes in serial position scores may be a useful in vivo method of tracking incipient AD.

Executive function and episodic memory composite scores in older adults: relations with sex, mood, and subjective sleep quality

ABSTRACT Executive function and episodic memory processes are particularly vulnerable to aging. We sought to learn the degree to which sex, mood, and subjective sleep quality might be related to executive function and episodic memory composite scores in community-dwelling older adults. We replicated Glisky and colleagues’ two-factor (i.e., executive function [N=263] versus episodic memory [N=151]) structure, and found that it did not significantly differ between males and females. Moderation analyses revealed no interactions between sex, mood, and sleep in predicting either composite score. However, females significantly outperformed males on the episodic memory composite, and on all the individual tests comprising it. Ours is the first study to look at sex differences in this battery’s factor structure and its potential relations with mood and sleep. Future longitudinal studies in both healthy and clinical populations will help us further probe the possible influence of these variables on executive function and episodic memory in aging.

0326 Influence of Sleep and Cardiovascular Health on Cognitive Outcomes in Older Adults

Abstract Introduction High and low sleep duration have been associated with reduced executive function (EF) and episodic memory (EM). However, causal pathways have not been identified. Cardiovascular health may contribute to the relationship between sleep and cognitive aging. Sleep disturbance has been associated with increased hypertension and heart disease in older adults, and cerebrovascular insufficiency has been consistently linked with cognitive decline. Therefore, the mediating and moderating effects of cardiovascular disease risk (CVD) on the relationship between sleep duration and longitudinal change in EF and EM were examined. Methods Statistical analyses were preregistered (osf.io/6yw7g). Average total sleep time (TST) over 2-6 nights was estimated using single-channel EEG at baseline (N=332). CVD was estimated using the abbreviated Framingham Heart Score approximately one year post-baseline. Outcome variables were linear change in EF and EM composite scores [BL1] per year up to 7 years after baseline. EF subtests measured semantic fluency, working memory, and task switching. EM subtests measured verbal associative memory, narrative episodic memory, and list learning. Covariates included age, gender, Alzheimer disease (AD) biomarkers (ratio of phosphorylated tau181 to amyloid-ß42), global cognition, and apnea-hypopnea index. Results Greater TST was linearly associated with reduced CVD (ß=-.157, p=.006). Quadratic effects of TST on EF and EM were observed (EF: ß=-.105, p=.002; EM: ß=-.203, p=.007). Lowest TST was related to greater reduction in EF; highest TST was related to greater reduction in EF and EM. Mediating effects of CVD for EF and EM were observed (ps&amp;lt;.05) but were non-significant when age and AD biomarkers were included (p=.10, p=.08, respectively). A non-significant trend indicated CVD moderated effects of TST on EF (ß=.10, p=.055), controlling for age and AD biomarkers. Less sleep combined with higher CVD tended to be associated with greater decline in EF. CVD did not moderate effects of TST on EM (ß=.07, p=.254). Conclusion Consistent with prior literature, CVD and TST were independently associated with cognitive decline. Although findings suggest that CVD may influence effects of TST on cognitive decline, more evidence is needed. Future analyses will examine alternative sleep measures (e.g., sleep efficiency, slow wave spectral density). Support (If Any) NIH: T32-AG000030, P01-AG03991, P01-AG026276, P30-AG066444.

Association Between Late-Life Neuropsychiatric Symptoms and Cognitive Decline in Relation to White Matter Hyperintensities and Amyloid Burden.

Neuropsychiatric symptoms (NPS) among cognitively normal older adults are increasingly recognized as risk factors for cognitive decline and impairment. However, the underlying mechanisms remain unclear. To examine whether biomarkers of Alzheimer's disease (amyloid burden) and cerebrovascular disease (white matter hyperintensity (WMH) volume) modify the association between NPS and cognitive decline among cognitively unimpaired older adults. Analyses included 193 cognitively unimpaired participants (M age = 70 years) from the BIOCARD study, including 148 with PET amyloid and WMH biomarker data. NPS were measured with Neuropsychiatric Inventory and Geriatric Depression Scale scores. Linear mixed effects models were used to examine the association between baseline NPS and longitudinal cognitive trajectories (M follow-up = 3.05 years), using separate models for global, episodic memory, and executive function cognitive composite scores. In a subset of individuals with biomarker data, we evaluated whether WMH or cortical amyloid burden modified the relationship between NPS and cognitive change (as indicated by the NPS×biomarker×time interactions). Higher baseline NPS were associated with lower executive function scores, but not a faster rate of decline in executive function. NPS symptoms were unrelated to the global or episodic memory composite scores, and there was little evidence of a relationship between NPS symptoms and cognitive change over time. The associations between NPS and cognitive decline did not differ by amyloid or WMH burden, and NPS were unrelated to amyloid and WMH burden. These results suggest that the effect of neuropsychiatric symptoms on executive dysfunction may occur through mechanisms outside of amyloid and cerebrovascular disease.

Effect of cognitive reserve and amyloid deposition on sleep‐dependent cognition in older adults

AbstractBackgroundSleep, especially slow wave sleep (SWS), favors efficient cognitive functioning. This effect may be impaired in aging, but might be modulated by cognitive reserve. Indeed, a study reported that highly educated older adults were able to better tolerate the negative effects of subjective sleep disturbances on verbal fluency scores. Growing evidence also suggests that sleep may favor amyloid clearance. In this context, we investigated the effect of cognitive reserve and amyloid deposition on the links between SWS and cognitive performance in older adults.MethodsBaseline data of 135 cognitively unimpaired older adults (mean age ± SD: 69.3 ± 3.8 y) from the Age‐Well cohort were analysed. Participants underwent a neuropsychological assessment, a polysomnography, and a florbetapir PET scan to measure amyloid deposition. Cognitive reserve was estimated using a socio‐behavioral proxy, the Lifetime of Experiences Questionnaire. We conducted linear regressions between SWS (% of total sleep time) and 1) executive functions and 2) episodic memory composite scores. Standardized residuals were extracted so that higher values reflect a better cognition than expected (i.e., greater cognitive resilience). Then, we performed linear regressions with these residuals as dependent variables and cognitive reserve or amyloid deposition as independent variables. Analyses were repeated with age, sex and the apnea‐hypopnea index as covariates.ResultsSWS (%) was positively associated with executive functions (p=0.021) and episodic memory (p=0.017) composite scores (Figure 1). For both cognitive domains, higher residuals were associated with better cognitive reserve and lower amyloid deposition (p&lt;0.05) (Figure 2). All links with cognitive reserve remained significant after controlling for the covariates (p&lt;0.05), while those with amyloid deposition were close to the significance threshold (p=0.085 and p=0.054 for executive functions and episodic memory respectively).ConclusionsIndividuals with higher cognitive reserve or, to a lesser extent, lower amyloid deposition, were able to better tolerate the effects of low amounts of SWS on executive and episodic memory performance. Cognitive reserve may help maintaining cognitive performance even when sleep is disrupted (i.e., cognitive resilience to sleep changes), while amyloid deposition would increase the vulnerability to poor sleep quality. These findings are important to understand the factors promoting successful aging.

BDNF VAL66MET polymorphism and memory decline across the spectrum of Alzheimer's disease

The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism has been shown to moderate the extent to which memory decline manifests in preclinical Alzheimer's disease (AD). To date, no study has examined the relationship between BDNF and memory in individuals across biologically confirmed AD clinical stages (i.e., Aβ+). We aimed to understand the effect of BDNF on episodic memory decline and clinical disease progression over 126 months in individuals with preclinical, prodromal and clinical AD. Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who were Aβ + (according to positron emission tomography), and cognitively normal (CN; n=238), classified as having mild cognitive impairment (MCI; n=80), or AD (n=66) were included in this study. Cognition was evaluated at 18 month intervals using an established episodic memory composite score over 126 months. We observed that in Aβ + CNs, Met66 was associated with greater memory decline with increasing age and were 1.5 times more likely to progress to MCI/AD over 126 months. In Aβ + MCIs, there was no effect of Met66 on memory decline or on disease progression to AD over 126 months. In Aβ + AD, Val66 homozygotes showed greater memory decline, while Met66 carriers performed at a constant and very impaired level. Our current results illustrate the importance of time and disease severity to clinicopathological models of the role of BDNF Val66Met in memory decline and AD clinical progression. Specifically, the effect of BDNF on memory decline is greatest in preclinical AD and reduces as AD clinical disease severity increases.

Genetic Risk for Alzheimer's Disease Moderates the Association Between Medial Temporal Lobe Volume and Episodic Memory Performance Among Older Adults.

A complex set of interactions between biological, genetic, and environmental factors likely underlies the development of Alzheimer's disease (AD). Identifying which of these factors is most associated with AD is important for early diagnosis and treatment. We sought to examine genetic risk and structural brain volume on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD. 686 adults (55-91 years old) completed a 3T MRI scan, baseline cognitive assessments, and biospecimen collection through the Alzheimer's Disease Neuroimaging Initiative. Hierarchical linear regression analyses examined main and interaction effects of medial temporal lobe (MTL) volume and polygenic hazard score (PHS), indicating genetic risk for AD, on a validated episodic memory composite score. Genetic risk moderated the relationship between MTL volume and memory, such that individuals with high PHS and lower hippocampal and entorhinal volume had lower memory composite scores [ΔF (1,677) = 4.057, p = 0.044, ΔR2 = 0.002]. Further analyses showed this effect was driven by the left hippocampus [ΔF(1,677) = 5.256, p = 0.022, ΔR2 = 0.003] and right entorhinal cortex [ΔF (1,677) = 6.078, p = 0.014, ΔR2 = 0.003]. Among those with high genetic risk for AD, lower volume was associated with poorer memory. Results suggest that the interaction between AD genetic risk and MTL volume increases the likelihood for memory impairment among older adults. Results from this study suggest that genetic risk and brain volume should be considered key factors in tracking cognitive decline.

MEDIAL TEMPORAL LOBE TAU IS STRONGLY RELATED TO EPISODIC MEMORY DECLINE IN AGING

The medial temporal lobe (MTL) is the earliest site of tau accumulation. MTL dysfunction may underlie episodic memory decline in normal aging and early dementia. Postmortem data indicate that transentorhinal cortex and hippocampus (HC) tau pathology is common over 60 years-of-age, while spread to inferior temporal (IFT) regions and worsening cognition is associated with beta-amyloid (Aβ). We used PET to investigate how in vivo tau accumulation in temporal lobe regions, Aβ deposition, and MTL atrophy measures contribute to memory and memory decline in cognitively normal older adults. Seventy-five subjects (77±6yrs) underwent [18F]AV-1451 tau PET, [11C]PiB amyloid PET, T1-weighted structural MRI, and neuropsychological assessment (60 with ≥ 2 sessions). T1-images were segmented (FreeSurfer v5.3) to derive volume/thickness measures, a global cortical PiB DVR, and regional AV-1451 measures in native space (80–100min SUVR, cerebellar gray reference, partial volume corrected). Mean SUVRs were derived from MTL and IFT, and temporal lobe subregions (after automated division along the anterior-posterior axis). An episodic memory composite score was derived by averaging Z-transformed verbal and visual early recall, late recall and recognition performance. Changes in memory were estimated by linear-mixed effects models. Stepwise multiple regressions identified the best predictor(s) for memory or memory change, among demographic variables, MTL and IFT tau, global Aβ, HC volume, and entorhinal (EC) thickness. Interactive effects of MTL or IFT tau x Aβ on memory were tested by general linear models. Contributions of temporal lobe subregions were assessed by subsequent regressions. Stepwise regressions identified MTL tau as the best predictor of memory and memory decline (R2=.34 and .33, p<.001). Correlations between MTL tau and memory were seen in both PiB- and PiB+ individuals (Figure). GLMs did not reveal any significant interactive effect of MTL or IFT tau with Aβ on memory. Among temporal lobe subregions, posterior EC and parahippocampal cortex best predicted memory (R2=.32), whereas medial IFT and posterior EC best predicted memory decline (R2=.34). Consistent with neuropathological studies, our data suggest close links between MTL tau pathology (particularly in posterior EC) and age-related memory dysfunction, with stronger decline associated with involvement of IFT regions. Relationship between episodic memory at session closest to AV-1451 tau scan and tau tracer uptake in the posterior EC (PiB- subjects: rPearson=-.43; rSpearman=-.41; PiB+ subjects: rPearson=-.52; rSpearman=-.54; all p<.001). A similar relationship was seen between memory and whole MTL mean SUVR, which we defined as average across Freesurfer-defined EC, para-hippocampal gyrus, hippocampus and amygdala. Posterior EC was defined here as the part of EC/parahippocampal gyrus (Freesurfer nomenclature) that covers the same slices as the anterior half of the hippocampus.

Impairments in Component Processes of Executive Function and Episodic Memory in Alcoholism, HIV Infection, and HIV Infection with Alcoholism Comorbidity.

Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV+ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy. HIV, ALC, HIV+ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times. HIV, ALC, and HIV+ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV+ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all 3 clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV+ALC, age was a unique predictor of Episodic Memory Composite score. Disease-specific and disease-overlapping patterns of impairment in HIV, ALC, and HIV+ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging.

Relationship between cerebrospinal fluid biomarkers of Alzheimer's disease and cognition in cognitively normal older adults

The pathophysiological processes underlying Alzheimer's disease (AD) are hypothesized to begin years to decades before clinical symptom onset, while individuals are still cognitively normal. Although many studies have examined the effect of biomarkers of amyloid pathology on measures of cognitive performance, less is known about the effect of tau pathology on cognitive performance. The present study examined the association between cerebrospinal fluid (CSF) biomarkers of AD pathology (amyloid, total tau (t-tau), and phosphorylated tau (p-tau)) and cognition in a large sample of cognitively normal middle-aged and older adults. Associations were examined with multivariate regressions, in which either amyloid and t-tau or amyloid and p-tau were included as simultaneous predictors of cognitive performance. Cognitive performance was measured with three composite scores assessing working memory, verbal episodic memory, and visuospatial episodic memory. In their respective models, CSF measures of both t-tau and p-tau were associated with the visuospatial episodic memory composite score (p<.001 and p=.02, respectively), but not with the other measures of cognition. In contrast, CSF amyloid was not significantly associated with cognitive performance, raising the possibility that measures of tau pathology have a more direct relationship with cognition in cognitively normal individuals. These results also suggest that tau pathology may have effects on visuospatial episodic memory during preclinical AD that precede alterations in other cognitive domains.

Memory and emotion processing performance contributes to the diagnosis of non-semantic primary progressive aphasia syndromes.

The two non-semantic variants of primary progressive aphasia (PPA), nonfluent/agrammatic PPA (nfv-PPA) and logopenic variant PPA (lv-PPA), share language features despite their different underlying pathology, and may be difficult to distinguish for non-language experts. To improve diagnostic accuracy of nfv-PPA and lv-PPA using tasks measuring non-language cognition and emotion processing. Thirty-eight dementia patients meeting diagnostic criteria for PPA (nfv-PPA 20, lv-PPA 18) and 21 matched healthy Controls underwent a comprehensive assessment of cognition and emotion processing, as well as a high-resolution structural MRI and a PiB-PET scan, a putative biomarker of Alzheimer's disease. Task performances were compared between the groups and those found to differ significantly were entered into a logistic regression analysis. Analyses revealed a double dissociation between nfv-PPA and lv-PPA. nfv-PPA exhibited significant emotion processing disturbance compared to lv-PPA and Controls. In contrast, only the lv-PPA group was significantly impaired on tasks of episodic memory. Logistic regression analyses showed that 87% of patients were correctly classified using emotion processing and episodic memory composite scores, together with a measure of visuospatial ability. Non-language presenting features can help differentiate between the two non-semantic PPA syndromes, with a double dissociation observed on tasks of episodic memory and emotion processing. Based on performance on these tasks, we propose a decision tree as a complementary method to differentiate between the two non-semantic variants. These findings have important clinical implications, with identification of patients who may potentially benefit existing therapeutic interventions currently available for Alzheimer's disease.

Intrinsic Connectivity Identifies the Hippocampus as a Main Crossroad between Alzheimer’s and Semantic Dementia-Targeted Networks

Alzheimer's disease (AD) and semantic dementia (SD) are both characterized by severe atrophy in the hippocampus, a brain region underlying episodic memory; paradoxically, episodic memory is relatively preserved in SD. Here, we used intrinsic connectivity analyses and showed that the brain networks differentially vulnerable to each disease converge to the hippocampus in the healthy brain. As neurodegeneration is thought to spread within preexisting networks, the common hippocampal atrophy in both diseases is likely due to its location at the crossroad between both vulnerable networks. Yet, we showed that in the normal brain, these networks harbor different functions, with episodic memory relying on the AD-vulnerable network only. Overall, disease-associated cognitive deficits seem to reflect the disruption of targeted networks more than atrophy in specific brain regions: in AD, over hippocampal atrophy, episodic memory deficits are likely due to disconnection within a memory-related network.