Episodic Memory Scores Research Articles

Brain age estimation by structural MRI in superagers: a BrainAGE approach in elderly people with youthful episodic memory

AbstractBackgroundAge‐related episodic memory decline is not the only trajectory of healthy ageing. Superagers are the living proof that an 80yo can have the memory of a 50‐60yo. We aim to estimate the biological brain age of superagers using the BrainAGE approach to understand the underlying ageing process. In the context of normal ageing, resistance refers to the avoidance of ageing effects and will translate into a deceleration of the ageing process, whereas resilience is the successful coping with age‐related changes and will translate into a similar estimated brain age and chronological age. We tested these hypotheses in this study.MethodA sample of 63 superagers (mean age 81.8 years ± 1.8 std, 60.3% women) and 55 age‐matched controls (mean age 82.4 years ± 1.9 std, 63.6% women) from the Vallecas Project cohort in Madrid, Spain, were selected according to their episodic memory score in the Free and Cued Selective Reminding Test. Superagers scored at or above the mean value of a 50‐56yo person, whereas controls scored within one standard deviation for their age. BrainAGE (“Brain Age Gap Estimation”) aggregates to a single value the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (Franke and Gaser 2019). The BrainAGE score was calculated for both groups as the difference between chronological age and estimated brain age. Positive values indicate an acceleration of the ageing process and negative values indicate a deceleration of the ageing process.ResultThe BrainAGE score of superagers was ‐0.5 years, showing that their estimated brain age is lower than their chronological age whereas the estimated brain age of the control group is similar to their chronological age. The difference in BrainAGE between the superager and the control group is significant (p = 1x10‐6). This result indicates a deceleration in the brain ageing process of superagers compared to age‐matched controls.ConclusionSuperagers showed a slowing of the structural brain age‐related changes compared to the control group. These results suggest that superagers, selected for their youthful episodic memory, show whole‐brain resistance to the ageing process.

Literacy, but not memory, is associated with hippocampal connectivity in illiterate adults

AbstractBackgroundThe role of hippocampal connectivity for good memory performance is well known in persons with high educational level. However, it is understudied the role of hippocampal connectivity in illiterate populations.MethodsThirty‐nine illiterate adults from Brazil underwent a literacy assessment, structural and resting state functional MRI and an episodic memory test (Free and Cued Selective Reminding Test). We correlated the hippocampal connectivity at rest with the free recall scores and the literacy scores. Analyzes were done in SPM 12, corrected for head motion and physiological BOLD signal.ResultsParticipants were most female (66%) and black (79%) and the mean age was 49 years‐old (±13.9). The mean score on free recall was 27.2 (±10.7) out of 48 points and the mean literacy score was 34.9 (±21.1) out of 100 points. The median hippocampal gray matter volume was 2.4 [0.9, 2.3]cm3 in the left and 2.1 [2.1, 2.4] cm3 in the right side. There was a significant connectivity between both hippocampi and the precuneus and the ventral medial prefrontal cortex. However, this connectivity did not correlate with episodic memory scores, but the right hippocampal connectivity correlated with the literacy scores (R2 = 0.13, p = 0.014, CI 1.0‐1.0). Furthermore, the hippocampal gray matter volume did not correlate with memory scores.ConclusionsAlthough we did not find a significant correlation between memory and the connectivity between both hippocampi and the precuneus and ventral medial prefrontal cortex, we found that this connectivity correlated with literacy scores on the right side. The lack of association with memory scores might be associated with low brain reserve in illiterate adults. The association between hippocampal connectivity and low literacy scores suggest a room for improvement if those adults learn how to read later in life.

Perceived discrimination and cognition in a middle age, racially diverse cohort

AbstractBackgroundRisk factors for Alzheimer’s disease (AD) include biologic (e.g. vascular), economic, and socio‐cultural factors. AD incidence and prevalence has been linked to race, and African American/Black individuals (AA/B) are at greater risk compared to non‐Hispanic Whites (NHW), due to physiological and social factors, however few clinical research studies are dedicated to prospective and thoughtful data collection on both physiology (biomarkers) and social/structural risk factors, including discrimination.MethodsWe enrolled 49 middle‐age, cognitively normal B/AA (n = 29) and NHW (n = 20) participants with a family history of AD, and examined correlations between cognition and a perceived discrimination. Cognitive assessments included tests of global cognition, executive function, verbal and visuospatial memory, and language. Six discrimination factors were derived from a larger battery of individually validated assessments of perceived discrimination including, Expanded Everyday Discrimination (EED), Major Experiences of Discrimination (MED), Chronic Work Discrimination and Harassment (WORK), and the Heightened Vigilance (HVIGIL). Factor scores derived from these assessments included ‘Disrespect’, ‘Aggression’, ‘Housing’, ‘Avoidance’, ‘Professional’, and ‘Personal’. Models controlled for education, income, race, and age.ResultsPerceived discrimination had an influence on cognitive scores in a race‐independent manner in this cohort. It was also found that this relationship maybe stratified by educational level. Participants were mostly women (73.5%) highly educated (42.9% post‐Graduate education) and B/AA participants reported more perceived discrimination compared to NHWs across all 6 composite discrimination factors. We observed a positive association between episodic memory score and the 'housing’ discrimination factor (p = 0.34 (0.03)), such that increased housing discrimination was associated with increased cognition. A negative correlation was observed between working memory and the discrimination factor ‘Professional’ (p = ‐0.3 (0.05)).ConclusionDiscrimination negatively affects health outcomes and disease risk. Here we report a negative correlation between working memory and ‘professional’ factor score. We also report a positive correlation between cognition and housing discrimination. This latter is likely explained by the relationship between discrimination and geographic mobility, highlighting the presence of systemic and situational racism across all levels of socioeconomic status. Future AD research should incorporate historical and current data collection on redlining, Area Deprivation Index (ADI), and social and housing mobility.

18F‐MK6240 tau in ento‐ and perihinal cortex is related to episodic memory in the earliest stages of Alzheimer’s disease

AbstractBackgroundIn a previous study, we showed the sensitivity of the Buschke Selective Reminding test Total Retention (BSRT TR) for detecting and predicting 4‐year cognitive change in cognitively intact older adults. Here, we examined how BSRT TR related to tau load.MethodThe study sample consisted of 29 cognitively intact participants of the Flemish Prevent AD cohort KU Leuven (CDR global=0, MMSE=28‐30, mean age=68.5 year) and eight memory‐clinic recruited patients with prodromal AD (CDR global=0.5, MMSE=21‐30, mean age=71 year). All participants underwent neuropsychological testing, MRI and 18F‐MK6240 PET. Structural T1‐weighted MRI images were processed using CAT12. Tau load was quantified as 18F‐MK6240 DVR with the inferior cerebellum used as reference region. The primary analysis was based on voxel‐wise regression analysis between 18F‐MK6240 DVR scans and BSRT TR mean scores, with age as covariate. The second primary endpoint was the correlation between BSRT TR mean scores and tau DVR in an entorhinal and perirhinal volume of interest (VOI) based on the Brainnetome atlas. The secondary analysis was a VOI analysis based on an early metaVOI also containing hippocampus, parahippocampus, fusiform gyrus and inferior temporal cortex. Results were compared to those obtained for other episodic memory scores (BSRT delayed recall (DR), Auditory Verbal Learning Test (AVLT) total learning (TL) and AVLT DR), and an MRI volumetric analysis.ResultVoxel‐wise regression analysis showed a negative correlation between BSRT TR mean and DVR in ento‐ and perirhinal cortex bilaterally (x=22, y=‐4, z=‐32, extent=612 voxels, cluster level pcorr<0.001) (x=‐30, y=‐22, z=‐20, extent=2910 voxels, cluster level pcorr<0.001) (Figure A). This was confirmed by the analysis of the entorhinal/perirhinal VOI (rho=‐0.44, p=0.0063; Figure B). Significant correlations with ento‐ and perirhinal DVR were also present for BSRT DR (rho=‐0.39, p=0.017) and AVLT TL (rho=‐0.41, p=0.012), but not for AVLT DR (rho=‐0.29, p=0.084). No significant correlation was found with tau in the early metaVOI for any of the verbal episodic memory measures. Voxel‐wise regression analysis between gray matter volume and BSRT TR mean scores did not show significant results.ConclusionThe earliest measurable tau aggregate levels in ento‐ and perirhinal cortex correlate with classical episodic memory parameters.

Leukocyte Surface Biomarkers Implicate Deficits of Innate Immunity in Late‐onset Alzheimer’s Disease

AbstractBackgroundAlzheimer’s disease (AD) is characterized by amyloid‐β (Aβ) plaques, neurofibrillary tangles, reactive astrogliosis, and microgliosis. Aberrant Aβ accumulation starts 20–30 years before clinical onset, so biomarker test is essential to diagnose people living with early AD. PET imaging and CSF measurements allow the diagnosis of preclinical and prodromal AD in research and clinical trials, but their invasiveness and costliness might limit their application in hospital setting. Therefore, developing non‐invasive population screening tests is necessary for the early diagnosis of AD. Recent genetic findings strongly implicate the role of innate and adaptive immunity in AD and suggest that a systemic failure of cell‐mediated Aβ clearance contributes to AD onset and progression. Our research question was to develop an immune‐related blood‐based biomarker test to facilitate the diagnosis and prognosis of AD. It was hypothesized that the pattern of immune‐related receptors and molecules expressed on peripheral leukocytes could differentiate people living with AD from healthy population.MethodWe recruited 180 and 200 participants from AIBL in two discovery phases and validated our findings by an independent cohort of 112 participants from AIBL. A total of 34 innate and adaptive immunity‐related leukocyte antigens on peripheral lymphocytes, monocytes, and neutrophils were examined by flow cytometry immunophenotyping. Data was analysed by logistic regression and ROC analyses.ResultWe identified upregulated CD35, CD59, CD91, RAGE, and Scara‐1 expressions and downregulated CD11c, CD18, CD36, CD163, MerTK, and P2X7 expressions on leukocytes of MCI/AD patients. Significant correlation between them and Aβ burden, episodic memory, and PACC score was observed, such as CD59 and CD91. Pathway analysis revealed upregulation of complement inhibition and downregulation of cargo receptor activity and Aβ clearance in AD. We proposed a marker panel including CD11c, CD59, CD91 and CD163 and this panel predicted patients’ PET Aβ status with AUC of 0.93 (0.88 to 0.97), which was repeated in validation cohort. Regarding adaptive immunity, we did not see significant results.ConclusionOur study suggested deficits in innate immunity in AD, which is consistent with genomic studies. Our proposed leukocyte‐based biomarker panel might be sensitive and practical for AD screening and diagnosis.

Loneliness predicts stronger negative associations between cerebrovascular, but not Alzheimer’s, pathology and cognition

AbstractBackgroundAlzheimer’s disease (AD) and cerebrovascular disease are the two most common pathologies underlying dementia. Loneliness is associated with faster cognitive decline and greater AD risk independent of pathology. Risk reduction efforts would benefit from knowing whether loneliness exacerbates the cognitive impact of pathology. Our objective was to characterize the interaction between loneliness and AD or cerebrovascular pathology on cognitive performance.MethodsParticipants with neuropathological data were drawn from the Religious Orders Study, the Memory and Aging Project, and the Minority Aging Research Study (Table 1). Loneliness was assessed with a modified version of the de Jong‐Gierveld Loneliness Scale. Amyloid and tau pathology were assessed jointly with the NIA‐Reagan scale as high/intermediate likelihood or low likelihood/no AD. Chronic infarcts and chronic microinfarcts were each assessed as present or not present. Composite domain scores for episodic memory, working memory, semantic memory, perceptual speed, and perceptual orientation were obtained from the study visit proximal to death. Separate general linear models were run for each domain and each pathology, including an interaction between loneliness and pathology and adjusting for covariates.ResultsGreater loneliness was associated with older age and lower education, and loneliness was greater in men compared to women, but not different by race or APOE‐ε4 (2). Loneliness was not associated with AD or cerebrovascular pathology (Table 3). Greater loneliness was independently associated with lower cognitive scores in all domains. Greater pathology was independently associated with lower episodic memory and semantic memory scores, while cerebrovascular disease was not independently associated with cognitive scores. We additionally found that negative associations between microinfarcts and cognitive scores in working memory, semantic memory, and perceptual orientation were stronger among individuals with greater (Table 4).ConclusionsNegative associations between loneliness and cognition are apparent across domains and independent of pathology. While loneliness does not appear to be related to AD or cerebrovascular pathology directly, it may increase susceptibility to cognitive impairment due to microinfarcts. Social support‐based interventions may benefit optimal brain aging, particularly in older adults exposed to greater loneliness.

Predictive value of a plasma p‐tau181‐specific assay for amyloid accumulation in asymptomatic Alzheimer’s Disease

AbstractBackgroundPlasma phosphorylated tau‐181 (p‐tau181) is one of the most reliable blood‐based biomarkers for Alzheimer’s Disease (AD), yet has been consistently quantified with assays employing an antibody cross‐reacting with p‐tau175. We investigated the ability of a novel phospho‐specific plasma p‐tau181 assay to predict longitudinal amyloid accumulation in cognitively unimpaired (CU) elderly.MethodsPlasma p‐tau181 was quantified with a novel Simoa‐based assay using a p‐tau181 specific antibody (ADx252) in a prospective longitudinal cohort of 78 CU elderly (baseline age[mean] = 70 years, 47% female, 51% APOE‐ε4 carriers). Plasma sampling, amyloid‐β (Aβ)‐PET ([18F]flutemetamol or [11C]PiB) and episodic memory tests (average Buschke Selective Reminding total retention /12) were performed at baseline and Aβ‐PET was repeated on average 5 years later (SD: 2, range 1‐10 years). Longitudinal amyloid accumulation was modelled through calculation of Aβ‐PET rate of change by dividing the difference between baseline and follow‐up tracer uptake (in Centiloids) by the time interval between scans (in years). A Spearman correlation matrix between longitudinal amyloid accumulation, plasma p‐tau181, baseline amyloid load, age and baseline episodic memory was calculated. Z‐scores of all variables were entered into a hierarchical regression analysis in a stepwise manner based on correlation strength and finally sex and APOE were added.ResultsBaseline plasma p‐tau181 correlated with longitudinal amyloid accumulation (ρ = 0.28, Figure 1A) as well as age (ρ = 0.31, Figure 1B). A negative correlation was found between age and baseline episodic memory scores (ρ = ‐0.33), and between p‐tau181 and baseline episodic memory scores (ρ = ‐0.19), although the latter did not reach significance. Apart from plasma p‐tau181, none of the other baseline variables correlated significantly with longitudinal amyloid accumulation (Figure 2). Hence, plasma p‐tau181 was entered into the base regression model. This base model (F(1,76) = 7.78, p = 0.007) explained 27% of the variance (R2) in longitudinal amyloid accumulation. Including additional predictors like demographics, clinical data or baseline amyloid load, did not further improve the model.ConclusionPlasma p‐tau181 measured with the novel phospho‐specific Simoa assay best reflects longitudinal amyloid accumulation in asymptomatic Alzheimer’s Disease with no additional predictive value of the other baseline factors included.

Childhood perceived financial status, current financial concerns, and late‐life cognition: Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundLow socioeconomic status in childhood has been associated with worse late‐life cognition. However, few studies have examined the association between perceived childhood financial status on late‐life cognition in this population.Method764 participants of the Study of Healthy Aging in African Americans (STAR), a cohort of Black Americans aged 50+ (mean age 62) reported their childhood financial status (response options: pretty well off (henceforth above average), about average (henceforth average) varied, or poor) and frequency of current financial concerns (coded as always/often, sometimes, never). Baseline executive function, semantic memory, and verbal episodic memory were assessed through the Spanish and English Neuropsychological Assessment Scales. Linear regression models estimated the associations of childhood financial status and current financial concerns with domain‐specific scores adjusting for age, sex, and education. Sensitivity analyses concurrently included childhood financial status and current financial concerns.ResultAmong participants, 68% were female, 28% reported poor childhood financial status, and 12% reported “always” or “often” having current financial concerns (Table 1). Compared to individuals reporting above average childhood finances, sematic memory scores were lower among those reporting average (β = ‐0.16; 95% CI: ‐0.32, 0.001; Figure 2), varied (β = ‐0.34; 95% CI: ‐0.61, ‐0.07), or poor childhood financial status (β = ‐0.20; 95% CI: ‐0.37, ‐0.03). There were no differences in executive function scores or verbal episodic memory scores by childhood financial status (Figures 1 and 3). Frequency of current financial concern was not associated with executive function, semantic memory, nor verbal episodic memory scores (Figures 1‐3). The association between childhood financial status and semantic memory scores persisted when additionally adjusted for frequency of current financial concerns. There were no associations between childhood financial status and current financial concerns with executive function or verbal episodic memory scores.ConclusionChildhood financial status was associated with lower semantic memory test performance, even after accounting for current financial concerns. Future studies including direct measurement of brain health (e.g. brain imaging) are needed to better illuminate associations between childhood socioeconomic status with late‐life brain health.

Does cognitive reserve or brain maintenance explain heterogeneity in episodic memory trajectories in late middle age?

AbstractBackgroundAging‐related episodic memory (EM) decline and Alzheimer’s disease (AD)‐related brain changes begin in late middle age around age 60. However, rate and severity of cognitive decline do not consistently correspond to the extent of neuropathological changes, suggesting a high degree of heterogeneity in EM trajectories. We tested if brain maintenance (BM; relative absence of changes in neural resources as a determinant of preserved cognition) and/or cognitive reserve (CR; a property of the brain that allows for sustained cognitive performance in the face of age‐related changes and brain insult or disease) explain individual differences and heterogeneity in EM in late middle age.MethodParticipants were 1604 men from the Vietnam Era Twin Study of Aging. A practice effect‐adjusted composite EM score based on six measures was calculated at three time points with mean ages of 56, 62, and 68. Young adult general cognitive ability (GCA) and lifetime years of education were used as proxy measures of CR. BM was assessed as relative change (from age 56 to 68) in cortical thickness and surface area in a bilateral cortical signature of AD regions‐of‐interest (N = 321). We used linear mixed effect modeling.ResultOn average, there was a significant decline in EM from age 56 to 68 (p<0.001). Education (p = 0.042) and young adult GCA (p<0.001) were positively related to EM, but there were no significant effects of education or GCA on the rate of EM change (all p’s≥0.316). Relative brain changes were not related to EM (all p’s≥0.067) and there were no significant interactions of CR proxies and brain changes on EM (all p’s≥0.379).ConclusionHigher education and higher young adult GCA were related to better EM performance across late middle age – with a stronger contribution of GCA compared to education – but EM change did not differ as a function of these proxy CR measures. Our results did not support effects of BM or CR on EM change in late middle age but rather reflected baseline differences in memory in those with low versus high education/cognitive ability. Whether differential change occurs at later ages or with increased AD pathology remains to be determined.

The Retrograde Memory for News Events Test (RM-NET) and the relationship between news event memory and performance on standard neuropsychological tests.

Novel tests of semantic memory (SM)-for example, memory for news events (NE; news facts) or famous personalities-are useful for estimating the severity of retrograde amnesia. Individuals with mild cognitive impairment exhibit relatively intact SM/language on traditional neuropsychological tests but exhibit consistent impairment on novel tests of SM, suggesting novel SM tests are dissimilar from traditional SM tests. To identify the relationship between NE memory and traditional cognitive measures, older adults (N = 51) completed a traditional neuropsychological battery and the Retrograde Memory News Events Test (RM-NET; a new test that robustly measures NE memory across the adult life span with high temporal resolution), and the relationship between performance on these tests was examined. Total RM-NET scores were more closely aligned with episodic memory scores than SM scores. The strength of the association between NE scores and episodic memory scores decreased as the age of NE memory increased. Tests of news events appear to reflect performance on traditional tests of episodic memory rather than SM, especially when recent news events are tested.

Long-interval intracortical inhibition in primary motor cortex related to working memory in middle-aged adults.

IntroductionExcitability of the primary motor cortex measured with TMS has been associated with cognitive dysfunctions in patient populations. However, only a few studies have explored this relationship in healthy adults, and even fewer have considered the role of biological sex.MethodsNinety-seven healthy middle-aged adults (53 male) completed a TMS protocol and a neuropsychological assessment. Resting Motor Threshold (RMT) and Long-Interval Intracortical Inhibition (LICI) were assessed in the left motor cortex and related to attention, episodic memory, working memory, reasoning, and global cognition composite scores to evaluate the relationship between cortical excitability and cognitive functioning.ResultsIn the whole sample, there was a significant association between LICI and cognition; specifically, higher motor inhibition was related to better working memory performance. When the sample was broken down by biological sex, LICI was only associated with working memory, reasoning, and global cognition in men. No associations were found between RMT and cognitive functions.ConclusionGreater intracortical inhibition, measured by LICI, could be a possible marker of working memory in healthy middle-aged adults, and biological sex plays a critical role in this association.

Association between greenspace exposure and different domains of cognitive function in the French CONSTANCES cohort

BACKGROUND AND AIM Greenspace has been suggested to be associated with better cognitive function in adults. We assessed the association between residential surrounding greenspace and different domains of cognition in the French CONSTANCES cohort. METHODS We included 76,482 participants aged 45 and older, who performed tests at enrollment (2012-2019) on three cognitive domains: episodic memory (fast free and cued recall), language skills (semantic and lexical fluency), and executive functions (digit-symbol substitution, trail making test part A and B [TMT-A and TMT-B]), and a global cognitive score (a composite of these six tests). Residential surrounding greenspace was quantified using satellite-based Normalized Difference Vegetation Index (NDVI) at 300m buffer around the participant’s home in the enrollment year. We modeled the cross-sectional associations for urban, suburban, isolated cities, rural, and Paris separately, using multiple linear regressions on standardized outcomes (TMT-A and TMT-B were log-transformed) adjusted for age, sex, education, recruitment center, neighborhood deprivation, and air pollution. RESULTS The participants were 57.6±7.2 years old, 54.9% women, and 49.7% with university education. Average NDVI at 300m buffer (IQR: 0.26) was 0.58±0.14, 0.67±0.12, 0.71±0.11, 0.81±0.08, and 0.35±0.09 for urban, suburban, isolated cities, rural, and Paris respectively. We found significant beneficial association between residential surrounding greenspace and semantic fluency at urban, suburban, isolated cities, and rural areas (ß=0.048 [95% CI: 0.018, 0.079], 0.068 [0.037, 0.098], 0.105 [0.033, 0.177], 0.096 [0.033, 0.158] respectively). We also observed similar beneficial associations for executive functions in urban and suburban areas. No associations with greenspace were found for episodic memory, lexical fluency, and global cognitive score in most communes of residence. CONCLUSION Exposure to greenspace could be beneficial for cognition, especially semantic and executive functions, in adults. Urban and suburban residents probably gain more cognitive benefits from greenspace. KEYWORDS Natural environment; Cognitive function; Alzheimer’s disease; Environmental epidemiology

Cognitive mechanisms underlying free recall in episodic memory performance across the lifespan: testing the control/representation model.

Episodic memory (EM) develops up to early adulthood, and declines in aging, following an inverted U-shaped profile. This study assessed the contribution of both Control (processes enabling adaptive and flexible behaviour in line with current goals) and Representation (crystallized schemas involved in memory and general knowledge) as factors likely to underlie this pattern of change. We hypothesized that these two cognitive resources are differentially involved in EM performance across development and aging. Participants from 8 to 80years were administered a free-recall task and tests measuring control and representation. Results show that EM and control scores follow an inverted U-shaped profile (i.e., quadratic relationship), whereas representation increases across the lifespan. EM was associated with representation at all ages, while it was associated with control only in the youngest children and in the adults groups. Representation mainly contributed to age-related difference in EM performance across development. Across aging, control, and to a lesser extent, representation, accounted for EM performance decline. These results showed that EM development and decline do not depend on the same cognitive resources, increased representation being crucial for EM development, and a decline in control with advancing age being responsible for the age-related change in EM performance.

Urbanization and Cognitive Function Among Middle-Aged and Old Adults in China.

Our study examined the effect of urbanization on cognitive function and its possible pathways among Chinese middle-aged and older adults independent of the influence of health-selective migration. Using data from the China Health and Retirement Longitudinal Study, we compared cognitive function among three groups (urbanized-rural residents, rural nonmigrants, and urban nonmigrants). Logistic regression and structural equation models were applied to explore the impact of urbanization on cognitive function and the potential mechanisms. Compared with the urbanized-rural group, urban nonmigrants had better cognitive function, with a significant coefficient of 1.56 (95% CI: 1.22, 1.89) for global cognition scores and 0.37 (95% CI: 0.22, 0.53) for episodic memory scores. The rural nonmigrants had the worst cognitive function (β = -0.79, 95% CI: -1.04, -0.55) and lower scores of mental intactness (β = -0.65, 95% CI: -0.84, -0.57) and episodic memory (β = -0.14, 95% CI: -0.26, -0.03). The association between urbanization and cognitive function was mainly mediated by income and living conditions among middle-aged and older adults. Rural people who experienced planned urbanization in China had higher cognitive scores than rural non-migrants. Urbanization could thus have a beneficial and cumulative effect on cognitive function. Improvements in living conditions and changes in income are the main drivers behind the relationship. However, urbanization could compensate for the negative impact on cognitive function from disadvantaged early-life conditions, but it cannot completely eliminate the gap between urbanized-rural people and urban nonmigrants.

Comparing relationships between health-related behaviour clustering and episodic memory trajectories in the United States of America and England: a longitudinal study

BackgroundHealth-related behaviours (HRBs) cluster within individuals. Evidence for the association between HRB clustering and cognitive functioning is limited. We aimed to examine and compare the associations between three HRB clusters: “multi-HRB cluster”, “inactive cluster” and “(ex-)smoking cluster” (identified in previous work based on HRBs including smoking, alcohol consumption, physical activity and social activity) and episodic memory trajectories among men and women, separately, in the United States of America (USA) and England.MethodsData were from the waves 10–14 (2010–2018) of the Health and Retirement Study in the USA and the waves 5–9 (2010–2018) of the English Longitudinal Study of Ageing in England. We included 17,750 US and 8,491 English participants aged 50 years and over. The gender-specific HRB clustering was identified at the baseline wave in 2010, including the multi-HRB (multiple positive behaviours), inactive and ex-smoking clusters in both US and English women, the multi-HRB, inactive and smoking clusters in US men, and only the multi-HRB and inactive clusters in English men. Episodic memory was measured by a sum score of immediate and delayed word recall tests across waves. For within country associations, a quadratic growth curve model (age-cohort model, allowing for random intercepts and slopes) was applied to assess the gender-stratified associations between HRB clustering and episodic memory trajectories, considering a range of confounding factors. For between country comparisons, we combined country-specific data into one pooled dataset and generated a country variable (0 = USA and 1 = England), which allowed us to quantify between-country inequalities in the trajectories of episodic memory over age across the HRB clusters. This hypothesis was formally tested by examining a quadratic growth curve model with the inclusion of a three-way interaction term (age × HRB clustering × country).ResultsWe found that within countries, US and English participants within the multi-HRB cluster had higher scores of episodic memory than their counterparts within the inactive and (ex-)smoking clusters. Between countries, among both men and women within each HRB cluster, faster declines in episodic memory were observed in England than in the USA (e.g., b England versus the USA for men: multi-HRB cluster = -0.05, 95%CI: -0.06, -0.03, b England versus the USA for women: ex-smoking cluster = -0.06, 95%CI: -0.07, -0.04). Additionally, the range of mean memory scores was larger in England than in the USA when comparing means between two cluster groups, including the range of means between inactive and multi-HRB cluster for men (b England versus the USA = -0.56, 95%CI: -0.85, -0.27), and between ex-smoking and multi-HRB cluster for women (b England versus the USA = -1.73, 95%CI: -1.97, -1.49).ConclusionsHRB clustering was associated with trajectories of episodic memory in both the USA and England. The effect of HRB clustering on episodic memory seemed larger in England than in the USA. Our study highlighted the importance of being aware of the interconnections between health behaviours for a better understanding of how these behaviours affect cognitive health. Governments, particularly in England, could pay more attention to the adverse effects of health behaviours on cognitive health in the ageing population.

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.

Prior test experience confounds longitudinal tracking of adolescent cognitive and motor development

BackgroundAccurate measurement of trajectories in longitudinal studies, considered the gold standard method for tracking functional growth during adolescence, decline in aging, and change after head injury, is subject to confounding by testing experience.MethodsWe measured change in cognitive and motor abilities over four test sessions (baseline and three annual assessments) in 154 male and 165 female participants (baseline age 12–21 years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. At each of the four test sessions, these participants were given a test battery using computerized administration and traditional pencil and paper tests that yielded accuracy and speed measures for multiple component cognitive (ion, Attention, Emotion, Episodic memory, Working memory, and General Ability) and motor (Ataxia and Speed) functions. The analysis aim was to dissociate neurodevelopment from testing experience by using an adaptation of the twice-minus-once tested method, which calculated the difference between longitudinal change (comprising developmental plus practice effects) and practice-free initial cross-sectional performance for each consecutive pairs of test sessions. Accordingly, the first set of analyses quantified the effects of learning (i.e., prior test experience) on accuracy and after speed domain scores. Then developmental effects were determined for each domain for accuracy and speed having removed the measured learning effects.ResultsThe greatest gains in performance occurred between the first and second sessions, especially in younger participants, regardless of sex, but practice gains continued to accrue thereafter for several functions. For all 8 accuracy composite scores, the developmental effect after accounting for learning was significant across age and was adequately described by linear fits. The learning-adjusted developmental effects for speed were adequately described by linear fits for ion, Emotion, Episodic Memory, General Ability, and Motor scores, although a nonlinear fit was better for Attention, Working Memory, and Average Speed scores.ConclusionThus, what appeared as accelerated cognitive and motor development was, in most cases, attributable to learning. Recognition of the substantial influence of prior testing experience is critical for accurate characterization of normal development and for developing norms for clinical neuropsychological investigations of conditions affecting the brain.

Altered Structural and Functional Patterns Within Executive Control Network Distinguish Frontal Glioma-Related Epilepsy.

BackgroundThe tumor invasion of the frontal lobe induces changes in the executive control network (ECN). It remains unclear whether epileptic seizures in frontal glioma patients exacerbate the structural and functional alterations within the ECN, and whether these changes can be used to identify glioma-related seizures at an early stage. This study aimed to investigate the altered structural and functional patterns of ECN in frontal gliomas without epilepsy (non-FGep) and frontal gliomas with epilepsy (FGep) and to evaluate whether the patterns can accurately distinguish glioma-related epilepsy.MethodsWe measured gray matter (GM) volume, regional homogeneity (ReHo), and functional connectivity (FC) within the ECN to identify the structural and functional changes in 50 patients with frontal gliomas (29 non-FGep and 21 FGep) and 39 healthy controls (CN). We assessed the relationships between the structural and functional changes and cognitive function using partial correlation analysis. Finally, we applied a pattern classification approach to test whether structural and functional abnormalities within the ECN can distinguish non-FGep and FGep from CN subjects.ResultsWithin the ECN, non-FGep and FGep showed increased local structure (GM) and function (ReHo), and decreased FC between brain regions compared to CN. Also, non-FGep and FGep showed differential patterns of structural and functional abnormalities within the ECN, and these abnormalities are more severe in FGep than in non-FGep. Lastly, FC between the right superior frontal gyrus and right dorsolateral prefrontal cortex was positively correlated with episodic memory scores in non-FGep and FGep. In particular, the support vector machine (SVM) classifier based on structural and functional abnormalities within ECN could accurately distinguish non-FGep and FGep from CN, and FGep from non-FGep on an individual basis with very high accuracy, area under the curve (AUC), sensitivity, and specificity.ConclusionTumor invasion of the frontal lobe induces local structural and functional reorganization within the ECN, exacerbated by the accompanying epileptic seizures. The ECN abnormalities can accurately distinguish the presence or absence of epileptic seizures in frontal glioma patients. These findings suggest that differential ECN patterns can assist in the early identification and intervention of epileptic seizures in frontal glioma patients.

Phenotypic Displays of Cholinergic Enzymes Associate With Markers of Inflammation, Neurofibrillary Tangles, and Neurodegeneration in Pre- and Early Symptomatic Dementia Subjects

BackgroundCholinergic drugs are the most commonly used drugs for the treatment of Alzheimer’s disease (AD). Therefore, a better understanding of the cholinergic system and its relation to both AD-related biomarkers and cognitive functions is of high importance.ObjectivesTo evaluate the relationships of cerebrospinal fluid (CSF) cholinergic enzymes with markers of amyloidosis, neurodegeneration, neurofibrillary tangles, inflammation and performance on verbal episodic memory in a memory clinic cohort.MethodsIn this cross-sectional study, 46 cholinergic drug-free subjects (median age = 71, 54% female, median MMSE = 28) were recruited from an Icelandic memory clinic cohort targeting early stages of cognitive impairment. Enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was measured in CSF as well as levels of amyloid-β1–42 (Aβ42), phosphorylated tau (P-tau), total-tau (T-tau), neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B), and glial fibrillary acidic protein (GFAP). Verbal episodic memory was assessed with the Rey Auditory Verbal Learning (RAVLT) and Story tests.ResultsNo significant relationships were found between CSF Aβ42 levels and AChE or BuChE activity (p > 0.05). In contrast, T-tau (r = 0.46, p = 0.001) and P-tau (r = 0.45, p = 0.002) levels correlated significantly with AChE activity. Although neurodegeneration markers T-tau and NFL did correlate with each other (r = 0.59, p < 0.001), NFL did not correlate with AChE (r = 0.25, p = 0.09) or BuChE (r = 0.27, p = 0.06). Inflammation markers S100B and YKL-40 both correlated significantly with AChE (S100B: r = 0.43, p = 0.003; YKL-40: r = 0.32, p = 0.03) and BuChE (S100B: r = 0.47, p < 0.001; YKL-40: r = 0.38, p = 0.009) activity. A weak correlation was detected between AChE activity and the composite score reflecting verbal episodic memory (r = −0.34, p = 0.02). LASSO regression analyses with a stability approach were performed for the selection of a set of measures best predicting cholinergic activity and verbal episodic memory score. S100B was the predictor with the highest model selection frequency for both AChE (68%) and BuChE (73%) activity. Age (91%) was the most reliable predictor for verbal episodic memory, with selection frequency of both cholinergic enzymes below 10%.ConclusionsResults indicate a relationship between higher activity of the ACh-degrading cholinergic enzymes with increased neurodegeneration, neurofibrillary tangles and inflammation in the stages of pre- and early symptomatic dementia, independent of CSF Aβ42 levels.

Investigating associations of delay discounting with brain structure, working memory, and episodic memory.

Delay discounting (DD), the preference for smaller and sooner rewards over larger and later ones, is an important behavioural phenomenon for daily functioning of increasing interest within psychopathology. The neurobiological mechanisms behind DD are not well understood and the literature on structural correlates of DD shows inconsistencies. Here we leveraged a large openly available dataset (n = 1196) to investigate associations with memory performance and gray and white matter correlates of DD using linked independent component analysis. Greater DD was related to smaller anterior temporal gray matter volume. Associations of DD with total cortical volume, subcortical volumes, markers of white matter microscopic organization, working memory, and episodic memory scores were not significant after controlling for education and income. Effects of size comparable to the one we identified would be unlikely to be replicated with sample sizes common in many previous studies in this domain, which may explain the incongruities in the literature. The paucity and small size of the effects detected in our data underscore the importance of using large samples together with methods that accommodate their statistical structure and appropriate control for confounders, as well as the need to devise paradigms with improved task parameter reliability in studies relating brain structure and cognitive abilities with DD.