Worse Verbal Memory Research Articles

Long-Term Depressive Symptom Trajectories and Midlife Cognition: The CARDIA Study.

The nature of associations between depressive symptoms and cognition early in the life course remains unclear, and racial differences in these associations are not well characterized. The aim of this study was to examine the relationship between trajectories of depressive symptom over 20 years, beginning in young adulthood, and cognitive functions in middle-age among Black and White adults. We used prospective data from participants of the Coronary Artery Risk Development in Young Adults Study. Depressive symptoms were measured at 5 study visits between 1990 and 2010 using the Center for Epidemiologic Studies Depression scale. We used latent class group-based modeling to identify 4 trajectories: "persistently low," "persistently medium," "medium decreasing," and "high increasing" depressive symptoms. In 2015, cognitive function was measured using the Digit Symbol Substitution Test (DSST), Stroop test (reverse coded), and Rey Auditory-Verbal Learning Test (RAVLT).We excluded participants who missed the cognitive battery or had no depressive symptoms measurements, resulting in a total of 3,117 participants. All cognitive tests were standardized, and linear regression was used to relate depressive trajectories with 2015 cognitive functions. The mean [SD] baseline age was 30.1 [3.6] years, and 57% were female. The associations between depressive symptoms and cognition significantly differed by race (p < 0.05). Among Black individuals, compared with having "persistently low," having "medium decreasing," "persistently medium," or "high increasing" depressive symptoms were associated with worse verbal memory, processing speed, and executive function scores (RAVLT persistently medium vs low: β = -0.30, 95% CI -0.48 to -0.12; and high increasing vs low: β = -0.49, 95% CI -0.70 to -0.27; DSST persistently medium vs low: β = -0.28, 95% CI -0.47 to -0.09; and high increasing vs low: β = -0.64, 95% CI -0.87 to -0.42; Stroop persistently medium vs low: β = -0.46, 95% CI -0.70 to -0.23; and high increasing vs low: β = -0.76, 95% CI -1.04 to -0.47). Associations were slightly weaker among White individuals, but we still found that having 'high increasing' depressive symptoms was associated with worse verbal memory and processing speed scores (high increasing vs low: β = -0.38, 95% CI -0.61 to -0.15; and β = -0.40, 95% CI -0.63 to -0.18, respectively). Prolonged exposure to elevated depressive symptoms beginning in young adulthood may result in worse cognitive function over midlife. This association was stronger among Black adults.

97 Exploring Urban-Rural Disparities in Alzheimer’s disease: Clinical characterization of a southern Nevada cohort

Objective:As the US population ages, the prevalence of Alzheimer’s disease and related dementias (AD/RD) is on the rise. This is especially true in rural America, where mortality rates due to AD/RD are rising faster than in metropolitan areas. To date, however, people living in rural communities are severely underrepresented in aging research. The Nevada Exploratory Alzheimer’s Disease Research Center (NVeADRC) seeks to address this gap. Here, we present preliminary cognitive data from our rural-dwelling cohort, as well as relevant demographic and clinical characteristics.Participants and Methods:Individuals with normal cognition (NC), mild cognitive impairment (MCI), and dementia due to Alzheimer’s disease (AD) living in rural communities, defined as a rural-urban commuting area (RUCA) code of 4 or higher, were enrolled through either clinic or community outreach. Eligibility for the observational cohort required: age &gt;55 years, primarily English-speaking, primary residence in a rural community, and availability of a study partner. Measures included the Uniform Data Set (v3), blood-based biomarkers, structural brain MRI, and portions of the PhenX Social Determinants of Health toolkit. Participants are seen at baseline and followed annually, with interim remote visits every 6 months. A multidisciplinary consensus diagnosis is rendered after each visit. Where feasible, a harmonized urban cohort followed by the Nevada Center for Neurodegeneration and Translational Neuroscience (CNTN) was used for comparison.Results:Fifty-six rural-dwelling (age=70.4±7.1 years; edu=15.2±2.6 years; 61% female) and 148 urban-dwelling (age=72.9±6.8 years; edu=15.8±2.7 years; 46% female) older adults were included; age significantly differed between cohorts but education did not. The rural cohort was 46% NC (MoCA=26.8±2.3; CDRsob=0.3±0.6), 32% MCI (MoCA=22.8±3.1; CDRsob=1.2±1.0), and 22% AD (MoCA=16.9±5.5; CDRsob=5.2±3.0). The urban cohort was 39% NC (MoCA=26.4±2.6; CDRsob=0.3±0.8), 44% MCI (MoCA=22.3±3.1; CDRsob=2.0±1.5) and 17% AD (MoCA=18.6±3.9; CDRsob=4.7±2.3). Rural communities were significantly more disadvantaged, as measured by the Area Deprivation Index (ADI), than urban communities (rural ADI=6.3±2.6; urban ADI=3.4±2.3; p&lt;.001). Fifty-percent of the rural cohort lives in a moderate to severely disadvantaged neighborhood (ADI Decile&gt;7) compared to 12% of the urban cohort, and 11% of individuals in the rural cohort reported living more than 30 miles from the nearest medical facility. Across the combined cohort, education was significantly correlated with ADI deciles (r=-.30, p&lt;.001), with people in the areas of highest disadvantage having the lowest education. Verbal memory was also inversely associated with ADI. There were no differences in clinical diagnosis as a function of ADI rank.Conclusions:Living in a rural community conveys a multifaceted array of risks and benefits, some of which differ from urban settings. The literature to date suggests that older adults living in rural communities are at significantly increased risk for morbidity and mortality due to AD/RD, though it is unclear why. Preliminary data from the NVeADRC show that increasing levels of neighborhood disadvantage were associated with lower levels of education and worse verbal memory in this convenience sample. The combined effect of low education and increased disadvantage account for some of the urban-rural differences in mortality that have been reported, though additional research on representative samples in this underrepresented population is critical.

6 The Moderating Role of Physical Activity on Hippocampal Iron Deposition and Memory Outcomes in Typically Aging Older Adults

Objective:Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.Participants and Methods:62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.Results:Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p &gt; 0.05) or interact with physical activity on verbal memory outcomes (p &gt; 0.05).Conclusions:Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.

Sex Differences in the Association Between Cumulative Use of Cannabis and Cognitive Function in Middle Age: The Coronary Artery Risk Development in Young Adults Study.

Background: Cannabis use may impair cognitive function (CF) differently in men and women, due to sex-specific differences in neurobiological mechanisms and environmental risk factors. Objective: Assess sex differences in the association between cumulative exposure to cannabis and cognitive performance in middle age. Methods: We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, including Black and White men and women 18-30 years old at baseline followed over 30 years. Our cross-sectional analysis of CF scores at year 30 was stratified by sex. We computed categories of cumulative exposure in "cannabis-years" (1 cannabis-year=365 days of use) from self-reported use every 2 to 5 years over 30 years. At years 25 and 30, we assessed CF with the Rey Auditory Verbal Learning Test (verbal memory), the Digit Symbol Substitution Test (processing speed), and the Stroop Interference Test (executive function). At year 30, additional measures included Category and Letter Fluency Test (verbal ability) and the Montreal Cognitive Assessment (global cognition). We computed standardized scores for each cognitive test and applied multivariable adjusted linear regression models for self-reported cumulative cannabis use, excluding participants who used cannabis within 24 h. In a secondary analysis, we examined the association between changes in current cannabis use and changes in CF between years 25 and 30. Results: By year 30, 1,352 men and 1,793 women had measures of CF; 87% (N=1,171) men and 84% (N=1,502) women reported ever cannabis use. Men had a mean cumulative use of 2.57 cannabis-years and women 1.29 cannabis-years. Self-reported cumulative cannabis use was associated with worse verbal memory in men (e.g., -0.49 standardized units [SU] for ≥5 cannabis-years of exposure; 95% CI=-0.76 to -0.23), but not in women (SU=0.02; 95% CI=-0.26 to 0.29). Other measures of CF were not associated with cannabis. Changes in current cannabis use between years 25 and 30 were not associated with CF in men or women. Conclusions: Self-reported cumulative cannabis exposure was associated with worse verbal memory in men but not in women. Researchers should consider stratified analyses by sex when testing the association between cannabis and cognition.

Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study

Impaired cognition is associated with lower quality of life and poor outcomes in schizophrenia. Brain glutamate may contribute to both clinical outcomes and cognition, but these relationships are not well-understood. We studied a multicentre cohort of 85 participants with non-affective psychosis using proton magnetic resonance spectroscopy. Glutamate neurometabolites were measured in the anterior cingulate cortex (ACC). Cognition was assessed using the Brief Assessment for Cognition in Schizophrenia (BACS). Patients were categorised as antipsychotic responders or non-responders based on treatment history and current symptom severity. Inverted U-shaped associations between glutamate or Glx (glutamate + glutamine) with BACS subscale and total scores were examined with regression analyses. We then tested for an interaction effect of the antipsychotic response group on the relationship between glutamate and cognition. ACC glutamate and Glx had a positive linear association with verbal memory after adjusting for age, sex and chlorpromazine equivalent dose (glutamate, β = 3.73, 95% CI = 1.26–6.20, P = 0.004; Glx, β = 3.38, 95% CI = 0.84–5.91, P = 0.01). This association did not differ between good and poor antipsychotic response groups. ACC glutamate was also positively associated with total BACS score (β = 3.12, 95% CI = 0.01–6.23, P = 0.046), but this was not significant after controlling for antipsychotic dose. Lower glutamatergic metabolites in the ACC were associated with worse verbal memory, and this relationship was independent of antipsychotic response. Further research on relationships between glutamate and cognition in antipsychotic responsive and non-responsive illness could aid the stratification of patient groups for targeted treatment interventions.

Resting state effective connectivity abnormalities of the Papez circuit and cognitive performance in multiple sclerosis.

The Papez circuit is central to memory and emotional processes. However, little is known about its involvement in multiple sclerosis (MS). We aimed to investigate abnormalities of resting state (RS) effective connectivity (EC) between regions of the Papez circuit in MS and their relationship with cognitive performances. Sixty-two MS patients and 64 healthy controls (HC) underwent neuropsychological assessment, 3D T1-weighted, and RS functional MRI. RS EC analysis was performed using SPM12 and dynamic causal modeling. RS EC abnormalities were investigated using parametric empirical Bayes models and were correlated with cognitive scores. Compared to HC, MS patients showed (posterior probability > 0.95) higher EC between the right entorhinal cortex and right subiculum, and lower EC from the anterior cingulate cortex (ACC) to the posterior cingulate cortex (PCC), from left to right subiculum, from left anterior thalamus to ACC, and within ACC and PCC. Lower RS EC from the ACC to the PCC correlated with worse global cognitive scores (rho = 0.19; p = 0.03), worse visuospatial memory (rho = 0.19; p = 0.03) and worse semantic fluency (rho = 0.21; p = 0.02). Lower RS EC from the left to the right subiculum correlated with worse verbal memory (rho = 0.20; p = 0.02), lower RS EC within the ACC correlated with worse attention (rho = -0.19; p = 0.04) and more severe brain atrophy (rho = -0.26; p = 0.003). Higher EC from the right entorhinal cortex to right subiculum correlated with worse semantic fluency (rho = 0.21; p = 0.02). In conclusion, MS patients showed altered RS EC within the Papez circuit. Abnormal RS EC involving cingulate cortices and hippocampal formation contributed to explain cognitive deficits.

A more unstable resting-state functional network in cognitively declining multiple sclerosis.

Cognitive impairment is common in people with multiple sclerosis and strongly affects their daily functioning. Reports have linked disturbed cognitive functioning in multiple sclerosis to changes in the organization of the functional network. In a healthy brain, communication between brain regions and which network a region belongs to is continuously and dynamically adapted to enable adequate cognitive function. However, this dynamic network adaptation has not been investigated in multiple sclerosis, and longitudinal network data remain particularly rare. Therefore, the aim of this study was to longitudinally identify patterns of dynamic network reconfigurations that are related to the worsening of cognitive decline in multiple sclerosis. Resting-state functional MRI and cognitive scores (expanded Brief Repeatable Battery of Neuropsychological tests) were acquired in 230 patients with multiple sclerosis and 59 matched healthy controls, at baseline (mean disease duration: 15 years) and at 5-year follow-up. A sliding-window approach was used for functional MRI analyses, where brain regions were dynamically assigned to one of seven literature-based subnetworks. Dynamic reconfigurations of subnetworks were characterized using measures of promiscuity (number of subnetworks switched to), flexibility (number of switches), cohesion (mutual switches) and disjointedness (independent switches). Cross-sectional differences between cognitive groups and longitudinal changes were assessed, as well as relations with structural damage and performance on specific cognitive domains. At baseline, 23% of patients were cognitively impaired (≥2/7 domains Z < −2) and 18% were mildly impaired (≥2/7 domains Z < −1.5). Longitudinally, 28% of patients declined over time (0.25 yearly change on ≥2/7 domains based on reliable change index). Cognitively impaired patients displayed more dynamic network reconfigurations across the whole brain compared with cognitively preserved patients and controls, i.e. showing higher promiscuity (P = 0.047), flexibility (P = 0.008) and cohesion (P = 0.008). Over time, cognitively declining patients showed a further increase in cohesion (P = 0.004), which was not seen in stable patients (P = 0.544). More cohesion was related to more severe structural damage (average r = 0.166, P = 0.015) and worse verbal memory (r = −0.156, P = 0.022), information processing speed (r = −0.202, P = 0.003) and working memory (r = −0.163, P = 0.017). Cognitively impaired multiple sclerosis patients exhibited a more unstable network reconfiguration compared to preserved patients, i.e. brain regions switched between subnetworks more often, which was related to structural damage. This shift to more unstable network reconfigurations was also demonstrated longitudinally in patients that showed cognitive decline only. These results indicate the potential relevance of a progressive destabilization of network topology for understanding cognitive decline in multiple sclerosis.

Effect of Hypertension Duration and Blood Pressure Control During Early Adulthood on Cognitive Function in Middle Age.

Elevated blood pressure (BP) is a risk factor for cognitive impairment. We aim to explore the association between the duration of hypertension in early adulthood, with cognitive function in midlife. Furthermore, we investigate whether this asssociation is altered among participants with controlled BP. This prospective study included 2,718 adults aged 18-30 years without hypertension at baseline who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Duration of hypertension was calculated based on repeat measurements of BP performed at 2, 5, 7, 10, 15, 20, and 25 years after baseline. Cognitive function was assessed at Year-25 using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Stroop test. After multivariable adjustment, a longer hypertension duration was associated with worse verbal memory (RAVLT, p trend = 0.002) but not with processing speed (DSST, p trend = 0.112) and executive function (Stroop test, p trend = 0.975). Among subgroups of participants with controlled (BP < 140/90 mmHg) and uncontrolled (SBP≥140 mmHg or DBP≥90 mmHg) BP at the time of cognitive assessment (i.e., Year-25 BP), longer duration of hypertension was associated with worse verbal memory. Similar results were observed in subgroups with controlled and uncontrolled average BP prior to cognitive assessment. Longer duration of hypertension during early adulthood is associated with worse verbal memory in midlife regardless of current or long-term BP control status. The potential risk of hypertension associated cognitive decline should not be overlooked in individuals with a long duration of hypertension, even if BP levels are controlled.

Restless Legs Syndrome Severity and Cognitive Function in Adults With Multiple Sclerosis: An Exploratory Pilot Study.

Restless legs syndrome (RLS) is a sleep disorder present in as many as 26% of persons with multiple sclerosis (MS) and can be associated with cognitive function. The present study examined the relationships between RLS symptoms (severity, frequency, occurrence) and cognitive function in adults with MS who have RLS. Twenty-two participants attended 1 laboratory session and completed the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Restless Legs Syndrome-6 Scale, and then the Brief International Cognitive Assessment for Multiple Sclerosis battery consisting of the Symbol Digit Modalities Test; California Verbal Learning Test, Second Edition; and Brief Visuospatial Memory Test-Revised. Nonparametric bivariate correlations indicated that worse IRLS total severity was associated with slower processing speed (ρ = -0.42), worse verbal memory (ρ = -0.63), and worse visual memory (ρ = -0.61); worse RLS severity at falling asleep was associated with worse verbal memory (ρ = -0.45) and worse visual memory (ρ = -0.55); and worse RLS severity during the day while active was associated with slower processing speed (ρ = -0.58), worse verbal memory (ρ = -0.52), and worse visual memory (ρ = -0.60). These results suggest that those with more severe RLS, including worse symptoms at falling asleep and during the day while active, might experience worse cognitive function, particularly processing speed and memory. Future research should evaluate whether treatment of RLS symptoms can offer new opportunities for managing cognitive dysfunction in adults with MS.

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer's Disease.

Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer's disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world's largest ADAD kindred and sex differences in the relationship between SCD and memory performance. We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

Associations Between 20-Year Lipid Variability Throughout Young Adulthood and Midlife Cognitive Function and Brain Integrity.

Little is known about long-term lipid variability in young adulthood in relation to cognitive function and brain integrity in midlife. We studied 3 328 adults from the Coronary Artery Risk Development in Young Adults. We defined low- and high-density lipoprotein (LDL and HDL) variability as the intraindividual standard deviation of lipid measurements over 20 years of young adulthood (1985-2005). Cognitive tests were administered in 2010. Brain scans were performed in 2010 on 714 participants. To facilitate comparison, cognitive tests and brain metrics were z-scored. Mean age at baseline was 25.4 years. Higher 20-year LDL variability was associated with worse verbal memory in midlife (β = -0.25, 95% CI: -0.42, -0.08), adjusted for important covariates. Higher 20-year HDL variability was associated with worse processing speed in midlife (β = -0.80, 95% CI: -1.18, -0.41) and brain integrity, for example, smaller total brain volume (β = -0.58, 95% CI: -0.82, -0.34) and worse total brain fractional anisotropy (β = -1.13, 95% CI: -1.87, -0.39). Higher long-term lipid variability in adulthood was associated with worse cognition and brain integrity in midlife, in a relatively young cohort.

Long-Term Disease Burden and Survivorship Issues After Surgery and Radiotherapy of Intracranial Meningioma Patients.

BACKGROUNDMany intracranial meningioma patients have an impaired health-related quality of life (HRQoL) and neurocognitive functioning up to 4 yr after intervention.OBJECTIVETo assess the long-term (≥5 yr) disease burden of meningioma patients.METHODSIn this multicenter cross-sectional study, patients ≥5 yr after intervention (including active magnetic resonance imaging (MRI) surveillance) were included and assessed for HRQoL (Short-Form Health Survey 36), neurocognitive functioning (neuropsychological assessment), anxiety and depression (Hospital Anxiety and Depression Scale), and work productivity (Short Form-Health and Labour Questionnaire). Multivariable and propensity score regression analyses were used to compare patients and controls, and different treatment strategies corrected for possible confounders. Clinically relevant differences were reported.RESULTSAt a median of 9 yr follow-up after intervention, meningioma patients (n = 190) reported more limitations due to physical (difference 12.5 points, P = .008) and emotional (13.3 points, P = .002) health problems compared with controls. Patients also had an increased risk to suffer from anxiety (odds ratio [OR]: 2.6, 95% CI: 1.2-5.7) and depression (OR: 3.7, 95% CI: 1.3-10.5). Neurocognitive deficits were found in 43% of patients. Although postoperative complications, radiotherapy, and reresection were associated with worse verbal memory, attention, and executive functioning when compared to patients resected once, the only clinically relevant association was between reresection and worse attention (–2.11, 95% CI: –3.52 to –0.07). Patients of working age less often had a paid job (48%) compared with the working-age Dutch population (72%) and reported more obstacles at work compared with controls.CONCLUSIONIn the long term, a large proportion of meningioma patients have impaired HRQoL, neurocognitive deficits, and high levels of anxiety or depression. Patients treated with 1 resection have the best neurocognitive functioning.

Early adulthood and midlife cardiovascular risk factors and late‐life cognition in KHANDLE: A lifecourse study of a diverse cohort

AbstractBackgroundMidlife cardiovascular risks (CVR) are associated with late‐life cognition and dementia. Prior studies that examine early and midlife CVR on cognitive aging in Asians, Blacks, and Latinos are limited.MethodsThe Kaiser Healthy Aging and Diverse Life Experiences Study (KHANDLE) is a cohort of community‐dwelling Kaiser Permanente members residing in Northern California (Asians (26%), Blacks (29%), Latinos (20%) and Whites (24%)) who completed a multiphasic health checkup (MHC) from 1977‐1985 (n=1,207; mean age=37.6). KHANDLE aims to evaluate how lifecourse factors influence late‐life brain health and cognitive decline and may impact race/ethnic disparities. Using linear regression, we examined the association between late‐life cognition and early/midlife hypertension, hyperlipidemia and overweight/obesity collected at MHC. Executive function, semantic memory and verbal episodic memory measured using the Spanish and English Neuropsychological Assessment Scales (SENAS) were z‐standardized and combined for a composite measure of overall cognition. We tested for effect modification by race/ethnicity. Models controlled for age at KHANDLE, age at MHC, gender, and education.ResultsAt KHANDLE baseline, mean age was 75.4(6.7). At MHC, 46% of participants were ages 26‐35, 47% ages 36‐49 and 7% ages 50‐65. Prevalence of 2+ CVR was highest in Blacks (24%), followed by Latinos (24%), Asians (15%), and Whites (13%). Across race/ethnicity, having 2+ risk factors was associated with lower cognition in all domains: Overall cognition β=‐0.35 (‐0.47, ‐0.23). Having hypertension, hyperlipidemia or being overweight/obese was associated with worse cognition in all race/ethnic groups and across all cognitive domains (see table). Effect estimates varied by race/ethnicity, but interactions were not statistically significant: Blacks with hypertension (n=108) had lower late‐life cognition than other groups, especially for semantic memory and verbal episodic memory; Latinos with hyperlipidemia (n=49) had worse verbal memory than other groups; whites who were overweight/obese (n=84) had lower late‐life cognition across all domains, while Asians who were overweight/obese (n=50) had better late‐life cognition than non‐Asian participants who were overweight/obese.ConclusionsEarly/midlife cardiovascular risk factors are associated with lower late‐life cognition in all race/ethnic groups. The association between specific cardiovascular risk factors and late‐life cognition may vary by race/ethnicity, but differences were not significant.

Associations between sleep and cognitive performance in a racially/ethnically diverse cohort: the Study of Women's Health Across the Nation.

To determine whether actigraphy-assessed indices of sleep are associated with cognitive performance in women, and explore whether these associations vary by race/ethnicity. Participants were 1,126 postmenopausal community-dwelling females (mean age 65 years) from the observational Study of Women's Health Across the Nation (SWAN); 25% were black, 46% white, 13% Chinese, 11% Japanese, and 5% Hispanic. Actigraphy-assessed sleep measures included total sleep time, wake after sleep onset (WASO), and fragmentation. Cognitive measures included immediate and delayed verbal memory, working memory, and information processing speed. All measures were assessed in conjunction with SWAN annual visit 15. Across the sample, after covariate adjustment, greater WASO and fragmentation were concurrently associated with slower information processing speed. Black participants had significantly worse sleep relative to other race/ethnic groups. Significant race/sleep interactions were observed; in black, but not white, participants, greater fragmentation was concurrently associated with worse verbal memory and slower information processing speed, and greater WASO was concurrently associated with slower information processing speed. Sleep-cognitive performance associations were not different in Chinese and Japanese participants relative to white participants. Greater wakefulness and fragmentation during sleep are concurrently associated with slower information processing. Sleep continuity impacted concurrent cognitive performance in black, but not white, women. This effect may not have been detected in white women because their sleep was largely within the normal range. Future longitudinal studies in diverse samples are critical to further understand whether race/ethnicity moderates the influence of sleep on cognitive performance.

A-04 The Relationship of ApoE Status and Cognition in Non-demented Older Adults

Abstract Objective Apolipoprotein (ApoE)-e4 is well established as a genetic risk factor for Alzheimer’s disease (AD) as well as a predictor for the rate of cognitive decline in AD. Among older adults without dementia, some research has found that e4 carriers have worse episodic memory compared to e4 non-carriers, whereas others have not found this association. The present study examined differences in cognitive performance between ApoE-e4 carriers and non-carriers. Method 91 non-demented individuals (age range: 55–87) were genotyped for ApoE (41 e4 carriers, 49 e4 non-carriers) and completed neuropsychological testing as a part of a longitudinal study at the Center for Neurodegeneration and Translational Neuroscience. Cognitively normal (CN) and mild cognitive impairment (MCI) participants were included (41 CN, 49 MCI). Group differences between e4 carriers and non-carriers were compared across cognitive measures after controlling for age, gender, and education. Results In the total sample, e4 carriers performed significantly worse across measures of verbal and nonverbal memory, as well as on the Boston Naming Test and Symbol Digit Modalities Test (all p’s &amp;lt; .05). No significant group differences were observed across visuospatial or executive function tasks. When diagnostic subgroups were examined, e4 carriers had worse verbal memory than non-carriers in the MCI group, but there was no effect of e4 status on cognition among CN participants. Conclusion(s) These findings support that ApoE-e4 positivity is associated with worse cognitive performance, especially on tasks related to medial temporal lobe function, among non-demented older adults. In MCI, worse verbal memory in e4 carriers likely reflects increased progression of underlying AD pathology.

Hot flashes are associated with altered brain function during a memory task.

Vasomotor symptoms (VMS) are associated with decreased memory performance and alterations in brain function. We conducted a preliminary examination of VMS and patterns of brain activity during a verbal memory task to provide insights into the VMS-related brain mechanisms that can contribute to memory problems in midlife women. Fourteen postmenopausal women (mean age 53.5, 64% African-American) with moderate-to-severe VMS (>35/wk) and not taking hormone therapy completed functional magnetic resonance imaging (fMRI) assessments during word encoding and recognition, 24-hour physiologic VMS monitoring, symptom questionnaires, and two verbal memory tests. In regression analyses, a higher number of physiologic VMS, but not reported VMS, was associated with worse verbal memory on immediate and delayed logical memory (r = 0.53 and r = 0.72, P < 0.05). On fMRI assessments, a higher number of physiologic VMS, but not subjective VMS, was associated with greater activation in the left orbitofrontal cortex, left medial and superior frontal gyrus, right superior frontal gyrus, and right parahippocampal gyrus during the encoding task (P < 0.005). During the recognition task, physiologic VMS were associated with greater activation in the left medial and superior frontal gyrus, left parahippocampal gyrus and hippocampus, right medial and superior frontal gyrus, right parahippocampal gyrus and hippocampus (P < 0.005), and with decreased activation in the ventral medial prefrontal cortex (P < 0.005). Those associations were independent of symptoms and hormone levels. Preliminary data suggest that VMS may contribute to memory performance through effects on the hippocampus and prefrontal cortex. Larger studies are warranted to determine the robustness of these initial observations. : Video Summary:http://links.lww.com/MENO/A508.

Awareness of Olfactory Dysfunction in Subjective Cognitive Decline, Mild Cognitive Decline, and Alzheimer\u2019s Disease

IntroductionHyposmia and metacognitive errors are related to aging, depression, male gender, and cognitive decline. The current study investigated the awareness of olfactory dysfunction in subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD), as well as the influence of additional factors.MethodsA sample of 641 patients, including controls, SCD, non-amnestic MCI (naMCI), amnestic MCI (aMCI), and AD patients, was assessed with the Sniffin’ Sticks odor identification test (OIT) and the subjective olfactory capability (SOC) scale, in addition to measures of depressive symptoms, verbal memory, and executive functioning. Olfactory awareness groups were formed by means of the cutoffs of the OIT and the SOC.ResultsModerate and small, although significant, correlations between the OIT and the SOC were found among the study groups, with a significant discrimination of measured olfactory function via subjective assessment existing among controls but not among patients with AD. Of all AD patients, 34% overrated their sense of smell while 21% correctly identified themselves as being hyposmic, as opposed to corresponding 6% and 1% of healthy elderly. Overraters and correct hyposmic participants showed higher age and worse verbal memory and executive functions.ConclusionsReduced odor identification might underlie the same pathological changes within the brain as cognitive impairment and could serve as an additional marker for the development of AD.ImplicationsAlthough people with AD are aware of hyposmia to some extent, the majority is affected by overestimation of the ability to smell, making the combination of subjective ratings and measures of olfactory function an interesting topic for further research.

Postconcussive Symptoms After Single and Repeated Concussions in 10- to 20-Year-Olds: A Cross-Sectional Study.

The objective was to characterize cognitive deficits and postconcussive symptoms in a pediatric population with no concussion, a single concussion, and ≥2 concussions, using a cross-sectional design. Cognitive function and postconcussive symptoms were assessed in participants (age 10-20) with no concussion (n = 1118), single concussion (n = 368), and repeated (≥2) concussions (n = 252). Analyses were adjusted for age and gender. Individuals with ≥2 concussions exhibited more total postconcussive symptoms; more loss of consciousness, amnesia and confusion; more headaches; and poorer cognitive function compared to no concussion and single concussion. Postconcussive symptoms may play a modulatory role in cognitive dysfunction after repeated concussions as those with loss of consciousness, amnesia, confusion, or headaches exhibited worse verbal memory, visual memory, visual-motor processing, and poorer impulse control compared to those without these symptoms. This analysis demonstrates that repeated concussions is associated with poorer cognitive function and postconcussive symptoms compared to a single concussion.

Verbal Memory Performance and Reduced Cortical Thickness of Brain Regions Along the Uncinate Fasciculus in Young Adult Cannabis Users.

Introduction: Memory impairment is one of the most commonly reported effects of cannabis use, especially among those who initiate use earlier, perhaps due to the effects of delta-9- tetrahydrocannabinol on cannabinoid (CB1) receptors in the brain. Studies have increasingly investigated whether cannabis use is associated with impairments in verbal memory, and with alterations in brain structures underlying verbal memory. The uncinate fasciculus (UF), a long-range white matter tract, connects regions with densely localized CB1 receptors that are important in verbal memory. This study investigated the impact of cannabis use on UF structures and its association with memory performance in young adult cannabis users (CU) and non-using controls (CON).Materials and Methods: Nineteen CU and 22 CON completed a verbal memory task and a neuroimaging protocol, in which diffusion tensor imaging and structural scans were collected. We compared memory performance, diffusion and tractography measures of the UF, and cortical thickness of regions connected by the UF, between CU and CON. In regions showing a significant group effect, we also examined associations between verbal memory performance, cortical thickness, and age of onset of cannabis use.Results: Compared to non-users, CU had worse memory performance, decreased fiber bundle length in the UF, and decreased cortical thickness of brain regions along the UF such as the entorhinal cortex and fusiform gyrus. Verbal memory performance was significantly associated with age of onset of cannabis use, indicating that those who initiated cannabis use at an earlier age performed worse. Cortical thickness of the entorhinal cortex was significantly correlated with age of first use and memory performance.Conclusion: This study provides evidence that cannabis use, especially when initiated at a young age, may be associated with worse verbal memory and altered neural development along the UF. Reductions in cortical thickness in regions implicated in memory processes may underlie weaknesses in verbal memory performance.

The Role of Age in Neurocognitive Functioning among Adult Allogeneic Hematopoietic Cell Transplant Recipients

Improvements in supportive care have enabled allogeneic hematopoietic cell transplantation (HCT) to be performed in increasingly older patients. HCT is associated with neurocognitive impairment, which may be exacerbated in older adults due to normal neurocognitive decline associated with aging. The goal of this study was to evaluate whether increasing age of allogeneic HCT recipients is associated with worse neurocognitive outcomes over time relative to a matched sample of individuals without cancer. Patients (n = 140; 42% female; M age, 51 years; range, 20 to 76 years; 31% with acute myelogenous leukemia) completed neurocognitive assessments before transplantation and 3 months and 1 year after transplantation. Controls (n = 75; 56% female; M age, 53 years; range, 21 to 74 years) completed assessments at comparable time intervals. Linear mixed models revealed that regardless of age, patients demonstrated worse performance than controls before transplantation in verbal memory, visual memory, and total neuropsychological performance, and over time in executive functioning. In addition, older age was associated with worse performance in verbal memory (P = .02) and verbal fluency (P = .05) over time in patients compared with controls. Specifically, older (65+ years) patients had worse verbal memory and verbal fluency than older and younger (<65 years) controls post-transplantation (Cohen's d = .22 to .39). These data indicate that age may be a risk factor for worse neurocognitive outcomes after allogeneic HCT. If replicated, our results suggest that older candidates for allogeneic HCT should be counseled regarding the risk of cognitive problems after transplantation.