Variance In Cognitive Performance Research Articles

An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors.

PurposeInspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance.Patients and methodsThe sample (n=220) was comprised of 138 postmenopausal women newly diagnosed with early stage breast cancer and 82 postmenopausal age- and education-matched healthy controls without breast cancer. Cognitive performance was assessed after primary surgery but prior to initiation of adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of neuropsychological tests encompassing eight cognitive function composite domains: attention, concentration, executive function, mental flexibility, psychomotor speed, verbal memory, visual memory, and visual working memory. In total, 131 SNPs were included in the analysis. Standard and robust multiple linear regression modeling was used to examine relationships between each domain and the presence or absence of one or more minor alleles for each SNP. Genetic risk/protection scores (GRSs) were calculated for each domain to evaluate the collective effect of possession of multiple risk/protective alleles.ResultsWith the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main effect and/or SNP by future prescribed treatment group interactions were observed for every gene between at least one domain and one or more SNPs. All GRSs were found to be significantly (P<0.001) associated with each respective domain score.ConclusionAssociations between host SNPs and computed GRSs and variability in pretreatment cognitive function performance support the study hypothesis, and warrant further investigations to identify biomarkers for breast cancer-related cognitive dysfunction.

Leisure Activities and Change in Cognitive Stability: A Multivariate Approach.

Aging is traditionally associated with cognitive decline, attested by slower reaction times and poorer performance in various cognitive tasks, but also by an increase in intraindividual variability (IIV) in cognitive performance. Results concerning how lifestyle activities protect from cognitive decline are mixed in the literature and all focused on how it affects mean performance. However, IIV has been proven to be an index more sensitive to age differences, and very little is known about the relationships between lifestyle activities and change in IIV in aging. This longitudinal study explores the association between frequency of physical, social, intellectual, artistic, or cultural activities and age-related change in various cognitive abilities, considering both mean performance and IIV. Ninety-six participants, aged 64–93 years, underwent a battery of cognitive tasks at four measurements over a seven-year period, and filled out a lifestyle activity questionnaire. Linear multilevel models were used to analyze the associations between change in cognitive performance and five types of activities. Results showed that the practice of leisure activities was more strongly associated with IIV than with mean performance, both when considering overall level and change in performance. Relationships with IIV were dependent of the cognitive tasks considered and overall results showed protective effects of cultural, physical and intellectual activities on IIV. These results underline the need for considering IIV in the study of age-related cognitive change.

Repeatability and consistency of individual behaviour in juvenile and adult Eurasian harvest mice

Knowledge on animal personality has provided new insights into evolutionary biology and animal ecology, as behavioural types have been shown to affect fitness. Animal personality is characterized by repeatable and consistent between-individual behavioural differences throughout time and across different situations. Behavioural repeatability within life history stages and consistency between life history stages should be checked for the independence of sex and age, as recent data have shown that males and females in some species may differ in the repeatability of behavioural traits, as well as in their consistency. We measured the repeatability and consistency of three behavioural and one cognitive traits in juvenile and adult Eurasian harvest mice (Micromys minutus). We found that exploration, activity and boldness were repeatable in juveniles and adults. Spatial recognition measured in a Y Maze was only repeatable in adult mice. Exploration, activity and boldness were consistent before and after maturation, as well as before and after first sexual contact. Data on spatial recognition provided little evidence for consistency. Further, we found some evidence for a litter effect on behaviours by comparing different linear mixed models. We concluded that harvest mice express animal personality traits as behaviours were repeatable across sexes and consistent across life history stages. The tested cognitive trait showed low repeatability and was less consistent across life history stages. Given the rising interest in individual variation in cognitive performance, and in its relationship to animal personality, we suggest that it is important to gather more data on the repeatability and consistency of cognitive traits.

Insulin resistance and cognitive performance in type 2 diabetes — The Maastricht study

AimsType 2 diabetes, hyperinsulinemia, and insulin resistance are associated with cognitive impairment. Experimental studies indicate that insulin signaling in the brain is related to cognitive performance. Here we evaluated whether insulin-related variables contribute to the variance in cognitive performance among individuals with type 2 diabetes. MethodsA total of 806 individuals with type 2 diabetes (mean age 62±8years, HbA1c 6.9±1.1%) completed a neuropsychological test battery. Insulin-related variables evaluated were: fasting plasma insulin, C-peptide, and the Homeostasis Model Assessment (HOMA2-IR; in individuals without insulin treatment; n=641). The unadjusted coefficient of determination (R2), obtained from multiple linear regression analyses, was used to estimate the proportion of variance in cognition explained by insulin-related variables. ResultsSex, age, and educational level together explained 18.0% (R2) of the variance in memory function, 26.5% in information processing speed, and 22.8% in executive function and attention. Fasting insulin, C-peptide, or HOMA2-IR did not increase the explained variance (maximum ΔR2 0.3%, P≥0.14). Similar results were obtained when insulin-related variables were added to models that additionally included glycemic control, cardiovascular risk factors, and depression. ConclusionsOur results show that measures of peripheral insulin resistance are unrelated to cognitive performance among individuals with adequately controlled type 2 diabetes.

Associations between pathologic tumor features and preadjuvant therapy cognitive performance in women diagnosed with breast cancer.

Intertumor heterogeneity has been proposed as a potential mechanism to account for variability in cognitive performance in women diagnosed with breast cancer. The purpose of this study was to explore associations between variation in pathologic tumor features (PTFs) and variability in preadjuvant therapy cognitive performance in postmenopausal women newly diagnosed with early‐stage breast cancer. Participants (N = 329) completed a comprehensive battery of neuropsychological tests to evaluate cognitive performance after primary surgery but prior to initiation of adjuvant anastrozole±chemotherapy. PTF data were abstracted from medical records. Robust multiple linear regression models were fit to estimate associations between individual PTFs and the cognitive function composite domain scores. All models controlled for age, estimated intelligence, and levels of depressive symptoms, anxiety, fatigue, and pain. Diagnosis of a HER2‐positive tumor contributed to poorer verbal (b = −0.287, P = 0.018), visual (b = −0.270, P = 0.001), and visual working (b = −0.490, P < 0.001) memory performance compared to diagnosis of a HER2‐negative tumor. Similarly, as HER2 immunohistochemistry classification score increased, verbal (b = −0.072, P = 0.093), visual (b = −0.081, P = 0.003), and visual working (b = −0.170, P < 0.001) memory performance score decreased. Associations with performance were also noted between location, focality/centricity, hormone receptor expression, cellular proliferation (i.e., Ki67), and Oncotype DX ® Breast Cancer Assay Recurrence Score®.) Our results suggest that certain PTFs related to more aggressive tumor phenotypes or inferior breast cancer prognosis may be implicated in poorer preadjuvant therapy cognitive performance. Follow‐up studies that include a cognitive assessment before primary surgery should be conducted to further delineate the role of intertumor heterogeneity on cognitive performance.

MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls

Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10−5) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects.

Cognitive reserve and cognitive performance of patients with focal frontal lesions

The Cognitive reserve (CR) hypothesis was put forward to account for the variability in cognitive performance of patients with similar degrees of brain pathology. Compensatory neural activity within the frontal lobes has often been associated with CR. For the first time we investigated the independent effects of two CR proxies, education and NART IQ, on measures of executive function, fluid intelligence, speed of information processing, verbal short term memory (vSTM), naming, and perception in a sample of 86 patients with focal, unilateral frontal lesions and 142 healthy controls. We fitted multiple linear regression models for each of the cognitive measures and found that only NART IQ predicted executive and naming performance. Neither education nor NART IQ predicted performance on fluid intelligence, processing speed, vSTM or perceptual abilities. Education and NART IQ did not modify the effect of lesion severity on cognitive impairment. We also found that age significantly predicted performance on executive tests and the majority of our other cognitive measures, except vSTM and GNT. Age was the only predictor for fluid intelligence. This latter finding suggests that age plays a role in executive performance over and above the contribution of CR proxies in patients with focal frontal lesions. Overall, our results suggest that the CR proxies do not appear to modify the relationship between cognitive impairment and frontal lesions.

Effect of an anti-malaria drug on behavioural performance on a problem-solving task: An experiment in wild great tits

Malaria parasites have been shown to decrease host fitness in several species in the wild and their detrimental effects on host cognitive ability are well established in humans. However, experimental demonstrations of detrimental effects on non-human host behaviour are currently limited. In this study, we experimentally tested whether injections of an anti-malaria drug affected short-term behavioural responses to a problem-solving task during breeding in a wild population of great tits (Parus major) naturally infected with malaria. Adult females treated against malaria were more active than control females, even though they were not more likely to solve the task or learn how to do so, suggesting that energetic constraints could shape differences in some behaviours while changes in cognitive performances might require more time for the neural system to recover or may depend mainly on infection at the developmental stage. Alternatively, parasite load might be a consequence, rather than a cause, of inter-individual variation in cognitive performance. These results also suggest that inter-individual as well as inter-population differences in some behavioural traits may be linked to blood parasite load.

Active explorers show low learning performance in a social insect.

An intriguing question in behavioral biology is whether consistent individual differences (called animal personalities) relate to variation in cognitive performance because commonly measured personality traits may be associated with risk-reward trade-offs. Social insects, whose learning abilities have been extensively characterized, show consistent behavioral variability, both at colony and at individual level. We investigated the possible link between personality traits and learning performance in the carpenter ant Camponotus aethiops. Exploratory activity, sociability, and aggression were assessed twice in ant foragers. Behaviors differed among individuals, they were partly repeatable across time and exploratory activity correlated positively with aggression. Learning abilities were quantified by differential conditioning of the maxilla-labium extension response, a task that requires cue perception and information storage. We found that exploratory activity of individual ants significantly predicted learning performance: “active-explorers” were slower in learning the task than “inactive-explorers”. The results suggest for the first time a link between a personality trait and cognitive performance in eusocial insects, and that the underlying individual variability could affect colony performance and success.

Cognitive Aging in the Seattle Longitudinal Study: Within-Person Associations of Primary Mental Abilities with Psychomotor Speed and Cognitive Flexibility

It has long been proposed that cognitive aging in fluid abilities is driven by age-related declines of processing speed. Although study of between-person associations generally supports this view, accumulating longitudinal between-person and within-person evidence indicates less strong associations between speed and fluid cognitive performance. Initial evidence also suggests that cognitive flexibility may explain within-person variability in cognitive performance. In the present study, we used up to nine waves of data over 56 years from a subsample of 582 participants of the Seattle Longitudinal Study to examine (a) within-person associations of psychomotor speed and cognitive flexibility with cognitive aging in primary mental abilities (including inductive reasoning, number ability, verbal meaning, spatial orientation, and word fluency); and (b) how these within-person associations change with age. In line with the processing speed theory, results revealed that within persons, primary mental abilities (including fluid, crystallized, and visualization measures) were indeed associated with psychomotor speed. We also observed age-related increases in within-person couplings between primary mental abilities and psychomotor speed. While the processing speed theory focuses primarily on associations with fluid abilities, age-related increases in coupling were found for a variety of ability domains. Within-person associations between primary mental abilities and cognitive flexibility were weaker and relatively stable with age. We discuss the role of speed and flexibility for cognitive aging.

The effect of dual tasking on foot kinematics in people with functional ankle instability

BackgroundSome cases of repeated inversion ankle sprains are thought to have a neurological basis and are termed functional ankle instability (FAI). In addition to factors local to the ankle, such as loss of proprioception, cognitive demands have the ability to influence motor control and may increase the risk of repetitive lateral sprains. ObjectiveThe purpose of this study was to investigate the effect of cognitive demand on foot kinematics in physically active people with functional ankle instability. Methods21 physically active participants with FAI and 19 matched healthy controls completed trials of normal walking (single task) and normal walking while performing a cognitive task (dual task). Foot motion relative to the shank was recorded. Cognitive performance, ankle kinematics and movement variability in single and dual task conditions was characterized. ResultsDuring normal walking, the ankle joint was significantly more inverted in FAI compared to the control group pre and post initial contact. Under dual task conditions, there was a statistically significant increase in frontal plane foot movement variability during the period 200ms pre and post initial contact in people with FAI compared to the control group (p<0.05). Dual task also significantly increased plantar flexion and inversion during the period 200ms pre and post initial contact in the FAI group (p<0.05). Conclusionparticipants with FAI demonstrated different ankle movement patterns and increased movement variability during a dual task condition. Cognitive load may increase risk of ankle instability in these people.

Effect size for the main cognitive function determinants in a large cross-sectional study.

The aim of our study was to examine the effect sizes of different cognitive function determinants in middle and early old age. Cognitive functions were assessed in 11 711 volunteers (45 to 75 years old), included in the French CONSTANCES cohort between January 2012 and May 2014, using the free and cued selective reminding test (FCSRT), verbal fluency tasks, digit-symbol substitution test (DSST) and trail making test (TMT), parts A and B. The effect sizes of socio-demographic (age, sex, education), lifestyle (alcohol, tobacco, physical activity), cardiovascular (diabetes, blood pressure) and psychological (depressive symptomatology) variables were computed as omega-squared coefficients (ω2 ; part of the variation of a neuropsychological score that is independently explained by a given variable). These sets of variables explained from R2 = 10% (semantic fluency) to R2 = 26% (DSST) of the total variance. In all tests, socio-demographic variables accounted for the greatest part of the explained variance. Age explained from ω2 = 0.5% (semantic fluency) to ω2 = 7.5% (DSST) of the total score variance, gender from ω2 = 5.2% (FCSRT) to a negligible part (semantic fluency or TMT) and education from ω2 = 7.2% (DSST) to ω2 = 1.4% (TMT-A). Behavioral, cardiovascular and psychological variables only slightly influenced the cognitive test results (all ω2 < 0.8%, most ω2 < 0.1%). Socio-demographic variables (age, gender and education) are the main variables associated with cognitive performance variations between 45 and 75 years of age in the general population.

Disrupted Brain Connectivity Patterns in Patients with Type 2 Diabetes.

Type 2 diabetes is associated with an increased risk of dementia. This study investigated the global connectivity patterns in the brains of patients with type 2 diabetes by using a functional MR imaging technique. Forty patients and 43 age-, sex-, and education-matched healthy controls underwent resting-state functional imaging in a 3T MR imaging unit. Degree centrality, a commonly used measurement of global connectivity, was computed for a full-brain exploration of the regions influenced by type 2 diabetes. We then examined the functional connectivity of each region by using the seed-based approach. Finally, voxelwise correlation analyses were performed to explore the relationship among the connectivity changes, cognitive performance, and diabetes-related variables. Patients exhibited decreased degree centrality in the left lingual gyrus and increased centrality in the right insula and dorsal anterior cingulate cortex (corrected P < .05). The occipital network anchored in the lingual gyrus showed extensively reduced connectivity, while the network connectivity of the insula and cingulate cortex (mostly included in the salience network) was significantly elevated (corrected P < .05). Correlational analyses revealed that in the diabetic group, impaired visual memory and executive function performance were correlated with occipital hypoconnectivity, while higher fasting plasma glucose levels and better executive functioning were related to anterior cingulate cortex hyperconnectivity (all corrected P values < .05). Similar effects were not detected in the controls. This preliminary study shows that network connectivity is altered in patients with type 2 diabetes, which may provide critical insight into the neural substrate of diabetes-related cognitive decline.

Low‐level environmental lead exposure still negatively associated with children's cognitive abilities

ObjectiveWe explored relationships between children's cognitive abilities measured with the Wechsler Intelligence Scale for Children‐Fourth Edition and blood lead levels.MethodsParticipants were 127 children (mean age = 7.9 years, standard deviation = 0.6) from Australian cities, Port Pirie, and Broken Hill, with low‐level blood lead concentrations (mean = 4.8 microgram/decilitre, standard deviation = 3.3, range = 1.0–19.3). Potential covariates (demographic, parental, familial, psycho‐social, pre‐ and post‐natal factors) were controlled statistically.ResultsUnadjusted analyses found moderate, continuous, and statistically significant inverse, non‐linear associations between blood lead level and three of the four cognitive indices that combine to deliver Full Scale IQ. In addition to blood lead level, variables that consistently explained most variance in cognitive performance were breastfeeding up to 6 months and stressful life events reported within the family for the past 12 months. In multiple regression analyses, after controlling for these, blood lead level remained a significant predictor of cognitive outcomes.ConclusionThese results support the hypothesis that blood lead levels below 10 micrograms/decilitre may still have a detrimental impact on children's cognitive abilities, supporting recent concern that there is no safe level of paediatric lead exposure.

Ecophysiology of cognition: How do environmentally induced changes in physiology affect cognitive performance?

Cognitive performance is based on brain functions, which have energetic demands and are modulated by physiological parameters such as metabolic hormones. As both environmental demands and environmental energy availability change seasonally, we propose that cognitive performance in free-living animals might also change seasonally due to phenotypic plasticity. This is part of an emerging research field, the 'ecophysiology of cognition': environmentally induced changes in physiological traits, such as blood glucose and hormone levels, are predicted to influence cognitive performance in free-living animals. Energy availability for the brain might change, and as such cognition, with changing energetic demands (e.g. reproduction) and changes of energy availability in the environment (e.g. winter, drought). Individuals spending more energy than they can currently obtain from their environment (allostatic overload type I) are expected to trade off energy investment between cognition and other life-sustaining processes or even reproduction. Environmental changes reducing energy availability might thus impair cognition. However, selection pressures such as predation risk, mate choice or social demands may act on the trade-off between energy saving and cognition. We assume that different environmental conditions can lead to three different trade-off outcomes: cognitive impairment, resilience or enhancement. Currently we cannot understand these trade-offs, because we lack information about changes in cognitive performance due to seasonal changes in energy availability and both the resulting changes in homeostasis (for example, blood glucose levels) and the associated changes in the mechanisms of allostasis (for example, hormone levels). Additionally, so far we know little about the fitness consequences of individual variation in cognitive performance. General cognitive abilities, such as attention and associative learning, might be more important in determining fitness than complex and specialized cognitive abilities, and easier to use for comparative study in a large number of species. We propose to study seasonal changes in cognitive performance depending on energy availability in populations facing different predation risks, and the resulting fitness consequences.

Training Affects Variability in Training Performance Both Within and Across Jobs

A partial test of a model of training performance variability was conducted. The current study examined variability in cognitive ability and training performance in job‐specific training. Several studies have found mean score differences in cognitive ability across jobs. Further, the variability in training outcomes among individuals within a job has been shown to vary across jobs. Reduced variability in training outcomes is a measure of training effectiveness. For this study data were grouped by job over several years. Participants were 116,310 enlistees enrolled in 108 US Air Force training specialties. Aptitude was measured by a verbal/math composite derived from the US military enlistment test, the Armed Services Vocational Aptitude Battery. Training performance was assessed by written tests of job‐related knowledge content. Predictive validity of the verbal/math composite ranged from .124 to .836 across jobs with a mean weighted value of 0.691. Substantial differences were observed for mean and variability of aptitude across jobs. Trainees in jobs with high aptitude requirements had higher mean aptitude and were less variable on aptitude than those in jobs with lower aptitude requirements. Further, trainees in high aptitude jobs had higher mean training performance scores and were less variable on performance than those in jobs with lower aptitude requirements. Finally, training performance was much less variable than aptitude. Training had the effect of reducing variability among trainees within jobs. This has the effect of producing a more homogenous set of trainees on trained content, which is beneficial to on‐the‐job training. Support was found for a part of the model.

Assessing the genetic overlap between BMI and cognitive function.

Obesity and low cognitive function are associated with multiple adverse health outcomes across the life course. They have a small phenotypic correlation (r=−0.11; high body mass index (BMI)−low cognitive function), but whether they have a shared genetic aetiology is unknown. We investigated the phenotypic and genetic correlations between the traits using data from 6815 unrelated, genotyped members of Generation Scotland, an ethnically homogeneous cohort from five sites across Scotland. Genetic correlations were estimated using the following: same-sample bivariate genome-wide complex trait analysis (GCTA)–GREML; independent samples bivariate GCTA–GREML using Generation Scotland for cognitive data and four other samples (n=20 806) for BMI; and bivariate LDSC analysis using the largest genome-wide association study (GWAS) summary data on cognitive function (n=48 462) and BMI (n=339 224) to date. The GWAS summary data were also used to create polygenic scores for the two traits, with within- and cross-trait prediction taking place in the independent Generation Scotland cohort. A large genetic correlation of −0.51 (s.e. 0.15) was observed using the same-sample GCTA–GREML approach compared with −0.10 (s.e. 0.08) from the independent-samples GCTA–GREML approach and −0.22 (s.e. 0.03) from the bivariate LDSC analysis. A genetic profile score using cognition-specific genetic variants accounts for 0.08% (P=0.020) of the variance in BMI and a genetic profile score using BMI-specific variants accounts for 0.42% (P=1.9 × 10−7) of the variance in cognitive function. Seven common genetic variants are significantly associated with both traits at P<5 × 10−5, which is significantly more than expected by chance (P=0.007). All these results suggest there are shared genetic contributions to BMI and cognitive function.

A Functional Cartography of Cognitive Systems.

One of the most remarkable features of the human brain is its ability to adapt rapidly and efficiently to external task demands. Novel and non-routine tasks, for example, are implemented faster than structural connections can be formed. The neural underpinnings of these dynamics are far from understood. Here we develop and apply novel methods in network science to quantify how patterns of functional connectivity between brain regions reconfigure as human subjects perform 64 different tasks. By applying dynamic community detection algorithms, we identify groups of brain regions that form putative functional communities, and we uncover changes in these groups across the 64-task battery. We summarize these reconfiguration patterns by quantifying the probability that two brain regions engage in the same network community (or putative functional module) across tasks. These tools enable us to demonstrate that classically defined cognitive systems—including visual, sensorimotor, auditory, default mode, fronto-parietal, cingulo-opercular and salience systems—engage dynamically in cohesive network communities across tasks. We define the network role that a cognitive system plays in these dynamics along the following two dimensions: (i) stability vs. flexibility and (ii) connected vs. isolated. The role of each system is therefore summarized by how stably that system is recruited over the 64 tasks, and how consistently that system interacts with other systems. Using this cartography, classically defined cognitive systems can be categorized as ephemeral integrators, stable loners, and anything in between. Our results provide a new conceptual framework for understanding the dynamic integration and recruitment of cognitive systems in enabling behavioral adaptability across both task and rest conditions. This work has important implications for understanding cognitive network reconfiguration during different task sets and its relationship to cognitive effort, individual variation in cognitive performance, and fatigue.

Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA).

Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age.

Role of Place in Explaining Racial Heterogeneity in Cognitive Outcomes among Older Adults.

Racially patterned disadvantage in Southern states, especially during the formative years of primary school, may contribute to enduring disparities in adult cognitive outcomes. Drawing on a lifecourse perspective, we examine whether state of school attendance affects cognitive outcomes in older adults and partially contributes to persistent racial disparities. Using data from older African American and white participants in the national Health and Retirement Study (HRS) and the New York based Washington Heights Inwood Cognitive Aging Project (WHICAP), we estimated age-and gender-adjusted multilevel models with random effects for states predicting years of education and cognitive outcomes (e.g., memory and vocabulary). We summarized the proportion of variation in outcomes attributable to state of school attendance and compared the magnitude of racial disparities across states. Among WHICAP African Americans, state of school attendance accounted for 9% of the variance in years of schooling, 6% of memory, and 12% of language. Among HRS African Americans, state of school attendance accounted for 13% of the variance in years of schooling and also contributed to variance in cognitive function (7%), memory (2%), and vocabulary (12%). Random slope models indicated state-level African American and white disparities in every Census region, with the largest racial differences in the South. State of school attendance may contribute to racial disparities in cognitive outcomes among older Americans. Despite tremendous within-state heterogeneity, state of school attendance also accounted for some variability in cognitive outcomes. Racial disparities in older Americans may reflect historical patterns of segregation and differential access to resources such as education.