Association of white matter hyperintensities and clinical vascular burden with depressive symptoms in Black older adults.

OBJECTIVES: Black older adults have a higher vascular burden compared to non-Hispanic White (NHW) older adults, which may put them at risk for a form of depression known as vascular depression (VaDep). The literature examining VaDep in Black older adults is sparse. The current study addressed this important gap by examining whether vascular burden was associated with depressive symptoms in Black older adults. METHODS: Participants included 113 Black older adults from the Healthy Brain Project, a substudy of the Health, Aging, and Body Composition Study. In multiple regression analyses, clinical vascular burden (sum of vascular conditions) and white matter hyperintensity (WMH) volume predicted depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale, controlling for demographic variables. Follow-up analyses compared the associations in the Black subsample and in 179 NHW older adults. RESULTS: Higher total WMH volume, but not clinically-defined vascular burden, predicted higher concurrent depressive symptoms and higher average depressive symptoms over 4 years. Similar associations were found between uncinate fasciculus (UF) WMHs and concurrent depressive symptoms and between superior longitudinal fasciculus WMHs and average depressive symptoms. The association between depressive symptoms and UF WMH was stronger in Black compared to NHW individuals. CONCLUSION: This research is consistent with the VaDep hypothesis and extends it to Black older adults, a group that has historically been underrepresented in the literature. Results highlight WMH in the UF as particularly relevant to depressive symptoms in Black older adults and suggest this group may be particularly vulnerable to the negative effects of WMH.

Prefrontal cortex activation while walking did not change but gait speed improved after a randomized physical therapy intervention.

BACKGROUND: Higher prefrontal cortex (PFC) activation while walking may indicate reduced gait automaticity. AIM: We examine whether PFC activation during walking improves after training in older adults at risk for mobility disability. METHODS: Forty-two adults aged ≥ 65 participated in a randomized clinical trial (NCT026637780) of a 12-week timing and coordination physical therapy intervention to improve walking (n = 20 intervention, n = 22 active control). PFC activation was measured by functional near-infrared spectroscopy (fNIRS) during four walking tasks over 15 m, each repeated 4 times: even surface walking, uneven surface walking, even dual-task, uneven dual-task; dual-task was reciting every other letter of the alphabet while walking. Gait speed and rate of correct letter generation were recorded. Linear mixed models tested between arm differences in change of fNIRS, gait speed, and letter generation from baseline to follow-up (12-week, 24-week, and 36-week). RESULTS: Intervention arms were similar in mean age (74.3 vs. 77.0) and baseline gait speed (0.96 vs. 0.93 m/s). Of 24 comparisons of between arm differences in the fNIRS signals, only two were significant which were not supported by differences at other follow-up times or on other tasks. Gait speed, particularly during dual-task conditions, and correct letter generation did improve post-intervention but improvements did not differ by arm. DISCUSSION AND CONCLUSIONS: After training, PFC activation during walking generally did not improve and did not differ by intervention arm. Improvements in gait speed without increased PFC activation may point toward more efficient neural control of walking.

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia.

Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI-MRA) in sub-Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood-based brain biomarkers of cerebral infarcts have been identified in non-SCA adults. Using plasma samples from a well-characterized cross-sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI-detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4-plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron-specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non-SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI-detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI-detected infarcts after adjusting for sex and age. All non-SCA controls and SCA participants lacking MRI-detected infarcts had low NfL levels. These data suggest potential utility of plasma-based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging.

Correction: Bohlke et al. The Effect of a Verbal Cognitive Task on Postural Sway Does Not Persist When the Task Is Over. Sensors 2021, 21, 8428.

There was an error in the original publication [...].

Exercise and the Risk of Mild Cognitive Impairment: Does the Effect Depend on Vascular Factors?

INTRODUCTION: Although exercise is associated with a lower risk for mild cognitive impairment (MCI), it is unclear whether its protective effect depends on the presence or absence of vascular factors. METHODS: In an exploratory study of data from a population-based cohort, 1254 participants aged 65+ years were followed for 10 years for incident MCI. The main effect of baseline total minutes of exercise per week (0 vs. 1 to 149 vs. 150+), and its interaction with several vascular factors, on risk for incident MCI was examined using Cox proportional hazards regression models, adjusting for demographics. RESULTS: Compared with no exercise, 1 to 149 minutes [hazard ratio (HR)=0.90; 95% confidence interval (95% CI), 0.69-1.16] and 150 or more minutes per week (HR=0.84; 95% CI, 0.66-1.07) of exercise lowered risk for incident MCI in a dose-dependent manner. The majority of interactions were not statistically significant, but risk reduction effect sizes of <0.75 suggested that exercise may have stronger effects among those without high cholesterol, never smoking, and not currently consuming alcohol; also, those with arrhythmia, coronary artery disease, and heart failure. Overall, there was a pattern of exercise being associated with lower MCI risk among those without vascular factors. CONCLUSIONS: Spending more time engaging in exercise each week may offer protection against MCI in late life, with some variation among those with different vascular conditions and risk factors. Our findings may help target subgroups for exercise recommendations and interventions, and also generate hypotheses to test regarding underlying mechanisms.

Functional correlates of self-reported energy levels in the Health, Aging and Body Composition Study.

BACKGROUND: Effects of fatigue on health in older age are well studied, yet little is known about the clinical relevance of energy perception. AIMS: To explore cross-sectional associations of self-reported energy with physical and mental health metrics in the Health, Aging, and Body Composition Study. METHODS: Participants rated their energy from 0 to 10; the outcome was energy dichotomized at the median (≥ 7 = higher energy). Four domains were assessed: depressive symptoms (Center for Epidemiologic Studies Depression Scale); physical performance (function: usual and rapid gait speed; fitness: 400-m walk time); physical activity (casual walking, walking for exercise, and intense exercise); and cognitive function (Modified Mini-Mental State Examination and Digit Symbol Substitution Test). Covariates bivariately associated with energy entered a multivariable logistic regression model, adjusted for demographics, chronic conditions, and strength. RESULTS: Depressive symptoms, physical performance and activity, but not cognition, were bivariately associated with energy (p < 0.0005). Younger age, male sex, greater strength, and absence of chronic conditions predicted higher energy (p < 0.001). In a multivariable model, depressive symptoms [adjusted odds ratio (aOR) 95% CI 0.69 (0.62, 0.76)] and 400-m walk times [aOR = 0.81 (0.72, 0.91)] were inversely associated with energy; usual and rapid gait speed [aOR = 1.3 (1.2, 1.4); aOR = 1.2 (1.1-1.4)], and time spent in intense exercise [aOR = 1.4 (1.1-1.7)] were positively associated with energy. DISCUSSION: In this cohort with a range of chronic conditions and fatigue, perceiving higher energy levels may reflect better emotional and physical health. CONCLUSION: Energy should be considered in multidimensional clinical assessments of older age.

The Effect of a Verbal Cognitive Task on Postural Sway Does Not Persist When the Task Is Over.

Dual-task balance studies explore interference between balance and cognitive tasks. This study is a descriptive analysis of accelerometry balance metrics to determine if a verbal cognitive task influences postural control after the task ends. Fifty-two healthy older adults (75 ± 6 years old, 30 female) performed standing balance and cognitive dual-tasks. An accelerometer recorded movement from before, during, and after the task (reciting every other letter of the alphabet). Thirty-six balance metrics were calculated for each task condition. The effect of the cognitive task on postural control was determined by a generalized linear model. Twelve variables, including anterior-posterior centroid frequency, peak frequency and entropy rate, medial-later entropy rate and wavelet entropy, and bandwidth in all directions, exhibited significant differences between baseline and cognitive task periods, but not between baseline and post-task periods. These results indicate that the verbal cognitive task did alter balance, but did not bring about persistent effects after the task had ended. Traditional balance measurements, i.e., root mean square and normalized path length, notably lacked significance, highlighting the potential to use other accelerometer metrics for the early detection of balance problems. These novel insights into the temporal dynamics of dual-task balance support current dual-task paradigms to reduce fall risk in older adults.

Regional Gray Matter Volume Links Rest-Activity Rhythm Fragmentation With Past Cognitive Decline.

OBJECTIVES: We examined the extent to which measures of neurodegeneration and cerebrovascular disease explain the rest-activity rhythm (RAR)-cognition link. METHODS: Seventy participants (mean age at MRI = 86, standard deviation (SD) = 2.6; 53% female) had cognitive, MRI, and accelerometer data. The slope of cognitive decline was defined applying a mixed model to 10 repeated Modified Mini Mental Status Test (3MS) measures over 14 years. Regional gray matter volume (GMV), white matter hyperintensities, and RARs were measured around year 12. RESULTS: Past 3MS decline was related to RAR fragmentation (per SD ß = -0.43, 95% confidence interval: -0.73, -0.14) and lower posterior parietal GMV (per standard deviation ß = 0.47, 95% confidence interval: 0.14, 0.79). Higher RAR fragmentation was related to lower posterior parietal GMV (Pearson r = -0.39, n = 70, p = 0.0007), which attenuated the association of RAR fragmentation and past cognitive decline by 17%. CONCLUSIONS: Longitudinal studies are warranted to understand the temporal relations and mechanisms linking RAR fragmentation and neurodegeneration.

Shared neural substrates of cognitive function and postural control in older adults.

INTRODUCTION: Poor cognitive function and postural control co-occur in older adults. It is unclear whether they share neural substrates. METHODS: Postural sway error during a novel visual tracking (VT) condition and gray matter volume (GMV) were compared between participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia (n = 179, mean age 82, 56% females, 56% white). Associations between VT error, cognitive function, and GMV were examined. RESULTS: Greater VT error was associated with having dementia compared to NC or MCI (odds ratio [95% CI] = 2.15 [1.38, 3.36] and 1.58 [1.05, 2.38]). Regions with lower GMV related to greater VT error and worse cognition were: bilateral hippocampi, parahippocampi, entorhinal, and parietal cortices (all P ≤0.05). GMV of bilateral hippocampi and left parahippocampus explained >20% of VT error between dementia and NC. DISCUSSION: Postural control during visuospatial tasks and dementia may share neural substrates, specifically memory-related regions.

Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study.

BACKGROUND: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited. METHODS: We aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1-12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second). RESULTS: Mean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5-12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23-1.68), p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ -2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01-1.86, p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95-24.3, p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30, p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected. CONCLUSIONS: The high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted.

Neuroimaging correlates of lateral postural control in older ambulatory adults.

BACKGROUND: In older adults, impaired postural control contributes to falls, a major source of morbidity. Understanding central mechanisms may help identify individuals at risk for impaired postural control. AIMS: To determine the relationship between gray matter volume (GMV), white matter hyperintensities (WMH), mean diffusivity (MD), and fractional anisotropy (FA) with lateral postural control. METHODS: Neuroimaging and postural control were assessed in 193 community-dwelling older adults (mean age 82, 55.4% female, 44.6% black). GMV, WMH, and diffusion tensor-derived markers of microstructure (MD and FA) were quantified for total brain and regions of interest. Lateral postural control was defined as the root mean square error (RMSE) of lateral sway during a visual feedback test. Associations were assessed with linear regression, adjusted for total brain atrophy and risk factors for impaired postural control. RESULTS: RMSE was higher for women than men (p < 0.001) and inversely correlated with gait speed (r = - 0.20, p = 0.01), modified mini-mental state (r = - 0.27, p < 0.001), digit symbol substitution test (r = - 0.20, p = 0.01) and quadriceps strength (r = - 0.18, p = 0.01). RMSE was inversely associated with GMV of bilateral precuneus (r = - 0.26, p = 0.01) and FA of corpus callosum and selected tracts in the right hemisphere (anterior thalamic radiation, cingulum, inferior longitudinal and fronto-occipital fasciculi), independent of covariates (r = - 0.34 to - 0.18, p ≤ 0.04). DISCUSSION: Lower GMV and microstructural white matter integrity in selected networks can explain worse lateral postural control in older ambulatory adults without neurologic diseases. CONCLUSION: Neuroimaging markers of poor postural control in healthy aging may help identify increased fall risk and design preventative fall strategies.

A population neuroscience approach to the study of cerebral small vessel disease in midlife and late life: an invited review.

Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon. We propose that the major gaps in this area are attributable to an incomplete characterization of cerebrovascular pathology, the populations being studied, and the temporality of exposure to risk factors. Specifically, currently available measures of age-related cerebral microvasculature changes are indirect, primarily related to parenchymal damage rather than direct quantification of small vessel damage, limiting the understanding of cerebral small vessel disease (cSVD) itself. Moreover, studies seldom account for variability in the health-related conditions or interactions with risk factors, which are likely determinants of cSVD pathogenesis. Finally, study designs are predominantly cross-sectional and/or have relied on single time point measures, leaving no clear evidence of time trajectories of risk factors or of change in cerebral microvasculature. We argue that more resources should be invested in 1) developing methodological approaches and basic science models to better understand the pathogenic and etiological nature of age-related brain microvascular diseases and 2) implementing state-of-the-science population study designs that account for the temporal evolution of cerebral microvascular changes in diverse populations across the lifespan.

Late-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia.

OBJECTIVE: To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution's magnitude. METHODS: Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (N = 2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores ≥8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D. RESULTS: Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12% faster time to MCI/dementia (time ratio [TR]: 0.88; 95% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95% CI: 0.88, 0.97); 64.5% of the total effect was mediated by late-life depressive symptoms. CONCLUSIONS: These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

Association of Hippocampal Substructure Resting-State Functional Connectivity with Memory Performance in Older Adults.

OBJECTIVES: Hippocampal hyperactivation marks preclinical dementia pathophysiology, potentially due to differences in the connectivity of specific medial temporal lobe structures. Our aims were to characterize the resting-state functional connectivity of medial temporal lobe sub-structures in older adults, and evaluate whether specific substructural (rather than global) functional connectivity relates to memory function. METHODS: In 15 adults (mean age: 69 years), we evaluated the resting state functional connectivity of medial temporal lobe substructures: dentate/Cornu Ammonis (CA) 4, CA1, CA2/3, subiculum, the molecular layer, entorhinal cortex, and parahippocampus. We used 7-Tesla susceptibility weighted imaging and magnetization-prepared rapid gradient echo sequences to segment substructures of the hippocampus, which were used as structural seeds for examining functional connectivity in a resting BOLD sequence. We then assessed correlations between functional connectivity with memory performance (short and long delay free recall on the California Verbal Learning Test [CVLT]). RESULTS: All the seed regions had significant connectivity within the temporal lobe (including the fusiform, temporal, and lingual gyri). The left CA1 was the only seed with significant functional connectivity to the amygdala. The left entorhinal cortex was the only seed to have significant functional connectivity with frontal cortex (anterior cingulate and superior frontal gyrus). Only higher left dentate-left lingual connectivity was associated with poorer CVLT performance (Spearman r = -0.81, p = 0.0003, Benjamini-Hochberg false discovery rate: 0.01) after multiple comparison correction. CONCLUSIONS: Rather than global hyper-connectivity of the medial temporal lobe, left dentate-lingual connectivity may provide a specific assay of medial temporal lobe hyper-connectivity relevant to memory in aging.

Longitudinal changes in physical function and physical activity in older adults.

BACKGROUND: physical function (PF) and physical activity (PA) both decline as adults age and have been linked to negative outcomes, including dementia, depression and cardiovascular diseases. Although declines in each are associated with numerous negative outcomes, the longitudinal relationship between these two measures is unclear. OBJECTIVE: to examine the dynamic, bidirectional associations between declines in PF and PA. DESIGN: prospective cohort. SETTING: the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. SUBJECTS: about 1,404 men and women, 76.96 ± 7.2 years, 62.4% female and 95.2% white. METHODS: over nine annual assessment cycles, PF was evaluated via the timed Up-and-Go task and PA via a self-reported questionnaire. Piecewise latent growth models examined bidirectional associations between PA and PF to determine whether the initial values (intercept) or early slope (cycles 1-5) (in either PF or PA) predicted later slope (cycles 5-9) (in either PF or PA). RESULTS: initial PF significantly predicted early (standardised ß= -0.10, P < 0.001) and later (standardised ß= -0.09, P = 0.01) PA slopes. Initial PA significantly predicted later (standardised ß = -0.09, P = 0.04) but not early PF slope. Associations were independent of baseline memory test scores, baseline cognitive status, later cognitive status and age. Early physical function slope neither predicts later PA slope nor did early PA slope predict later PF slope (both P values >0.10). CONCLUSIONS: the relationship between PF and PA is bidirectional, with PF more consistently predicting declines of PA, both in the short- and long-term. Intervening on PF impairments may improve PA engagement, which could in turn promote PF and translate to beneficial effects on cognitive function, cardiovascular health and mood.

Regional Gray Matter Volumes as Related to Psychomotor Slowing in Adults with Type 1 Diabetes.

OBJECTIVE: Psychomotor slowing is a common cognitive complication in type 1 diabetes (T1D), but its neuroanatomical correlates and risk factors are unclear. In nondiabetic adults, smaller gray matter volume (GMV) and presence of white matter hyperintensities are associated with psychomotor slowing. We hypothesize that smaller GMV in prefronto-parietal regions explains T1D-related psychomotor slowing. We also inspect the contribution of microvascular disease and hyperglycemia. METHODS: GMV, white matter hyperintensities (WMH), and glucose levels were measured concurrently with a test of psychomotor speed (Digit Symbol Substitution Test [DSST]) in 95 adults with childhood-onset T1D (mean age/duration = 49/41 years) and 135 similarly aged non-T1D adults. Linear regression models tested associations between DSST and regional GMV, controlling for T1D, sex, and education; a bootstrapping method tested whether regional GMV explained between-group differences in DSST. For the T1D cohort, voxel-based and a priori regions-of-interest methods further tested associations between GMV and DSST, adjusting for WMH, hyperglycemia, and age. RESULTS: Bilateral putamen, but no other regions examined, significantly attenuated DSST differences between the cohorts (bootstrapped unstandardized indirect effects: -3.49, -3.26; 95% confidence interval = -5.49 to -1.80, -5.29 to -1.44, left and right putamen, respectively). Among T1D, DSST was positively associated with GMV of bilateral putamen and left thalamus. Neither WMH, hyperglycemia, age, nor other factors substantially modified these relationships. CONCLUSIONS: For middle-aged adults with T1D and cerebral microvascular disease, GMV of basal ganglia may play a critical role in regulating psychomotor speed, as measured via DSST. Studies to quantify the impact of basal ganglia atrophy concurrent with WMH progression on psychomotor slowing are warranted.

Hippocampal Response to a 24-Month Physical Activity Intervention in Sedentary Older Adults.

BACKGROUND: Greater hippocampal volume is observed in healthy older adults after short-term structured exercise. Whether long-term exposure to real-world physical activity (PA) programs has similar effects for sedentary older adults with impaired mobility and comorbid conditions is not known. HYPOTHESIS: A long-term moderate intensity regimen of PA is related to larger volume of the hippocampus in older adults at risk for mobility disability. We further explore whether these associations are modified by factors known to be related to dementia. METHODS: Twenty-six sedentary adults at risk for mobility disability participated in a 24-month randomized intervention program of physical activity (PA, N = 10, age: 74.9 years, 7 women) or health education (HE, N = 16, age: 76.8 years, 14 women). Volumes of total hippocampus, dentate gyrus, and cornu ammonis were measured at baseline and at 24-month follow-up using 7-Tesla magnetic resonance imaging. Between-group volumetric differences at 24 months were adjusted for sessions attended and baseline volumes. The contribution of each dementia-related factor was tested separately for education, APOE, diabetes, cardiovascular diseases, white matter hyperintensities, and brain atrophy. RESULTS: Between-group differences were significant for left hippocampus, left cornu ammonis, and right hippocampus. Adjustment for regional baseline volume attenuated the associations to statistically nonsignificant for right hippocampus and left conru ammonis; associations for left hippocampus were robust for all adjustments. Results were similar after adjustment for dementia-related factors. CONCLUSIONS: In this group of sedentary older adults there was a hippocampal response to a long-term program of moderate-intensity PA. Future studies should examine whether hippocampal response could explain the beneficial effects of PA on cognition for vulnerable older adults.

Neighborhood Socioeconomic Status and Cognitive Function in Late Life.

Neighborhood socioeconomic status (NSES) is associated with cognitive function, independently of individual demographic, health, and socioeconomic characteristics. However, research has been largely cross-sectional, and mechanisms of the association are unknown. In 1992-1993, Cardiovascular Health Study participants (n = 3,595; mean age = 74.8 years; 15.7% black) underwent cognitive testing and magnetic resonance imaging of white matter hyperintensities (WMH), and their addresses were geocoded. NSES was calculated using 1990 US Census data (block groups; 6 measures of wealth, education, and occupation). The Modified Mini-Mental State Examination (3MS) was used to assess general cognition, and the Digit Symbol Substitution Test (DSST) was used to assess speed of processing annually for 6 years. Associations of race-specific NSES tertiles with 3MS, DSST, and WMH were estimated using linear mixed-effects models accounting for geographic clustering, stratified by race, and adjusted for demographic, health, and individual socioeconomic status (education, income, lifetime occupational status) variables. In fully adjusted models, higher NSES was associated with higher 3MS scores in blacks (mean difference between highest and lowest NSES = 2.4 points; P = 0.004) and whites (mean difference = 0.7 points; P = 0.02) at baseline but not with changes in 3MS over time. NSES was marginally associated with DSST and was not associated with WMH. Adjustment for WMH did not attenuate NSES-3MS associations. Associations of NSES with cognition in late adulthood differ by race, are not explained by WMH, and are evident only at baseline.