Search

Purpose: Declining energy and increasing fatigue, common in older age, predict neurodegenerative conditions, but their neural substrates are not known. We examined brain resting state connectivity in relation to declining self-reported energy levels (SEL) and occurrence of fatigue over time., Methods: We examined resting-state functional MRI in 272 community dwelling older adults participating in the Health Aging and Body Composition Study (mean age 83 years; 57.4 % female; 40.8 % Black) with measures of fatigue and SEL collected at regular intervals over the prior ten years. Functional connectivity (FC) between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with prior fatigue state (reporting fatigue at least once or never reporting fatigue), and with SEL decline (divided into stable or declining SEL groups) and adjusted for demographic, physical function, mood, cognition, and comorbidities., Results: Higher cortico-striatal FC in the right limbic network was associated with lower odds of reporting fatigue (better) at least once during the study period (adjusted odds ratio [95 % confidence interval], p-value: (0.747 [0.582, 0.955], 0.020), independent of SEL. Higher cortico-striatal FC in the right executive network was associated with higher odds of declining SEL (worse) during the study period (adjusted odds ratio [95 % confidence interval], p-value: (1.31 [1.01, 1.69], 0.041), independent of fatigue. Associations with other networks were not significant., Conclusions: In this cohort of older adults, the cortico-striatal functional connectivity of declining SEL appears distinct from that underlying fatigue. Studies to further assess the neural correlates of energy and fatigue, and their independent contribution to neurodegenerative conditions are warranted., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Age-related mobility limitations are debilitating and common. Cerebral white matter hyperintensities (WMH) and conditions affecting other systems are known contributors, but have been studied in isolation., Methods: In 2,703 adults aged 65 years or older, we assessed cross-sectional and longitudinal gait speed and mobility disability (self-reported difficulty walking half mile) in those with and without high burden of MRI-defined WMH along with six other conditions (OCs) affecting mobility: gender-specific weak grip; poor self-reported vision; gender-specific lowest quartile of forced vital capacity; self-reported joint pain; ankle-arm index less than 0.9; and body mass index (BMI) greater than 30 kg/m2. Separate regression models adjusted for age, gender, and race were repeated for each OC and based on a 4-level predictor: -WMH/-OC; -WMH/+OC; +WMH/-OC; and +WMH/+OC., Results: Gait speed was fastest in those with -WMH/-OC and slowest for those with +WMH/+OC. Gait speed was similar for either WMH or one of the OC (p range: .07-.9), except for BMI. Those with a high BMI had slower gait speed than those with WMH (p = .01). Declines in gait speed over 6 years were similar for all groups. Results for both prevalent and incident mobility disability showed that associations for WMH and OC were similar for weak grip, poor vision, and low forced vital capacity (p range: .1-.7). Having joint pain, low ankle-arm index, or high BMI was associated with higher prevalent and incident mobility disability compared with having WMH (p range: <.001-.02)., Conclusions: Cerebral WMH should be considered along with conditions affecting mobility from other systems when considering risk and treatment for mobility limitations., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The development of Type 1 diabetes mellitus (T1DM) within the first 7 years of life has been linked to poorer cognitive performance. Adults with T1DM have altered functional brain connectivity, but no studies have examined whether earlier age of T1DM onset is associated with functional connectivity later in life. Accordingly, we tested the relationship between age of onset and resting state functional connectivity in a cohort of middle-aged adults with childhood-onset T1DM., Methods: Participants were from a subsample of the Pittsburgh Epidemiology of Diabetes Complications cohort and included 66 adults (mean age = 47.54 years, 32 men). Resting state blood oxygen level-dependent activity was used to calculate mean connectivity for eight functional brain networks. A multivariate analysis of variance examined associations between age of onset and network connectivity. Diffusion tensor and fluid-attenuated inversion recovery images were analyzed to identify microstructural alterations and white-matter hyperintensity volumes., Results: Later childhood onset of T1DM was associated with lower connectivity (F(8,57) = 2.40, p = .026). A significant interaction was present for current age such that an inverse association with age of onset for functional connectivity was present in older individuals (F(8,55) = 2.88, p = .035). Lower connectivity was associated with older age, increased white-matter hyperintensity volume, and lower microstructural integrity., Conclusions: Diagnosis of T1DM later in childhood may be associated with lower brain functional connectivity, particularly in those surviving into older ages. These alterations may be an early marker for subsequent cognitive decrements. Future studies are warranted to understand the pathways underlying these associations.

Objective: To assess whether the volume of callosal hyperintensities in the genu and splenium of older adults with mobility impairment is differentially associated with the degree of gain in gait speed after 2 types of gait interventions., Design: Single-blind randomized controlled trial of 2 types of gait exercises in older adults., Setting: Research center in an academic institution., Participants: Ambulatory adults (N=44) aged ≥65 years with a slow and variable gait., Intervention: Twelve-week physical therapist-guided trial of a conventional walking, endurance, balance, and strength (WEBS) intervention (n=20) versus a timing and coordination of gait (TC) intervention (n=22)., Main Outcome Measure: Gain in gait speed after the intervention and its relation to callosal hyperintensities in the genu and splenium of the corpus callosum., Results: Gait speed improved in both the WEBS group (mean change, 0.16m/s) and the TC group (mean change, 0.21m/s; both P<.05). The volume of white matter hypertintensities (WMHs) in the genu was differentially associated with gait speed gain (group × genual WMH interaction, P=.05). Greater genual WMH volume was related to a smaller gait speed gain in the WEBS group (P=.01) but not in the TC (P=.10) group. Splenial WMH volume was not differentially associated with gait speed gain (interaction, P=.90)., Conclusions: Callosal hyperintensities differentially influence gait speed gain by the type of gait rehabilitation. Mobility impaired older adults with genual hyperintensities may benefit from a rehabilitation program focused on motor skill learning rather than on strength and endurance training., (Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (ROIs) in a group of community-dwelling elders with and without diabetes., Research Design and Methods: MRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized β values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROIs. Models were adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total brain volume (TBV)., Results: In multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMHs. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results., Conclusions: In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline.

Background: Short-term adherence to physical activity (PA) in older adults improves psychomotor processing abilities and is associated with greater brain activation. It is not known whether these associations are also significant for longer-term adherence to moderate-intensity activities., Methods: We measured the cross-sectional association of regular walking with brain activation while performing the digit symbol substitution test (DSST). Participants of the lifestyle interventions and independence for elders-pilot study were examined 2 years after completing a 1-year treatment, consisting of either PA or education in successful aging (SA). Data were obtained from 20 PA participants who reported having remained active for 2 years after the end of the treatment and from 10 SA participants who reported having remained sedentary during the same period (mean age: 81.5 and 80.8 years). Complete brain activation and behavioral data were available for 17 PA and 10 SA participants., Results: Two years after the formal intervention had ended, the PA group engaged in more minutes of moderate activity and had significantly greater DSST score and higher brain activation within regions important for processing speed (left dorsolateral prefrontal, posterior parietal, and anterior cingulate cortices). Associations were independent of self-reported health, blood pressure, cognition, medication records, gray matter atrophy, and white matter hyperintensities., Conclusions: Persistent engagement in PA may have beneficial effects on psychomotor processing speed and brain activation, even for moderate levels and even when started late in life. Future studies are warranted to assess whether these beneficial effects are explained by delayed neuronal degeneration and/or new neurogenesis.

Context: Older adults responding to executive control function (ECF) tasks show greater brain activation on functional MRI (fMRI). It is not clear whether greater fMRI activation indicates a strategy to compensate for underlying brain structural abnormalities while maintaining higher performance., Objective: To identify the patterns of fMRI activation in relationship with ECF performance and with brain structural abnormalities., Design: Cross-sectional analysis., Main Variables of Interest: fMRI activation, accuracy while performing an ECF task (Digit Symbol Substitution Test), and volume of white matter hyperintensities and of total brain atrophy., Setting: Cohort of community-dwelling older adults., Participants: Data were obtained on 25 older adults (20 women, 81 years mean age)., Outcome Measure: Accuracy (number of correct response/total number of responses) while performing the Digit Symbol Substitution Test., Results: Greater accuracy was significantly associated with greater peak fMRI activation, from ECF regions, including left middle frontal gyrus and right posterior parietal cortex. Greater WMH was associated with lower activation within accuracy-related regions. The interaction of accuracy by white matter hyperintensity volume was significant within the left posterior parietal region. Specifically, the correlation of white matter hyperintensity volume with fMRI activation varied as a function of accuracy and it was positive for greater accuracy. Associations with brain atrophy were not significant., Conclusions: Recruitment of additional areas and overall greater brain activation in older adults is associated with higher performance. Posterior parietal activation may be particularly important to maintain higher accuracy in the presence of underlying brain connectivity structural abnormalities., (Copyright 2009 Elsevier Inc. All rights reserved.)

Background and Purpose: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer's disease (AD) among cognitively normal older adults., Methods: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60% women, 81% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD., Results: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions., Conclusions: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.

White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy-connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P<0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies (e.g. [Taylor, W.D., MacFall, J.R., Steffens, D.C., Payne, M.E., Provenzale, J.M., Krishnan, K.R., 2003. Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (3), 539-544.]), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large NeuroImage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders.

Objectives: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance., Design: Longitudinal analysis, average follow-up time: 4.0 years., Setting: Cardiovascular Health Study (CHS)., Participants: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4)., Measurements: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand)., Results: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed., Conclusion: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.

Background: Attentional control of executive cognitive function (ECF) decreases in older individuals with Alzheimer Disease (AD). In order to examine early AD-related changes in the neural substrates of ECF attentional control, we measured activation dorsolateral prefrontal (dLPFC), posterior parietal (PPC), and anterior cingulate cortex (ACC) in adults with mild cognitively impairment (MCI) and in cognitively normal (CN) adults., Methods: Functional magnetic resonance imaging analysis of brain activation in MCI (n = 8, mean age 79.5) and CN (n = 8 mean age 81.5) during increasing loads of attentional demands., Results: MCI and CN older adults performed with similar accuracy and reaction time. MCI had greater activation than CN in PPC (right p = .03 and left p = .05) and dlPFC areas (right p = .002 and left p = .004), while activation in ACC was similar in the two groups. Response to increasing loads of the task differed by group: MCI selectively engaged bilateral PPC (right p = .03, left p = .04), while CN subjects increased bilateral dlPFC activation (right p = .005 and left p = .02) and ACC activation (p = .04). Among MCI, greater load-related changes in PPC activity were associated with smaller load-related changes in accuracy rates (r = -.85, p = .07) and greater increases in reaction times (r = .97, p = .01). In CN subjects, load-related change in PPC activation was associated with load-related change in reaction time (r = .76, p = .02) but not with changes in accuracy rates., Conclusions: PPC and dlPFC may show early functional changes associated with MCI.

Objectives: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/mild cognitive impairment)., Design: Cross-sectional., Setting: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults., Participants: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS., Measurements: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status., Results: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status., Conclusion: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status.

Recent positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies in humans have localized the frontal eye field (FEF) to the precentral sulcus (PCS). In macaque monkeys, low-threshold microstimulation and single unit recording studies have located a saccadic subregion of FEF in a restricted area along the anterior wall of the arcuate sulcus and a pursuit subregion located deeper in the sulcus close to the fundus. The functional organization and anatomical location of these two FEF subregions are still to be defined in humans. In the present study, we used fMRI with high spatial resolution image acquisition at 3.0 Tesla to map the saccade- and pursuit-related areas of FEF within the two walls of the PCS in 11 subjects. We localized the saccade-related area to the upper portion of the anterior wall of the precentral sulcus and the pursuit-related area to a deeper region along the anterior wall, extending in some subjects to the fundus or deep posterior wall. These findings localize distinct pursuit and saccadic subregions of FEF in humans and demonstrate a high degree of homology in the organization of these FEF subregions in the human and the macaque monkey.

IntroductionMild parkinsonian signs (MPS) are associated with morbidity. Identification of MPS progression markers may be vital for preventive management, yet has not been pursued. This study aimed to ascertain clinical/neuroimaging features predictive of MPS progression.Methods205 participants in the Health ABC Study were included. MPS was defined using published guidelines. MPS progression was evaluated by determining UPDRS-III change between baseline and follow-up ≥2 years later. Standard brain MRI and DTI were obtained at baseline. Correlation coefficients between demographics, vascular risk factors, imaging markers, and UPDRS-III change were adjusted for follow-up time. Linear regression was used to adjust for possible confounders in the relationship between imaging markers and MPS progression.Results30% of participants had baseline MPS. Demographics and risk factors did not differ significantly between participants with MPS (MPS+) and without MPS (MPS-). Mean follow-up time was 3.8±0.8 years. Older age, male gender, diabetes were associated with faster rate of UPDRS-III change in MPS- but not MPS+ participants. Among MPS- participants, the only imaging marker associated with faster UPDRS-III progression was higher gray matter mean diffusivity (MD), widespread in various cortico-subcortical bihemispheric regions, independent of age, gender, diabetes. No imaging features were associated with UPDRS-III change among MPS+ participants.ConclusionsLower gray matter integrity predicted MPS progression in those who did not have baseline MPS. Microstructural imaging may capture early changes related to MPS development, prior to macrostructural change. Any future management promoting gray matter preservation may inhibit MPS development.

BackgroundPhysical activity (PA) is a promising strategy for the promotion of brain health, although substantial variation exists in the effects of PA at the individual level. Given the greater prevalence and faster progression of Alzheimer's disease in women compared to men, and known sex differences in brain architecture, analysis of sex differences in the relationship between PA, cognition, and brain region volumes is warranted.MethodsTo address this, we conducted secondary analyses of data from the Health, Aging, and Body Composition study. To determine whether longitudinal changes in PA over 10 years predicted declines in global cognitive functioning and executive functions and processing speed differently in males and females, latent growth curve modeling was utilized. Magnetic resonance imaging was performed at year 10, and the hippocampus and dorsolateral prefrontal cortex were identified as regions of interest.ResultsMaintaining PA over 10 years predicted less declines in executive functions and processing speed in females but not males. Maintaining PA over 10 years was significantly associated with greater volume of the left dorsolateral prefrontal cortex, a brain region involved in executive functions, in year 10 in females only. Maintaining physical activity was associated with better global cognitive function in both males and females, and also predicted volume of the left hippocampus, albeit in different directions with females showing a negative relationship and males showing a positive relationship.ConclusionsThese findings suggest that the relationship of PA with cognition and its neurobiological correlates differ by sex, with females apparently benefiting from PA to a greater extent than males. Development of personalized, tailored exercise recommendations to promote healthy brain aging should account for sex differences.

ObjectiveMild parkinsonian signs (MPS) are an underappreciated neurologic condition in older adults; we assessed associations of MPS with measures of dopaminergic (catechol-O-methyltransferase [COMT] genotype, an indicator of synaptic dopamine levels) and vascular (white matter hyperintensities [WMH], an indicator of cerebral small vessel disease) factors.MethodsIn a cohort of older adults (mean age 82.6 years [SD 2.6]; 58.0% female; 38.8% black), we assessed cross-sectional associations of WMH volume and COMT Val158Met (rs4680) genotype (n = 35 Met/Met, n = 180 Val carriers) with MPS by regression models adjusted for demographic and health characteristics. Interactions between WMH and COMT were assessed and analyses were repeated stratified by COMT genotype (Met/Met related to higher synaptic dopamine vs Val carriers related to lower synaptic dopamine).ResultsMPS was present in 42.3% of our sample. WMH (odds ratio [OR] 1.16, confidence interval [CI] 1.05-1.27) but not COMT (Met/Met compared to Val carrier: OR 0.62, CI 0.27-1.42) was related to MPS. There was a significant interaction between WMH and COMT (p = 0.03). Stratified analyses reveled a strong association between WMH and MPS among COMT Val carriers (OR 1.23, CI 1.09-1.38), but not for Met/Met (OR 0.68, CI 0.45-1.02), independent of covariates.ConclusionsWMH had a direct relation with MPS. In contrast, COMT was not associated with MPS, but it did modify the effect of WMH on MPS. The dopaminergic system may provide compensation for the effects of WMH on MPS. These findings suggest that MPS has a vascular rather than dopaminergic origin in older adults, but both factors are important in MPS manifestation.

ObjectiveTo identify the shared neuroimaging signature of gait slowing and cognitive impairment.MethodsWe assessed a cohort of older adults (n = 175, mean age 73 years, 57% female, 65% white) with repeated measures of gait speed over 14 years, MRI for gray matter volume (GMV) at year 10 or 11, and adjudicated cognitive status at year 14. Gait slowing was calculated by bayesian slopes corrected for intercepts, with higher values indicating faster decline. GMV was normalized to intracranial volume, with lower values indicating greater atrophy for 10 regions of interest (hippocampus, anterior and posterior cingulate, primary and supplementary motor cortices, posterior parietal lobe, middle frontal lobe, caudate, putamen, pallidum). Nonparametric correlations adjusted for demographics, comorbidities, muscle strength, and knee pain assessed associations of time to walk with GMV. Logistic regression models calculated odds ratios (ORs) of gait slowing with dementia or mild cognitive impairment with and without adjustment for GMV.ResultsGait slowing was associated with cognitive impairment at year 14 (OR per 0.1 s/y slowing 1.47; 95% confidence interval 1.04-2.07). The right hippocampus was the only region that was related to both gait slowing (ρ = -0.16, p = 0.03) and cognitive impairment (OR 0.17, p = 0.009). Adjustment for right hippocampal volume attenuated the association of gait slowing with cognitive impairment by 23%.ConclusionsThe association between gait slowing and cognitive impairment is supported by a shared neural substrate that includes a smaller right hippocampus. This finding underscores the value of long-term gait slowing as an early indicator of dementia risk.

BackgroundAssociations between orthostatic blood pressure and cognitive status (CS) have been described with conflicting results.ObjectiveWe hypothesize that long-term exposure to lower orthostatic blood pressure is related to having worse CS later in life and that atrophy of regions involved in central regulation of autonomic function mediate these associations.MethodsThree-to-four measures of orthostatic blood pressure were obtained from 1997-2003 in a longitudinal cohort of aging, and average systolic orthostatic blood pressure response (ASOBPR) was computed as % change in systolic blood pressure from sit-to-stand measured at one minute post stand. CS was determined in 2010-2012 by clinician-adjudication (n = 240; age = 87.1±2.6; 59% women; 37% black) with a subsample also undergoing concurrent structural neuroimaging (n = 129). Gray matter volume of regions related to autonomic function was measured. Multinomial regression was used to compare ASOBPR in those who were cognitively intact versus those with a diagnosis of mild cognitive impairment or dementia, controlling for demographics, trajectories of seated blood pressure, incident cardiovascular risk/events and medications measured from 1997 to 2012. Models were repeated in the subsample with neuroimaging, before and after adjustment for regional gray matter volume.ResultsThere was an inverse association between ASOBPR and probability of dementia diagnosis (9% lower probability for each % point higher ASOBPR: OR 0.91, CI95%  = 0.85-0.98; p = 0.01). Associations were similar in the subgroup with neuroimaging before and after adjustment for regional gray matter volume.ConclusionASOBPR may be an early marker of risk of dementia in older adults living in the community.

ObjectiveTo examine the relationship between gait speed and prior 10 years interleukin-6 (IL-6) burden in older adults. We then assessed whether white matter characteristics influence this relationship.MethodsIn 179 community-dwelling older adults, gait speed was assessed on an automated walkway and serum IL-6 was assayed on ELISA. Concurrently, white matter characteristics were assessed on MRI by quantifying volume of white matter hyperintensities (WMH), a marker of small vessel disease, and normal-appearing white matter on fractional anisotropy (NAWM-FA), a marker of axonal integrity. IL-6 was assayed at regular intervals at gait assessment and over the prior 10 years and estimates of sustained 10-year IL-6 exposure and the rate of change in IL-6 over 10 years were obtained. Multivariate linear regressions were used to examine the relationships among sustained IL-6 exposure, rate of change in IL-6, gait speed, and white matter characteristics.ResultsIn this sample (age 83 years, 58% female, 41% black, gait speed 0.9 m/s), higher sustained IL-6 levels, but not the rate of change in IL-6 or IL-6 at gait assessment, was significantly related to slower gait (β = -0.27, p < 0.001) and to higher WMH (β = 0.23, p = 0.002), but not NAWM-FA, withstanding covariate adjustments. WMH accounted for 30% attenuation in the relationship between higher sustained IL-6 levels and slower gait speed (p = 0.043) in the mediation analyses.ConclusionsSustained exposure to high IL-6 over 10 years rather than the rate of change in IL-6 or an isolated high IL-6 level may adversely affect gait speed by influencing cerebral WMH.

The neuroprotective effects of physical activity (PA) are consistently shown in older adults, but the neural substrates, particularly in white matter (WM), are understudied, especially in very old adults with the fastest growth rate and the highest risk of dementia. This study quantified the association between PA and WM integrity in adults over 80. The moderating effects of cardiometabolic conditions, physical functional limitations and WM hyperintensities were also examined, as they can affect PA and brain integrity. Fractional anisotropy (FA) from normal-appearing WM via diffusion tensor imaging and WM hyperintensities were obtained in 90 participants (mean age = 87.4, 51.1% female, 55.6% white) with concurrent objective measures of steps, active energy expenditure (AEE in kcal), duration (min), and intensity (metabolic equivalents, METs) via SenseWear Armband. Clinical adjudication of cognitive status, prevalence of stroke and diabetes, systolic blood pressure, and gait speed were assessed at time of neuroimaging. Participants were on average sedentary (mean ± SD/day: 1766 ± 1345 steps, 202 ± 311 kcal, 211 ± 39 min, 1.8 ± 1.1 METs). Higher steps, AEE and duration, but not intensity, were significantly associated with higher FA. Associations were localized in frontal and temporal areas. Moderating effects of cardiometabolic conditions, physical functional limitations, and WM hyperintensities were not significant. Neither FA nor PA was related to cognitive status. Older adults with a sedentary lifestyle and a wide range of cardiometabolic conditions and physical functional limitations, displayed higher WM integrity in relation to higher PA. Studies of very old adults to quantify the role of PA in reducing dementia burden via WM integrity are warranted.

Protracted systemic inflammation has been associated with adverse effects on cognition and brain structure and may accelerate neurodegenerative disease processes; however, it is less clear whether changes in inflammation are associated with brain structure. We studied 276 black and white older adults (mean age = 83 years at time of imaging) enrolled in a prospective study of aging. Inflammation (measured with c-reactive protein, CRP) was assessed repeatedly over 6 years (i.e., year 2, 4, 6, and 8). Brain magnetic resonance imaging (MRIs) were obtained at years 10-11 with diffusion tensor imaging; regions of interest included late-myelinating areas vulnerable to aging, including frontal-parietal (superior longitudinal fasciculus [SLF]-dorsal) and temporal (SLF-temporal; uncinate) white matter tracts. Mean CRP values significantly declined (t = -5.54, p < 0.0001) over 6 years, and subject-specific slopes (best linear unbiased predictors of slopes) all showed a decline (mean = -0.57, standard deviation = 0.53) for our participant sample. More than 50% of study participants were still in the moderate to high cardiovascular risk range based on CRP values at year 8. After controlling for demographics, vascular risk factors and MRI white matter hyperintensities, larger decreases in CRP values over time were significantly associated with higher fractional anisotropy in the SLF-dorsal (beta = -0.0052, standard error [SE] = 0.003; 95% confidence interval [CI] = -0.0103 to -0.0025, p = 0.04), SLF-temporal (beta = -0.0109, SE = 0.004; 95% CI = -0.0189 to -0.0029, p = 0.008), and uncinate (beta = -0.0067, SE = 0.003; 95% CI = -0.0132 to -0.0001, p = 0.05) fasciculi. Results suggest that in a prospective cohort of older individuals, faster declines in inflammation over time are related to indicators of white matter health, even after accounting for vascular risk factors.

In older adults, depressive symptoms are associated with lower quality of life, high morbidity and mortality. This study aims to identify brain magnetic resonance imaging (MRI) features associated with late-life depressive symptoms in the population. Older community-dwelling adults (n=314) from the Health ABC study underwent brain MRI. Logistic regression was used to characterize the relationships between depressive symptoms (Center for Epidemiologic Studies of Depression scale, CES-D) and the following whole-brain variables: white matter hyperintensity (WMH) burden, fractional anisotropy (FA), and gray matter volume (GMV). Analyses examining possible regional differences between the CES-D groups controlled for Modified Mini-Mental State Examination score and diabetes status. The relative importance of localization of the markers was examined by comparing the distribution of significant peaks across the brain. Each whole-brain variable showed loss of integrity associated with high CES-D. For GMV, the odds ratio (OR)=0.84 (95% confidence interval (CI) 0.74, 0.96); for FA, OR=0.714 (95% CI 0.57, 0.88); for WMH, OR=1.89 (95%CI 1.33, 2.69). Voxel-wise analyses and patterns of peak significance showed non-specific patterns for white matter measures. Loss of GMV was most significant in the bilateral insula and anterior cingulate cortex. This study supports a cerebrovascular pattern for depressive symptoms in older adults. The localization of gray matter changes to the insula, a watershed area and a hub of affective circuits, suggests an etiological pathway from ischemia to increased depressive burden.

OBJECTIVE: To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (ROIs) in a group of community-dwelling elders with and without diabetes. RESEARCH DESIGN AND METHODS: MRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized β values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROIs. Models were adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total brain volume (TBV). RESULTS: In multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMHs. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results. CONCLUSIONS: In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline.

Summary: 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. [ABSTRACT FROM AUTHOR]

Background: Cognitive reserve (CR) protects against cognitive decline and dementia but its relation to mobility impairment has not been established. To address this important gap in the literature, we conducted a longitudinal investigation to test the hypothesis that higher baseline CR was associated with a lower risk of developing mobility impairment in older adults. Methods: Participants were dementia‐free older adults who received brain magnetic resonance imaging and had gait speed assessments during follow‐up. Using the residuals approach, CR was computed as the variance in the Modified Mini‐Mental Status Examination total score, that was left after accounting for structural brain integrity, education, and race. Mobility impairment was defined using a validated cutoff score in gait speed of 0.8 m/s. Logistic regression models using general estimating equations were utilized to examine longitudinal associations between baseline CR and the risk of developing mobility impairment across repeated assessments. Results: Of the participants (n = 237; mean age = 82 years; %female = 56%) who were free of mobility impairment at baseline, 103 developed mobility impairment during follow‐up (mean = 3.1 years). Higher CR at baseline was associated with a lower risk of developing incident mobility impairment—odds ratio (OR) = 0.819, 0.67–0.98, p = 0.038 (unadjusted); OR = 0.815, 0.67–0.99, p = 0.04 (adjusted for socio‐demographic variables and depression); OR = 0.819, 0.68–0.88, p = 0.035 (adjusted for illness history); OR = 0.824, 0.68–0.99, p = 0.045 (adjusted for white matter hyperintensities); OR = 0.795, 0.65–0.95, p = 0.016 (adjusted for falls history). Conclusion: Higher CR at baseline was protective against developing incident mobility impairment during follow‐up among community‐residing older adults. [ABSTRACT FROM AUTHOR]

Objective Social engagement (SE) may protect against cognitive decline in older adults. We estimate associations of SE with gray matter (GM) microstructure in regions of interest (ROI) relevant to social cognition, among community-dwelling older adults. Method Cross-sectional analysis of 293 Health ABC study participants who underwent 3 Tesla magnetic resonance imaging with diffusion tensor and free from cognitive impairment was conducted. Linear regression models tested associations between SE index (marital status, not living alone, social activities, work, and volunteering) and mean diffusivity (MD) of GM ROIs, adjusted for age, race, gender, and education. Hearing and activities of daily living (ADL) difficulties were tested as confounders. Effect modification by gender was tested with interaction terms and stratification by gender. Results Higher SE was significantly related to lower MD (greater GM microstructural integrity) (shown as standardized estimate [ p -value]) in left middle frontal gyrus-orbital part: −.168 (.005), left caudate nucleus: −.141 (.02), left temporal pole-middle temporal gyrus: −.136 (.03), right middle frontal gyrus: −.160 (.006), right superior frontal gyrus-orbital part: −.187 (.002), and right middle frontal gyrus-orbital part: −.124 (.04), when adjusted for demographic attributes. Associations were robust to adjustments for hearing or ADL difficulty. There was significant effect modification by gender for some ROIs, with associations only for females. Discussion SE is related to greater microstructural integrity of specific GM regions relevant to social cognition, that have described roles in dementia. SE may therefore be a useful preventive mechanism against loss of GM integrity in older adults. [ABSTRACT FROM AUTHOR]

Background: Walking speed during fast-paced walking task has been associated with cognitive function. It is unclear what underlying brain structures are related to fast-paced walking. We investigated the association of gray matter (GM) density with fast-paced walking speed and usual-paced walking speed.Methods: We collected data from 284 older adults from a subset of the Health, Aging, and Body composition study (mean age = 83 [SD = 2.8], 58% women, 41% black). Voxel-wise analyses on magnetic resonance imaging data identified regions of the brain where GM density was associated with fast-paced walking speed. We then extracted GM density for all identified regions and modeled the association with fast-paced walking speed after adjusting for demographic factors, clinical factors, and cognitive function. Analyses were repeated for usual-paced walking. Regions with beta coefficients ≥0.3 m/s were considered to be meaningfully correlated.Results: GM density of clusters from cortical regions in the right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus were positively correlated with fast-paced walking speed in adjusted models. Adjustment for cognitive function had little impact on the findings. Caudate was correlated with usual paced walking speed at coefficient ≥0.3 m/s after adjustment of demographic factors and clinical factors, but not after further adjustment of cognitive function.Conclusions: Fast-paced walking speed was correlated with GM density of right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus, and could potentially provide evidence about subclinical structural change of brain related to aging. [ABSTRACT FROM AUTHOR]

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 β = -0.43, 95% confidence interval: -0.73, -0.14) and lower posterior parietal GMV (per standard deviation β = 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. [ABSTRACT FROM AUTHOR]

Adults with homozygous sickle cell anemia have, on average, lower cognitive function than unaffected controls. The mechanisms underlying cognitive deterioration in this population are poorly understood, but cerebral small vessel disease (CSVD) is likely to be implicated. We conducted a systematic review using the Prisma Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of articles that included both measures of cognitive function and magnetic resonance imaging (MRI) neuroimaging markers of small vessel disease. While all five studies we identified reported small vessel disease by MRI, only two of them found a significant relationship between structural changes and cognitive performance. Differences in methodologies and small sample sizes likely accounted for the discrepancies between the studies. We conclude that while MRI is a valuable tool to identify markers of CSVD in this population, larger studies are needed to definitely establish a link between MRI-detectable abnormalities and cognitive function in sickle cell anemia. [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities (WMH), a common marker of cerebral small vessel disease, and lower microstructural integrity of normal-appearing white matter are associated with slower gait. How these cerebral measures interact in relation to slower gait is unknown. We assessed whether microstructural integrity of normal-appearing white matter, measured by fractional anisotropy (FA), moderates the association of higher WMH with slower gait.Methods: WMH, FA, and gait speed were acquired for 265 community-dwelling older adults (average age = 82.9 years).Results: The inverse association between WMH and gait was robust to adjustment for age, gender, muscle strength, obesity, stroke, and hypertension (fully adjusted model: βs = -0.19, p = .001). The interaction between WMH and FA was significant; analyses stratified by FA showed that the inverse association between WMH and gait speed was significant only for those with low FA (FA < median, fully adjusted model: βs = -0.28, p = .001). Voxel-based results were similar for participants with FA less than median, there was an inverse association between gait speed and WMH which extended throughout the white matter (genu and body of corpus callosum, anterior limb of internal capsule, corona radiata, and superior longitudinal and fronto-occipital fasciculus). In contrast, for participants with FA ≥ median, the association was limited to the genu of corpus callosum, the cingulum, and the inferior longitudinal fasciculus.Conclusions: Microstructural integrity is a moderating factor in the association between WMH and gait. Future studies should examine whether higher microstructural integrity represents a source of compensation in those with greater WMH burden to maintain function in late life. [ABSTRACT FROM AUTHOR]

Objectives To examine whether white matter hyperintensities ( WMHs) on brain magnetic resonance imaging ( MRI) in tracts in older adults with mobility impairment are linked to outcomes of gait rehabilitation interventions. Design Twelve-week randomized controlled single-blind trial. Setting University-based mobility research laboratory. Participants Ambulatory adults aged 65 and older with mobility impairment. Intervention A conventional gait intervention focusing on walking, endurance, balance, and strength ( WEBS, n = 21) and a task-oriented intervention focused on timing and coordination of gait ( TC, n = 23). Measurements Self-paced gait speed was measured over an instrumented walkway before and after the intervention, and WMH and brain volumes were quantified on preintervention brain MRI using an automated segmentation process. A white matter tract atlas was overlaid on the segmented images to measure tract WMH volumes, and WMH volumes were normalized to total brain volume. Aggregate WMH volumes in all white matter tracts and individual WMH volumes in specific longitudinal tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus, and fronto-occipital fasciculus) and the cingulum were measured. Results Gait speed gains in the TC group were of the same magnitude, independent of WMH volume measures in all except the cingulum, but in the WEBS group, gain in gait speed was smaller with greater overall tract WMH volumes ( P < .001) and with greater WMH volume in the three longitudinal tracts ( P < .001 to .02). Conclusion Gains in gait speed with two types of gait rehabilitation are associated with individual differences in WMHs. Task-oriented therapy that targets timing and coordination of gait may particularly benefit older adults with WMHs in brain tracts that influence gait and cognition. [ABSTRACT FROM AUTHOR]

Background: slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests.Hypothesis: we hypothesise that slower information processing explains this association, while tests of language or memory will not.Methods: data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index).Results: in linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association.Conclusions: we conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait. [ABSTRACT FROM PUBLISHER]

To examine whether the association between hypertension and decline in gait speed is significant in well-functioning older adults and whether other health-related factors, such as brain, kidney, and heart function, can explain it. Longitudinal cohort study. Cardiovascular Health Study. Of 2,733 potential participants with a brain magnetic resonance imaging (MRI) scan, measures of mobility and systolic blood pressure (BP), no self-reported disability in 1992 to 1994 (baseline), and with at least 1 follow-up gait speed measurement through 1997 to 1999, 643 (aged 73.6, 57% female, 15% black) who had received a second MRI in 1997 to 1999 and an additional gait speed measure in 2005 to 2006 were included. Mixed models with random slopes and intercepts were adjusted for age, race, and sex. Main explanatory factors included white matter hyperintensity progression, baseline cystatin-C, and left cardiac ventricular mass. Incidence of stroke and dementia, BP trajectories, and intake of antihypertensive medications during follow-up were tested as other potential explanatory factors. Higher systolic BP was associated with faster rate of gait speed decline in this selected group of 643 participants, and results were similar in the parent cohort (N=2,733). Participants with high BP (n=293) had a significantly faster rate of gait speed decline than those with baseline BP less than 140/90 mmHg and no history of hypertension (n=350). Rates were similar for those with history of hypertension who were uncontrolled (n=110) or controlled (n=87) at baseline and for those who were newly diagnosed (n=96) at baseline. Adjustment for explanatory factors or for other covariates (education, prevalent cardiovascular disease, physical activity, vision, mood, cognition, muscle strength, body mass index, osteoporosis) did not change the results. High BP accelerates gait slowing in well-functioning older adults over a long period of time, even for those who control their BP or develop hypertension later in life. Health-related measurements did not explain these associations. Future studies to investigate the mechanisms linking hypertension to slowing gait in older adults are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess whether markers of micro- and macrostructural brain abnormalities are associated with slower gait in older men and women independent of each other, and also independent of health-related conditions and of behavioral, cognitive and peripheral function. Methods: Magnetization transfer ratio [MTR], white matter hyperintensities [WMH], brain atrophy [BA] and brain infarcts [BI] were measured in 795 participants of the AGES-Reykjavik Study cohort (mean 75.6 years, 58.9% women). Results: In women, lower MTR, higher WMH and BA, but not BI, remained associated with slower gait independent of each other and of other covariates. In men, WMH and BA, but not MTR or BI, remained associated with slower gait independently of each other. Only muscle strength, executive control function and depression test scores substantially attenuated these associations. Interpretations: MTR in older adults may be an important additional marker of brain abnormalities associated with slower gait. Studies to explore the relationship between brain micro- and macrostructural abnormalities with gait and the role of mediating factors are warranted. [Copyright &y& Elsevier]

Background. In community-dwelling older adults, greater mobility impairment is associated with greater burden of diffuse brain structural abnormalities, such as higher white matter hyperintensities. This study examined the association between gray matter volumes of regions related to motor control, gait, and balance and whether this association is independent of burden of white matter hyperintensities. Methods. A random sample of 327 participants of the Cardiovascular Health Study (78.3 ± 4.1 years old, 57% women) contributed brain magnetic resonance imaging (MRI) and mobility data. A brain imaging automated method measured gray matter volume in cerebellum, basal ganglia, and prefrontal and parietal cortex in both hemispheres. Gait speed was measured while walking 15 feet at usual pace. Standing balance was assessed by timing tandem stance. Associations between each region's volume and gait speed or balance were measured before and after adjustment for demographics, head size, cardiovascular risk factors, and 0-9 grading scores of white matter hyperintensities. Results. Smaller left cerebellum and left prefrontal regions were associated with slower gait, independently of covariates and of white matter hyperintensities. Smaller right putamen, right posterior superior parietal cortex, and both left and right cerebellum were associated with balance difficulty, independently of covariates and white matter hyperintensities. Conclusions. Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities. [ABSTRACT FROM AUTHOR]

Abstract: Atlas-based segmentation of MR brain images typically uses a single atlas (e.g., MNI Colin27) for region identification. Normal individual variations in human brain structures present a significant challenge for atlas selection. Previous researches mainly focused on how to create a specific template for different requirements (e.g., for a certain population). We address atlas selection with a different approach: instead of choosing a fixed brain atlas, we use a family of brain templates for atlas-based segmentation. For each subject and each region, the template selection method automatically chooses the ‘best’ template with the highest local registration accuracy, based on normalized mutual information. The region classification performances of the template selection method and the single template method were quantified by the overlap ratios (ORs) and intraclass correlation coefficients (ICCs) between the manual tracings and the respective automated labeled results. Two groups of brain images and multiple regions of interest (ROIs), including the right anterior cingulate cortex (ACC) and several subcortical structures, were tested for both methods. We found that the template selection method produced significantly higher ORs than did the single template method across all of the 13 analyzed ROIs (two-tailed paired t-test, right ACC at t(8)=4.353, p =0.0024; right amygdala, matched paired t test t(8)>3.175, p <0.013; for the remaining ROIs, t(8)=4.36, p <0.002). The template selection method also provided more reliable volume estimates than the single template method with increased ICCs. Moreover, the improved accuracy of atlas-based segmentation using optimum templates approaches the accuracy of manual tracing, and thus is valid for automated brain imaging analyses. [Copyright &y& Elsevier]

Supplemental digital content is available in the text. Identifying promoters of cerebral small vein integrity is important to counter vascular contributions to cognitive impairment and dementia. Purpose: In this preliminary investigation, the effects of a randomized 24-month physical activity (PA) intervention on changes in cerebral small vein integrity were compared to those of a health education (HE) control. Methods: Cerebral small vein integrity was measured in 24 older adults (n = 8, PA; n = 16, HE) using ultra-high field MRI before and at the end of the 24-month intervention. Deep medullary veins were defined as straight or tortuous; percent change in straight length, tortuous length, and tortuosity ratio were computed. Microbleed count and white matter hyperintensities were also rated. Results: Accelerometry-based values of PA increased by 17.2% in the PA group but declined by 28.0% in the HE group. The PA group, but not the HE group, had a significant increase in straight vein length from baseline to 24-month follow-up (P = 0.02 and P = 0.21, respectively); the between-group difference in percent change in straight length was significant (increase: median, 93.6%; interquartile range, 112.9 for PA; median, 28.4%; interquartile range, 90.6 for HE; P = 0.07). Between group differences in other markers were nonsignificant. Conclusions: Increasing PA in late-life may promote cerebral small vein integrity. This should be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Abstract This pilot work examined associations of brain grey matter volumes (GMV) with perceived fatigability in older adults to elucidate disablement mechanisms. A subsample (n = 29; age = 77.2 ± 5.5; 86% female) of participants from the Lifestyle Interventions and Independence for Elders (LIFE) Study was utilized to quantify GMV for regions of interest in the basal ganglia and limbic system normalized to intracranial volume. The Pittsburgh Fatigability Scale measured physical and mental fatigability (score 0–50; higher physical fatigability ≥ 15; higher mental fatigability ≥ 13). We used an exploratory alpha level of p < 0.1. Nineteen (66%) participants had higher physical fatigability, 19 (66%) had higher mental fatigability, of these, 17 (57%) had both. Right hippocampal volumes/ICV were smaller in participants with higher verses lower physical fatigability (0.261 ± 0.039 vs. 0.273 ± 0.022, p = 0.07); associations were similar for right putamen and bilateral thalamus. Higher mental fatigability was associated with smaller right hippocampus, thalamus, and posterior cingulum and bilateral amygdala. Higher fatigability in older adults may be associated with smaller volumes of the basal ganglia and limbic system, indicating mechanisms for further exploration. Highlights • Provides initial evidence that fatigability in aging has a neurobiological component • Specific regions in the basal ganglia and limbic system may be related to fatigability. • Regions were similar for physical and mental, but more regions associated with mental fatigability. [ABSTRACT FROM AUTHOR]