Endothelial Function Is Associated with White Matter Microstructure and Executive Function in Older Adults.
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ABSTRACT:
SUBMITTER: Johnson NF
PROVIDER: S-EPMC5539079 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:ContextOlder 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.ObjectiveTo identify the patterns of fMRI activation in relationship with ECF performance and with brain structural abnormalities.DesignCross-sectional analysis.Main variables of interestfMRI activation, accuracy while performing an ECF task (Digit Symbol Substitution Test), and volume of white matter hyperintensities and of total brain atrophy.SettingCohort of community-dwelling older adults.ParticipantsData were obtained on 25 older adults (20 women, 81 years mean age).Outcome measureAccuracy (number of correct response/total number of responses) while performing the Digit Symbol Substitution Test.ResultsGreater 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.ConclusionsRecruitment 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.
| S-EPMC2818521 | biostudies-literature
Project description:Cerebrospinal fluid (CSF) neurofilament light (NFL) is a protein biomarker of axonal injury. To study whether NFL is associated with diffusion tensor imaging (DTI) measurements of white matter (WM) microstructure, Vanderbilt Memory & Aging Project participants with normal cognition (n = 77), early mild cognitive impairment (n = 15), and MCI (n = 55) underwent lumbar puncture to obtain CSF and 3T brain MRI. Voxel-wise analyses cross-sectionally related NFL to DTI metrics, adjusting for demographic and vascular risk factors. Increased NFL correlated with multiple DTI metrics (p-values < 0.05). An NFL × diagnosis interaction (excluding early mild cognitive impairment) on WM microstructure (p-values < 0.05) was detected, with associations strongest among MCI. Multiple NFL × CSF biomarker interactions were detected. Associations between NFL and worse WM metrics were strongest among amyloid-β42-negative, tau-positive, and suspected nonamyloid pathology participants. Findings suggest increased NFL, a biomarker of axonal injury, is correlated with compromised WM microstructure. Results highlight the role of elevated NFL in predicting WM damage in cognitively impaired older adults who are amyloid-negative, tau-positive, or meet suspected nonamyloid pathology criteria.
| S-EPMC6119102 | biostudies-literature
Project description:Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.
| S-EPMC4894643 | biostudies-literature
Project description:Children with prenatal exposure to cocaine are at higher risk for negative behavioral function and attention difficulties, and have demonstrated brain diffusion abnormalities in frontal white matter regions. However, brain regions beyond frontal and callosal areas have not been investigated using diffusion tensor imaging (DTI). DTI data were collected on 42 youth aged 14-16 years; subjects were divided into three groups based on detailed exposure histories: those with prenatal exposure to cocaine but not alcohol (prenatal cocaine exposure (PCE), n=12), prenatal exposure to cocaine and alcohol (cocaine and alcohol exposure (CAE), n=17), and controls (n=13). Tractography was performed and along-tract diffusion parameters were examined for group differences and correlations with executive function measures. In the right arcuate fasciculus and cingulum, the CAE group had higher fractional anisotropy (FA) and/or lower mean diffusivity (MD) than the other two groups. The PCE group demonstrated lower FA in the right arcuate and higher MD in the splenium of the corpus callosum than controls. Diffusion parameters in tracts with group differences correlated with measures of executive function. In conclusion, these diffusion differences in adolescents with prenatal cocaine exposure suggest localized, long-term structural brain alterations that may underlie attention and response-inhibition difficulties.
| S-EPMC3812806 | biostudies-literature
Project description:Left ventricular (LV) hypertrophy is associated with cerebrovascular disease and cognitive decline. Increased LV mass index is a subclinical imaging marker that precedes overt LV hypertrophy. This study relates LV mass index to white matter microstructure and cognition among older adults with normal cognition and mild cognitive impairment. Vanderbilt Memory & Aging Project participants free of clinical stroke, dementia, and heart failure (n=318, 73±7 years, 58% male, 39% mild cognitive impairment) underwent brain magnetic resonance imaging, cardiac magnetic resonance, and neuropsychological assessment. Voxelwise analyses related LV mass index (g/m2) to diffusion tensor imaging metrics. Models adjusted for age, sex, education, race/ethnicity, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E-ε4 status. Secondary analyses included a LV mass index×diagnosis interaction term with follow-up models stratified by diagnosis. With identical covariates, linear regression models related LV mass index to neuropsychological performances. Increased LV mass index related to altered white matter microstructure (P<0.05). In models stratified by diagnosis, associations between LV mass index and diffusion tensor imaging were present among mild cognitive impairment participants only (P<0.05). LV mass index was related only to worse visuospatial memory performance (β=-0.003, P=0.036), an observation that would not withstand correction for multiple testing. In the absence of prevalent heart failure and clinical stroke, increased LV mass index corresponds to altered white matter microstructure, particularly among older adults with clinical symptoms of prodromal dementia. Findings highlight the potential link between subclinical LV remodeling and cerebral white matter microstructure vulnerability.
| S-EPMC6064880 | biostudies-literature
Project description:Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65-88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = -0.18, FDR-p = 0.02; right β = -0.20, FDR-p = 0.01) and right medial orbitofrontal (β = -0.17, FDR-p = 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = -0.21, FDR-p = 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function.
| S-EPMC8273864 | biostudies-literature
Project description:Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH) mediates this association.Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function.Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 ?g/ml increase in plasma O3PUFA associated with 4 s less change in executive decline per year of aging (p = 0.02, fully adjusted model). O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model.Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation.
| S-EPMC3863786 | biostudies-other
Project description:BackgroundPoor social health has been linked to a risk of neuropsychiatric disorders. Neuroimaging studies have shown associations between social health and global white matter microstructural integrity. We aimed to identify which white matter tracts are involved in these associations.MethodsSocial health markers (loneliness, perceived social support, and partnership status) and white matter microstructural integrity of 15 white matter tracts (identified with probabilistic tractography after diffusion magnetic resonance imaging) were collected for 3352 participants (mean age 58.4 years, 54.9% female) from 2002 to 2008 in the Rotterdam Study. Cross-sectional associations were studied using multivariable linear regression.ResultsLoneliness was associated with higher mean diffusivity (MD) in the superior thalamic radiation and the parahippocampal part of the cingulum (standardized mean difference for both tracts: 0.21, 95% CI, 0.09 to 0.34). Better perceived social support was associated with lower MD in the forceps minor (standardized mean difference per point increase in social support: -0.06, 95% CI, -0.09 to -0.03), inferior fronto-occipital fasciculus, and uncinate fasciculus. In male participants, better perceived social support was associated with lower MD in the forceps minor, and not having a partner was associated with lower fractional anisotropy in the forceps minor. Loneliness was associated with higher MD in the superior thalamic radiation in female participants only.ConclusionsSocial health was associated with tract-specific white matter microstructure. Loneliness was associated with lower integrity of limbic and sensorimotor tracts, whereas better perceived social support was associated with higher integrity of association and commissural tracts, indicating that social health domains involve distinct neural pathways of the brain.
| S-EPMC10593878 | biostudies-literature
Project description:BackgroundStudies have investigated white matter microstructure in relation to late-life cognitive impairments, with fractional anisotropy (FA) and mean diffusivity (MD) measures thought to capture demyelination and axonal degradation. However, new post-processing methods allow isolation of free water (FW), which captures extracellular fluid contributions such as atrophy and neuroinflammation, from tissue components. FW also appears to be highly relevant to late-life cognitive impairment. Here, we evaluated whether executive functions are associated with FW, and FA and MD corrected for FW (FAFWcorr and MDFWcorr).MethodWe examined 489 non-demented men in the Vietnam Era Twin Study of Aging (VETSA) at mean age 68. Two latent factors capturing 'common executive function' and 'working-memory specific' processes were estimated based on 6 tasks. Analyses focused on 11 cortical white matter tracts across three metrics: FW, FAFWcorr, and MDFWcorr.ResultsBetter 'common executive function' was associated with lower FW across 9 of the 11 tracts. There were no significant associations with intracellular metrics after false discovery rate correction. Effects also appeared driven by individuals with MCI (13.7% of the sample). Working memory-specific tasks showed some associations with FAFWcorr, including the triangularis portion of the inferior frontal gyrus. There was no evidence that cognitive reserve (i.e., general cognitive ability assessed in early adulthood) moderated these associations between executive function and FW or FA.DiscussionExecutive function abilities in early old age are associated primarily with extracellular fluid (FW) as opposed to white matter (FAFWcorr or MDFWcorr). Moderation analyses suggested cognitive reserve does not play a strong role in these associations, at least in this sample of non-demented men.
| S-EPMC9731853 | biostudies-literature
Project description:ObjectiveTo investigate the potential relationship between insulin resistance (IR) and white matter (WM) microstructure using diffusion tensor imaging in cognitively healthy middle-aged and older adults.MethodsDiffusion tensor imaging was acquired from 127 individuals (age range 41-86 years). IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Participants were divided into 2 groups based on HOMA-IR values: "high HOMA-IR" (?2.5, n = 27) and "low HOMA-IR" (<2.5, n = 100). Cross-sectional voxel-based comparisons were performed using Tract-Based Spatial Statistics and anatomically defined regions of interest analysis.ResultsThe high HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity.ConclusionsIn generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults.
| S-EPMC4105251 | biostudies-literature