Effect of Aerobic Exercise on White Matter Tract Microstructure in Young and Middle-Aged Healthy Adults.
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ABSTRACT:
SUBMITTER: Predovan D
PROVIDER: S-EPMC8283503 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Whether head size and/or biological sex influence proxies of white matter (WM) microstructure such as fractional anisotropy (FA) and mean diffusivity (MD) remains controversial. Diffusion tensor imaging (DTI) indices are also associated with age, but there are large discrepancies in the spatial distribution and timeline of age-related differences reported. The aim of this study was to evaluate the associations between intracranial volume (ICV), sex, and age and DTI indices from WM in a population-based study of healthy individuals (n = 812) aged 50-66 in the Nord-Trøndelag health survey. Semiautomated tractography and tract-based spatial statistics (TBSS) analyses were performed on the entire sample and in an ICV-matched sample of men and women. The tractography results showed a similar positive association between ICV and FA in all major WM tracts in men and women. Associations between ICV and MD, radial diffusivity and axial diffusivity were also found, but to a lesser extent than FA. The TBSS results showed that both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV only women had areas with higher FA. The ICV matched analysis also demonstrated that only women had areas of higher FA. Age was negatively associated with FA across the entire WM skeleton in the TBSS analysis, independent of both sex and ICV. Combined, these findings demonstrated that both ICV and sex contributed to variation in DTI indices and emphasized the importance of considering ICV as a covariate in DTI analysis.
| S-EPMC9842919 | biostudies-literature
Project description:BACKGROUND:The ε4 allele of the apolipoprotein E gene (APOE-ε4) is the strongest genetic factor for late-onset Alzheimer's disease. During middle age, cognitively healthy APOE-ε4 carriers already show several brain alterations that resemble those of Alzheimer's disease (AD), but to a subtler degree. These include microstructural white matter (WM) changes that have been proposed as one of the earliest structural events in the AD cascade. However, previous studies have focused mainly on comparison of APOE-ε4 carriers vs noncarriers. Therefore, the extent and magnitude of the brain alterations in healthy ε4 homozygotes, who are the individuals at highest risk, remain to be characterized in detail. METHODS:We examined mean, axial, and radial water diffusivity (MD, AxD, and RD, respectively) and fractional anisotropy in the WM as measured by diffusion-weighted imaging in 532 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 207 heterozygotes, and 257 noncarriers). We examined the impact of age and APOE genotype on these parameters using tract-based spatial statistics. RESULTS:Healthy APOE-ε4 homozygotes display increased WM diffusivity in regions known to be affected by AD. The effects in AxD were much smaller than in RD, suggesting a disruption of the myelin sheath rather than pure axonal damage. CONCLUSIONS:These findings could be interpreted as the result of the reduced capacity of the ε4 isoform of the APOE protein to keep cholesterol homeostasis in the brain. Because cerebral lipid metabolism is strongly related to the pathogenesis of AD, our results shed light on the possible mechanisms through which the APOE-ε4 genotype is associated with an increased risk of AD.
| S-EPMC5968505 | 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
Project description:BackgroundThe brain is the most cholesterol-rich organ and myelin contains 70% of total brain cholesterol. Statins are potent cholesterol-lowing medications used by millions of adults for prevention of vascular disease, yet the effect of statins on cholesterol-rich brain white matter (WM) is largely unknown.MethodsWe used longitudinal neuroimaging data acquired from 73 healthy, cognitively unimpaired, statin-naïve, middle-aged adults during an 18-month randomized controlled trial of simvastatin 40 mg daily (n = 35) or matching placebo (n = 38). ANCOVA models (covariates: age, sex, APOE-ɛ4) tested the effect of treatment group on percent change in WM, gray matter (GM), and WM hyperintensity (WMH) neuroimaging measures at each study visit. Mediation analysis tested the indirect effects of simvastatin on WM microstructure through change in serum total cholesterol levels.ResultsAt 18 months, the simvastatin group showed a significant preservation in global WM fractional anisotropy (β = 0.88%, 95% CI 0.27 to 1.50, P = 0.005), radial diffusivity (β = -1.10%, 95% CI -2.13 to -0.06, P = 0.039), and WM volume (β = 0.72%, 95% CI 0.13 to 1.32, P = 0.018) relative to the placebo group. There was no significant effect of simvastatin on GM or WMH volume. Change in serum total cholesterol mediated approximately 30% of the effect of simvastatin on WM microstructure.ConclusionsSimvastatin treatment in healthy, middle-aged adults resulted in preserved WM microstructure and volume at 18 months. The partial mediation by serum cholesterol reduction suggests both peripheral and central mechanisms. Future studies are needed to determine whether these effects persist and translate to cognitive outcomes.Trial registrationNCT00939822 (ClinicalTrials.gov).
| S-EPMC8351379 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Traditional cardiovascular risk factors have been associated with white matter disease. Because hypertension results in vascular stiffness and impaired cerebral perfusion, we hypothesized that it would be the most relevant risk factor for microstructural white matter disruption in apparently healthy middle-aged individuals with a family history of early-onset coronary artery disease. MATERIALS AND METHODS:This was a cross-sectional analysis of participants in the Genetic Study of Atherosclerosis Risk with DTI. Regional fractional anisotropy of 181 segmented brain regions was measured using Eve WM Atlas. Risk factors were examined using univariate analysis for 48 regions representing deep WM structures. Minimal multivariable linear regression models adjusting for age, sex, and race and maximal linear regression models adjusting for cardiovascular risk factors were performed for regions meeting the Bonferroni threshold in the initial analysis. RESULTS:Included were 116 subjects (mean age, 49 ± 11 years; 57% men) with a moderate load of cardiovascular risk factors. Subjects with hypertension had significantly lower regional fractional anisotropy in the right cingulum and left stria terminalis in the minimal and maximal regression models. Additionally, there was lower regional fractional anisotropy in the left fornix in the maximal model and right sagittal stratum in the minimal model. Systolic blood pressure values were significantly associated with regional fractional anisotropy in the left superior longitudinal fasciculus in the maximal model. There were no significant differences among regional fractional anisotropy values for other cardiovascular risk factors. CONCLUSIONS:In middle-aged apparently healthy individuals with susceptibility to vascular disease, among all known cardiovascular risk factors, hypertension was associated with microstructural WM disruption.
| S-EPMC6368444 | biostudies-literature
Project description:ObjectivesWe hypothesized that integrated motor-visual functions measured by manipulative manual dexterity are affected by white matter lesion (WML) burden as measured on cranial MRI across relevant brain regions in subjects at risk of preclinical occult vascular disease.MethodsA real-time cross-sectional study of healthy subjects aged 29 to 74 years with a family history of early-onset coronary artery disease (n = 714; mean age, 51 ± 11 years; mean education, 14 ± 3 years; 42% male; 38% black) were identified from probands with coronary artery disease diagnosed before age 60 years. WMLs on 3-tesla brain MRI and Grooved Pegboard scores were measured.ResultsWMLs were observed at all ages. Mean pegboard scores were 108 ± 18, similar to normal populations. In unadjusted analysis, WMLs and pegboard scores were significantly correlated by region (total WMLs, r = 0.34, p = 0.0001; frontal [r = 0.34, p < 0.0001], insula [r = 0.31, p < 0.0001], parietal [r = 0.31, p < 0.0001], and temporal [r = 0.17, p < 0.0001]). In multivariate analysis predicting (log) pegboard score adjusted for age, sex, race, education, regional or total volumes, and familial non-independence, total WML volume (p = 5.79E - 05) and regional WML volumes (p < 0.01) retained statistical significance in all but the youngest age quartile (29-43 years).ConclusionsGreater WML volumes in different brain regions are associated with higher pegboard scores (worse performance) independent of age, sex, race, education, and total or regional volumes. This suggests that small vessel cerebrovascular disease may be present in healthy individuals in a preclinical state with measurable impact on complex integrative functions in individuals with excess risk of clinical vascular disease.
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Project description:We aimed to extend our knowledge on the relationship between physical fitness (PF) and both white matter microstructure and cognition through in-depth investigation of various cognitive domains while accounting for potentially relevant nuisance covariates in a well-powered sample. To this end, associations between walking endurance, diffusion-tensor-imaging (DTI) based measures of fractional anisotropy (FA) within brain white matter and cognitive measures included in the NIH Toolbox Cognition Battery were investigated in a sample of n = 1206 healthy, young adults (mean age = 28.8; 45.5% male) as part of the human connectome project. Higher levels of endurance were associated with widespread higher FA (pFWE < 0.05) as well as with enhanced global cognitive function (p < 0.001). Significant positive relationships between endurance and cognitive performance were similarly found for almost all cognitive domains. Higher FA was significantly associated with enhanced global cognitive function (p < 0.001) and FA was shown to significantly mediate the association between walking endurance and cognitive performance. Inclusion of potentially relevant nuisance covariates including gender, age, education, BMI, HBA1c, and arterial blood pressure did not change the overall pattern of results. These findings support the notion of a beneficial and potentially protective effect of PF on brain structure and cognition.
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Project description:White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants [N = 561 (45-75 years)] enriched for Alzheimer's disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (APOE-ε4). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects.
| S-EPMC7572336 | biostudies-literature
Project description:Individual differences in white matter tract microstructure, measured with diffusion tensor imaging (DTI), demonstrate substantial heritability. However, it is unclear to what extent this heritability reflects global genetic influences or tract-specific genetic influences. The goal of the current study was to quantify the proportion of genetic and environmental variance in white matter tracts attributable to global versus tract-specific influences. We assessed fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) across 11 tracts and 22 subdivisions of these tracts in 392 middle-aged male twins from the Vietnam Era Twin Study of Aging (VETSA). In principal component analyses of the 11 white matter tracts, the first component, which represents the global signal, explained 50.1% and 62.5% of the variance in FA and MD, respectively. Similarly, the first principal component of the 22 tract subdivisions explained 38.4% and 47.0% of the variance in FA and MD, respectively. Twin modeling revealed that DTI measures of all tracts and subdivisions were heritable, and that genetic influences on global FA and MD accounted for approximately half of the heritability in the tracts or tract subdivisions. Similar results were observed for the AD and RD diffusion metrics. These findings underscore the importance of controlling for DTI global signals when measuring associations between specific tracts and outcomes such as cognitive ability, neurological and psychiatric disorders, and brain aging.
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Project description:The human brain undergoes dramatic structural change over the life span. In a large imaging cohort of 801 individuals aged 7-84 years, we applied quantitative relaxometry and diffusion microstructure imaging in combination with diffusion tractography to investigate tissue property dynamics across the human life span. Significant nonlinear aging effects were consistently observed across tracts and tissue measures. The age at which white matter (WM) fascicles attain peak maturation varies substantially across tissue measurements and tracts. These observations of heterochronicity and spatial heterogeneity of tract maturation highlight the importance of using multiple tissue measurements to investigate each region of the WM. Our data further provide additional quantitative evidence in support of the last-in-first-out retrogenesis hypothesis of aging, demonstrating a strong correlational relationship between peak maturational timing and the extent of quadratic measurement differences across the life span for the most myelin sensitive measures. These findings present an important baseline from which to assess divergence from normative aging trends in developmental and degenerative disorders, and to further investigate the mechanisms connecting WM microstructure to cognition.
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