Plasma BDNF is associated with age-related white matter atrophy but not with cognitive function in older, non-demented adults.
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ABSTRACT:
SUBMITTER: Driscoll I
PROVIDER: S-EPMC3327651 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:ObjectiveThis study examined the association of lifetime experiences, measured by a cognitive reserve (CR) composite score composed of years of education, literacy, and vocabulary measures, to level and rate of change in white matter microstructure, as assessed by diffusion tensor imaging (DTI) measures. We also examined whether the relationship between the proxy CR composite score and white matter microstructure was modified by participant age, APOE-ε4 genetic status, and level of vascular risk.MethodsA sample of 192 non-demented (n = 166 cognitively normal, n = 26 mild cognitive impairment) older adults [mean age = 70.17 (SD = 8.5) years] from the BIOCARD study underwent longitudinal DTI (mean follow-up = 2.5 years, max = 4.7 years). White matter microstructure was quantified by fractional anisotropy (FA) and radial diffusivity (RD) values in global white matter tracts and medial temporal lobe (MTL) white matter tracts.ResultsUsing longitudinal linear mixed effect models, we found that FA decreased over time and RD increased over time in both the global and MTL DTI composites, but the rate of change in these DTI measures was not related to level of CR. However, there were significant interactions between the CR composite score and age for global RD in the full sample, and for global FA, global RD, and MTL RD among those with normal cognition. These interactions indicated that among participants with a lower baseline age, higher CR composite scores were associated with higher FA and lower RD values, while among participants with higher age at baseline, higher CR composite scores were associated with lower FA and higher RD values. Furthermore, these relationships were not modified by APOE-ε4 genotype or level of vascular risk.ConclusionThe association between level of CR and DTI measures differs by age, suggesting a possible neuroprotective effect of CR among late middle-aged adults that shifts to a compensatory effect among older adults.
| S-EPMC9226781 | biostudies-literature
Project description:Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG) and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function.
| S-EPMC5539079 | biostudies-other
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:BACKGROUND:Associations between orthostatic blood pressure and cognitive status (CS) have been described with conflicting results. OBJECTIVE:We 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. METHODS:Three-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. RESULTS:There 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. CONCLUSION:ASOBPR may be an early marker of risk of dementia in older adults living in the community.
| S-EPMC5545885 | biostudies-literature
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:Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (? = -0.14, p < 0.01) and processing speed (? = -0.19, p < 0.001). WMH were also associated independently with lower age 11 IQ (? = -0.08, p < 0.05) and hypertension. In conclusion, having more WMH is significantly associated with lower cognitive ability, after accounting for prior ability, age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging.
| S-EPMC3898072 | biostudies-literature
Project description:Previous research has shown that bilingual speakers have higher levels of cognitive control than comparable monolinguals, especially at older ages. The present study investigates a possible neural correlate of this behavioral effect. Given that white matter (WM) integrity decreases with age in adulthood, we tested the hypothesis that bilingualism is associated with maintenance of WM in older people. Using diffusion tensor imaging, we found higher WM integrity in older people who were lifelong bilinguals than in monolinguals. This maintained integrity was measured by fractional anisotropy (FA) and was found in the corpus callosum extending to the superior and inferior longitudinal fasciculi. We also hypothesized that stronger WM connections would be associated with more widely distributed patterns of functional connectivity in bilinguals. We tested this by assessing the resting-state functional connectivity of frontal lobe regions adjacent to WM areas with group differences in FA. Bilinguals showed stronger anterior to posterior functional connectivity compared to monolinguals. These results are the first evidence that maintained WM integrity is related to lifelong naturally occurring experience; the resulting enhanced structural and functional connectivity may provide a neural basis for "brain reserve."
| S-EPMC3259110 | biostudies-other
Project description:ObjectiveTo test the hypothesis that physical activity modifies the association between white matter hyperintensity (WMH) burden and motor function in healthy older persons without dementia.MethodsTotal daily activity (exercise and nonexercise physical activity) was measured for up to 11 days with actigraphy (Actical; Philips Respironics, Bend, OR) in 167 older adults without dementia participating in the Rush Memory and Aging Project. Eleven motor performances were summarized into a previously described global motor score. WMH volume was expressed as percent of intracranial volume. Linear regression models, adjusted for age, education, and sex, were performed with total WMH volume as the predictor and global motor score as the outcome. Terms for total daily physical activity and its interaction with WMH volume were then added to the model.ResultsHigher WMH burden was associated with lower motor function (p = 0.006), and total daily activity was positively associated with motor function (p = 0.002). Total daily activity modified the association between WMH and motor function (p = 0.007). WMH burden was not associated with motor function in persons with high activity (90th percentile). By contrast, higher WMH burden remained associated with lower motor function in persons with average (50th percentile; estimate = -0.304, slope = -0.133) and low (10th percentile; estimate = -1.793, slope = -0.241) activity.ConclusionsHigher levels of physical activity may reduce the effect of WMH burden on motor function in healthy older adults.
| S-EPMC4388751 | biostudies-literature
Project description:ObjectiveThere are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer's dementia.MethodsWe studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates.ResultsHigher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = -0.33, p = .002; Cohort 2: β = -0.36, p = .03) and parietal ROIs (Cohort 1: β = -0.31, p = .01; Cohort 2: β = -0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = -0.38, p = .01; Cohort 2: β = -0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP.ConclusionsPlasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.
| S-EPMC8692495 | biostudies-literature
Project description:Aging entails a multifaceted complex of changes in macro- and micro-structural properties of human brain gray matter (GM) and white matter (WM) tissues, as well as in intellectual abilities. To better capture tissue-specific brain aging, we combined volume and distribution properties of diffusivity indices to derive subject-specific age scores for each tissue. We compared age-related variance between younger and older adults for GM and WM age scores, and tested whether tissue-specific age scores could explain different effects of aging on fluid (Gf) and crystalized (Gc) intelligence in younger and older adults. Chronological age was strongly associated with GM (R2 = 0.73) and WM (R2 = 0.57) age scores. The GM age score accounted for significantly more variance in chronological age in younger relative to older adults (p < 0.001), whereas the WM age score accounted for significantly more variance in chronological age in older compared to younger adults (p < 0.025). Consistent with existing literature, younger adults outperformed older adults in Gf while older adults outperformed younger adults in Gc. The GM age score was negatively associated with Gf in younger adults (p < 0.02), whereas the WM age score was negatively associated with Gc in older adults (p < 0.02). Our results provide evidence for differences in the effects of age on GM and WM in younger versus older adults that may contribute to age-related differences in Gf and Gc.
| S-EPMC8428193 | biostudies-literature