Blood Pressure, Internal Carotid Artery Flow Parameters, and Age-Related White Matter Hyperintensities

White matter hyperintensities (WMH) are associated with hypertension. We examined interactions between blood pressure (BP), internal carotid artery (ICA) flow velocity parameters and WMH. We obtained BP measurements from 694 community-dwelling subjects at mean ages 69.6 (±0.8) and again at 72.6 (±0.7) years, plus brain MRI and ICA ultrasound at age 73±1 years. Diastolic and mean BP decreased and pulse pressure increased but systolic BP did not change between 70 and 73 years. Multiple linear regression, corrected for vascular disease and risk factors, showed that WMH at age 73 were associated with history of hypertension (β=0.13, p<0.001) and with BP at age 70 (systolic β=0.08, mean β=0.09, diastolic β=0.08, all p<0.05); similar but attenuated associations were seen for BP at age 73. Lower diastolic BP and higher pulse pressure were associated with higher ICA pulsatility index at age 73 (diastolic BP: standardized β, age 70=−0.24, p<0.001; pulse pressure age 70 β=0.19, p<0.001). WMH were associated with higher ICA pulsatility index (β=0.13, p=0.002) after adjusting for BP and correction for multiple testing. Therefore falling diastolic BP and increased pulse pressure are associated with increased ICA pulsatility index, which in turn is associated with WMH. This suggests that hypertension and WMH may either associate indirectly because hypertension increases arterial stiffness which leads to WMH over time, or co-associate through advancing age and stiffer vessels, or both. Reducing vascular stiffness may reduce WMH progression and should be tested in randomised trials, in addition to testing antihypertensive therapy

Association of allostatic load with brain structure and cognitive ability in later life

AbstractAllostatic load (AL) has been proposed as a general framework for understanding the cumulative effects of life stress on individuals. Despite growing interest in AL, limited research has been conducted on aging samples. We consider the association of AL (operationalized by a range of inflammatory, cardiovascular, and metabolic measures) with a range of brain volume measurements and cognitive ability in a large cohort sample of older adults (n = 658, mean age = 72.5 years, standard deviation = 0.7) using structural equation modeling. AL was significantly inversely associated with total brain volume (range of standardized β = −0.16 to −0.20) and white-matter volume (−0.35 to −0.36) and positively with hippocampal volume (0.10–0.15) but not gray-matter volume (0.04). AL was also significantly inversely associated with general cognitive ability (range β = −0.13 to −0.20), processing speed (−0.20 to −0.22), and knowledge (−0.18 to −0.20) but not memory or nonverbal reasoning. The associations of AL with cognitive abilities were not mediated by these brain volume measures. AL did not predict cognitive change from age 11 to approximately age 73. The findings suggest a link between AL and later life brain health and cognitive functioning

Progression of white matter disease and cortical thinning are not related in older community-dwelling subjects

Background and Purpose— We assessed cross-sectional and longitudinal relationships between whole brain white matter hyperintensity (WMH) volume and regional cortical thickness. Methods— We measured WMH volume and regional cortical thickness on magnetic resonance imaging at ≈73 and ≈76 years in 351 community-dwelling subjects from the Lothian Birth Cohort 1936. We used multiple linear regression to calculate cross-sectional and longitudinal associations between regional cortical thickness and WMH volume controlling for age, sex, Mini Mental State Examination, education, intelligence quotient at age 11, and vascular risk factors. Results— We found cross-sectional associations between WMH volume and cortical thickness within and surrounding the Sylvian fissure at 73 and 76 years (rho=−0.276, Q=0.004). However, we found no significant longitudinal associations between (1) baseline WMH volume and change in cortical thickness; (2) baseline cortical thickness and change in WMH volume; or (3) change in WMH volume and change in cortical thickness. Conclusions— Our results show that WMH volume and cortical thinning both worsen with age and are associated cross-sectionally within and surrounding the Sylvian fissure. However, changes in WMH volume and cortical thinning from 73 to 76 years are not associated longitudinally in these relatively healthy older subjects. The underlying cause(s) of WMH growth and cortical thinning have yet to be fully determined

Brain volumetric changes and cognitive ageing during the eighth decade of life

Later‐life changes in brain tissue volumes—decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)—are strong candidates to explain some of the variation in ageing‐related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow‐age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow‐up). We used latent variable modeling to extract error‐free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r‐values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life

Trait Conscientiousness and the Personality Meta-Trait Stability are Associated with Regional White Matter Microstructure

Establishing the neural bases of individual differences in personality has been an enduring topic of interest. However, while a growing literature has sought to characterize grey matter correlates of personality traits, little attention to date has been focused on regional white matter correlates of personality, especially for the personality traits agreeableness, conscientiousness and openness. To rectify this gap in knowledge we used a large sample (n > 550) of older adults who provided data on both personality (International Personality Item Pool) and white matter tract-specific fractional anisotropy (FA) from diffusion tensor MRI. Results indicated that conscientiousness was associated with greater FA in the left uncinate fasciculus (β = 0.17, P < 0.001). We also examined links between FA and the personality meta-trait ‘stability’, which is defined as the common variance underlying agreeableness, conscientiousness, and neuroticism/emotional stability. We observed an association between left uncinate fasciculus FA and stability (β = 0.27, P < 0.001), which fully accounted for the link between left uncinate fasciculus FA and conscientiousness. In sum, these results provide novel evidence for links between regional white matter microstructure and key traits of human personality, specifically conscientiousness and the meta-trait, stability. Future research is recommended to replicate and address the causal directions of these associations

Brain White Matter Tract Integrity and Cognitive Abilities in Community-Dwelling Older People: The Lothian Birth Cohort, 1936

Objective The present study investigates associations between brain white matter tract integrity and cognitive abilities in community-dwelling older people (N = 655). We explored two potential confounds of white matter tract−cognition associations in later life: (a) whether the associations between tracts and specific cognitive abilities are accounted for by general cognitive ability (g); and (b) how the presence of atrophy and white matter lesions affect these associations. Method Tract integrity was determined using quantitative diffusion magnetic resonance imaging tractography (tract-averaged fractional anisotropy [FA]). Using confirmatory factor analysis, we compared first-order and bifactor models to investigate whether specific tract-ability associations were accounted for by g. Results Significant associations were found between g and FA in bilateral anterior thalamic radiations (r range: .16−.18, p < .01), uncinate (r range: .19−.26, p < .001), arcuate fasciculi (r range: .11−.12, p < .05), and the splenium of corpus callosum (r = .14, p < .01). After controlling for g within the bifactor model, some significant specific cognitive domain associations remained. Results also suggest that the primary effects of controlling for whole brain integrity were on g associations, not specific abilities. Conclusion Results suggest that g accounts for most of, but not all, the tract−cognition associations in the current data. When controlling for age-related overall brain structural changes, only minor attenuations of the tract−cognition associations were found, and these were primarily with g. In totality, the results highlight the importance of controlling for g when investigating associations between specific cognitive abilities and neuropsychology variables

Personality, Health, and Brain Integrity:The Lothian Birth Cohort Study 1936

Objective: To explore associations between the 5-factor model (FFM; neuroticism, extraversion, openness/intellect, agreeableness, and conscientiousness), personality traits, and measures of whole-brain integrity in a large sample of older people, and to test whether these associations are mediated by health-related behaviors. Method: Participants from the Lothian Birth Cohort 1936 completed the International Personality Item Pool measure, a 5-factor public-domain personality measure (http://ipip.ori.org), and underwent a structural magnetic resonance brain scan at the mean age of 73 years, yielding 3 measures of whole brain integrity: average white matter fractional anisotropy (FA), brain-tissue loss, and white matter hyperintensities (N = 529 to 565). Correlational and mediation analyses were used to test the potential mediating effects of health-related behaviors on the associations between personality and integrity. Results: Lower conscientiousness was consistently associated with brain-tissue loss (β = −0.11, p < 0.01), lower FA (β = 0.16, p < 0.001) and white matter hyperintensities (β = −0.10, p < 0.05). Smoking, alcohol consumption, diet, physical activity, body mass index and a composite health-behavior variable displayed significant associations with measures of brain integrity (range of r = 0.10 to 0.25). The direct effects of conscientiousness on brain integrity were mediated to some degree by health behaviors, with the proportions of explained direct effects ranging from 0.1% to 13.7%. Conclusion: Conscientiousness was associated with all 3 measures of brain integrity, which we tentatively interpret as the effects of personality on brain aging. Small proportions of the direct effects were mediated by individual health behaviors. Results provide initial indications that lifetime stable personality traits may influence brain health in later life through health-promoting behaviors. (PsycINFO Database Record (c) 2016 APA, all rights reserved

Coupled changes in brain white matter microstructure and fluid intelligence in later life

Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and aging-related cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical “disconnection” partly explains cognitive aging

Structural brain MRI trait polygenic score prediction of cognitive abilities

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