scholarly journals Erythrocyte omega-3 index, ambient fine particle exposure, and brain aging

Neurology ◽  
2020 ◽  
Vol 95 (8) ◽  
pp. e995-e1007
Author(s):  
Cheng Chen ◽  
Pengcheng Xun ◽  
Joel D. Kaufman ◽  
Kathleen M. Hayden ◽  
Mark A. Espeland ◽  
...  
Keyword(s):  
White Matter ◽  
Linear Models ◽  
Elderly Women ◽  
Brain Aging ◽  
Brain Mri ◽  
Brain Regions ◽  
Dietary Intakes ◽  
Omega 3 ◽  
Brain Volumes ◽  
Spatiotemporal Model

ObjectiveTo examine whether long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) levels modify the potential neurotoxic effects of particle matter with diameters <2.5 µm (PM2.5) exposure on normal-appearing brain volumes among dementia-free elderly women.MethodsA total of 1,315 women (age 65–80 years) free of dementia were enrolled in an observational study between 1996 and 1999 and underwent structural brain MRI in 2005 to 2006. According to prospectively collected and geocoded participant addresses, we used a spatiotemporal model to estimate the 3-year average PM2.5 exposure before the MRI. We examined the joint associations of baseline LCn3PUFAs in red blood cells (RBCs) and PM2.5 exposure with brain volumes in generalized linear models.ResultsAfter adjustment for potential confounders, participants with higher levels of RBC LCn3PUFA had significantly greater volumes of white matter and hippocampus. For each interquartile increment (2.02%) in omega-3 index, the average volume was 5.03 cm3 (p < 0.01) greater in the white matter and 0.08 cm3 (p = 0.03) greater in the hippocampus. The associations with RBC docosahexaenoic acid and eicosapentaenoic acid levels were similar. Higher LCn3PUFA attenuated the inverse associations between PM2.5 exposure and white matter volumes in the total brain and multimodal association areas (frontal, parietal, and temporal; all p for interaction <0.05), while the associations with other brain regions were not modified. Consistent results were found for dietary intakes of LCn3PUFAs and nonfried fish.ConclusionsFindings from this prospective cohort study among elderly women suggest that the benefits of LCn3PUFAs on brain aging may include the protection against potential adverse effects of air pollution on white matter volumes.

Abstract MP46: Growth Factors Are Associated With Imaging Markers of Brain Aging in Young Adults

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Claudia L Satizabal ◽  
Alexa Beiser ◽  
Jayandra J Himali ◽  
Rhoda Au ◽  
Philip A Wolf ◽  
...  
Keyword(s):  
Young Adults ◽  
Growth Factors ◽  
White Matter ◽  
Growth Factor ◽  
White Matter Hyperintensities ◽  
Brain Aging ◽  
Brain Mri ◽  
Blood Draw ◽  
Brain Volumes ◽  
Angiopoietin 2

Metabolic and vascular dysregulation are related to stroke, cognitive decline and dementia. Growth factor biomarkers of these processes, such as Insulin-like Growth Factor 1 (IGF1) and Vascular Endothelial Growth Factor (VEGF) have been associated with risk of neurodegeneration and stroke in middle-aged and older Framingham participants. Additionally, hepatocyte growth factor (HGF) and angiopoietin 2 are novel biomarkers of interest as they have been related to cardiovascular events. As abnormal brain changes probably start years before clinical symptoms, we hypothesize that circulating growth factors are related to MRI endophenotypes of brain aging. We included 1,877 individuals aged 46±8 years from the Framingham Study. Blood samples were collected during 2008-2011, and used to measure IGF1, VEGF, HGF, angiopoietin 2 and its receptor tyrosine kinase (TIE2). Participants underwent brain MRI examination (2009-2013) from which brain volumes and white matter hyperintensities were estimated. We related growth factor levels to brain MRI markers adjusting for age, sex, time between blood draw and MRI, and cardiovascular risk factors. Lower IGF1, as well as higher HGF and angiopoietin 2 levels were associated with higher ventricular volumes indicative of brain shrinkage. Higher TIE2 levels were associated with lower total brain and gray matter volumes, while higher angiopoietin 2 levels were associated with lower white matter volumes. Lower IGF1 levels were also associated with reduced hippocampal volumes. Finally, higher TIE2 levels were associated with larger white matter hyperintensities. Our results suggest that growth factors are associated with neurodegenerative and cerebrovascular markers of brain aging in healthy young adults. Whereas IGF1 seems protective, higher levels of HGF, angiopoietin 2 and TIE2 were associated with greater subclinical brain injury. These associations expand our understanding of the earliest stages of brain aging. We will extend our findings by analyzing cognitive outcomes.

Abstract P123: Prospective Association Between Periodontal Disease And Brain Imaging Markers Of Cerebrovascular And Neurodegenerative Disease: The Atherosclerosis Risk In Communities Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Hamdi S Adam ◽  
Kamakshi Lakshminarayan ◽  
Wendy Wang ◽  
Faye L Norby ◽  
Thomas Mosley ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Brain Aging ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Standardized Uptake Value ◽  
Tissue Loss ◽  
Total Brain Volume ◽  
Brain Volumes ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk

Background: Periodontal disease (PD) is associated positively with neurocognitive outcomes. Few studies have investigated the relationship between PD and indicators of brain aging and vascular changes. Hypothesis: PD is associated with greater cerebral small vessel disease, lower total and regional brain volumes and elevated β-amyloid (Aβ) deposition. Methods: We included 6,793 participants who received full-mouth periodontal examinations and tooth counts at Visit 4 (1996-1998) of the Atherosclerosis Risk in Communities Study. We used a modified 3-level version of the Periodontal Profile Class to categorize PD based on severity and extent of gingival inflammation and tissue loss. Among participants who attended Visit 5 (2011-2013), n=1,306 received a brain MRI and n=248 received a PET scan. Total brain volume, Alzheimer’s disease signature volume, and presence of microhemorrhages and cerebral infarctions were ascertained via 3T MRI; Aβ deposition was assessed from PET. We regressed brain volumes on baseline PD status using weighted multivariable linear regression. Presence of cerebrovascular microhemorrhages, infarctions, or elevated Aβ (standardized uptake value ratio>1.2) were regressed on PD category using logistic models. We examined the interaction between Apolipoprotein E ε4 ( APOE ) allele possession and PD categories on the Aβ outcome. Results: Prevalence of baseline periodontal disease was 73% (959/1306) and 87% (206/248) among the MRI and PET subgroups, respectively. PD was not associated with volumetric brain measures nor microhemorrhages. PD was inversely associated with the odds of subcortical and lacunar infarctions. PD and Aβ were not associated in main effect or interaction analyses, although there was a notably stronger association among carriers of APOE . Conclusion: PD was not associated with altered brain structure, cerebral microhemorrhages or elevated Aβ deposition. Counter to the hypothesis, PD and complete tooth loss were inversely associated with cerebral infarctions.

Regional brain volumes, microstructure and neurodevelopment in moderate–late preterm children

2020 ◽  
Vol 105 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Claire E Kelly ◽  
Deanne K Thompson ◽  
Alicia J Spittle ◽  
Jian Chen ◽  
Marc L Seal ◽  
...  
Keyword(s):  
White Matter ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Developmental Outcomes ◽  
Late Preterm ◽  
Brain Volumes ◽  
Regional Brain ◽  
White Matter Microstructure ◽  
Cortical Grey Matter

ObjectiveTo explore whether regional brain volume and white matter microstructure at term-equivalent age (TEA) are associated with development at 2 years of age in children born moderate–late preterm (MLPT).Study designA cohort of MLPT infants had brain MRI at approximately TEA (38–44 weeks’ postmenstrual age) and had a developmental assessment (Bayley Scales of Infant and Toddler Development and Infant Toddler Social Emotional Assessment) at 2 years’ corrected age. Relationships between cortical grey matter and white matter volumes and 2-year developmental outcomes were explored using voxel-based morphometry. Relationships between diffusion tensor measures of white matter microstructure (fractional anisotropy (FA) and axial (AD), radial (RD) and mean (MD) diffusivities) and 2-year developmental outcomes were explored using tract-based spatial statistics.Results189 MLPT children had data from at least one MRI modality (volumetric or diffusion) and data for at least one developmental domain. Larger cortical grey and white matter volumes in many brain regions, and higher FA and lower AD, RD and MD in several major white matter regions, were associated with better cognitive and language scores. There was little evidence that cortical grey matter and white matter volumes and white matter microstructure were associated with motor and behavioural outcomes.ConclusionsRegional cortical grey matter and white matter volumes and white matter microstructure are associated with cognitive and language development at 2 years of age in MLPT children. Thus, early alterations to brain volumes and microstructure may contribute to some of the developmental deficits described in MLPT children.

scholarly journals Arterial stiffness and dementia pathology

Neurology ◽  
2018 ◽  
Vol 90 (14) ◽  
pp. e1248-e1256 ◽  
Author(s):  
Timothy M. Hughes ◽  
Lynne E. Wagenknecht ◽  
Suzanne Craft ◽  
Akiva Mintz ◽  
Gerardo Heiss ◽  
...  
Keyword(s):  
White Matter ◽  
Arterial Stiffness ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Volume Ratio ◽  
Cognitive Testing ◽  
White Matter Hyperintensity ◽  
Cross Sectional ◽  
Brain Volumes ◽  
Atherosclerosis Risk In Communities

ObjectiveArterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts.MethodsThe Atherosclerosis Risk in Communities (ARIC)–Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([18F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE ε4 status. We examined the cross-sectional relationships including interactions by race, APOE ε4 status, and cognition.ResultsAmong the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01–1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease–susceptible regions (in mm3, β = −1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2–2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1–2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE ε4 status.ConclusionsArterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.

Slow-wave Sleep and MRI Markers of Brain Aging in a Community-based Sample

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011377
Author(s):  
Andree-Ann Baril ◽  
Alexa S Beiser ◽  
Vincent Mysliwiec ◽  
Erlan Sanchez ◽  
Charles S DeCarli ◽  
...  
Keyword(s):  
White Matter ◽  
Slow Wave ◽  
White Matter Hyperintensities ◽  
Slow Wave Sleep ◽  
Brain Volume ◽  
Brain Aging ◽  
Brain Mri ◽  
Community Based ◽  
Brain Infarcts ◽  
Absolute Duration

Objective:To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI.Methods:We studied 492 participants (58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE4 carrier status, stroke risk factors, sleeping pill use, body mass index and depression.Results:Less slow-wave sleep was associated with lower cortical brain volume (absolute duration, β[standard error]: 0.20[0.08], p=0.015; percentage, 0.16[0.08], p=0.044), lower subcortical brain volume (percentage, 0.03[0.02], p=0.034), and higher white matter hyperintensities volume (absolute duration, -0.12[0.05], p=0.010; percentage -0.10[0.04], p=0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts.Conclusion:Loss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

scholarly journals Maternal Dietary Intake of Omega-3 Fatty Acids Correlates Positively with Regional Brain Volumes in 1-Month-Old Term Infants

2019 ◽  
Vol 30 (4) ◽  
pp. 2057-2069 ◽  
Author(s):  
Sarah U Morton ◽  
Rutvi Vyas ◽  
Borjan Gagoski ◽  
Catherine Vu ◽  
Jonathan Litt ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Vitamin B12 ◽  
Maternal Nutrition ◽  
Brain Regions ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Neurodevelopmental Outcomes ◽  
Term Infants ◽  
Brain Volumes ◽  
Infant Brain

Abstract Maternal nutrition is an important factor for infant neurodevelopment. However, prior magnetic resonance imaging (MRI) studies on maternal nutrients and infant brain have focused mostly on preterm infants or on few specific nutrients and few specific brain regions. We present a first study in term-born infants, comprehensively correlating 73 maternal nutrients with infant brain morphometry at the regional (61 regions) and voxel (over 300 000 voxel) levels. Both maternal nutrition intake diaries and infant MRI were collected at 1 month of life (0.9 ± 0.5 months) for 92 term-born infants (among them, 54 infants were purely breastfed and 19 were breastfed most of the time). Intake of nutrients was assessed via standardized food frequency questionnaire. No nutrient was significantly correlated with any of the volumes of the 61 autosegmented brain regions. However, increased volumes within subregions of the frontal cortex and corpus callosum at the voxel level were positively correlated with maternal intake of omega-3 fatty acids, retinol (vitamin A) and vitamin B12, both with and without correction for postmenstrual age and sex (P &lt; 0.05, q &lt; 0.05 after false discovery rate correction). Omega-3 fatty acids remained significantly correlated with infant brain volumes after subsetting to the 54 infants who were exclusively breastfed, but retinol and vitamin B12 did not. This provides an impetus for future larger studies to better characterize the effect size of dietary variation and correlation with neurodevelopmental outcomes, which can lead to improved nutritional guidance during pregnancy and lactation.

Abstract WP192: Periventricular White Matter Hyperintensities Are Associated With Functional Decline: The Northern Manhattan Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mandip S Dhamoon ◽  
Ying-Kuen Cheung ◽  
Ahmet M Bagci ◽  
Chensy Marquez ◽  
Noam Alperin ◽  
...  
Keyword(s):  
White Matter ◽  
Repeated Measures ◽  
Brain Mri ◽  
Large Population ◽  
Functional Decline ◽  
Brain Regions ◽  
White Matter Hyperintensity ◽  
Periventricular White Matter ◽  
Brain White Matter

Background: We previously showed that overall brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. However, it was unclear whether WMHV in particular brain regions was more predictive of decline. We hypothesized that WMHV in particular brain regions would be more predictive of functional decline. Methods: In the Northern Manhattan MRI study, participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions (brainstem, cerebellum, and bilateral frontal, occipital, temporal, and parietal lobes, and bilateral anterior and posterior periventricular white matter [PVWM]) was determined separately by combining bimodal image intensity distribution and atlas based methods. Participants had annual functional assessments with the Barthel index (BI, range 0-100) over a mean of 7.3 years and were followed for stroke and myocardial infarction (MI). Due to multiple collinear variables, lasso regression was used to select regional WMHV variables, and adjusted generalized estimating equations models estimated associations with baseline BI and change over time. Results: Among 1195 participants, mean age was 71 (SD 9) years, 460 (39%) were male, 802 (67%) had hypertension and 224 (19%) diabetes. Using lasso regularization, only right anterior PVWM was selected, and each SD increase was associated with accelerated functional decline, of -0.95 additional BI points per year (95% CI -1.20, -0.70) in an unadjusted model, -0.92 points per year (95% CI -1.18, -0.67) with baseline covariate adjustment, and -0.87 points per year (95% CI -1.12, -0.62) after adjusting for stroke and MI. This decline was in addition to a mean decline of -1.13 (95% CI -1.29, -0.97), -1.19 (95% CI -1.36, -1.01), and -1.04 (95% CI -1.21, -0.88) BI points per year, respectively. Conclusions: In this large population-based study with long-term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline. Periventricular WMHV may have a greater effect on mobility due to dysfunction in descending leg motor tracts.

The Relationship Between Isolated Hypertension with Brain Volumes in UK Biobank

2021 ◽  
Author(s):  
Danielle Newby ◽  
Laura Winchester ◽  
William Sproviero ◽  
Marco Fernandes ◽  
Upamanyu Ghose ◽  
...  
Keyword(s):  
White Matter ◽  
Grey Matter ◽  
Brain Mri ◽  
Uk Biobank ◽  
Brain Health ◽  
Brain Volumes ◽  
Dementia Risk ◽  
Diastolic Hypertension ◽  
The Impact ◽  
The Relationship

Hypertension is a well-established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertension, such as, isolated hypertension on brain health and its comparison to systolic-diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure or systolic-diastolic hypertension using the largest cohort of healthy individuals. Using the UK Biobank cohort, we carried out a cross-sectional study using 29775 participants [mean age 63 years, 53% female] with BP measurements and brain MRI data. We used linear regression models adjusted for multiple confounders to compare a variety of global, sub cortical and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic-diastolic hypertension. The results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller grey matter but larger white matter microstructures and macrostructures compared to normotensives. However, isolated hypertensives had larger total grey matter and smaller white matter traits when comparing these regions with participants with systolic-diastolic hypertension.These results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic-diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.

Abstract WP451: Cognitive Impairment in Cardiac Disease - Neuroimaging Associations

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jane Cannon ◽  
Mark Findlay ◽  
Krishna Dani ◽  
Jesse Dawson ◽  
David A Dickie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Cardiac Disease ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Perivascular Spaces ◽  
Intracranial Volume ◽  
Brain Volumes ◽  
Multivariable Models ◽  
Cardiac Status

Introduction: Atrial fibrillation (AF) and heart failure (HF) are associated with cognitive impairment. We used neuroimaging to describe if this association is explained by cardioembolism or other mechanisms. Methods: We included adults with HF (ejection fraction<45%) and AF but no stroke history. Healthy volunteer controls were matched, 1:2 ratio. Participants were assessed with Repeatable Battery for the Assessment of Neurospychological Status (RBANS), Hospital Anxiety and Depression Score (HADS) and 3-T brain MRI. Scans were graded for:infarct, enlarged perivascular spaces, microbleeds, global and regional (hippocampal) atrophy with consensus scoring by four raters using validated, ordinal assessment scales. Brain volumes were semi-automatically acquired using cluster analysis of T1-weighted and FLAIR voxel intensities and diffeomorphic atlas-based segmentation. CSF, hippocampal and white matter volumes were corrected for intracranial volume. We described univariable differences between groups and then created multivariable models where cardiac status was the dependent variable, RBANS and MRI data were the predictors. Results: Of 50 participants, AF-HF (n=34) had poorer RBANS (MD:16.9, SE:3.44; p<0.001). Differences were independent of education and HADS. Infarcts and ordinal markers of atrophy were significantly different between groups, SVD markers were increased in AF-HF but did not reach significance. Quantitative measures of white matter differed between groups but measures of atrophy did not.(Table) On multivariable models, no imaging feature was independently associated with cardiac status. Discussion: The association between cognitive impairment and cardiac disease may not be solely driven by occult cardioembolism; small vessel disease and other, neuroimaging independent, factors also interact. Differences between ordinal scales and quantitative scores suggest that future studies should use robust volumetric analyses.

Abstract 51: Effects of Vascular Risk Factors on Microstructural White Matter: A Voxel-Based Longitudinal Diffusion Tensor Imaging Study

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Pauline Maillard ◽  
Evan Fletcher ◽  
Owen Carmichael ◽  
Dan Mungas ◽  
Bruce Reed ◽  
...  
Keyword(s):  
Risk Factors ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Brain Aging ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Local Contraction

Background: Diabetes mellitus type II (DMT2) and hypertension (HTN) have been reported as increasing the risk of dementia. Because recent cross-sectional diffusion tensor imaging (DTI) studies have identified association between vascular risk factors (VRF) and microstructural white matter (WM) abnormalities in elderly, longitudinal DTI studies are needed to determine whether VRF may be associated with accelerated WM degeneration over time. Methods: 114 cognitively normal participants from University of California, Davis Alzheimer’s Disease Center, aged 73.9±6.7, received a comprehensive clinical evaluation and brain MRI including T1-weighted and DTI sequences on two dates (mean delay: 3.3 years). Baseline and follow-up FA maps were calculated, aligned, and subtracted to provide FA change ([[Unable to Display Character: &#8710;]]FA) maps and warped to a common template (MDT). Coregistration of baseline and follow-up T1 maps to MDT enabled computation of Jacobian images (i.e. the local contraction factor). VRF score (VRFS) was computed as the sum of DMT2, HTN and hyperlipidemia (HYP) incidence based on the subject’s medical history. We then used voxel-based linear regressions to relate annual [[Unable to Display Character: &#8710;]]FA and Jacobian determinants to VRFS, adjusting for potential confounders. Resulting T maps were corrected for multiple comparisons. Results: Poorer VRF score was associated with higher rate of [[Unable to Display Character: &#8710;]]FA loss and of GM atrophy with regions most heavily implicated including the corpus callosum and the frontal GM (see Figure1). Conclusions: This is one of very few studies of longitudinal DTI change in the elderly. DMT2, HTH and HYP are associated with accelerated WM degeneration and GM atrophy in areas whose integrity is known to be reduced in mild cognitive impairment and dementia. Future work should clarify the independent role of these vascular risk factors in accelerating brain aging.

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