Log-transformed White Matter Hyperintensity Volume Research Articles

Consistency of associations of systolic and diastolic blood pressure with white matter hyperintensities: A meta-analysis.

BackgroundWhite matter hyperintensities are the commonest manifestation of cerebral small vessel disease, associated with stroke, functional impairment, and cognitive decline. They are commonly preceded by hypertension, but the magnitude and clinical importance of this association is unclear.AimsQuantify the relationship between blood pressure and white matter hyperintensities across studies.MethodsPubMed and EMBASE were searched for studies reporting associations between concurrent or historic blood pressure and white matter hyperintensities. Beta coefficients from linear models were extracted, whether standardized, unstandardized, unadjusted or adjusted for age, sex, and cardiovascular risk factors. Beta-coefficients were combined by fixed and random effects meta-analysis, combining standardized beta-coefficients or unstandardized coefficients measured by consistent methods.ResultsTwenty-five of 3230 papers were eligible, including 53,392 participants. Systolic blood pressure was significantly associated with white matter hyperintensity volume (WMHV) after maximal adjustment (standardized beta 0.096, 95%CI 0.06–0.133, p < 0.001, I2 = 65%), including for concurrent readings (b = 0.106, p < 0.001) or readings five years previously (b = 0.077, p < 0.001), and for younger or older populations (mean age < 65: b = 0.114; >65 b = 0.069). Unstandardized, adjusted associations were similar for raw WMHV, log-transformed WMHV, or WMHV as percentage of intracranial volume. Unadjusted associations with systolic blood pressure (SBP) were greater (standardized beta = 0.273, 0.262–0.284, p < 0.0001). However, while associations with DBP were weaker than SBP (standardized beta = 0.065, p < 0.001), they were minimally affected by adjustment for age.ConclusionsA standard deviation increase in SBP is associated with 10% of a standard deviation increase in WMHV, providing the current best estimate of the potential reduction in progression of white matter hyperintensities expected with good control of blood pressure.

Association of childhood lead exposure with MRI measurements of structural brain integrity in midlife

BACKGROUND AND AIM: Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown. This study tested the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife. METHODS: Hypotheses tested in the Dunedin Study, a New Zealand-based population-representative 1972-1973 birth cohort (N=564 analytic sample) followed to age 45 years. Childhood blood-lead levels measured at age 11 years were combined with MRI-measures of brain integrity at age 45 years, including gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy), and brainAGE, a composite index of the gap between chronological age and a machine-learning algorithm-estimated brain age. Age-45 cognitive function was also assessed, objectively via the Wechsler Adult Intelligence Scale–IV and subjectively via informant and self-reports. RESULTS:Mean(SD) age-11 blood-lead level was 10.99(4.63)µg/dL. After adjusting for covariates, each 5µg/dL higher childhood blood-lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95%CI:-2.35,-0.02, P=.05), 0.10-cm3 smaller hippocampal volume (95%CI:-0.17,-0.03, P=.006), lower global fractional anisotropy (b=-0.12, 95%CI:-0.24,-0.01, P=.04), and 0.77-years older brainAGE (95%CI:0.02, 1.51, P=.05). There were no statistically significant associations between blood-lead level and log-transformed white matter hyperintensity volume (b=0.05 log mm3, 95%CI:-0.02, 0.13, P=.17) or mean cortical thickness (b=-0.004 mm, 95%CI:-0.012, 0.004, P=.39). Each 5µg/dL higher childhood blood-lead level was significantly associated with a 2.07-point lower score (95%CI:-3.39,-0.74, P=.002) in age-45 IQ, and a 0.12-point higher score (95%CI:0.01, 0.23, P=.03) on informant-rated cognitive problems. There was no statistically significant association between childhood blood-lead levels and self-reported cognitive problems (b=-0.02 points, 95%CI: -0.10, 0.07, P=.68). CONCLUSIONS:In this four-decade study, higher childhood blood-lead level was associated with lower structural brain integrity in midlife. Childhood lead exposure may have long-term consequences for adult brain health. KEYWORDS: Heavy metals, Neurodegenerative outcomes, Environmental epidemiology

Abstract MP26: Silent Small-vessel Cerebrovascular Disease In Individuals With A Family History Of Coronary Heart Disease: The Atherosclerosis Risk In Communities (ARIC) Study

Background: It is established that a family history of coronary heart disease (FHCHD) is associated with coronary atherosclerosis in healthy first-degree relatives, but the extent to which FHCHD is associated with silent cerebrovascular disease (cSVD) is unknown. We hypothesized a higher prevalence of cSVD in healthy persons with FHCHD, independent of traditional risk factors, compared to those without FHCHD. Methods: ARIC is a community-based cohort study with self-reported family history data and brain magnetic resonance imaging (visit 5; 2011-13). The association between binary markers of cSVD (lacunar infarcts and/or cerebral microbleeds), or log-transformed white matter hyperintensity volume (WMH), and FHCHD (parent and/or sibling), or number of relatives was examined using separate adjusted multivariable logistic or linear regression models respectively. Sensitivity analysis (N=183) excluded prevalent CHD. Race interaction terms were included. Results: Of 1828 participants (76±5yo, 60% female, 28% black), 787 had FHCHD (699 parental, 209 sibling FHCHD). There were increased adjusted odds of lacunar infarct among those with parental FHCHD (Table). An increased odds of cerebral microbleeds were seen among those with sibling history but not parental. Effect estimates were similar when excluding those with prevalent CHD (Table). Greater number of siblings affected was associated with higher odds of lacunar infarct (OR 1.35, CI 1.04-1.74), lobar (OR 1.53, CI 1.12-2.09) and subcortical microbleeds (OR 1.30, CI 1.01-1.66). Odds of a lacunar infarct being present were higher among blacks (p-interaction 0.04) with paternal FHCHD (OR 2.20, CI 1.35-3.58) compared to whites (OR 1.17, CI 0.87-1.56). Neither FHCHD nor number of affected relatives was associated with WMH. Conclusions: Our results suggest that some cSVD manifestations are associated with FHCHD, potentially representing shared mechanisms in different vascular beds, and perhaps a genetic propensity for vascular disease.

Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife

Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown. To test the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife. The Dunedin Study followed a population-representative 1972-1973 birth cohort in New Zealand (N = 564 analytic sample) to age 45 years (until April 2019). Childhood blood lead levels measured at age 11 years. Structural brain integrity at age 45 years assessed via MRI (primary outcomes): gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy [theoretical range, 0 {diffusion is perfectly isotropic} to 100 {diffusion is perfectly anisotropic}]), and the Brain Age Gap Estimation (BrainAGE), a composite index of the gap between chronological age and a machine learning algorithm-estimated brain age (0 indicates a brain age equivalent to chronological age; positive and negative values represent an older and younger brain age, respectively). Cognitive function at age 45 years was assessed objectively via the Wechsler Adult Intelligence Scale IV (IQ range, 40-160, standardized to a mean of 100 [SD, 15]) and subjectively via informant and self-reports (z-score units; scale mean, 0 [SD, 1]). Of 1037 original participants, 997 were alive at age 45 years, of whom 564 (57%) had received lead testing at age 11 years (302 [54%] male) (median follow-up, 34 [interquartile range, 33.7-34.7] years). Mean blood lead level at age 11 years was 10.99 (SD, 4.63) μg/dL. After adjusting for covariates, each 5-μg/dL higher childhood blood lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95% CI, -2.35 to -0.02 cm2; P = .05), 0.10-cm3 smaller hippocampal volume (95% CI, -0.17 to -0.03 cm3; P = .006), lower global fractional anisotropy (b = -0.12; 95% CI, -0.24 to -0.01; P = .04), and a BrainAGE index 0.77 years older (95% CI, 0.02-1.51 years; P = .05) at age 45 years. There were no statistically significant associations between blood lead level and log-transformed white matter hyperintensity volume (b = 0.05 log mm3; 95% CI, -0.02 to 0.13 log mm3; P = .17) or mean cortical thickness (b = -0.004 mm; 95% CI, -0.012 to 0.004 mm; P = .39). Each 5-μg/dL higher childhood blood lead level was significantly associated with a 2.07-point lower IQ score at age 45 years (95% CI, -3.39 to -0.74; P = .002) and a 0.12-point higher score on informant-rated cognitive problems (95% CI, 0.01-0.23; P = .03). There was no statistically significant association between childhood blood lead levels and self-reported cognitive problems (b = -0.02 points; 95% CI, -0.10 to 0.07; P = .68). In this longitudinal cohort study with a median 34-year follow-up, higher childhood blood lead level was associated with differences in some MRI measures of brain structure that suggested lower structural brain integrity in midlife. Because of the large number of statistical comparisons, some findings may represent type I error.

Replication of Top Loci From COL4A1/2 Associated With White Matter Hyperintensity Burden in Patients With Ischemic Stroke.

The purpose of this study was to replicate the top loci associated with white matter hyperintensity (WMH) phenotypes identified by large genome-wide association studies and the loci identified from the previous candidate gene studies. A total of 946 Geisinger MyCode patients with acute ischemic stroke with validated European ancestry and magnetic resonance imaging data were included in this study. Log-transformed WMH volume, as a quantitative trait, was calculated by a fully automated quantification process. The genome-wide association studies was carried out by a linear mixed regression model (GEMMA). A candidate-single nucleotide polymorphism analysis by including known single nucleotide polymorphisms, reported from a meta-analysis and several large GWAS for WMH, was conducted in all cases and binary converted extreme cases. No genome-wide significantly associated variants were identified. In a candidate-single nucleotide polymorphism study, rs9515201 (COL4A2) and rs3744028 (TRIM65), 2 known genetic loci, showed nominal or trend of association with the WMH volume (β=0.13 and P=0.001 for rs9515201; β=0.094 and P=0.094 for rs3744028), and replicated in a subset of extreme cases versus controls (odds ratio=1.78, P=7.74×10-4 for rs9515201; odds ratio=1.53, P=0.047 for rs3744028, respectively). MTHFR677 cytosine/thymine (rs1801133) also showed an association with the binary WMH with odds ratio=1.47 for T allele (P=0.019). Replication of COL4A1/2 associated with WMH reassures that the genetic risk factors for monogenic and polygenic ischemic stroke are shared at gene level.

Revised Framingham Stroke Risk Profile: Association with Cognitive Status and MRI-Derived Volumetric Measures.

The Framingham Stroke Risk Profile (FSRP) was created in 1991 to estimate 10-year risk of stroke. It was revised in 2017 (rFSRP) to reflect the modern data on vascular risk factors and stroke risk. This study examined the association between the rFSRP and cognitive and brain aging outcomes among participants from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS). Cross-sectional rFSRP was computed at baseline for 19,309 participants (mean age = 72.84, SD = 8.48) from the NACC-UDS [9,697 (50.2%) normal cognition, 4,705 (24.4%) MCI, 4,907 (25.4%) dementia]. Multivariable linear, logistic, or ordinal regressions examined the association between the rFSRP and diagnostic status, neuropsychological test performance, CDR® Sum of Boxes, as well as total brain volume (TBV), hippocampal volume (HCV), and log-transformed white matter hyperintensities (WMH) for an MRI subset (n = 1,196). Models controlled for age, sex, education, racial identity, APOEɛ4 status, and estimated intracranial volume for MRI models. The mean rFSRP probability was 10.42% (min = 0.50%, max = 95.71%). Higher rFSRP scores corresponded to greater CDR Sum of Boxes (β= 0.02, p = 0.028) and worse performance on: Trail Making Test A (β= 0.05, p < 0.001) and B (β= 0.057, p < 0.001), and Digit Symbol (β= -0.058, p < 0.001). Higher rFSRP scores were associated with increased odds for a greater volume of log-transformed WMH (OR = 1.02 per quartile, p = 0.015). No associations were observed for diagnosis, episodic memory or language test scores, HCV, or TBV. These results support the rFSRP as a useful metric to facilitate clinical research on the associations between cerebrovascular disease and cognitive and brain aging.

Prospectively Collected Cardiovascular Biomarkers and White Matter Hyperintensity Volume in Ischemic Stroke Patients

Background: Few prospective cohort studies collect detailed information on stroke characteristics among individuals who experience ischemic stroke, including white matter hyperintensity volume, and thus cannot explore how prospectively collected biomarkers prior to the stroke influence white matter hyperintensity volume. We explored the association between a large panel of prospectively collected lipid and inflammatory biomarkers and white matter hyperintensity volume among participants in the Women's Health Study with incident ischemic stroke. Methods: Among Women's Health Study participants with first ischemic stroke who had baseline serum biomarkers and available magnetic resonance imaging, we measured white matter hyperintensity volume using a validated semi-automated method. Linear regression was used to explore the associations between biomarkers and log-transformed white matter hyperintensity volume. Results: After multivariate adjustment, a 1% increment in HbA1c% was associated with an increase in white matter hyperintensity volume (P value = .05). Evidence of a nonlinear association between high density lipoprotein cholesterol levels and ApoA1 levels with white matter hyperintensity volume was noted (P values for nonlinearity = .01 and .001, respectively). No other biomarkers were significantly associated with white matter hyperintensity volume. Conclusions: Chronic hyperglycemia as evidenced by HbA1c levels measured years prior to stroke is associated with white matter hyperintensity volume at the time of stroke. Additional research is needed to explain why low levels of high density lipoprotein cholesterol levels and ApoA1 may be associated with similar white matter hyperintensity volume as high levels.

Abstract TP476: White Matter Hyperintensity Burden is Associated With Poor Collateral Flow and Worse Outcomes in an Acute Ischemic Stroke Cohort

Introduction: White matter hyperintensity volume (WMHv), a quantitative neuroimaging biomarker of cerebral small vessel disease (CSVD), is associated worse outcomes after ischemic stroke. In this study, we hypothesized that worse outcomes in CSVD patients were due to poor collateral flow during acute ischemia. Methods: 47 patients with acute ischemic stroke (AIS) were prospectively enrolled in this study. Serial MRIs were performed at 3 hours and 30 days after stroke onset. 3-hour FLAIR images were used to determine WMHv, after manually delineating lesions with MIPAV. An index of collateral flow (delayed perfusion to the penumbra) was determined by subtracting core volume (volume of tissue with ADC&lt;600) from the volume of brain tissue with Tmax&gt;2. Patient’s NIHSS was scored at 3 hours and 30 days after stroke onset and the difference was calculated (ΔNIHSS). Log-transformed WMHv was correlated to ΔNIHSS and the collateral flow index, using Pearson correlation. Results: Mean age = 63.9 years (SD 13.5); 37% female; median 3-hour NIHSS = 13 (IQR 6.5-20); median change in NIHSS between 3h and 30d = 4 (IQR: 0-7); median core volume = 13cm3 (IQR 4.3-35.6); median WMHv = 1.257cm3 (IQR 641-3595). WMHv was associated with reduced improvement in ΔNIHSS (R=-0.42, ρ=0.005). Furthermore, WMHv demonstrated a trend for association with poor collateral flow (R=-0.28, ρ=0.062). In this dataset, we will explore the relationship between WMHv and other tissue-based metrics of collateral flow, including the hypoperfusion intensity ratio (HIR) and the cerebral blood volume ratio (rCBV). Conclusions: Our study confirms that patients with CSVD have worse outcomes after AIS. The data also raise the possibility that these worse outcomes in CSVD patients may be mediated by compromised collateral flow in the setting of acute ischemia.

Prospectively collected lifestyle and health information as risk factors for white matter hyperintensity volume in stroke patients.

Most studies of white matter hyperintensity volume (WMHV) in stroke patients lack reliable information on antecedent exposure to vascular risk factors. By leveraging prospective cohort data, we explored associations between lifestyle and health factors assessed 1year prior to stroke and WMHV in individuals who experienced an ischemic stroke. This analysis was nested within two large prospective studies of initially healthy individuals. Information on lifestyle factors and health conditions was collected prior to the stroke event through annual or biannual questionnaires. For individuals who experienced their first confirmed ischemic stroke and had available magnetic resonance imaging, we measured WMHV using a validated semiautomated method. Linear regression was used to explore associations between lifestyle factors and health conditions and log-transformed WMHV. We measured WMHV in 345 participants with a first ischemic stroke event (mean age = 74.4years; 24.9% male). After multivariate adjustment, history of diabetes was associated with decreased WMHV (p value = 0.06) while history of transient ischemic attack (p value = 0.09) and hypertension (p value = 0.07) were associated with increased WMHV. Most lifestyle factors and health conditions measured 1year prior to stroke were not associated with WMHV measured at the time of ischemic stroke. Future studies could examine whether long term exposure to these factors impacts diffuse microvascular ischemic brain injury among stroke patients.

Abstract 136: Genetics of White Matter Hyperintensity Burden in Patients With Ischemic Stroke: The MRI-GENIE Study

Introduction: The MRI-Genetics Interface Exploration (MRI-GENIE) study is the first international collaboration that aims to facilitate genetic discoveries in clinical cohorts of patients with acute ischemic stroke (AIS). We have amassed the largest-to-date collection of AIS cases with brain MRI scans and genome-wide genotyping to test the role of genetic susceptibility in MRI-based cerebrovascular traits. Objective/Hypothesis: To elucidate the genetic architecture of white matter hyperintensity (WMH) burden in AIS patients. Methods: Using a novel automated algorithm, we extracted WMH volume (WMHv) from clinical MRI scans of 2704 AIS patients (age 63.1 ± 14.7 years, 60.6% male) of European ancestry. Quality control (QC) measures were undertaken per subject and per SNP, excluding subjects with non-European ancestry and poor genotyping, as well as SNPs deviating from Hardy-Weinberg equilibrium and high levels of missingness. Imputation to the Haplotype Reference Consortium (HRC version r1.1) was conducted for 1712 remaining subjects with 2.8 million SNPs on the Michigan Imputation Server. After exclusion of poorly imputed SNPs (R 2 &lt;0.5) and SNPs with minor allele frequency &lt; 1%, 7.7 million SNPs remained for further analysis. Genome-wide association testing of natural log-transformed WMHv on the allelic dosage per SNP was adjusted for age, sex and principal components 1-10. Results: Genome-wide association testing has identified a novel locus on chromosome 2 (T allele at rs72856504) near the LDL Receptor related Protein 1B gene (LRP1B) that was significantly associated with WMHv burden in AIS (β=0.54, SE=0.098, p=3.65*10 -8 ). Conclusion: We have identified a novel locus (T allele rs72856504) on chromosome 2 near the LRP1B gene, which is specific for WMH in AIS and has not been previosuly described in stroke-free WMH cohorts. A replication effort involving additional independent cohorts of AIS patients with brain MRI and genome-wide genotyping is ongoing.

Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure.

Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but whether it is related to structural changes in the brain is not clear. We examined the associations between residential long-term exposure to ambient air pollution and markers of brain aging using magnetic resonance imaging. Framingham Offspring Study participants who attended the seventh examination were at least 60 years old and free of dementia and stroke were included. We evaluated associations between exposures (fine particulate matter [PM2.5] and residential proximity to major roadways) and measures of total cerebral brain volume, hippocampal volume, white matter hyperintensity volume (log-transformed and extensive white matter hyperintensity volume for age), and covert brain infarcts. Models were adjusted for age, clinical covariates, indicators of socioeconomic position, and temporal trends. A 2-μg/m(3) increase in PM2.5 was associated with -0.32% (95% confidence interval, -0.59 to -0.05) smaller total cerebral brain volume and 1.46 (95% confidence interval, 1.10 to 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% confidence interval, 0.01 to 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter. Exposure to elevated levels of PM2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy, and with higher odds of covert brain infarcts. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia- and stroke-free persons.

Long-Term Exposure to Fine Particulate Matter and Residential Proximity to Major Roads and Measures of Brain Structure

Background: Long-term exposure to ambient air pollution is associated with lower cognitive function in elderly people, but whether it is related to structural changes in the brain is not clear. We examined the association between residential long-term exposure to ambient air pollution and markers of brain structure using magnetic resonance imaging (MRI). Methods: Framingham Offspring Study participants who attended the 7th exam (1998- 2001), were age=60 years and free of dementia and stroke (1999-2005) were included in the study. Residential proximity to major roadways and modeled estimates of fine particulate matter (PM2.5 1-year average exposure in 2001) were assessed for New England and New York State. We constructed linear regression models of the cross- sectional associations between PM2.5 exposures and measures of total cerebral brain volume, hippocampal volume, and log-transformed white matter hyperintensity volume (WMH) adjusting for age, season, temporal trends, indicators of socioeconomic position, and clinical covariates. We hypothesized that higher exposures would be associated with smaller total cerebral brain and hippocampal volumes and larger WMH. Results: For 975 eligible participants (mean age 69 ± standard deviation 6, 52% female), a 2 µg/m3 increase in PM2.5 was associated with smaller total cerebral brain volume % (-0.29, 95% Confidence Interval (CI): -0.55, -0.02) but not with hippocampal volume or log WMH. The association between living close to a major road (50 m away versus 400 m on the log scale) and log WMH % had wide confidence intervals (-0.08, 95%CI: -0.17, 0.01) and there was no evidence of associations with other outcomes. Conclusions: Elevated exposure to PM2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia and stroke free persons.

Sleep duration is associated with white matter hyperintensity volume in older adults: the Northern Manhattan Study.

Self-reports of long or short sleep durations have indicated an association with cardiovascular morbidity and mortality, but there are limited data evaluating their association with white matter hyperintensity volume (WMHV), a marker of cerebral small vessel disease. We conducted a cross-sectional analysis of self-reported sleep duration to test for a correlation with white matter hyperintensities, measured by quantitative magnetic resonance imaging (MRI), in the Northern Manhattan Study. We used multivariable linear regression models to assess associations between both short (<6 h) and long (≥9 h) sleep durations and log-transformed WMHV, adjusting for demographic, behavioural and vascular risk factors. A total of 1244 participants, mean age 70 ± 9 years, 61% women and 68% Hispanics were analysed with magnetic resonance brain imaging and self-reported sleep duration. Short sleep was reported by 23% (n = 293) and long sleep by 10% (n = 121) of the sample. Long sleep (β = 0.178; P = 0.035), but not short sleep (β = -0.053; P = 0.357), was associated with greater log-WMHV in fully adjusted models. We observed an interaction between sleep duration, diabetes mellitus and log-WMHV (P = 0.07). In fully adjusted models, stratified analysis showed that long sleep duration was associated with greater WMHV only in those with diabetes (β = 0.78; P = 0.0314), but not in those without diabetes (β = 0.022; P = 0.2), whereas short sleep was not associated with white matter hyperintensities in those with or without diabetes. In conclusion, long sleep duration was associated with a greater burden of white matter lesions in this stroke-free urban sample. The association was seen mainly among those with diabetes mellitus.

Mediterranean diet and white matter hyperintensity volume in the Northern Manhattan Study.

To examine the association between a Mediterranean-style diet (MeDi) and brain magnetic resonance imaging white matter hyperintensity volume (WMHV). A cross-sectional analysis within a longitudinal population-based cohort study. A semiquantitative food frequency questionnaire was administered, and a score (range, 0-9) was calculated to reflect increasing similarity to the MeDi pattern. The Northern Manhattan Study. A total of 1091 participants, of whom 966 had dietary information (mean age, 72 years; 59.3% women, 64.6% Hispanic, 15.6% white, and 17.5% black). The WMHV was measured by quantitative brain magnetic resonance imaging. Linear regression models were constructed to examine the association between the MeDi score and the log-transformed WMHV as a proportion of total cranial volume, controlling for sociodemographic and vascular risk factors. On the MeDi scale, 11.6% scored 0 to 2, 15.8% scored 3, 23.0% scored 4, 23.5% scored 5, and 26.1% scored 6 to 9. Each 1-point increase in MeDi score was associated with a lower log WMHV (β=-.04, P=.01). The only MeDi score component that was an independent predictor of WMHV was the ratio of monounsaturated to saturated fat (β=-.20, P=.001). A MeDi was associated with a lower WMHV burden, a marker of small vessel damage in the brain. However, white matter hyperintensities are etiologically heterogenous and can include neurodegeneration. Replication by other population-based studies is needed.