P4-110: White matter hyperintensities in American Indian Alzheimer's disease patients and Indian controls

Abstract

Previous research suggests that cerebral vascular pathology may synergize with Alzheimer disease (AD) pathology, leading to earlier onset of clinical dementia symptoms and more severe dementia than produced by AD pathology alone. Evidence from pathological and clinical studies suggests that WMHs are at least partially due to the effects of cerebrovascular disease and aging and may be increased by elevated homocysteine levels. As part of a larger study exploring the relationship of cardiovascular comorbidities and risk factors in American Indians, brain MRI images of 11 Indian AD subjects and 9 age-matched Indian controls were obtained. White matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV) were calculated. AD subjects and controls did not differ significantly in gender, history of hypertension, diabetes, or history of high cholesterol, although a history of hypertension and diabetes was more common among AD subjects. No subject had a history of myocardial infarction or stroke. AD and control groups did not differ in age (range for all subjects was 61–89 years), % Native American heritage, waist size or body mass index. Median Native American heritage was 50% or greater in both groups. Education ranged from 5–13 years in the AD group and 12–16 years in controls. Median plasma homocysteine concentration was higher in AD subjects (11 μmol/L vs. 9.8 μmol/L), but was not statistically significant. Because of small sample size, neuroimaging findings did not differ significantly between the 2 groups, but AD subjects clearly had greater WMHV (median 15.64 vs. 5.52 cc), greater WMHV/WBV ratio (median 1.63 vs. 0.65 %), and a far greater range of WMHV. With AD subjects and controls combined, WBV correlated with BMI and age. WMHV and WMHV/WBV correlated inversely with MMSE scores (p = 0.001, 0.002, respectively), WMHV correlated positively with % Native American Heritage (p = 0.047), and WMHV/WBV correlation negatively with education (p = 0.040). This study gave further evidence of the influence of hypertension and diabetes on the clinical expression of AD and on brain changes associated with vascular disease in American Indians.