Neurophysiological Correlates of Leukoaraiosis in Alzheimer's Disease, Mild Cognitive Impairment, and Nondemented Elderly

Leukoaraiosis (LA) refers to neurodegenerative white matter changes that are associated with age and appear as areas of hyperintensity on magnetic resonance imaging (Hachinski, Potter, and Merskey, 1987). Leukoaraiosis has been associated with cognitive impairment and vascular risk factors in nondemented elderly (DeCarli et al., 1995; deGroot et al., 2000), while the relationship with demented elderly is unclear. The current study examined the severity of LA, the relationship between vascular risk factors and LA, and associations between neuropsychological functioning and LA across three groups with varied levels of cognitive functioning. Total LA was more severe among subjects with Alzheimer's Disease (AD, n = 30) than those with Mild Cognitive Impairment (MCI, n = 30) and nondemented elderly (NE, n = 30), but MCI did not have more severe LA than NE. Periventricular and subcortical LA were more severe in AD than MCI, but not NE. Age was a significant predictor of both periventricular and subcortical LA, but hypertension and homocysteine were not independently related to LA. Total LA was inversely associated with neuropsychological performance for all subjects, though correlations were low to moderate (r = -.23 to r = -.36), and were not significant after controlling for the effects of age and cerebral atrophy. Within the AD group, several significant positive correlations between LA and neuropsychological measures emerged, but were reduced when controlling for age, but not atrophy. Results for periventricular LA were similar to total LA findings, while subcortical LA had fewer correlations with neuropsychological measures. Neuropsychological measures of general cognitive functioning, verbal fluency, memory, and executive functioning were associated with increased total and periventricular LA, while measures assessing confrontation naming, visuoconstructional ability, and attention were less affected. Across all subjects, age and cerebral atrophy contributed to associations between neuropsychological performance and LA. Despite greater atrophy and LA in the AD group, neuropsychological functioning was not associated with increased LA within the AD group in the current study. This suggests that relationships between LA and neuropsychological functioning may be identifiable in normal controls, but that disease characteristics play a larger role in cognition in dementia populations such as Alzheimer's disease.