White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age.

OBJECTIVE: Examine the association of white matter hyperintensities (WMH) with risk of incident mild cognitive impairment (MCI) and rate of decline in multiple cognitive systems in community-based older persons.

METHODS: Participants ( n = 354) were older persons initially free of cognitive impairment from two ongoing longitudinal epidemiologic studies of aging. All underwent brain magnetic resonance imaging (MRI) for quantification of WMH and gray matter volumes and detailed annual clinical evaluations including 17 cognitive tests. Proportional hazards models were used to examine the relationship between WMH and incident MCI, and mixed-effects models were used to examine the relationship between WMH and decline in global cognition and five specific cognitive systems.

RESULTS: During up to about 6 years of follow-up (mean = 4.1), 106 (30% of 354) persons developed MCI. In a proportional hazards model adjusted for age, gender, and education, WMH volume was associated with a substantially increased risk of MCI ( P < 0.001). Thus, a person with a high WMH volume (90th percentile) was about 2.7 times more likely to develop MCI compared to a person with a low volume (10th percentile). WMH volume also was associated with an increased rate of decline in global cognition ( P < 0.001), perceptual speed, working memory, episodic memory, and semantic memory. Associations persisted after adjustment for total gray matter volume, vascular risk factors, and vascular diseases.

INTERPRETATION: WMH contribute to the development of MCI and are associated with progressive decline in multiple cognitive systems in old age.