Acceleration of White Matter Hyperintensity Burden Preceding Onset of Mild Cognitive Impairment (S24.006)

Abstract

Objective: Determine the timing of white matter hyperintensity (WMH) burden acceleration in relation to mild cognitive impairment (MCI) onset. Background Cerebral white matter change, observed as hyperintensities on T2 MRI, are very common in cognitively intact elderly. Those with greater baseline and rates of WMH accumulation are at increased risk of MCI, a likely precursor of progressive dementia. The timing of acceleration of WMH increase relative to clinical transition to MCI has not been established. Design/Methods: 189 cognitively intact older volunteers from the Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MCI was defined as being the first of two consecutive Clinical Dementia Rating scores of 0.5 or higher. The time before MCI, when the change in WMH burden accelerates, was assessed using a mixed-effects model with a change point for subjects who developed MCI during follow up. Results: During a follow up duration of up to 22.2 years, 135 subjects developed MCI. Acceleration in %WMH volume increase occurred 10.6 years before MCI onset. On average, the annual rate of change in %WMH increased an additional 3.3% after the change point. Acceleration in %ventricular CSF volume increase and total brain volume decrease occurred 3.7 and 5.0 years before the onset of MCI, respectively. Out of 63 volunteers who converted to MCI and had autopsy, only 28.5% had Alzheimer9s disease (AD) as the sole etiology of their dementia, while almost just as many had both AD and significant ischemic cerebrovascular disease present. Conclusions: Acceleration in WMH burden, a common indicator of cerebrovascular disease in the elderly, is a pathological change that emerges early in the pre-symptomatic phase leading to MCI. Monitoring longitudinal WMH change may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease specific modifying therapies prior to dementia onset. Supported by: NIH (P30 AG08017, M01 RR000334, R01 AG024059), Department of Veterans Affairs, Storms Family Fund at the Oregon Community Foundation, T&J Meyer Foundation. Disclosure: Dr. Silbert has nothing to disclose. Dr. Dodge has nothing to disclose. Dr. Perkins has nothing to disclose. Dr. Lahna has nothing to disclose. Dr. Kaye has received personal compensation for activities with Eli Lilly & Company as a participant on a data safety and monitoring board. Dr. Kaye has received research support from Elan Corporation, Danone Medical, Bristol-Myers Squibb Company, Satoris, and Intel.