PT  - JOURNAL ARTICLE
AU  - Lisa C. Silbert
AU  - Hiroko H. Dodge
AU  - Louie G. Perkins
AU  - Lena Sherbakov
AU  - David Lahna
AU  - Deniz Erten-Lyons
AU  - Randall Woltjer
AU  - Lynne Shinto
AU  - Jeffrey A. Kaye
TI  - Trajectory of white matter hyperintensity burden preceding mild cognitive impairment
AID  - 10.1212/WNL.0b013e3182661f2b
DP  - 2012 Aug 21
TA  - Neurology
PG  - 741--747
VI  - 79
IP  - 8
4099  - http://n.neurology.org/content/79/8/741.short
4100  - http://n.neurology.org/content/79/8/741.full
SO  - Neurology2012 Aug 21; 79
AB  - Objective: To determine the time of acceleration in white matter hyperintensity (WMH) burden, a common indicator of cerebrovascular pathology, in relation to conversion to mild cognitive impairment (MCI) in the elderly. Methods: A total of 181 cognitively intact elderly volunteers from the longitudinal, prospective, Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MRIs were analyzed for imaging markers of neurodegeneration: WMH and ventricular CSF (vCSF) volumes. The time before MCI, when the changes in WMH and vCSF burden accelerate, 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 19.6 years, 134 subjects converted to 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 %vCSF volume increase occurred 3.7 years before the onset of MCI. Out of 63 subjects who converted to MCI and had autopsy, only 28.5% had Alzheimer disease (AD) as the sole etiology of their dementia, while almost just as many (24%) 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 pathologic change that emerges early in the presymptomatic phase leading to MCI. Longitudinal changes in WMH may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease-modifying therapies prior to dementia onset. AD=Alzheimer disease; CDR=Clinical Dementia Rating; CI=confidence interval; FLAIR=fluid-attenuated inversion recovery; HTN=hypertension; ICV=intracranial volume; LBD=Lewy body disease; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; OBAS=Oregon Brain Aging Study; TE=echo time; TR=repetition time; VaD=vascular dementia; vCSF=ventricular CSF; WMH=white matter hyperintensity.