TY - JOUR
T1 - Trajectory of white matter hyperintensity burden preceding mild cognitive impairment
AU - Silbert, Lisa C.
AU - Dodge, Hiroko H.
AU - Perkins, Louie G.
AU - Sherbakov, Lena
AU - Lahna, David
AU - Erten-Lyons, Deniz
AU - Woltjer, Randall
AU - Shinto, Lynne
AU - Kaye, Jeffrey A.
N1 - Funding Information:
L. Silbert receives research support from the NIH (1R01AG036772, P30 AG008017, P50 NS062684). She also receives reimbursement through Medicare or commercial insurance plans for providing clinical assessment and care for patients and for intraoperative neurophysiological monitoring, and is salaried to see patients at the Portland VA Medical Center. H. Dodge receives research support from the NIH (P30 AG008017, R01 AG033581), is chair of the Data Core Steering committee at the National Alzheimer's Coordinating Center, is a member of the Uniform Data Set (UDS) Neuropsychology Work Group for the National Alzheimer's Coordinating Center Clinical Task Force, and serves on Statistical Review Board for International Psychogeriatrics. L. Perkins, L. Sherbakov, and D. Lhana report no disclosures. D. Erten-Lyons receives research support from the Department of Veterans Affairs (Career Development Award grant) and the NIH. She also receives reimbursement through Medicare or commercial insurance plans for providing clinical assessment and care for patients and is salaried to see patients at the Portland VA Medical Center. R. Woltjer reports no disclosures. L. Shinto receives support from the NIH (R01 AG033613). She also receives reimbursement through commercial insurance plans for providing clinical assessment and care for patients. J. Kaye receives research support from the Department of Veterans Affairs (Merit Review grant) and the NIH (P30 AG008017, R01 AG024059, P30 AG024978, U01 AG010483); directs a center that receives research support from the NIH, Elan Corporation, and Intel Corporation; receives reimbursement through Medicare or commercial insurance plans for providing clinical assessment and care for patients; is salaried to see patients at the Portland VA Medical Center; and serves as an unpaid Chair of the Technology Professional Interest Area work group for the National Alzheimer's Association and as an unpaid Commissioner for the Center for Aging Services and Technologies Go to Neurology.org for full disclosures.
Funding Information:
Study funding: Supported in part by grants from the Department of Veterans Affairs and National Institutes of Health (1R01AG036772, P30 AG008017, R01 AG024059, R01 AG 033581, AT00066), the Max Millis Fund for Neurological Research, the Storms Family Fund at the Oregon Community Foundation, and the T&J Meyer Family Foundation.
PY - 2012/8/21
Y1 - 2012/8/21
N2 - 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 toMCI 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.
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 toMCI 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.
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U2 - 10.1212/WNL.0b013e3182661f2b
DO - 10.1212/WNL.0b013e3182661f2b
M3 - Article
C2 - 22843262
AN - SCOPUS:84866137019
SN - 0028-3878
VL - 79
SP - 741
EP - 747
JO - Neurology
JF - Neurology
IS - 8
ER -