期刊
NEUROLOGY
卷 76, 期 16, 页码 1395-1402出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182166e96
关键词
-
资金
- NIH [NIA R01-AG29411, R21-AG29840, P50-AG005134, P01-AG09466, P01-AG14449, P30-AG10161, R01-AG17917, R01-AG10688, NCRR P41-RR14075, U24-RR021382]
- Alzheimer's Association
- Mental Illness and Neuroscience Discovery (MIND) Institute
- Illinois Department of Public Health
- Ceregene
- Danone Research B.V.
- Eisai Inc.
- Elan Corporation
- Merck Serono
- Pamlab, L.L.C.
- Orasi, Inc.
- Pfizer Inc
- Illinois Department of Public Aid Alzheimer's Disease Assistance Center
- Janssen
- Bristol-Myers-Squibb
- NIH/NIA
- Anonymous Foundation
- American Health Assistance Foundation
- Fidelity Biosciences
Objective: Since Alzheimer disease (AD) neuropathology is thought to develop years before dementia, it may be possible to detect subtle AD-related atrophy in preclinical AD. Here we hypothesized that the disease signature of AD-related cortical thinning, previously identified in patients with mild AD dementia, would be useful as a biomarker to detect anatomic abnormalities consistent with AD in cognitively normal (CN) adults who develop AD dementia after longitudinal follow-up. Methods: We studied 2 independent samples of adults who were CN when scanned. In sample 1, 8 individuals developing AD dementia (CN-AD converters) after an average of 11.1 years were compared to 25 individuals who remained CN (CN-stable). In sample 2, 7 CN-AD converters (average follow-up 7.1 years) were compared to 25 CN-stable individuals. Results: AD-signature cortical thinning in CN-AD converters in both samples was remarkably similar, about 0.2 mm (p < 0.05). Despite this small absolute difference, Cohen d effect sizes for these differences were very large (> 1). Of the 11 CN individuals with baseline low AD-signature thickness (>= 1 SD below cohort mean), 55% developed AD dementia over nearly the next decade, while none of the 9 high AD-signature thickness individuals (>= 1 SD above mean) developed dementia. This marker predicted time to diagnosis of dementia (hazard ratio = 3.4, p < 0.0005); 1 SD of thinning increased dementia risk by 3.4. Conclusions: By focusing on cortical regions known to be affected in AD dementia, subtle but reliable atrophy is identifiable in asymptomatic individuals nearly a decade before dementia, making this measure a potentially important imaging biomarker of early neurodegeneration. Neurology (R) 2011; 76: 1395-1402
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