|Title||Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Dickerson, BC, Stoub, TR, Shah, RC, Sperling, RA, Killiany, RJ, Albert, MS, Hyman, BT, Blacker, D, Detoledo-Morrell, L|
|Date Published||2011 Apr 19|
|Keywords||Aged, Aged, 80 and over, Alzheimer Disease, Biomarkers, Cerebral Cortex, Chi-Square Distribution, Cognition, Dementia, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Mental Status Schedule, Predictive Value of Tests, Regression Analysis|
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 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
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.
|PubMed Central ID||PMC3087406|
|Grant List||K24 AG035007 / AG / NIA NIH HHS / United States |
P01-AG09466 / AG / NIA NIH HHS / United States
P01-AG14449 / AG / NIA NIH HHS / United States
P30-AG10161 / AG / NIA NIH HHS / United States
P41-RR14075 / RR / NCRR NIH HHS / United States
P50-AG005134 / AG / NIA NIH HHS / United States
R01 AG029411 / AG / NIA NIH HHS / United States
R01-AG10688 / AG / NIA NIH HHS / United States
R01-AG17917 / AG / NIA NIH HHS / United States
R01-AG29411 / AG / NIA NIH HHS / United States
R21-AG29840 / AG / NIA NIH HHS / United States
U24-RR021382 / RR / NCRR NIH HHS / United States