PT  - JOURNAL ARTICLE
AU  - B.C. Dickerson
AU  - T.R. Stoub
AU  - R.C. Shah
AU  - R.A. Sperling
AU  - R.J. Killiany
AU  - M.S. Albert
AU  - B.T. Hyman
AU  - D. Blacker
AU  - L. deToledo-Morrell
TI  - Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults
AID  - 10.1212/WNL.0b013e3182166e96
DP  - 2011 Apr 19
TA  - Neurology
PG  - 1395--1402
VI  - 76
IP  - 16
4099  - http://n.neurology.org/content/76/16/1395.short
4100  - http://n.neurology.org/content/76/16/1395.full
SO  - Neurology2011 Apr 19; 76
AB  - 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.