RT Journal Article
SR Electronic
T1 Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 1395
OP 1402
DO 10.1212/WNL.0b013e3182166e96
VO 76
IS 16
A1 B.C. Dickerson
A1 T.R. Stoub
A1 R.C. Shah
A1 R.A. Sperling
A1 R.J. Killiany
A1 M.S. Albert
A1 B.T. Hyman
A1 D. Blacker
A1 L. deToledo-Morrell
YR 2011
UL http://n.neurology.org/content/76/16/1395.abstract
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.