P1‐311: Testing the new diagnostic criteria for Preclinical Alzheimer's disease: MRI biomarker of Alzheimer's disease‐related atrophy in cognitively normal individuals predicts cognitive decline

dementia, it may be possible to detect subtle AD-related a trophy in preclinical AD. Here we hypothesized that the “disease signature” of AD-related cortical thinning, previously identified in mild AD dementia patients, 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 two independent samples of adults who were CN when scanned. In sample #1, 8 individuals developing AD dementia (CN-ADConverters) after an average of 11.1 years were compared to 25 individuals whore mained 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 0.2mm (p < 0.05). Despite this small absolute difference, Cohen’s d effect sizes for these differences were very large ( > 1). Of the 11 CN individuals with baseline Low AD-signature Thickness ( 1 standard deviation(S.D.) below cohort mean), 55% developed AD dementia over nearly the next decade, while none of the 9 High AD-signature Thickness individuals ( 1S.D. above mean) developed dementia. This marker predicted time to diagnosis of dementia (H.R.1⁄4 3.4, p< 0.0005); one S.D. 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.