Introduction: An Alzheimer's disease (AD) biomarker adjusted for age-related brain changes should improve specificity for AD-related pathological burden.
Methods: We calculated a brain-age-adjusted "personalized AD cortical thickness index" (pADi) in mild cognitive impairment patients from the Alzheimer's Disease Neuroimaging Initiative. We performed receiver operating characteristic analysis for discrimination between patients with and without cerebrospinal fluid evidence of AD and logistic regression in an independent sample to determine if a dichotomized pADi predicted conversion to AD dementia.
Results: Receiver operating characteristic area under the curve was 0.69 and 0.72 in the two samples. Three empirical methods identified the same cut-point for pADi in the discovery sample. In the validation sample, 83% of pADi+ mild cognitive impairment patients were cerebrospinal fluid AD biomarker positive. pADi+ mild cognitive impairment patients (n = 63, 38%) were more likely to progress to AD dementia after 1 (odds ratio = 2.9) and 3 (odds ratio = 2.6) years.
Discussion: The pADi is a personalized, magnetic resonance imaging-derived AD biomarker that predicts progression to dementia.
Keywords: AD index; AD signature; Alzheimer's disease; Cortical thickness; Mild cognitive impairment.