The cortical signature of prodromal AD: regional thinning predicts mild AD dementia.
OBJECTIVE
We previously used exploratory analyses across the entire cortex to determine that mild Alzheimer disease (AD) is reliably associated with a cortical signature of thinning in specific limbic and association regions. Here we investigated whether the cortical signature of AD-related thinning is present in individuals with questionable AD dementia (QAD) and whether a greater degree of regional cortical thinning predicts mild AD dementia.


METHODS
Participants included 49 older adults with mild impairment consistent with mild cognitive impairment (Clinical Dementia Rating [CDR] = 0.5) at the time of structural MRI scanning. Cortical thickness was measured in nine regions of interest (ROIs) identified previously from a comparison of patients with mild AD and controls.


RESULTS
Longitudinal clinical follow-up revealed that 20 participants converted to mild AD dementia (progressors) while 29 remained stable (nonprogressors) approximately 2.5 years after scanning. At baseline, QAD participants showed a milder degree of cortical thinning than typically seen in mild AD, and CDR Sum-of-Boxes correlated with thickness in temporal and parietal ROIs. Compared to nonprogressors, progressors showed temporal and parietal thinning. Using receiver operating characteristic curves, the thickness of an aggregate measure of these regions predicted progression to mild AD with 83% sensitivity and 65% specificity.


CONCLUSIONS
Thinning in specific cortical areas known to be affected by Alzheimer disease (AD) is detectable in individuals with questionable AD dementia (QAD) and predicts conversion to mild AD dementia. This method could be useful for identifying individuals at relatively high risk for imminent progression from QAD to mild AD dementia, which may be of value in clinical trials.
Bakkour
Akram
A
Department of Psychiatry, Massachusetts Alzheimer's Disease Research Center and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Morris
John C
JC
Dickerson
Bradford C
BC
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012984:Software
D015415:Biomarkers