Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?☆

Whitwell, Jennifer L.Tosakulwong, NirubolWeigand, Stephen D.Senjem, Matthew L.Lowe, Val J.Gunter, Jeffrey L.Boeve, Bradley F.Knopman, David S.Dickerson, BradfordPetersen, Ronald C.Jack, Clifford R.2014-03-102013Whitwell, J. L., N. Tosakulwong, S. D. Weigand, M. L. Senjem, V. J. Lowe, J. L. Gunter, B. F. Boeve, et al. 2013. “Does amyloid deposition produce a specific atrophic signature in cognitively normal subjects?☆.” NeuroImage : Clinical 2 (1): 249-257. doi:10.1016/j.nicl.2013.01.006. http://dx.doi.org/10.1016/j.nicl.2013.01.006.2213-1582http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878936The objective of our study was to evaluate whether cognitively normal (CN) elderly participants showing elevated cortical beta-amyloid (Aβ) deposition have a consistent neuroanatomical signature of brain atrophy that may characterize preclinical Alzheimer's disease (AD). 115 CN participants who were Aβ-positive (CN +) by amyloid PET imaging; 115 CN participants who were Aβ-negative (CN −); and 88 Aβ-positive mild cognitive impairment or AD participants (MCI/AD +) were identified. Cortical thickness (FreeSurfer) and gray matter volume (SPM5) were measured for 28 regions-of-interest (ROIs) across the brain and compared across groups. ROIs that best discriminated CN − from CN + differed for FreeSurfer cortical thickness and SPM5 gray matter volume. Group-wise discrimination was poor with a high degree of uncertainty in terms of the rank ordering of ROIs. In contrast, both techniques showed strong and consistent findings comparing MCI/AD + to both CN − and CN + groups, with entorhinal cortex, middle and inferior temporal lobe, inferior parietal lobe, and hippocampus providing the best discrimination for both techniques. Concordance across techniques was higher for the CN − and CN + versus MCI/AD + comparisons, compared to the CN − versus CN + comparison. The weak and inconsistent nature of the findings across technique in this study cast doubt on the existence of a reliable neuroanatomical signature of preclinical AD in elderly PiB-positive CN participants.en-USAmyloidPreclinicalAlzheimer's diseaseFreesurferVoxel-based morphometryCognitively normalDoes amyloid deposition produce a specific atrophic signature in cognitively normal subjects?☆Journal Article2014-03-1010.1016/j.nicl.2013.01.006