Prognosis of conversion of mild cognitive impairment to Alzheimer's dementia by voxel-wise Cox regression based on FDG PET data

• Published in: NeuroImage clinical 2019-01, Vol.21, p.101637, Article 101637
• Main Authors: Sörensen, Arnd, Blazhenets, Ganna, Rücker, Gerta, Schiller, Florian, Meyer, Philipp Tobias, Frings, Lars
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer's dementia; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - metabolism; Cox model; Disease Progression; FDG PET; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Male; Mild cognitive impairment; Positron-Emission Tomography - trends; Prognosis
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2018.101637

The value of 18F-fluorodeoxyglucose (FDG) PET for the prognosis of conversion from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. In the present work, the identification of cerebral metabolic patterns with significant prognostic value for conversion of MCI patients to AD is investigated with voxel-based Cox regression, which in contrast to common categorical comparisons also utilizes time information. FDG PET data of 544 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were randomly split into two equally-sized datasets (training and test). Within a median follow-up duration of 47 months (95% CI: 46–48 months) 181 patients developed AD. In the training dataset, voxel-wise Cox regressions were used to identify regions associated with conversion of MCI to AD. These were compared to regions identified by a classical group comparison (analysis of covariance (ANCOVA) with statistical parametric mapping (SPM) 8) between converters and non-converters (both adjusted for apolipoprotein E (APOE) genotype, mini-mental state examination (MMSE) score, age, sex and education). In the test dataset, normalized FDG uptake within significant brain regions from voxel-wise Cox- and ANCOVA analyses (Cox- and ANCOVA- regions of interest (ROI), respectively) and clinical variables APOE status, MMSE score and education were tested in different Cox models (adjusted for age, sex) including: (1) only clinical variables, (2) only normalized FDG uptake in ANCOVA-ROI, (3) only normalized FDG uptake from Cox-ROI, (4) clinical variables plus FDG uptake in ANCOVA-ROI, (5) clinical variables plus FDG uptake from Cox-ROI. Conversion-related regions with relative hypometabolism comprised parts of the temporo-parietal and posterior cingulate cortex/precuneus for voxel-wise ANCOVA, plus frontal regions for voxel-wise Cox regression (both p