Longitudinal Patterns of Cortical Atrophy on MRI in Patients With Alzheimer Disease With and Without Lewy Body Pathology

Background And Objectives: Although Alzheimer disease (AD) and dementia with Lewy bodies (DLBs) represent 2 different pathologies, they have clinical overlap, and there is a significant degree of co-occurrence of their neuropathologic findings. Many studies have examined imaging characteristics in clinically diagnosed patients; however, there is a relative lack of longitudinal studies that have studied patients with pathologic confirmation. We examined whether there were differences in longitudinal patterns of cortical atrophy between patients with both AD and DLB (AD/DLB) vs those with AD alone.

Methods: We collected and analyzed clinical and neuroimaging data from the AD Neuroimaging Initiative (ADNI) database for patients who underwent autopsy. The rates of change in various neuropsychological assessments were not significantly different between patients with AD/DLB and AD, and each group had neuropsychological outcomes consistent with disease progression. For our neuroimaging analysis, we used a linear mixed-effects model to examine whether there were longitudinal differences in cortical rates of atrophy between patients with AD/DLB and AD.

Results: Autopsies and serial neuroimaging were available on 48 patients (24 AD and 24 AD/DLB). Patients with AD alone had significantly higher atrophy rates in the left cuneus, lateral occipital, and parahippocampal regions over time when compared with patients with concomitant DLB, after covarying for interval from imaging to autopsy, sex, and total estimated intracranial volume. Site ID was included as a random effect to account for site differences. For these regions, the rate of decline over time in the AD/DLB group was less steep by a difference of 0.1887, 0.395, and 0.0989, respectively ( = 0.022, 0.006, and 0.006). The lattermost left cuneus volume measurement and Braak Lewy score had a Pearson product-moment correlation of 0.37, = 0.009, while the lattermost left parahippocampal volume measurement and Braak neurofibrillary tangle score had a Pearson product-moment correlation of -0.327, = 0.02.

Discussion: Patients with AD had more significant atrophy in the left cuneus, lateral occipital, and parahippocampal regions when compared with patients with AD/DLB. These regions are known to distinguish DLB and AD pathology cross-sectionally but here are shown to distinguish longitudinal disease progression.