Cerebral perfusion correlates of domain-specific cognitive function in Alzheimer's disease and dementia with Lewy bodies
TL;DR
Distinct patterns of cerebral perfusion-cognition relationships characterize AD and DLB, reflecting differential regional vulnerabilities underlying cognitive decline, which may contribute to improved understanding of the pathophysiology underlying cognitive decline and support disease monitoring.
Abstract
Background Differentiating Alzheimer's disease (AD) from dementia with Lewy bodies (DLB) remains challenging because of overlapping symptoms and frequent co-pathology. Although cerebral perfusion abnormalities are well described in both disorders, how domain-specific cognitive decline relates to regional perfusion patterns remains incompletely understood. Objective To investigate disease-specific associations between regional cerebral perfusion and domain-specific cognitive performance in patients with AD and DLB. Methods Amyloid-positive patients with AD and probable patients with DLB, each with at least one abnormal neuroimaging biomarker, underwent 123I-iodoamphetamine single-photon emission computed tomography and Addenbrooke's Cognitive Examination III (ACE-III). Regional cerebral perfusion was compared among 57 patients with AD, 72 with DLB, and 44 healthy controls. Voxel-wise regression analyses examined associations between perfusion and ACE-III total and domain scores. Results Compared with controls, patients with AD showed reduced cerebral perfusion in the posterior cingulate, precuneus, and temporo-parietal cortices, whereas patients with DLB showed posterior cortical hypoperfusion with relatively preserved posterior cingulate perfusion. Direct comparisons revealed limited differences, including posterior cingulate and hippocampal hypoperfusion in patients with AD, and occipital hypoperfusion in patients with DLB. Cognitive decline in patients with AD correlated with left-lateralized temporo-parietal hypoperfusion across multiple domains, with cerebellar and sensorimotor hyperperfusion. Patients with DLB showed limited perfusion–cognition coupling, except for robust associations between bilateral posterior regions and visuospatial performance. Conclusions Distinct patterns of cerebral perfusion-cognition relationships characterize AD and DLB, reflecting differential regional vulnerabilities underlying cognitive decline. These findings may contribute to improved understanding of the pathophysiology underlying cognitive decline and support disease monitoring.