Quantitative neurodegenerative pathology does not explain the degree of hippocampal atrophy on MRI in degenerative dementia

Abstract

The purpose of this study was to investigate the neuropathological substrates underlying in vivo hippocampal atrophy on magnetic resonance imaging (MRI) in autopsy confirmed neurodegenerative dementia cases. Thirty-one neuropathologically verified cases (23 with Lewy body dementia (LBD) and eight with Alzheimer's disease (AD)) were included who had undergone an MRI scan close to death (mean 1.5 years). Manual volumetric measurements were undertaken for the hippocampus, entorhinal cortex and amygdala on MRI, along with quantitative neuropathological analysis of plaque, tangle and Lewy body pathology in the same regions. The relationship between neuropathology and MRI volumes was assessed using correlations and linear regression. Hippocampal and amygdala volumes were significantly smaller in cases with AD than with LBD, but there was no difference in entorhinal cortex volume. Analysing all cases together, a significant positive correlation was observed between normalised hippocampal volume and percent area of Lewy bodies in the hippocampus (r=0.449, p=0.017) but not with tangles (r=0.059, p=0.766) or plaques (r=-0.361, p=0.119). There were no other significant correlations between regional MRI volume and measures of neuropathology. Regression analysis showed that overall diagnosis of AD rather than burden of individual pathological changes was the most significant predictor of hippocampal volume loss in autopsy confirmed cases. Our results suggest that (i) hippocampal and amygdala but not entorhinal cortex, volumes differ between AD and LBD and (ii) factors other than current markers of neurodegenerative pathological change are responsible for atrophy of medial temporal lobe structures in AD and LBD.