Association of Hippocampal Subfields, CSF Biomarkers, and Cognition in Patients With Parkinson Disease Without Dementia.

Abstract

To examine whether hippocampal volume loss is primarily associated with cognitive status or pathologic β-amyloid 1-42 (Aβ42) levels, this study compared hippocampal subfield volumes between patients with Parkinson disease (PD) with mild cognitive impairment (PD-MCI) and without cognitive impairment (PD-CN) and between patients with low and high Aβ42 levels, in addition exploring the relationship among hippocampal subfield volumes, CSF biomarkers (Aβ42, phosphorylated and total tau), neuropsychological tests, and activities of daily living. Forty-five patients with PD without dementia underwent CSF analyses and MRI as well as comprehensive motor and neuropsychological examinations. Hippocampal segmentation was conducted using FreeSurfer image analysis suite 6.0. Regression models were used to compare hippocampal subfield volumes between groups, and partial correlations defined the association between variables while controlling for intracranial volume (ICV). Linear regressions revealed cognitive group as a statistically significant predictor of both the hippocampal-amygdaloid transition area (HATA; β = -0.23, 95% CI -0.44 to -0.02) and the cornu ammonis 1 region (CA1; β = -0.28, 95% confidence interval [CI] -0.56 to -0.02), independent of disease duration and ICV, with patients with PD-MCI showing significantly smaller volumes than PD-CN. In contrast, no subfields were predicted by Aβ42 levels. Smaller hippocampal volumes were associated with worse performance on memory, language, spatial working memory, and executive functioning tests. The subiculum was negatively correlated with total tau levels (r = -0.37, 95% CI -0.60 to -0.09). Cognitive status, but not CSF Aβ42, predicted hippocampal volumes, specifically the CA1 and HATA. Hippocampal subfields were associated with various cognitive domains, as well as with tau pathology.