T1 MRI reveals differential hippocampal atrophy in Lewy Body Disorders with and without Alzheimer’s copathology

Abstract

AbstractBackgroundLewy body disorders (LBD) include Parkinson disease (PD), Parkinson disease dementia (PDD), and dementia with Lewy bodies (DLB). LBD are the second leading cause of neurodegenerative dementia after Alzheimer’s disease (AD). An estimated 50% of LBD patients have coexisting AD pathology (LBD+AD), which correlates with shorter time to dementia and death. Autopsy evidence suggests that verbal memory impairment correlates with the severity of hippocampal tau pathology in LBD. However, it is unknown whether greater hippocampal tau burden in LBD+AD causes neurodegeneration detectable by in vivo structural MRI, and whether hippocampal atrophy explains verbal memory impairment.MethodUsing a case‐control design, we studied 87 patients with clinical diagnoses of LBD (PD, n = 52; PDD, n = 12; DLB, n = 23) with available T1 MRI and AD biomarkers or, and cognitively‐normal controls (n = 131). AD copathology was defined hierarchically by: a) AD “intermediate” or “high” by ABC neuropathologic criteria; 2) positive amyloid PET; and 3) CSF total tau:β‐amyloid1‐42 ratio > 0.3 (autopsy‐validated cutpoint). The Automated Segmentation of Hippocampal Subfields (ASHS) pipeline was applied to subjects’ T1 MRIs. Hippocampal volume (HV) was compared between controls, LBD‐AD, and LBD+AD, and correlated with verbal memory scores. Linear regression was used to test the association of AD copathology (independent variable) and HV (dependent variable), covarying for age, sex, education, and clinical diagnosis.ResultStatistically significant differences (ANOVA p = 0.002) in bilateral HV (expressed as percentage of intracranial volume) were seen between groups (mean 0.456for controls, 0.444±0.045 for LBD‐AD, and 0.416±0.063 for LBD+AD). Tukey’s test showed significant differences between LBD+AD vs controls (p = 0.001) and LBD+AD vs. LBD‐AD (p = 0.047). Linear regression showed statistically significant association of LBD+AD with bilateral HV (p = 0.034). Among all LBD patients, hippocampal volume positively correlated with verbal memory (immediate recall: r2 = 0.24, p = 0.033, delayed recall: r2 = 0.22, p = 0.042, recognition discrimination r2 = 0.58, p<0.001).ConclusionIn patients with LBD, AD copathology is associated with increased hippocampal atrophy as measured by in vivo T1 MRI, which correlates with greater verbal memory deficits. This work supports the that AD copathology impairs cognition in LBD via hippocampal neurodegeneration.