Objective: Determine if Alzheimer disease (AD) subjects with Lewy bodies show sympathetic cardiac denervation.

Background: Comorbid Lewy body (LB) pathology is very common in AD, and may confound clinical trial design- yet there is no in-vivo test to identify it. Tissue studies have shown cardiac sympathetic denervation in Parkinson disease and dementia with Lewy bodies, but have not been explored in mixed AD/LB cases.

Methods: We analyzed 30 cases with autopsy-confirmed AD/DLB, 30 AD/LB not meeting dementia with Lewy bodies (DLB) criteria, 30 AD-no LB, 30 incidental Lewy body disease (ILBD) and 22 controls without LB. Using tyrosine hydroxylase (TH) staining of epicardial and myocardial tissue, we tested the hypothesis that AD/LB will be distinguishable from AD without LB by the loss of cardiac noradrenergic nerve fibers, supporting the feasibility of clinically separating these conditions using cardiac nuclear imaging. Staining was graded on a 0-3 point Likert scale, (0=absent, 1=sparse, 2=moderate, 3=numerous).

Results: Kruskal-Wallis analysis of variance between groups indicated a significant difference (p = 0.008) between the groups (medians: control 2.5; ILBD 1.5; AD-DLB 1.0; PD 1.0; AD-LB 3.0; AD-no LB 2.0), and subsequent pair-wise Mann-Whitney analysis showed that PD (p = 0.014) and DLB (p = 0.008) subjects have significantly reduced TH fiber density as compared to controls. The TH density in ILBD hearts was midway between the control and PD or DLB groups but the difference was too small for this to reach significance (p = 0.16).

Conclusions: The clear separation of DLB from controls based on cardiac TH fiber density is the first report of a statistically significant difference between these groups. Our data therefore strengthen the rationale for using cardiac nuclear imaging with a noradrenergic nuclear imaging ligand, meta-iodobenzylguanidine (MIBG) to separate DLB from AD with DLB, an important concept as most cases of AD/DLB are not recognized as such during life. Our results indicate that MIBG would not be likely to clinically separate the AD/LB from AD subjects without LB.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/are-lewy-bodies-associated-with-sympathetic-pathology-in-dementia-subjects/