Objective: To examine if immune cell changes are present in early stages of Dementia with Lewy Bodies (DLB).

Background: Evidence for inflammation in synucleinopathies has been building. An extensive number of studies have documented inflammation and immune cell changes in Parkinson’s disease (PD), while much less is known about DLB. Post-mortem DLB brains show evidence of T-cell infiltration, and flow cytometry and cytokine measures in DLB subjects have suggested that inflammation is present in DLB. However, there is limited understanding if immune cell changes are present at the earliest stages of DLB.

Method: We recruited a small, exploratory cohort of nine subjects with Mild Cognitive Impairment – Lewy Bodies (MCI-LB) as part of the broader Alabama Udall cohort study, which has been examining the role of inflammation in early, de novo PD. Inclusion criteria included at least two of five core features: fluctuating cognition; visual hallucinations, stereotyped illusions, and/or recurring delusions; REM sleep behavior disorder, Parkinsonism; and impaired visuospatial performance. The MCI-LB cohort was compared to subjects with de novo PD (n=64) and healthy controls (n=70) from the larger Alabama Udall cohort. Subjects underwent clinical assessments, including Movement Disorder Society-United Parkinson’s Disease rating scale (MDS-UPDRS). Subjects also underwent comprehensive cognitive assessment meeting Level II diagnostic MCI assessment recommendations by the MDS task force. Blood was obtained for flow cytometry, cytokine, and chemokine analyses.

Results: Baseline demographics and medical history were comparable between groups. As expected, significant differences in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, and MDS-UPDRS scores were observed between the three groups. MCI-LB subjects demonstrated poorer cognitive composite scores compared to PD participants, and the cognitive profile for the MCI-LB group differed from that for the PD group. While no plasma cytokine or chemokine differences were noted between controls and MCI-LB, the MCI-LB subjects demonstrated a 60% reduction in mature neutrophils along with increases in the natural killer cell subset (CD56^–CD16⁺) compared to controls using flow cytometry.

Conclusion: Our data show changes in immune cells in MCI-LB compared to control. A larger cohort study is needed to validate these findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/immune-cell-changes-in-early-dementia-with-lewy-bodies/