Objective: To examine if brain inflammation measured by ¹⁸F-DPA-714 imaging is associated with cognitive change in subjects with early Parkinson’s disease (PD).

Background: Evidence for the role of inflammation in PD has been growing. PET imaging for the 18-kD translocator protein (TSPO), a mitochondrial protein enriched in microglia, astrocytes, and peripheral immune cells, has been used as a marker of brain inflammation. Our group previously showed that binding for the TSPO binding ligand ¹⁸F-DPA-714 was significantly increased in the cortex, putamen, and thalamus in de novo PD. Whether this brain inflammation is associated with subsequent cognitive progression in PD is unknown.

Method: We enrolled subjects with de novo PD (n=64) and age-matched healthy controls (n=70). Inclusion criteria for PD subjects included a diagnosis of PD by UK Brain Bank criteria within 2 years of onset and no prior treatment with PD medications. Subjects underwent baseline and annual clinical assessments, including the Movement Disorder Society-United Parkinson’s Disease rating scale (MDS-UPDRS), and cognitive assessment meeting Level II diagnostic MCI assessment recommendations by the MDS task force. Blood was obtained annually for flow cytometry. Subjects underwent ¹⁸F-DPA-714 imaging at baseline if eligible and consented.

Results: We examined clinical and cognitive assessments at baseline and 24 months after enrollment. As observed at baseline, PD subjects showed significant differences compared to controls in University of Pennsylvania Smell Identification Test, Schwab and England Activities of Daily Living, and MDS-UPDRS scores at 24 months. Analysis of the cognitive data collected at 24 months showed clear evidence of cognitive progression in the PD group relative to controls: a decrease of 0.11 in the composite Z score change over time was observed in PD relative to control. Higher baseline TSPO signal in the thalamus correlated with slower cognitive decline at 24 months in the PD group. We also observed alterations in B-cell and natural killer cell subsets in PD subjects at 24 months.

Conclusion: Our data point to an association between baseline brain inflammation and cognitive progression at 24 months. We also observed continued evidence of peripheral immune cell changes in PD subjects at 24 months. Longitudinal follow-up of this cohort up to 60 months is in process.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/baseline-brain-inflammation-is-associated-with-less-cognitive-progression-at-24-months-in-subjects-with-de-novo-parkinsons-disease/