Reactive astrocytes as imaged with 11C‐DED in patients with different dementia disorders

Abstract Background Neuroinflammation, which receives ever increasing interest in neurodegenerative diseases, comprises a heterogeneous cascade of events that are thought to be related to the downstream neurodegeneration. The aim of this study was to evaluate the binding of 11 C‐Deuterium‐L‐Deprenyl PET (DED) as a measure of reactive astrocytes in patients with different dementia disorders, and to assess its association with other disease biomarkers. Method Eleven patients with a clinical diagnosis of semantic variant of primary progressive aphasia (svPPA, n = 5) and behavioral variant of frontotemporal dementia (bvFTD, n = 6) were recruited. All patients had a cerebrospinal fluid biomarker profile that was inconsistent with Alzheimer’s disease (AD) or a negative amyloid‐β PET scan. The imaging protocol included 11 C‐DED‐PET, 18 F‐FDG‐PET, and a 3D T1 MRI. A group of amyloid‐beta positive patients with AD (n = 20) that underwent similar investigations were used for comparison. Z‐scores were created for 11 C‐DED binding (Patlak slopes) and tracer relative delivery (R1 parameter) relative to that of healthy controls (HC; n = 20), for assessing the load of reactive astrocytes and cerebral perfusion, respectively. Result The patients with svPPA and bvFTD showed significantly higher 11 C‐DED binding in frontotemporal areas, compared to HC. Patients with AD showed significantly higher 11 C‐DED binding in temporo‐occipital areas, compared to HC. The regional distribution of 11 C‐DED binding in the patients with svPPA and bvFTD was consistent with the expected underlying pattern of neurodegeneration in those disorders, although the load of binding was heterogeneous across patients with the same clinical diagnosis. Conclusion Reactive astrocytes appear to be a common feature of different dementia disorders, although the regional pattern of reactivity differs. Ongoing work evaluates the relationship between patterns of reactive astrocyte activation, cerebral perfusion, glucose metabolism, atrophy, and cognitive performance.