Comparing patterns of brain amyloid deposition in Parkinson’s disease to Alzheimer’s disease and cognitively normal controls using [¹⁸F] florbetapir PET imaging

Objectives: Cognitive impairment is increasingly recognized as an important clinical feature of Parkinson’s disease (PD), with prevalence of dementia reaching 80% in long-term patients (1, 2). The role of beta-amyloid plaque formation in PD-associated cognitive impairment has been explored but remains uncertain (3-7). Using [18F]florbetapir PET imaging, brain beta-amyloid deposition was measured in a cohort of non-demented PD patients and compared to age-matched cohort of Alzheimer’s disease (AD) subjects and normal controls.

Methods: 40 non-demented PD patients (mean 67±8 years; 14 females) underwent [18F]florbetapir PET brain imaging at our institution. [18F]florbetapir PET brain imaging studies from 40 AD patients (age 67±7.9 years; 17 females) and 40 normal controls (69±6.7 years; 18 females) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI 2) for age-matched comparison. In the PD cohort, 25 were cognitively normal (PD-normal) and 15 had mild cognitive impairment (PD-MCI) based on consensus by expert raters. Regional brain [18F]florbetapir uptake was quantified using a T1-weight MRI-based method with the automated anatomical labeling atlas examining cortical and striatal regions of interest (ROI). To calculate standardized uptake value ratio (SUVR), regional uptake values were normalized to multiple reference regions including cerebellar cortex, whole cerebellum, brainstem, and supratentorial white matter (8-10). Partial volume correction (PVC), using a geometric transfer matrix method, was conducted to account for scanner resolution differences. Regional SUVR differences were examined using ANOVA with Tukey post-hoc test.

Results: In PD, the right globus pallidus (GP) demonstrated significantly increased amyloid deposition compared to AD and age-matched controls no matter the reference region used (p < 0.001). In cerebellar reference region-normalized ROIs, no differences were observed between PD and age-matched controls (except for right GP). However, when the supratentorial white matter reference region was used, all cortical and striatal regions examined showed significant increases (p < 0.05) in amyloid deposition in the PD group compared to controls. As expected, AD patients demonstrated significantly increased amyloid deposition compared to both PD patients and controls in nearly all cortical ROIs examined.

Conclusion: Elevated PET signal in GP as determined by [18F]florbetapir suggests that amyloidosis in PD may have a different effect on brain function than in AD. We also found that supratentorial white matter as reference region compared to other more established, cerebellar-based regions may provide a more sensitive quantification strategy to detect subtle changes in amyloid deposition when using [18F]florbetapir. Research Support: This study was funded or supported by the National Institutes of Health: P50-NS053488, P30-AG010124, R43-NS063607, and K08-NS093127, and by Avid Radiopharmaceuticals, Inc. References: (1) M. A. Hely, W. G. Reid, M. A. Adena, G. M. Halliday, J. G. Morris, Mov Disord 23, 837 (Apr 30, 2008). (2) D. Aarsland, K. Andersen, J. P. Larsen, A. Lolk, P. Kragh-Sorensen, Arch Neurol 60, 387 (Mar, 2003).(3) N. Shah et al., Mov Disord 31, 111 (Jan, 2016).(4) D. H. Hepp et al., J Neuropathol Exp Neurol 75, 936 (Oct, 2016).(5) M. Petrou et al., Mov Disord 30, 928 (Jun, 2015).(6). K. A. Frey, M. Petrou, Clin Transl Imaging 3, 57 (Feb 01, 2015).(7) M. C. Campbell et al., Neurology 81, 520 (Aug 06, 2013).(8) C. Hutton et al., Eur J Nucl Med Mol Imaging 42, 725 (Apr, 2015).(9) M. Brendel et al., Neuroimage 108, 450 (Mar, 2015).(10) A. S. Fleisher et al., Arch Neurol 68, 1404 (Nov, 2011).