α4β2* Nicotinic acetylcholine receptor (α4β2*) binding in dementia associated with Parkinson’s disease: A 2-[18F]F-A85380 (2FA)-PET study

Objectives The cumulative incidence of dementia in Parkinson’s disease may be as high as 80-90%. Using α4β2*-specific 2FA-PET, we have shown that in PD without dementia (PD) there is lower (sub)cortical α4β2* binding which is partially associated with mild cognitive impairment. In this study, using 2FA-PET, α4β2* availability in dementia associated with PD (PDD) was determined and compared with PD and normal controls (N) matched for age, severity of disease and depressive symptoms.

Methods Non-smoking 15 PD (67±5ys; MMSE 28.5±1.2, DemTect 14.1±2.5; BDI 6.3±3.6; Hoehn&Yahr 2.4±0.8), 10 PDD (70±7ys; MMSE 21.3±6.6 [p≤0.001]; DemTect 8.0±4.1 [p≤0.001]; BDI 10.3±5.9; Hoehn&Yahr 2.9±0.7) and 16 age-matched N (65±6ys; MMSE≥28; DemTect≥13) underwent 2FA-PET. Parametric images of the binding potential (2FA-BP) using corpus callosum as reference region were determined (Logan plot; VOI-/SPM-analysis). Significance at p≤0.05 (SPM p≤0.001).

Results Compared with N, in PDD and less pronounced in PD, there was lower 2FA-BP in the temporo-parieto-occipital cortices, anterior/posterior cingulate cortices and cerebellum (p≤0.001). Furthermore, compared with N, in PDD there was significantly lower 2FA-BP in the caudate nucleus, putamen, insular and frontal cortices and (para)hippocampus. Compared with PD, in PDD, 2FA-BP was lower in the neocortex (especially parietal), posterior cingulate and insular cortices (p≤0,001).

Conclusions Compared with N or PD, we demonstrate for the first time that in PDD there is widespread lower α4β2* binding in subcortical and especially cortical regions which are involved in cognitive processing. Our findings suggest that α4β2* and 2FA-PET might become a pivotal target and biomarker for drug development and diagnostics in PDD