Association between lower α4β2* nicotinic acetylcholine receptor binding and nonmotor symptoms in early drug naive Parkinson disease: A 2-[18F]F-A-85380 (2FA) PET study

Objectives Nonmotor (cognitive and mood) symptoms are common in early drug naive Parkinson disease (PD). α4β2* nicotinic acetylcholine receptors (α4β2*-nAChR) play a role for cognition and mood. To investigate α4β2*-nAChR availability and its relationship to cognitive and depressive symptoms, early drug naive PD were studied using α4β2*-nAChR specific 2FA-PET and neuro tests.

Methods Twenty non-smoking, early drug naive PD patients (66±7 ys; Hoehn&Yahr 1.6±0.7; duration 0.4±0.5 ys; MMSE 28.4±1.4; DemTect 13.8±2.7; BDI 8.1±5.2) and 9 age-comparable normal controls (N; 59±10 ys; MMSE 29.4±1.3; DemTect 16.8±1.9; BDI 3.7±2.3) underwent 2FA-PET. Parametric images of the binding potential using corpus callosum as reference region were determined (Logan plot; VOI-/SPM-analysis). Significance at p<0.05 (SPM p≤0.001; age-corrected).

Results SPM-analysis revealed that compared to N, in PD 2FA-BP was significantly reduced in the striatum, frontal, cingulate, temporal, parietal and occipital cortices, (para)hippocampus, amygdala and cerebellum. Compared to N, PD performed significantly worse in DemTect and BDI. In PD, the degree of cognitive symptoms (DemTect) correlated significantly with reduced 2FA-BP in small clusters in the frontal, cingulate, temporal and parietal cortices and the degree of depressive symptoms (BDI) with reduced 2FA-BP, more pronounced, in larger clusters in the frontal, cingulate and occipital cortices, thalamus, hypothalamus and cerebellum.

Conclusions There is cortico-striato-cerebellar reduction of α4β2*-nAChR availability in early drug naive PD. Furthermore, mild cognitive symptoms are related to lower cortical α4β2*-nAChR and mild depressive symptoms to lower cortico-(para)limbic α4β2*-nAChR binding in early drug naive PD. 2FA-PET of α4β2*-nAChR might become a pivotal biomarker to assess nonmotor symptoms even in early PD