Diabetes mellitus may predispose toward a Parkinson-like pathology, and when present in patients with Parkinson disease, can induce a more aggressive phenotype.

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There is mounting evidence regarding the role of impairment in neuromodulatory networks for neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. However, the role of neuromodulatory networks in multiple sclerosis (MS) has not been assessed. We applied resting-state functional connectivity and graph theory to investigate the changes in the functional connectivity within neuromodulatory networks including the serotonergic, noradrenergic, cholinergic, and dopaminergic systems in MS. Twenty-nine MS patients and twenty-four age- and gender-matched healthy controls performed clinical and cognitive assessments including the expanded disability status score, symbol digit modalities test, and Hamilton Depression rating scale. We demonstrated a diffuse reorganization of network topography (P < 0.01) in serotonergic, cholinergic, noradrenergic, and dopaminergic networks in patients with MS. Serotonergic, noradrenergic, and cholinergic network functional connectivity derangement was associated with disease duration, EDSS, and depressive symptoms (P < 0.01). Derangements in serotonergic, noradrenergic, cholinergic, and dopaminergic network impairment were associated with cognitive abilities (P < 0.01). Our results indicate that functional connectivity changes within neuromodulatory networks might be a useful tool in predicting disability burden over time, and could serve as a surrogate endpoint to assess efficacy for symptomatic treatments.

IntroductionSleep disturbances are common non-motor symptoms in Parkinson's disease (PD). Experimental studies suggest involvement of the serotonergic system in the regulation of sleep and arousal. Using [11C]DASB positron emission tomography, a marker of serotonin transporter availability, we investigated whether sleep dysfunction is associated with serotonergic dysfunction in PD.MethodsWe studied 14 PD patients with sleep dysfunction, 14 PD without sleep dysfunction, and 12 healthy controls. Groups were matched for age, disease duration, severity of motor symptoms, daily intake of levodopa equivalent units, body-mass-index, depression and fatigue. [11C]DASB non-displaceable binding potential (BPND) was calculated for regions with a role in the regulation of sleep and arousal.Results[11C]DASB BPND was reduced by 32–49% in PD patients with sleep dysfunction, and 14–25% in PD without sleep dysfunction, compared to healthy controls. PD patients with sleep dysfunction had lower [11C]DASB BPND in caudate (P < 0.01), putamen (P < 0.001), ventral striatum (P < 0.001), thalamus (P < 0.05), hypothalamus (P < 0.001) and raphe nuclei (P < 0.01), compared to PD without sleep dysfunction. Higher severity of sleep symptoms (assessed with Parkinson Disease Sleep Scale) correlated with lower [11C]DASB binding in caudate (r = 0.77; P < 0.001), putamen (r = 0.84; P < 0.001), ventral striatum (r = 0.86; P < 0.001), thalamus (r = 0.79; P < 0.001), hypothalamus (r = 0.90; P < 0.001) and raphe nuclei (r = 0.83; P < 0.001).ConclusionsOur findings demonstrate that sleep dysfunction in PD is associated with reduced serotonergic function in the midbrain raphe, basal ganglia and hypothalamus. Strategies to increase serotonin levels in the brain could be a promising approach to treat sleep dysfunction in PD, and may also have relevance in other neurodegenerative disorders.

Purpose We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [ 18 F]florbetapir PET-MR imaging. Methods We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [ 18 F]florbetapir PET-MR and both a clinical and cognitive assessment. [ 18 F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70-90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling. Results [ 18 F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions (coeff. = −0.15, P < 0.001, coeff. = −0.12, P < 0.001 and coeff. = −0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (−10.9%, P = 0.005). SUV 70-90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26). Conclusion Our findings demonstrate that [ 18 F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [ 18 F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.