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We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson’s disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels—measured by 31phosphorous magnetic resonance spectroscopy—and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials. publishedVersion

During listening, acoustic features of sounds are extracted in the auditory system (in the auditory brainstem, thalamus, and auditory cortex). To establish auditory percepts of melodies and rhythms (i.e., to establish auditory “Gestalten” and auditory objects), sound information is buffered and processed in the auditory sensory memory. Musical structure is then processed based on acoustical similarities and rhythmical organization, and according to (implicit) knowledge about musical regularities underlying scales, melodic and harmonic progressions, etc. These structures are based on both local and (hierarchically organized) nonlocal dependencies. In addition, music can evoke representations of meaningful concepts, and elicit emotions. This chapter reviews neural correlates of these processes, with regard to both brain-electric responses to sounds, and the neuroanatomical architecture of music perception.