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Regional cerebral phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was performed in 10 non- demented Parkinson's disease patients and nine age-matched control subjects. Five of the patients undergoing (31)P-MRS and four additional Parkinson's disease patients had cerebral 2-[(18)F]fluoro-2-deoxy-D-glucose PET ((18)FDG-PET), the results of which were compared with those of eight age-matched control subjects. All Parkinson's disease patients underwent neuropsychological testing including performance and verbal subtests of the Wechsler Adult Intelligence Scale-Revised, Boston Naming Test, Controlled Oral Word Association test (FAS Test) and California Learning Test to exclude clinical dementia. (31)P MR spectra from right and left temporo-parietal cortex, occipital cortex and a central voxel incorporating basal ganglia and brainstem were obtained. (31)P MR peak area ratios of signals from phosphomonoesters (PMEs), inorganic phosphate (P(i)), phosphodiesters (PDEs), alpha-ATP, gamma-ATP and phosphocreatine (PCr) relative to beta-ATP were measured. Relative percentage peak areas of PMEs, P(i), PDEs, PCr, and alpha-, beta- and gamma-ATP signals were also measured with respect to the total (31)P-MRS signal. Significant bilateral increases in the P(i)/beta-ATP ratio were found in temporoparietal cortex (P = 0.002 right and P = 0.014 left cortex) for the non-demented Parkinson's disease patients compared with controls. In the right temporoparietal cortex, there was also a significant increase in the mean relative percentage P(i) (P = 0.001). (18)FDG-PET revealed absolute bilateral reductions in glucose metabolism after partial volume effect correction in posterior parietal and temporal cortical grey matter (P < 0.01 and P < 0.05, respectively) for the Parkinson's disease group, using both volume of interest analysis and statistical parametric mapping. There were significant correlations between right temporoparietal P(i)/beta-ATP ratios and estimated reductions in performance IQ (r = 0.96, P < 0.001). Left temporoparietal P(i)/beta-ATP ratios correlated with full scale IQ and verbal IQ (r = -0.82, P = 0.006, r = -0.86, P = 0.003, respectively). In summary, temporoparietal cortical hypometabolism was seen in non-demented Parkinson's disease patients with both (31)P-MRS and (18)FDG-PET, suggesting that both glycolytic and oxidative pathways are impaired. This dysfunction may reflect either the presence of primary cortical pathology or deafferentation of striato-cortical projections. (31)P-MRS and (18)FDG-PET may both provide useful predictors of future cognitive impairment in a subset of Parkinson's disease patients who go on to develop dementia.

In this Review, Figure 4 was incorrectly positioned, cutting off some of the labels. This has been corrected in the online version of the article. The editors apologize to the authors and readers for this error. C O R R E C T I O NNATURE REVIEWS | NEUROSCIENCE www.nature.com/nrn © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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We studied eight clinically non-demented PD patients and ten age-matched controls with serial volumetric T1-weighted MRI. All PD patients underwent full neuropsychological testing at baseline and follow up scans. Sub-voxel coregistration of the serial MRI scans with quantification of changes in total brain substance and ventricular size per year was performed. The PD patients had significant reductions in both percentage and absolute annual brain volume loss when compared to age-matched controls (p < 0.001). There were significant correlations between reductions in percentage brain volume loss and estimated reductions in performance IQ (r = 0.841, p = 0.004) and full scale IQ (r = 0.63, p = 0.049), measured by subtracting IQ measures at time of follow up scan from premorbid estimates. In conclusion, PD patients have a significant rate of median brain volume loss [10.35 (range) 6.69-16.90 ml/year] with no significant loss seen in age-matched controls, and these changes correlate with global measures of cognitive decline. Further longitudinal studies could evaluate whether serial volumetric MRI is a useful technique in predicting the preclinical onset of dementia in Parkinson's disease patients, and its role in the assessment of putative treatments for slowing disease progression.

SUMMARY1. Systemic and regional haemodynamic responses, including superior mesenteric artery blood flow, were measured during stimuli which increase sympatho-neural activity in age-matched normal subjects (controls) and in two groups of patients with sympathetic failure (pure autonomic failure and multiple system atrophy). The stimuli included the pressor tests (mental arithmetic, cutaneous cold and isometric exercise) and head-up tilt.2. In the controls, the blood pressure did not rise in some during mental arithmetic, but rose in all subjects during cutaneous cold and isometric exercise and was maintained during head-up tilt. In sympathetic failure patients, blood pressure was unchanged during each pressor test and fell during head-up tilt.3. In the controls, superior mesenteric artery blood flow did not fall significantly during mental arithmetic but fell (with a corresponding rise in calculated superior mesenteric artery vascular resistance), during cutaneous cold, isometric exercise and head-up tilt. In sympathetic failure patients, there were no changes in superior mesenteric artery blood flow and vascular resistance during the pressor tests and head-up tilt.4. There were no changes in cardiac index or forearm blood flow during each pressor test in both controls and patients. Cardiac index fell and forearm vascular resistance rose during head-up tilt in the controls only.5. In conclusion, active constriction of the superior mesenteric artery occurs in normal subjects during sympatho-neural activation induced by stimuli such as cutaneous cold, isometric exercise and head-up tilt. This does not occur in patients with sympathetic failure and probably contributes to postural hypotension, emphasizing the role of the splanchnic vascular bed in overall blood pressure control. This study confirms the necessity of integrity of sympathetic pathways in the neural control of the splanchnic vascular bed.

Background and purposeDopamine agonists in Parkinson's disease (PD) are associated with impulse control disorders (ICDs) and other compulsive behaviours (together called ICD behaviours). The frequency of ICD behaviours reported as adverse events (AEs) in long‐term studies of rotigotine transdermal patch in PD was evaluated.MethodsThis was a post hoc analysis of six open‐label extension studies up to 6 years in duration. Analyses included patients treated with rotigotine for at least 6 months and administered the modified Minnesota Impulse Disorders Interview. ICD behaviours reported as AEs were identified and categorized.ResultsFor 786 patients, the mean (±SD) exposure to rotigotine was 49.4 ± 17.6 months. 71 (9.0%) patients reported 106 ICD AEs cumulatively. Occurrence was similar across categories: 2.5% patients reported ‘compulsive sexual behaviour’, 2.3% ‘buying disorder’, 2.0% ‘compulsive gambling’, 1.7% ‘compulsive eating’ and 1.7% ‘punding behaviour’. Examining at 6‐month intervals, the incidence was relatively low during the first 30 months; it was higher over the next 30 months, peaking in the 54–60‐month period. No ICD AEs were serious, and 97% were mild or moderate in intensity. Study discontinuation occurred in seven (9.9%) patients with ICD AEs; these then resolved in five patients. Dose reduction occurred for 23 AEs, with the majority (73.9%) resolving.ConclusionsIn this analysis of >750 patients with PD treated with rotigotine, the frequency of ICD behaviour AEs was 9.0%, with a specific incidence timeline observed. Active surveillance as duration of treatment increases may help early identification and management; once ICD behaviours are present rotigotine dose reduction may be considered.

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.