Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease.

BACKGROUND: Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson's disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. OBJECTIVE: To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. METHODS: We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). RESULTS: We found a significant inverse association between smoking initiation and PD (ORIVW per 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60-0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. CONCLUSION: Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

In vivo evidence for decreased scyllo-inositol levels in the supplementary motor area of patients with Progressive Supranuclear Palsy: A proton MR spectroscopy study.

INTRODUCTION: Several structural and functional neuroimaging studies have shown that the Supplementary Motor Area (SMA) is affected by tau pathology in patients with Progressive Supranuclear Palsy (PSP). The aim of the study was to investigate the biochemical profile of SMA in PSP patients, using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Sixteen PSP patients and 18 healthy controls participated in this study. 1H-MRS was performed by using a Point RESolving Spectroscopy (PRESS) single-voxel sequence implemented on a 3-T scanner. A voxel of 25 × 25 × 15 mm involving the right and left SMA was acquired in all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine with phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), glutamate + glutamine (Glx), glutathione (GSH), myo-Inositol (mI) and Scyllo-Inositol (Scyllo) were calculated using a version 6.3-1K of the fitting program LCModel. Comparative analysis was performed on both absolute concentrations and ratio values relative to Cr. RESULTS: PSP patients showed a significant decrease in Scyllo concentration and Scyllo/Cr ratio values in SMA, compared to controls, whereas no difference between groups was found for the other ratio values. Of note, the attention and working memory functions were positively related to Scyllo and Scyllo/Cr values in PSP patients. CONCLUSIONS: Our study demonstrates that Scyllo and Scyllo/Cr were significantly reduced in the SMA of PSP patients. Because Scyllo seems to be able to protect against formation of toxic fibrils of amyloid-beta fragments and tau oligomers deposition, these preliminary findings may open new perspectives to investigate Scyllo as a new potential disease-modifying therapy for PSP.

Increased glutamate + glutamine levels in the thalamus of patients with essential tremor: A preliminary proton MR spectroscopic study.

INTRODUCTION: The aim of this study was to investigate the thalamic biochemical profile in patients with essential tremor (ET), using proton magnetic resonance spectroscopy (1H-MRS), and to explore the correlations between clinical and biochemical data. METHODS: Sixteen patients with ET and 14 healthy controls participated in this study. After conventional MR imaging, single-voxel 1H-MRS (TR = 2000 ms; TE = 28 ms) was performed by using a PROBE-SV system implemented on a 3-T scanner. A voxel of 10 × 10 × 15 mm involving the ventrointermediate (Vim) nucleus was acquired in each thalamus of all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine + phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), and glutamate + glutamine (Glx) were calculated using a version 6.3-1 K of the fitting program LCModel for each voxel. Comparative and correlation analyses were performed on the NAA, Cr, Cho, and Glx concentrations, as well as on the values of the NAA/Cr, a neural density marker, Cho/Cr, a membrane marker, and Glx/Cr, an intracellular neurotransmitter marker. RESULTS: Patients with ET showed a significant increase in Glx concentration and Glx/Cr ratio values in both thalami, compared to healthy controls, whereas no difference inter-group was found for the other metabolites and NAA/Cr and Cho/Cr ratio values. Of note, the tremor severity was positively related to increased Glx concentrations and Glx/Cr ratio values in ET group. CONCLUSIONS: Our study shows that 1H-MRS can highlight in vivo metabolic abnormalities in the thalami of ET patients, supporting the evidence that the increase of thalamic glutamatergic transmission can play a role in developing of tremor in ET.

Thalamic neurometabolic alterations in tremulous Parkinson's disease: A preliminary proton MR spectroscopy study.

INTRODUCTION: The objective of this study was to investigate the thalamic biochemical changes in tremor-dominant Parkinson's disease (tPD) patients in comparison with essential tremor with resting tremor (rET) patients, by using proton MR spectroscopy (1H-MRS). METHODS: Fourteen tPD patients, 12 rET patients and 10 controls participated in this study. All patients underwent dopamine transporter single-photon emission computed tomography (DAT-SPECT) with 123I-ioflupane, and a short-echo single-voxel 1H-MRS on a 3T scanner. A voxel of 10 × 15 × 10 mm involving the Vim nucleus was acquired in both thalami of all subjects. Peak areas of N-acetyl-aspartate (NAA), creatine (Cr), glycerophosphocholine (Cho), and glutamate (Glu) were measured for each voxel using LCModel. The NAA/Cr, Cho/Cr, and Glu/Cr ratios were then calculated. RESULTS: DAT-SPECT was abnormal in tPD patients, whereas it was normal in rET patients. Patients with tPD showed a significant reduction of NAA/Cr and Cho/Cr in the thalami compared to rET and healthy controls; whereas there were no significant differences between rET patients and controls. The combination of thalamic NAA/Cr and Cho/Cr ratios showed a 100% accuracy in distinguishing tPD patients from rET patients and controls. CONCLUSIONS: This study provides preliminary evidence that thalamic neurometabolic abnormalities occur in tremor-dominant phenotype of PD, and suggests that 1H-MRS can help differentiate patients with tPD from those with rET.