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.

Voluptuary Habits and Risk of Frontotemporal Dementia: A Case Control Retrospective Study.

Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14-0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10-0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81-0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work.

Multifunctional liposomes interact with Abeta in human biological fluids: Therapeutic implications for Alzheimer's disease.

The accumulation of extracellular amyloid beta (Abeta42) both in brain and in cerebral vessels characterizes Alzheimer's disease (AD) pathogenesis. Recently, the possibility to functionalize nanoparticles (NPs) surface with Abeta42 binding molecules, making them suitable tools for reducing Abeta42 burden has been shown effective in models of AD. Aim of this work consisted in proving that NPs might be effective in sequestering Abeta42 in biological fluids, such as CSF and plasma. This demonstration is extremely important considering that these Abeta42 pools are in continuum with the brain parenchyma with drainage of Abeta from interstitial brain tissue to blood vessel and plasma. In this work, liposomes (LIP) were functionalized as previously shown in order to promote high-affinity Abeta binding, i.e., either with, phosphatidic acid (PA), or a modified Apolipoprotein E-derived peptide (mApo), or with a curcumin derivative (TREG); Abeta42 levels were determined by ELISA in CSF and plasma samples. mApo-PA-LIP (25 and 250 µM) mildly albeit significantly sequestered Abeta42 proteins in CSF samples obtained from healthy subjects (p < 0.01). Analogously a significant binding (∼20%) of Abeta42 (p < 0.001) was demonstrated following exposure to all functionalized liposomes in plasma samples obtained from selected AD or Down's syndrome patients expressing high levels of Abeta42. The same results were obtained by quantifying Abeta42 content after removal of liposome-bound Abeta by using gel filtration chromatography or ultracentrifugation on a discontinuous sucrose density gradient. In conclusion, we demonstrate that functionalized liposomes significantly sequester Abeta42 in human biological fluids. These data may be critical for future in vivo administration tests using NPs for promoting sink effect.

Pilot trial of osteopathic manipulative therapy for patients with frequent episodic tension-type headache.

CONTEXT: Osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) may be used for managing headache pain and related disability, but there is a need for high-quality randomized controlled trials to assess the effectiveness of this intervention. OBJECTIVE: To explore the efficacy of OMTh for pain management in frequent episodic tension-type headache (TTH). DESIGN: Single-blind randomized placebo-controlled pilot study. SETTING: Patients were recruited from 5 primary care settings. PATIENTS: Forty-four patients who were affected by frequent episodic TTH and not taking any drugs for prophylactic management of episodic TTH were recruited. INTERVENTIONS: Patients were randomly allocated to an experimental or control group. The experimental group received corrective OMTh techniques, tailored for each patient; the control group received assessment of the cranial rhythmic impulse (sham therapy). The study included a 1-month baseline period, a 1-month treatment period, and a 3-month follow-up period. MAIN OUTCOME MEASURES: The primary outcome was the change in patient-reported headache frequency, and secondary outcomes included changes in headache pain intensity (discrete score, 1 [lowest perceived pain] to 5 [worst perceived pain]), over-the-counter medication use, and Headache Disability Inventory score. RESULTS: Forty patients completed the study (OMTh, n=21; control, n=19). The OMTh group had a significant reduction in headache frequency over time that persisted 1 month (approximate reduction, 40%; P<.001) and 3 months (approximate reduction, 50%; P<.001) after the end of treatment. Moreover, there was an absolute difference between the 2 treatment groups at the end of the study, with a 33% lower frequency of headache in the OMTh group (P<.001). CONCLUSION: This feasibility study demonstrated the efficacy of OMTh in the management of frequent episodic TTH, compared with sham therapy in a control group. Osteopathic manipulative therapy may be preferred over other treatment modalities and may benefit patients who have adverse effects to medications or who have difficulty complying with pharmacologic regimens. This protocol may serve as a model for future studies.