Reproductive factors,exogenous estrogen use,and risk of Parkinson's disease

To determine if reproductive factors or exogenous estrogen are associated with risk of Parkinson's disease (PD), we conducted a prospective study with 22 years of follow‐up among postmenopausal participants in the Nurses' Health Study. Relative risks (RRs) and 95% confidence intervals (CIs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use. Use of postmenopausal hormones, however, may modify the associations of smoking and caffeine intake with PD risk. The inverse relation between smoking and PD risk was attenuated among ever users of postmenopausal hormones (P for interaction = 0.05). Similar results were obtained for caffeine (P for interaction = 0.09). In exploratory analyses, women using progestin‐only hormones were found to have an increased PD risk, but this result was based on a very small number of cases (n = 4). In this large longitudinal study, we found no evidence of a beneficial effect of exogenous or endogenous estrogens on risk of PD. The use of postmenopausal hormone use may interact with other risk factors, but findings are preliminary and need confirmation in other populations. © 2009 Movement Disorder Society     

Glycation in Parkinson's disease and Alzheimer's disease

Glycation is a spontaneous age‐dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α‐synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society     

Female reproductive factors,menopausal hormone use,and Parkinson's disease

The objective of this study was to examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson's disease (PD) among postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to 71 years in the NIH‐AARP Diet and Health Study, who completed a baseline questionnaire in 1995–1996 and a follow‐up survey in 2004–2006. A total of 410 self‐reported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78‐1.79) for women with natural menopause aged <45, 1.19 (95% CI, 0.88‐1.61) for those aged 45 to 49, and 1.33 (95% CI, 0.91‐1.93) for those aged 55 or older. We found that oral contraceptive use for ≥10 years (vs. never used) was associated with lower PD risk (OR, 0.59; 95% CI, 0.38‐0.92), but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non–hormone users at baseline, current hormone users for <5 years showed a higher risk of PD (OR, 1.52; 95% CI, 1.11‐2.08). However, no associations were observed for past hormone users or current users of ≥5 years. Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long‐term oral contraceptive use and current hormone therapy warrant further investigations. © 2013 International Parkinson and Movement Disorder Society     

Is there seasonal variation in risk of Parkinson's disease?

Recent studies suggest that, for many adult‐onset neurological diseases, persons born at a certain time of year are at higher risk of the disease. Small‐scale studies have suggested that persons born in the spring may be at higher risk of developing Parkinson's disease (PD) late in life. There have also been suggestions that there are clusters of PD birth dates in the years of major influenza pandemics. To determine whether there is any seasonal variation in the birth dates of PD patients, we examined birth dates of 8,168 PD patients collected from subspecialty movement disorder clinics across Canada. Patterns of seasonality of birth were examined and compared with the general Canadian population. In addition, we compared counts of patients born in the years of major influenza pandemics with the number born in the surrounding years. We found no evidence of systematic seasonal variation in PD incidence by birth date, or of clustering of birth dates during influenza pandemic years in PD patients. © 2006 Movement Disorder Society     

Polychlorinated biphenyls in prospectively collected serum and Parkinson's disease risk

Evidence suggests possible Parkinson's disease (PD)–relevant neural effects of exposure to polychlorinated biphenyls. Limited epidemiological evidence suggests that polychlorinated biphenyl exposure may increase PD risk, but no studies have involved biomarkers of polychlorinated biphenyl exposure before PD onset. We examined the prospective association between serum polychlorinated biphenyls and PD. We conducted a nested case–control study within the Finnish Mobile Clinic Health Examination Survey with serum samples collected during 1968–1972 and analyzed in 2005–2007 for polychlorinated biphenyls. Incident PD cases were identified through the Social Insurance Institution's registry and were confirmed by medical record review (n = 101). Controls (n = 349) were matched on age, sex, municipality, and vital status. We used logistic regression to estimate adjusted odds ratios. There was no evidence of increasing risk of PD with increasing polychlorinated biphenyl exposure in adjusted analyses. Instead, there was a trend toward lower odds of PD with increasing serum polychlorinated biphenyl concentrations, which was most pronounced for the sum of all measured polychlorinated biphenyl congeners and the sum of dioxin‐like congeners. Compared with that of those in the lowest quintile, the odds ratio of PD among those in the highest quintile of total polychlorinated biphenyls was 0.29 (95% confidence interval, 0.12–0.70; P trend = .02) and for dioxin‐like congeners was 0.34 (95% confidence interval, 0.13–0.90; P trend = .05). These results do not support an increased risk of PD from polychlorinated biphenyl exposure and instead suggest a possible protective effect of polychlorinated biphenyl exposure. © 2012 Movement Disorder Society     

Physical therapy and occupational therapy in Parkinson's disease

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in daily activities. In this narrative review, we address the limitations that people with Parkinson's disease may encounter despite optimal medical management, and we clarify both the unique and shared approaches that physical therapists and occupational therapists can apply in treating these limitations.     

Do risk factors for Alzheimer's disease predict dementia in Parkinson's disease? An exploratory study

The extent to which concomitant Alzheimer's disease (AD) is etiologically related to the development of dementia in Parkinson's disease (PD) remains controversial. We explored the association of four risk factors associated with AD, including head injury, smoking, hypertension, and diabetes mellitus, with incident dementia in PD. A cohort of 180 nondemented PD patients from the Washington Heights community in northern Manhattan, New York, completed a risk factor questionnaire at baseline and was followed annually with neurological and neuropsychological evaluations. The association of baseline variables with incident dementia was analyzed by using Cox proportional hazards models. All analyses controlled for age at baseline, gender, years of education, duration of PD, and total Unified Parkinson's Disease Rating Scale (UPDRS) motor score at baseline. Of 180 patients (mean age, 71.0 +/- 10.3 years), 52 (29%) became demented during a mean follow-up period of 3.6 +/- 2.2 years. Head injury risk ratio ([RR] 0.9; 95% confidence interval [CI], 0.4-2.2; P = 0.9), hypertension (RR, 0.7; 95% CI, 0.4-1.4, P = 0.3), and diabetes mellitus (RR, 0.8; 95% CI, 0.3-2.3; P = 0.7) were not significantly associated with incident dementia in the Cox models. Patients who reported having ever smoked were at increased risk for the development of dementia compared with nonsmokers (RR, 2.0; 95% CI, 1.0-3.9; P = 0.05). Current smoking was significantly associated with incident dementia (RR, 4.5; 95% CI, 1.2-16.4; P = 0.02), whereas past smoking approached significance (RR, 1.9; 95% CI, 0.9-3.7; P = 0.07). Although an inverse association between smoking and PD has been reported in several studies, our study showed a positive association between smoking and dementia in the setting of PD. The association of smoking with incident dementia in PD deserves further study.     

Art therapy for Parkinson's disease

ObjectiveTo explore the potential rehabilitative effect of art therapy and its underlying mechanisms in Parkinson's disease (PD).MethodsObservational study of eighteen patients with PD, followed in a prospective, open-label, exploratory trial. Before and after twenty sessions of art therapy, PD patients were assessed with the UPDRS, Pegboard Test, Timed Up and Go Test (TUG), Beck Depression Inventory (BDI), Modified Fatigue Impact Scale and PROMIS-Self-Efficacy, Montreal Cognitive Assessment, Rey-Osterrieth Complex Figure Test (RCFT), Benton Visual Recognition Test (BVRT), Navon Test, Visual Search, and Stop Signal Task. Eye movements were recorded during the BVRT. Resting-state functional MRI (rs-fMRI) was also performed to assess functional connectivity (FC) changes within the dorsal attention (DAN), executive control (ECN), fronto-occipital (FOC), salience (SAL), primary and secondary visual (V1, V2) brain networks. We also tested fourteen age-matched healthy controls at baseline.ResultsAt baseline, PD patients showed abnormal visual-cognitive functions and eye movements. Analyses of rs-fMRI showed increased functional connectivity within DAN and ECN in patients compared to controls. Following art therapy, performance improved on Navon test, eye tracking, and UPDRS scores. Rs-fMRI analysis revealed significantly increased FC levels in brain regions within V1 and V2 networks.InterpretationArt therapy improves overall visual-cognitive skills and visual exploration strategies as well as general motor function in patients with PD. The changes in brain connectivity highlight a functional reorganization of visual networks.     

Recreational physical activity and risk of Parkinson's disease

The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men ≥ 23 metabolic equivalent task‐hours/week [MET‐h/wk], women ≥ 18.5 MET‐h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men ≥ 16 MET‐h/wk, women ≥ 11.5 MET‐h/wk) to the lowest (0 MET‐h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow‐up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD. © 2007 Movement Disorder Society     

Prenatal and early life factors and risk of Parkinson's disease

Few studies have investigated the relation between early life factors and risk of Parkinson's disease (PD), although a potential role of exposures during pregnancy and childhood has been hypothesized. The study population comprised participants in two prospective cohorts: the Nurses' Health Study (121,701 female nurses followed up from 1976–2002) and the Health Professionals Follow‐up Study (51,529 male health professionals followed up from 1986–2002). PD risk was examined in relation to season of birth, birthweight, parental age at birth, preterm birth, multiple birth, ever having been breast‐fed, and handedness. We identified 659 incident PD cases. No significant relation with PD was observed for birthweight, paternal age, preterm birth, multiple birth, and having been breast‐fed. A modest nonsignificant association was suggested for season of birth (30% higher risk of PD associated with spring versus winter birth) and for older maternal age at birth (75% increased risk among those with mothers aged 30 years and older versus younger than 20 years). Left‐handedness was associated with a 62% increased risk of PD in women but not in men. Further investigation of the relation between prenatal, perinatal, or neonatal factors and PD in other study populations is suggested. © 2010 Movement Disorder Society     

Acupuncture therapy for the symptoms of Parkinson's disease.

Interest in alternative medical treatments, including acupuncture, is increasing. Alternative treatments must be subjected to the same objective standards as all medical treatments. A non-blinded pilot study of the safety, tolerability, and efficacy of acupuncture (ACUPX) for the symptoms of (PD) was performed. Twenty PD patients (mean age, 68 years; disease duration, 8.5 years; Hoehn and Yahr [H&Y] stage, 2.2; Unified Parkinson's Disease Rating Scale score [UPDRS], 38.7) each received acupuncture treatments by a licensed acupuncturist. All patients were treated with two acupuncture treatment sessions per week. The first seven patients received 10 treatments and the last 13 patients 16 treatments. Patients were evaluated before and after ACUPX with the Sickness Impact Profile (SIP); UPDRS; H & Y; Schwab and England (S & E); Beck Anxiety Inventory (BAI); Beck Depression Inventory (BDI); quantitative motor tests, including timed evaluations of arm pronation supination movements, finger dexterity, finger movements between two fixed measured points, and the stand-walk-sit test; and a patient questionnaire designed for the study. Following ACUPX, there were no significant changes in the UPDRS, H&Y, S&E, BAI, BDI, quantitative motor tests, total SIP or the two SIP Dimension scores. Analysis of the 12 SIP categories not corrected for multiple comparisons revealed a post-ACUPX improvement in the sleep and rest category only (P = 0.03). On the patient questionnaire, 85% of patients reported subjective improvement of individual symptoms including tremor, walking, handwriting, slowness, pain, sleep, depression, and anxiety. There were no adverse effects. ACUPX therapy is safe and well tolerated in PD patients. A range of PD and behavioral scales failed to show improvement following ACUPX other than sleep benefit, although patients reported other discrete symptomatic improvements. A broad battery of tests in PD patients suggested that ACUPX resulted in improvement of sleep and rest only. This finding needs to be verified using more in-depth and controlled evaluation of ACUPX for PD-related sleep disturbance.     

Prospective study of phobic anxiety and risk of Parkinson's disease.

Anxiety disorders are common in Parkinson's disease (PD). However, the risk of PD among people with anxiety has not been examined in a prospective cohort study. We examined this relation prospectively within the Health Professionals Follow-Up Study, a cohort of US male health professionals. In 1988, anxiety was assessed using the Crown-Crisp phobic anxiety index in 35,815 men without PD, stroke, or cancer at baseline. There were 189 incident cases of PD during 12 years of follow-up. After adjusting for age, smoking, and caffeine intake, the relative risk of PD among men with the highest level of anxiety (Crown-Crisp index scores of 4 and above) was 1.5 (95% CI = 1.0-2.1; P-trend = 0.01) compared to men with the lowest level of anxiety. This positive association persisted after excluding cases of PD with onset in the first 2 years of follow-up. Use of anxiolytic medication was also associated with an elevated risk of PD (RR= 1.6; 95% CI = 0.9-3.1), but adjusting for this potential confounder did not materially affect the association between anxiety and risk of PD. Our results suggest that anxiety is a risk factor for PD. Whether this association is causal or the result of shared underlying biology remains a question.     

Comorbid cancer in Parkinson's disease

The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age‐ and sex‐matched control subjects identified during two periods (1994–1995 and 2000–2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD–cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD–cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non‐PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54–1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70–1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40–5.2; after PD, RR = 1.6; 95% CI 0.71–3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking. © 2010 Movement Disorder Society.     

Measuring therapy adherence in Parkinson's disease: a comparison of methods

The objective of this study was to assess different methods of measuring therapy adherence in Parkinson's disease (PD). In a single centre observational study, 112 patients with idiopathic PD were randomised to a crossover trial of active monitoring (n = 69, simple tablet count and electronic monitoring), or to no monitoring (n = 43, control group). All patients completed a self report and visual analogue scale (VAS) indicating therapy intake. In the active monitoring group, 56 (81% of cases) used > or = 80% of their medication, and 13 (19% of cases) used <80%, based on electronic monitoring. Median adherence for self report was 100% (interquartile range (IQR) 100 to 100) and for VAS was 100% (IQR 95 to 100), in both active and control groups. Patients taking > or = 80% of prescribed medication had a median total adherence of 98% (IQR 93 to 101) by electronic monitoring, which was similar to that from other METHODS: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; simple tablet count 98%, IQR 89 to 100. Median total adherence in patients taking <80% of medication was significantly lower by electronic monitoring (69%, IQR 44 to 74) than by other methods: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; and simple tablet count 90%, IQR 78 to 100 (all p<0.0001). Sensitivities of self report (10%), VAS (17%), and simple tablet count (50%) were all low for detecting suboptimal medicine intake. Self report, VAS, and simple tablet counts are insensitive as predictors of suboptimal medicine usage in PD. How patients take their medicines influences interpretation of the therapy response and consequent management decisions, with implications for clinical trial analysis and clinical practice.     

Perceived imbalance and risk of Parkinson's disease

We prospectively examined associations between perceived imbalance and Parkinson's disease (PD) risk in the Health Professional Follow‐up Study (HPFS), and Nurses' Health Study (NHS). We included 39,087 men and 82,299 women free of PD at baseline (1990) in the current analyses. We documented 449 incident PD cases during 12 years follow‐up. Subjects who reported difficulty with balance before 1990 (baseline) were 1.8 more times likely to develop PD, relative to those who reported no balance difficulty (pooled multivariate RR = 1.8; 95% CI: 1.3, 2.5; P < 0.0001). When we further examined associations between perceived imbalance at baseline and PD onset during different time periods, we found a significant elevation of PD risk only during the first 4 years of follow‐up. This result suggests that the imbalance may in some cases be an early sign of PD, and may represent the onset of motor symptoms although they have not been clinically recognized. © 2008 Movement Disorder Society     

Variants in estrogen‐related genes and risk of Parkinson's disease

Incidence rates of Parkinson's disease are higher in men than in women at all ages, and these differences may be a result of the neuroprotective effects of estrogen on the nigrostriatal pathway. We investigated the association of common variants in 4 estrogen‐related genes with Parkinson's disease. Tagging single‐nucleotide polymorphisms in the CYP19A1, ESR1, ESR2, and PRDM2 genes were selected from the International Haplotype Map and genotyped in 1103 Parkinson's disease cases from the upper Midwest of the United States and in 1103 individually matched controls (654 unaffected siblings, and 449 unrelated controls from the same region). Of 137 informative single‐nucleotide polymorphisms, 2 PRDM2 single‐nucleotide polymorphisms were significantly associated with an increased risk of Parkinson's disease at the Bonferroni‐corrected significance level of 0.0004 (rs2744690: OR, 1.54; SE(logOR), .109; 99.96% CI, 1.05–2.26; uncorrected P = .0001; rs2744687: OR, 1.53; SE(logOR), .113; 99.96% CI, 1.03–2.29, uncorrected P = .0002); the association was significant in the women‐only stratum but not in the men‐only stratum. An additional 6 single‐nucleotide polymorphisms in PRDM2, 2 in ESR1, 1 in ESR2, and 1 in CYP19A1 had significant P values in the overall sample before Bonferroni correction. None of the single‐nucleotide polymorphisms were significantly associated with age at onset of Parkinson's disease after Bonferroni correction. Our results confirm the association of PRDM2 variants with Parkinson's disease susceptibility, especially in women. © 2011 Movement Disorder Society