Background: We previously screened 400 elderly Costa Ricans for neurodegenerative disease. Those reporting occupational pesticide exposure (18%) had an increased Parkinson's disease (PD) risk (OR 2.57, 95% CI 0.91-7.26), and worse cognition (Mini-Mental States Exam (MMSE) 24.5 versus 25.9 points, p=0.01). We subsequently measured long-lasting organochlorine pesticides (β-HCH, DDE, DDT, and dieldrin) in a sub-sample ( n=89). Dieldrin and β-HCH have been linked to PD, and DDE to Alzheimer's disease. Methods: We ran regression models for MMSE and tremor-at-rest to assess associations with pesticides in 89 subjects. Results: The percent of β-HCH, DDE, DDT (parent compound for DDE), and dieldrin above their limit of detection (LOD) were 100%, 93%, 75%, and 57%, respectively. Tremor-at-rest was found in 21 subjects, and the mean MMSE was 25. Those who reported occupational pesticide exposure ( n=36) had more detectable dieldrin samples ( p=0.005), and higher mean levels of dieldrin ( p=0.01), than those not reporting exposure. Other pesticides did not differ between those with and without self-reported occupational exposure. There was a positive but non-significant trend of higher risk for tremor-at-rest with higher dieldrin ( p=0.10 for linear trend). Neither DDE nor DDT showed a relationship with MMSE. However, after excluding two outliers with the lowest MMSE scores, higher DDT levels showed some modest association with lower MMSE ( p=0.09 for linear trend). Conclusions: Our data are limited by small sample size. However, dieldrin was high in our population, has been previously linked to PD, and could be partly responsible for the excess PD risk seen in our population.
Objective:A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort.Methods:We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects.Results:We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study.Conclusions:Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.
The integration of mental and neurologic services in healthcare is a global priority. The universal Social Security of Costa Rica aspires to develop national screening of neurodegenerative disorders among the elderly, as part of the non-communicable disease agenda. This study assessed the feasibility of routine screening for Parkinson's disease (PD) and Alzheimer's disease (AD) within the public healthcare system of Costa Rica. The population (aged ≥65) in the catchment areas of two primary healthcare clinics was targeted for motor and cognitive screening during routine annual health check-ups. The screening followed a tiered three-step approach, with increasing specificity. Step 1 involved a two-symptom questionnaire (tremor-at-rest; balance) and a spiral drawing test for motor assessment, as well as a three-word recall and animal category fluency test for cognitive assessment. Step 2 (for those failing Step 1) was a 10-item version of the Unified Parkinson Disease Rating Scale and the Mini-Mental State Examination. Step 3 (for those failing Step 2) was a comprehensive neurologic exam with definitive diagnosis of PD, AD, mild cognitive impairment (MCI), other disorders, or subjects who were healthy. Screening parameters and disease prevalence were calculated. Of the 401 screened subjects (80% of target population), 370 (92%), 163 (45%), and 81 (56%) failed in Step 1, Step 2, and Step 3, respectively. Thirty-three, 20, and 35 patients were diagnosed with PD, AD, and MCI, respectively (7 were PD with MCI/AD); 90% were new cases. Step 1 sensitivities of motor and cognitive assessments regarding Step 2 were both 93%, and Step 2 sensitivities regarding definitive diagnosis 100 and 96%, respectively. Specificities for Step 1 motor and cognitive tests were low (23% and 29%, respectively) and for Step 2 tests acceptable (76%, 94%). Based on international data, PD prevalence was 3.7 times higher than expected; AD prevalence was as expected. Proposed protocol adjustments will increase test specificity and reduce administration time. A routine screening program is feasible within the public healthcare system of Costa Rica.
Background and objectives: Slowed and curved rapid eye movements, saccades, are the well-known features of progressive supranuclear palsy (PSP). We hypothesized that the saccades in PSP are not only slow and curved, but they are also irregular and have timing deficits. Methods: We tested this hypothesis in 12 patients with PSP by measuring vertical and horizontal visually guided saccades using a limbus tracker. Results: Both, horizontal and vertical saccades were slow and had irregular trajectory and velocity profiles, but deficits were much more robust in vertical saccades. The irregularity in the saccade velocity was due to premature interruptions that either completely stopped the eyes, or moved the eyes at much slower velocity along or in the opposite direction of the ongoing saccade. The direction of the eyes' trajectory was often changed after the interruption. We simulated a conductance based single-compartment model of the burst neurons embedded in local feedback circuit for saccade generation. This model mimicked anatomical and physiological realism, while allowing the liberty to selectively change the activation of individual burst neurons or the pause neurons. The PSP saccades were comparable to the simulations during reduced activity of the inhibitory and excitatory burst neurons. Conclusion: PSP saccades are due to the paucity in burst generation at the excitatory and imprecise timing signal from the inhibitory burst neurons. Premature discharge of the inhibitory burst neuron further leads to breaks in the saccade trajectory, and maladaptive superior colliculus activity leading to aberrant saccades changing the intended trajectory of the ongoing saccade.
Gait dysfunction and postural instability are two debilitating symptoms in persons with Parkinson's disease (PD). Tai Chi exercise has recently gained attention as an attractive intervention for persons with PD because of its known potential to reduce falls and improve postural control, walking abilities, and safety at a low cost. The purpose of this report is to investigate the effect of Tai Chi exercise on dynamic postural control during gait initiation and gait performance in persons with idiopathic PD, and to determine whether these benefits could be replicated in two different environments, as complementary projects. In these two separate projects, a total of 45 participants with PD were randomly assigned to either a Tai Chi group or a control group. The Tai Chi groups in both projects completed a 16-week Tai Chi exercise session, while the control groups consisted of either a placebo (i.e., Qi-Gong) or non-exercise group. Tai Chi did not significantly improve Unified Parkinson's Disease Rating Scale Part III score, selected gait initiation parameters or gait performance in either project. Combined results from both projects suggest that 16 weeks of class-based Tai Chi were ineffective in improving either gait initiation, gait performance, or reducing parkinsonian disability in this subset of persons with PD. Thus the use of short-term Tai Chi exercise should require further study before being considered a valuable therapeutic intervention for these domains in PD.
Aim: Determine the efficacy of behavioral therapy for urinary symptoms in Parkinson's disease. Methods: Randomized trial of behavioral therapy compared with control condition among adults (aged 54-85 years, 74% male, 10% Black/ 83% White) with Parkinson's and greater than or equal to 4 incontinence episodes weekly. Behavioral therapy included pelvic floor muscle exercises, bladder training, fluid and constipation management. Both groups completed bladder diary self-monitoring. Outcomes included diary-derived incontinence and ICIQ-overactive bladder (OAB) score (range, 0-16) with bother and quality of life questionnaires (higher scores = worse outcomes). Results: Fifty-three participants randomized and 47 reported 8-week outcomes including 26 behavioral therapy and 21 control. Behavioral vs control participants were similar with respect to age (71.0 ± 6.1 vs 69.7 ± 8.2 years), sex (70% vs 78% male), motor score, cognition, mean weekly incontinence episodes (13.9 ± 9.6 vs 15.1 ± 11.1) and OAB symptoms (8.9 ± 2.4 vs 8.3 ± 2.2). Weekly incontinence reduction was similar between behavioral (−6.2 ± 8.7) and control participants (−6.5 ± 13.8) (P = 0.89). After multiple imputation analysis, behavioral therapy participants reported statistically similar reduction in OAB symptoms compared to control (−3.1 ± 2.8 vs −1.9 ± 2.2, P = 0.19); however quality of life (−22.6 ± 19.1 vs −7.0 ± 18.4, P = 0.048) and bother (−12.6 ± 17.2 vs − 6.7 ± 8.8, P = 0.037) improved significantly more with behavioral therapy. Conclusion: Self-monitoring resulted in fewer urinary symptoms; however, only multicomponent behavioral therapy was associated with reduced bother and improved quality of life. Providers should consider behavioral therapy as initial treatment for urinary symptoms in Parkinson's disease.
by
Kelvin L Chou;
Jordan J. Elm;
Catherine L. Wielinski;
David K. Simon;
Michael J. Aminoff;
Chadwick W. Christine;
Grace S. Liang;
Robert A. Hauser;
Lewis Sudarsky;
Chizoba C. Umeh;
Tiffini Voss;
Jorge Juncos;
John Y. Fang;
James T. Boyd;
Ivan Bodis-Wollner;
Zoltan Mari;
John C. Morgan;
Anne-Marie Wills;
Stephen L. Lee;
Sotirios A. Parashos
Background Recognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals. Objective To examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset. Methods The LS-1 database included 1741 early treated PD subjects (median 4 year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate. Results 728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy. Conclusion Falls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD.
Background
Carriers of the FMR1 premutation allele are at a significantly increased risk for a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). This disorder is distinct from fragile X syndrome (FXS) in its molecular aetiology and clinical presentation. The primary features of FXTAS are late-onset intention tremor and gait ataxia. Associated features include parkinsonism, neuropsychological dysfunction, autonomic dysfunction and peripheral neuropathy.
Aim
To investigate the usefulness of a quantitative neurological test battery implemented through the CATSYS instrument to identify preclinical symptoms of FXTAS.
Methods
Both premutation carriers with 70–199 repeats (62 men) and their low-repeat allele carrier siblings (27 men), identified through families with an individual affected with FXS, were tested.
Results
As expected, because of its sensitivity, use of the instrument allowed identification of tremor in 23% of men who had not self-reported tremor, and ataxia in 30% of men who had not self-reported ataxia. Among subjects with self-reported tremor and ataxia, we found significant concordance between measures of the CATSYS system and the self-report.
Conclusion
Rates of these traits among premutation carriers and low-repeat allele carrier siblings could be identified, and are presented in this paper, along with the minimum estimates of age-related prevalence.
by
Irene Litvan;
Peter SJ Lees;
Christopher Cunningham;
Shesh N Rai;
Alexander C Cambon;
David G Standaert;
Connie Marras;
Jorge Juncos;
David Riley;
Stephen Reich
Background: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. Methods: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. Results: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. Conclusions: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors.
Aim Characterize clinical factors related to nocturia and sleep disruption in Parkinson disease (PD) using polysomnography (PSG). Methods Sixty-three PD patients were recruited regardless of sleep or voiding complaints from a university-based movement disorders clinic for a 48 hr inpatient PSG protocol. Nocturia frequency and bother related to urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) and were corroborated by measurements of PSG-defined sleep made immediately preceding and subsequent to each in-lab voiding episode. PSG measures included whole-night total sleep time (TST), sleep efficiency (SE), apnea/hypopnea index (AHI), and time to PSG-defined sleep following nocturia episodes. Differences between groups were assessed using Mantel-Haenszel chi-square, t-tests, or Wilcoxon signed rank tests. Linear regression was used to assess factors associated with reported nocturia frequency. Results Sixty patients completed the IPSS. Thirty-seven (61%) reported at least two nocturia episodes nightly; those individuals demonstrated lower PSG-defined SE (P = 0.01) and TST (P = 0.02) than patients with 0-1 episodes. Participants reporting 2-3 episodes of nocturia with high bother on the IPSS (n = 12) demonstrated lower whole-night TST (280.5 ± 116.1 min vs. 372.5 ± 58.7 min, P = 0.03) and worse SE (59.2 ± 22.7% vs. 75.9 ± 11.2%, P = 0.04) when compared to participants with 2-3 episodes of nocturia with low bother (n = 13). Conclusions These results verify objectively that PD patients with nocturia have poor sleep. Furthermore, among individuals with comparable levels of reported nocturia, higher bother is associated with poorer sleep as defined on PSG.