Neuropsychiatric comorbidities in Huntington's and Parkinson's Disease: A United States claims database analysis.

OBJECTIVE: Huntington's disease is a rare, genetic, neurodegenerative disease characterized by a triad of cognitive, behavioral, and motor symptoms. The condition gradually results in increasing disability, loss of independence, and ultimately death. Our objective was to use United States claims data (which offer valuable insight into the natural history of disease) to compare the prevalent comorbidities of people with Huntington's disease against matched controls with Parkinson's disease or with no major neurodegenerative diseases (general population controls). We also assess medication use in people with Huntington's disease. METHODS: This was a retrospective, observational study using data from the IBM MarketScan® Databases. Cases and controls were matched 1:1, and comorbidities were analyzed in each group during 2017. Medications were also assessed in the Huntington's disease cohort. Eligible cases had ≥ 2 diagnostic codes for Huntington's disease; controls had ≥ 2 codes for Parkinson's disease (with no record of Huntington's disease), or, for general population controls, no record of Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, or dementia. RESULTS: A total of 587 matched individuals were assessed in each cohort. Depression and anxiety were more common in Huntington's disease versus Parkinson's disease (odds ratios: 1.51 and 1.16, respectively). Other conditions more common in Huntington's disease included dementia, communication/speech problems, dysphagia, and falls. The use of antidepressant (59.9%) and antipsychotic (39.5%) medications was frequent among Huntington's disease cases. INTERPRETATION: These data highlight the prevalence of psychiatric, cognitive, communication, swallowing, and mobility problems in people with Huntington's disease, underscoring the need for holistic expert care of these individuals.

Inventory of real world data sources in Parkinson's disease.

BACKGROUND: Real world data have an important role to play in the evaluation of epidemiology and burden of disease; and in assisting health-care decision-makers, especially related to coverage and payment decisions. However, there is currently no overview of the existing longitudinal real world data sources in Parkinson's disease (PD) in the USA. Such an assessment can be very helpful, to support a future effort to harmonize real world data collection and use the available resources in an optimal way. METHODS: The objective of this comprehensive literature review is to systematically identify and describe the longitudinal, real world data sources in PD in the USA, and to provide a summary of their measurements (categorized into 8 main dimensions: motor and neurological functions, cognition, psychiatry, activities of daily living, sleep, quality of life, autonomic symptoms and other). The literature search was performed using MEDLINE, EMBASE and internet key word search. RESULTS: Of the 53 data sources identified between May and August 2016, 16 were still ongoing. Current medications (81%) and comorbidities (79%) were frequently collected, in comparison to medical imaging (36%), genetic information (30%), caregiver burden (11%) and healthcare costs (2%). Many different measurements (n = 108) were performed and an interesting variability among used measurements was revealed. CONCLUSIONS: Many longitudinal real world data sources on PD exist. Different types of measurements have been performed over time. To allow comparison and pooling of these multiple data sources, it will be essential to harmonize practices in terms of types of measurements.

Development and validation of an algorithm for identifying urinary retention in a cohort of patients with epilepsy in a large US administrative claims database.

PURPOSE: The aim of this study was to develop and validate an insurance claims-based algorithm for identifying urinary retention (UR) in epilepsy patients receiving antiepileptic drugs to facilitate safety monitoring. METHODS: Data from the HealthCore Integrated Research Database(SM) in 2008-2011 (retrospective) and 2012-2013 (prospective) were used to identify epilepsy patients with UR. During the retrospective phase, three algorithms identified potential UR: (i) UR diagnosis code with a catheterization procedure code; (ii) UR diagnosis code alone; or (iii) diagnosis with UR-related symptoms. Medical records for 50 randomly selected patients satisfying ≥1 algorithm were reviewed by urologists to ascertain UR status. Positive predictive value (PPV) and 95% confidence intervals (CI) were calculated for the three component algorithms and the overall algorithm (defined as satisfying ≥1 component algorithms). Algorithms were refined using urologist review notes. In the prospective phase, the UR algorithm was refined using medical records for an additional 150 cases. RESULTS: In the retrospective phase, the PPV of the overall algorithm was 72.0% (95%CI: 57.5-83.8%). Algorithm 3 performed poorly and was dropped. Algorithm 1 was unchanged; urinary incontinence and cystitis were added as exclusionary diagnoses to Algorithm 2. The PPV for the modified overall algorithm was 89.2% (74.6-97.0%). In the prospective phase, the PPV for the modified overall algorithm was 76.0% (68.4-82.6%). Upon adding overactive bladder, nocturia and urinary frequency as exclusionary diagnoses, the PPV for the final overall algorithm was 81.9% (73.7-88.4%). CONCLUSIONS: The current UR algorithm yielded a PPV > 80% and could be used for more accurate identification of UR among epilepsy patients in a large claims database.

Occurrence and Recurrence of Attempted Suicide Among People With Epilepsy.

IMPORTANCE: People with epilepsy have a 5-fold increased risk of suicide. Less is known about attempted suicide and whether psychiatric disorders and antiepileptic drugs modify the risk of attempted suicide. OBJECTIVES: To estimate the magnitude of the association between attempted suicide and epilepsy by comparing a first suicide attempt and a second suicide attempt (hereafter referred to as a recurrent suicide attempt) among people before they received a diagnosis of epilepsy (case patients) with a first suicide attempt and a recurrent suicide attempt among people without epilepsy (control patients), and to evaluate the effect of comorbid psychiatric disorders and the exclusion of antiepileptic drug prescriptions on this association. DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study in the United Kingdom of case patients with incident epilepsy and control patients without a history of epilepsy in a general practice setting using Clinical Practice Research Datalink. The case patients with incident epilepsy were identified between 1987 and 2013 and were 10 to 60 years of age. The control patients for each case patient were 4 randomly selected people who did not receive a diagnosis of epilepsy before the case patient's epilepsy was diagnosed (the index date), matched by year of birth, sex, and general practice for a control to case ratio of 4 to 1. MAIN OUTCOMES AND MEASURES: Hazard ratio for incident and recurrent suicide attempts among case patients with epilepsy compared with control patients without. RESULTS: For 14,059 case patients (median age, 36 years [range, 10-60 years]) who later had an onset of epilepsy vs 56,184 control patients (median age, 36 years [range, 10-60 years]), the risk was increased 2.9-fold (95% CI, 2.5- to 3.4-fold) for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy. For 278 case patients (median age, 37 years [range, 10-61 years]) who later had an onset of epilepsy vs 434 control patients (median age, 35 years [range, 11-61 years]), the risk was increased 1.8-fold (95% CI, 1.3- to 2.5-fold) for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed. Exclusion of antiepileptic drugs prescribed before the index date did not meaningfully alter the findings, nor did separate analyses of patients with and patients without diagnosed psychiatric disorders. CONCLUSIONS AND RELEVANCE: Suicide attempts and recurrent suicide attempts are associated with epilepsy even before epilepsy manifests, suggesting a common underlying biology. Our findings indicate that both incident and recurrent suicide attempts are associated with incident epilepsy in the absence of antiepileptic drugs and in the absence of diagnosed psychiatric disorders, further strengthening the evidence for a common underlying etiology with an as-yet-unknown mechanism.

Physician and Pharmacist Understanding of the Risk of Urinary Retention with Retigabine (Ezogabine): A REMS Assessment Survey.

BACKGROUND: The Risk Evaluation and Mitigation Strategy (REMS) for retigabine/ezogabine (RTG/EZG) required an evaluation of the effectiveness of the communication plan to communicate about the risks with use of RTG/EZG. OBJECTIVE: GlaxoSmithKline conducted a survey to assess understanding of the risk of urinary retention (UR) with RTG/EZG and to evaluate the effectiveness of the communication plan. METHODS: This was a US-based, cross-sectional, non-interventional, observational survey, conducted from February to April 2013, of physicians who had prescribed RTG/EZG in the past year, and pharmacists who had dispensed an antiepileptic drug within the past 3 months. Thirteen primary objective questions (five specific to UR risk) were included in the survey, which assessed healthcare professionals' (HCPs') understanding of UR risk and symptoms of acute UR associated with RTG/EZG. The primary outcome was the proportion of HCPs correctly answering each question. For each question, a proportion of correct responses ≥80 % was considered to represent sufficient understanding of associated risks. RESULTS: Of 1028 HCPs screened, 373 participated. Six of 13 questions (3/5 specific to UR risk) met the ≥80 % threshold for correct responses in the physician cohort. No questions achieved this threshold in the total pharmacist group; however, four questions scored ≥80 % when stratified by pharmacists who had dispensed RTG/EZG. CONCLUSIONS: Results demonstrated a mixed level of understanding of aspects of UR risk associated with RTG/EZG, although some risk questions did not meet the 80 % threshold, especially among pharmacists. This is likely to have been due to the short time that RTG/EZG has been available and its limited use. This study provides the first evaluation of the REMS communication plan on the risk of UR with RTG/EZG.

European Survey of Prescriber Understanding of Risks Associated with Retigabine.

BACKGROUND: We conducted a survey to assess physicians' knowledge and understanding of key risks associated with retigabine. OBJECTIVE: The survey evaluated the effectiveness of the educational plan for retigabine, as specified in the GlaxoSmithKline (GSK) European Risk Management Plan. METHODS: This was a cross-sectional survey of physicians across seven European countries (Denmark, Germany, Norway, Slovakia, Spain, Switzerland, and the UK) who had prescribed an antiepileptic drug at least once within the past 3 months, and to whom a letter containing the retigabine Physician's Guide was sent. The survey included multiple-choice and closed-ended questions. Primary outcome was the proportion of physicians correctly answering questions related to retigabine-associated risks. Point estimates for the proportion of correct responses and associated confidence intervals were calculated. RESULTS: Overall, 294 prescribers completed the survey between November 2012 and October 2013. Generally, physicians had adequate knowledge of the retigabine indication (78-92 % correct responses). Specific dose-related knowledge (57-74 %) and management of individual risks (20-77 %) were recalled less well. Subgroup analyses showed that both the 189 physicians who read the retigabine education letter and the 144 who had prescribed retigabine had better recall of the risks associated with retigabine (20-78 %) than those who did not. CONCLUSIONS: Overall, physicians were aware, to varying degrees, of the risks associated with retigabine. Subsequent to the conduct of this survey, GSK has made further changes to the product labeling for retigabine, sent an updated 'Dear Healthcare Professional' letter, and initiated another EU survey to assess how effectively specific risks associated with retigabine use are communicated. Clinical trials registration number NCT01721213.

Parkinson's Disease Case Ascertainment in the EPIC Cohort: The NeuroEPIC4PD Study.

BACKGROUND/AIMS: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. METHODS: The following three-phase procedure was used: (1) elaboration of a NeuroEPIC4PD template for clinical data collection, (2) identification of all potential PD cases via record linkage and (3) validation of the diagnosis through clinical record revision, in a population of 220,494 subjects recruited in 7 European countries. All cases were labelled with the NeuroEPIC4PD diagnoses of 'definite', 'very likely', 'probable', or 'possible' PD. RESULTS: A total of 881 PD cases were identified, with over 2,741,780 person-years of follow-up (199 definite, 275 very likely, 146 probable, and 261 possible). Of these, 734 were incident cases. The mean age at diagnosis was 67.9 years (SD 9.2) and 458 patients (52.0%) were men. Bradykinesia was the most frequent presenting motor sign (76.5%). Tremor-dominant and akinetic rigid forms of PD were the most common types of PD. A total of 289 patients (32.8%) were dead at the time of the last follow-up. CONCLUSIONS: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies.

Sudden unexpected death in epilepsy in lamotrigine randomized-controlled trials.

PURPOSE: Nonrandomized studies of the relationship of antiepileptic drugs (AEDs) with sudden unexpected death in epilepsy (SUDEP) may be susceptible to confounding by tonic-clonic seizure frequency, polypharmacy, and other potential risk factors for SUDEP. We evaluated the risk of SUDEP with lamotrigine (LTG) compared to active comparators and placebo in randomized controlled clinical trials conducted by GlaxoSmithKline (GSK) between 1984 and 2009. METHODS: Among 7,774 subjects in 42 randomized clinical trials, there were 39 all-cause deaths. Ten deaths occurred >2 weeks after discontinuation of study medication and were excluded. Narrative summaries of deaths were independently reviewed by three clinical experts (TT, LH, DF), who were blinded to randomized treatment arm. The risk of definite or probable SUDEP was compared between treatment arms for each trial type (placebo-controlled, active-comparator, crossover), using exact statistical methods. KEY FINDINGS: Of 29 on-treatment deaths, eight were definite/probable SUDEP, four were possible SUDEP, and 17 were non-SUDEP. The overall, unadjusted rate of definite/probable SUDEP for LTG was 2.2 events per 1,000-patient years (95% confidence interval [95% CI] 0.70-5.4). The odds ratios (OR) for on-treatment, definite/probable SUDEP in LTG arms relative to comparator arms, adjusted for length of exposure and trial, were the following: placebo-controlled, OR 0.22 (95% CI 0.00-3.14; p = 0.26); active-comparator, OR 2.18 (95% CI 0.17-117; p = 0.89); and placebo-controlled cross-over, OR 1.08 (95% CI 0.00-42.2; p = 1.0). SIGNIFICANCE: There was no statistically significant difference in rate of SUDEP between LTG and comparator groups. However, the CIs were wide and a clinically important effect cannot be excluded.

Epilepsy, suicidality, and psychiatric disorders: a bidirectional association.

OBJECTIVE: A study was undertaken to determine whether psychiatric disorders associated with suicide are more common in incident epilepsy than in matched controls without epilepsy, before and after epilepsy diagnosis. METHODS: A matched, longitudinal cohort study was conducted in the UK General Practice Research Database. A total of 3,773 cases diagnosed with epilepsy between the ages of 10 and 60 years were compared to 14,025 controls matched by year of birth, sex, general practice, and years of medical records before the index date. We examined first diagnosis of psychosis, depression, anxiety, and suicidality in each of the 3 years before and after the index date and annual prevalence of suicide. Referent diagnoses were eczema and acute surgery. The incidence rate ratio (IRR) was calculated for each year in the study period; the prevalence ratio (PR) was calculated for suicidality. RESULTS: The IRR of psychosis, depression, and anxiety was significantly increased for all years before epilepsy diagnosis (IRR, 1.5-15.7) and after diagnosis (IRR, 2.2-10.9) and for suicidality before epilepsy diagnosis (IRR, 3.1-4.5) and 1 year after diagnosis (IRR, 5.3). The PR was increased for suicide attempt before epilepsy onset (PR, 2.6-5.2) and after onset (PR, 2.4-5.6). Eczema and acute surgery were both associated with epilepsy in the first and third year after diagnosis. INTERPRETATION: Epilepsy is associated with an increased onset of psychiatric disorders and suicide before and after epilepsy diagnosis. These relations suggest common underlying pathophysiological mechanisms that both lower seizure threshold and increase risk for psychiatric disorders and suicide.

Incidence of new-onset seizures in mild to moderate Alzheimer disease.

OBJECTIVE: To estimate the incidence rate and predictors of seizures in patients with mild to moderate Alzheimer disease (AD). DESIGN: Cohort study of patients with mild to moderate AD in clinical trials. Risk factors for potential seizures were evaluated by stratified descriptive statistics and univariable and multivariable Cox proportional hazards regressions. SETTING: Pooled patient-level data from 10 Alzheimer Disease Cooperative Study clinical trials in mild to moderate AD from 1995 to 2010. PATIENTS: Three thousand seventy-eight subjects randomized to the treatment or placebo arms of 10 AD clinical trials. Screening Mini-Mental State Examination scores ranged between 10 and 28. RESULTS: Eighteen seizures were reported in 3078 randomized subjects, with an incidence rate of 484 per 100 000 person-years (95% CI, 287-764). Statistically significant independent risk factors for seizure were younger age (adjusted hazard ratio, 0.80; 95% CI, 0.69-0.93 per every 5 years of age), greater cognitive impairment at baseline (adjusted hazard ratio, 2.79; 95% CI, 1.06-7.33 for Mini-Mental State Examination scores <18 compared with Mini-Mental State Examination scores ≥18), and antipsychotic use at baseline (adjusted hazard ratio, 3.47; 95% CI, 1.33-9.08). CONCLUSIONS: Seizure rates in patients with mild to moderate AD in clinical trials are similar to rates observed in longer observational cohort studies, but they are greater than expected in the general elderly population. Younger age, greater degree of cognitive impairment, and history of antipsychotic use were independent risk factors for new-onset seizures in AD.

Exploring differential prescribing between anti-epileptic drugs in epilepsy patients with a history of mood disorders.

PURPOSE: To explore differential prescribing of anti-epileptic drugs (AEDs) to patients with epilepsy by history of mood disorder. METHODS: Epilepsy was defined as at least one diagnosis code and one AED prescription, and all patients must have been on the database 182 days before and after their first AED prescription. The Integrated HealthCare Information Services (IHCIS) insurance claims database included 44 557 patients with epilepsy between January 1997 and March 2007. The General Practice Research Database (GPRD) included 16 904 patients with epilepsy up to March 2007. Patients were categorized by their first use of specified AEDs. Mood disorders were defined as diagnosis codes for depression and bipolar disorder, or anti-depressant use. The unadjusted odds ratios and 95% confidence intervals for a history of mood disorder diagnosis ever or within the three months prior to AED use were calculated with carbamazepine and oxcarbazepine (CBZ) as the referent. RESULTS: In the US IHCIS, a history of mood disorders was significantly more common in new users of most AEDs compared to CBZ new users, indicating differential prescribing. Clonazepam and gabapentin were the most commonly prescribed AEDs in patients with epilepsy and a history of mood disorders.In the UK GPRD, there was less evidence of differential prescribing of AEDs, although gabapentin was prescribed most often to epilepsy patients with a history of mood disorders. CONCLUSIONS: Any observational studies of AEDs and suicidality would have to consider potential channeling bias by history of mood disorders, which is a major risk factor for suicide.

Estimated life expectancy of Parkinson's patients compared with the UK population.

OBJECTIVE: To calculate the best possible estimates for age specific life expectancy (LE) and anticipated age at the time of death (AAD) in patients with Parkinson's disease (PD) compared with the general population in the UK. These may be of greater value to patients than standardised mortality ratios (SMRs), which are usually reported in studies on mortality in PD. METHODS: A literature review identified articles with data on age stratified life expectancy or SMRs to calculate estimations of LE using the Gompertz function and data on mortality and LE in the UK from the Office of National Statistics and Actuarial Department for the year 2003. RESULTS: Two UK studies and four from Western Europe were used to estimate LE and AAD for patients with PD from SMRs. The mean LEs of patients with PD compared with the general population were: 38 (SD 5) years for onset between 25 and 39 years compared with 49 (SD 5) years; 21 (SD 5) years for onset between 40 and 64 years compared with 31 (SD 7) years; and 5 (SD 4) years for onset age > or = 65 years compared with 9 (SD 5) years. The average AAD of patients with PD with onset between 25 and 39 years was 71 (SD 3) years and considerably lower than that of the general population (82 (SD 2) years). The difference between average AAD for older individuals with PD (onset > or = 65 years) and the general population was smaller, with an AAD of approximately 88 (SD 7) years compared with 91 (SD 5) years. CONCLUSIONS: The calculations showed that LE and AAD in PD are reduced for all onset ages but this reduction is greatest in individuals with a young onset. While the results are average estimates, these can provide useful indications of LE and AAD.

Screening for Lrrk2 G2019S and clinical comparison of Tunisian and North American Caucasian Parkinson's disease families.

Mutations in the leucine-rich repeat kinase-2 gene (LRRK2) are responsible for some forms of familial as well as sporadic Parkinson's disease (PD). The purpose of this study was to examine the frequency of a single pathogenic mutation (6055G > A) in the kinase domain of this gene in United States and Tunisian familial PD and to compare clinical characteristics between patients with and without the mutation. Standardized case report forms were used for clinical and demographic data collection. We investigated the frequency of the most common substitution of LRRK2 (G2019S, 6055G>A) and its impact on epidemiological and phenotypic features. The frequency of mutations in Tunisian families was 42% (38/91) and in U.S. families 2.6% (1/39), with the unique opportunity to compare homozygous (n = 23) and heterozygous (n = 109) Tunisian carriers of G2019S substitutions. Individuals with G2019S substitutions had an older age at onset but few other differences compared with families negative for the substitution. Patients with LRRK2 mutations had typical clinical features of PD. Comparisons between individuals with heterozygous and homozygous LRRK2 mutations suggested that gene dosage was not correlated with phenotypic differences; however, the estimated penetrance was greater in homozygotes across all age groups.

Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations.

BACKGROUND: The G2019S mutation is the most common pathogenic substitution in the leucine-rich repeat kinase 2 (LRRK2) gene, which has recently been identified in familial and sporadic Parkinson disease (PD). OBJECTIVES: To report the clinical characteristics of PD patients with homozygous LRRK2 6055G>A (G2019S) mutations and to compare them with previously published descriptions of heterozygous patients. DESIGN: Descriptive clinical report from an international consortium of studies. Subjects Patients with familial PD and homozygous LRRK2 mutations included 23 Tunisians, 2 Algerians, 2 US patients, 1 Canadian, and 1 Moroccan. RESULTS: There were no observable differences between the homozygote and heterozygote phenotypes. CONCLUSIONS: Parkinson disease related to LRRK2 is characterized by typical clinical features, and the similarities between patients with homozygous and heterozygous mutations do not support a gene dosage effect.

The frequency and validity of self-reported diagnosis of Parkinson's Disease in the UK elderly: MRC CFAS cohort.

BACKGROUND: Estimates of the incidence and prevalence of chronic diseases can be made using established cohort studies but these estimates may have lower reliability if based purely on self-reported diagnosis. METHODS: The MRC Cognitive Function & Ageing Study (MRC CFAS) has collected longitudinal data from a population-based random sample of 13004 individuals over the age of 65 years from 5 centres within the UK. Participants were asked at baseline and after a two-year follow-up whether they had received a diagnosis of Parkinson's disease. Our aim was to make estimates of the incidence and prevalence of PD using self-reporting, and then investigate the validity of self-reported diagnosis using other data sources where available, namely death certification and neuropathological examination. RESULTS: The self-reported prevalence of Parkinson's disease (PD) amongst these individuals increases with age from 0.7% (95%CI 0.5-0.9) for 65-75, 1.4% (95%CI 1.0-1.7) for 75-85, and 1.6% (95%CI 1.0-2.3) for 85+ age groups respectively. The overall incidence of self reported PD in this cohort was 200/100,000 per year (95%CI 144-278). Only 40% of the deceased individuals reporting prevalent PD and 35% of those reporting incident PD had diagnoses of PD recorded on their death certificates. Neuropathological examination of individuals reporting PD also showed typical PD changes in only 40%, with the remainder showing basal ganglia pathologies causing parkinsonism rather than true PD pathology. CONCLUSION: Self-reporting of PD status may be used as a screening tool to identify patients for epidemiological study, but inevitably identifies a heterogeneous group of movement disorders patients. Within this group, age, male sex, a family history of PD and reduced cigarette smoking appear to act as independent risk factors for self-reported PD.

What is the evidence for a premorbid parkinsonian personality: a systematic review.

Rigid and introverted personality type has been suggested as possibly associated with risk of Parkinson's disease (PD). However, to be a risk, the measurement of personality must precede the onset of PD, more than simply reported as personality in PD cases. Several reviews have been published examining the literature base for this suggestion; however, the issue of "premorbid" personality measurement was not emphasized. MEDLINE, EMBASE, and PSYCHINFO databases were searched for existing systematic reviews or meta-analyses, and none were found that fulfilled this criterion. The databases were searched systematically for primary research articles. Articles without robust methodology were excluded based on published quality scoring criteria. No articles met all selection criteria. Four articles met most selection criteria and three of them reported significant differences in personality features said to be present before PD onset and between PD cases and controls. PD cases were more introverted, cautious, socially alert, and tense than controls. Although the instruments used to characterize personality varied widely across studies, the general descriptions of PD patients included nervous, cautious, rigid, and conventional. There do appear to be parkinsonian characteristics, but these studies were all retrospective. To confirm that personality traits precede PD onset and are a risk for this condition, prospective research is required. Even then, the term "premorbid" is difficult to define due to the unknown latent period before onset of PD. Additional research would involve correlating personality characteristics to activities or changes in the brain.

Self-reported parkinsonian symptoms in the EPIC-Norfolk cohort.

BACKGROUND: Parkinsonian symptoms have been associated with increased morbidity and mortality. Several studies have reported on the prevalence of signs and symptoms. Symptoms questionnaires can identify potential PD cases for further neurological examination to save resources. They can also provide information about how much of the population reports specific signs and symptoms. The objective of the study was to determine the self-reported prevalence of parkinsonian symptoms from a questionnaire, and to examine their association with age and self-reported Parkinson's disease in a large cohort. METHODS: A cross-sectional study was conducted within a sub-cohort of the EPIC-Norfolk (European Prospective Investigation of Cancer) cohort study. RESULTS: The prevalence of six self-reported parkinsonian symptoms are reported for 11,539 individuals who answered all symptoms questions (62% of sub-cohort): rest tremor (4%), difficulty starting to walk (4%), difficulty getting out of a chair (6%), slower walking (34%), smaller handwriting (micrographia- 9%), and less acute sense of smell (olfactory dysfunction- 9%). The presence of individual symptoms increased with age except for difficulty getting out of a chair. CONCLUSION: The results support previous findings that the presence of self-reported parkinsonian symptoms is strongly associated with age and self-reported PD diagnosis. The data also provide information regarding the prevalence of symptoms in a large, younger population of adults than previously reported in the literature.

A systematic review of nutritional risk factors of Parkinson's disease.

A wide variety of nutritional exposures have been proposed as possible risk factors for Parkinson's disease (PD) with plausible biological hypotheses. Many studies have explored these hypotheses, but as yet no comprehensive systematic review of the literature has been available. MEDLINE, EMBASE, and WEB OF SCIENCE databases were searched for existing systematic reviews or meta-analyses of nutrition and PD, and one meta-analysis of coffee drinking and one meta-analysis of antioxidants were identified. The databases were searched for primary research articles, and articles without robust methodology were excluded by specified criteria. Seven cohort studies and thirty-three case-control (CC) studies are included in the present systematic review. The majority of studies did not find significant associations between nutritional factors and PD. Coffee drinking and alcohol intake were the only exposures with a relatively large number of studies, and meta-analyses of each supported inverse associations with PD. Factors that were reported by at least one CC study to have significantly increased consumption among cases compared with controls were: vegetables, lutein, xanthophylls, xanthins, carbohydrates, monosaccharides, junk food, refined sugar, lactose, animal fat, total fat, nuts and seeds, tea, Fe, and total energy. Factors consumed significantly less often among cases were: fish, egg, potatoes, bread, alcohol, coffee, tea, niacin, pantothenic acid, folate and pyridoxine. In three cohort studies, two reported borderline decreased relative risks and one a significant increased risk with vitamin C intake. One cohort reported an inverse association between caffeine intake and PD. Three cohorts reported significant positive association in men between dairy products and PD.