Comorbid conditions associated with Parkinson's disease: a population-based study.

The burden of comorbidity in Parkinson's disease (PD) remains unclear. All Olmsted County, Minnesota, residents with incident PD in 1976-1995 (n = 197) plus one age- and sex-matched non-PD referent subject per case were followed for all clinical diagnoses from 5 years before through 15 years after index (i.e., year of PD onset for each case and same year for the referent subject). Both members of a case-referent pair were censored at death or emigration of either member to ensure equivalent follow-up. Cases and referent subjects were compared for summary comorbidity (Charlson index) and for the likelihood of having one or more diagnoses within each International Classification of Diseases chapter/subchapter. Before index, the groups were similar for all comparisons. After index, cases had a higher likelihood of diagnoses within the chapters "Mental Disorders" and "Diseases of the Genitourinary System," and within the subchapters "Organic Psychotic Conditions," "Other Psychoses," "Neurotic/Personality/Other Nonpsychotic Disorders," "Hereditary/Degenerative Diseases of Central Nervous System," "Symptoms," "Other Diseases of Digestive System," "Other Diseases of Urinary System," "Diseases of Veins/Lymphatics/Other Circulatory System Diseases," "Fractures of Lower Limb," "Other Diseases of Skin/Subcutaneous Tissue," "Osteopathies/Chrondropathies/Acquired Musculoskeletal Deformities," and "Pneumonia and Influenza." The excess morbidity and mortality observed for persons with PD are consistent with recognized PD sequelae.     

Direct costs of managing Parkinson's disease in India: concerns in a developing country.

Medicines and surgical interventions improve the quality of life of Parkinson's disease (PD) patients. These are still expensive options and are unaffordable to those living in developing countries. Managing PD in Indians who have a low annual gross national income (GNI; 450-540 US dollars) and for whom only a few (3%) have health insurance is a challenge. We interviewed 175 consecutive PD patients regarding health insurance and money spent for treatment. The annual income of nearly half the patients was less than rupees 50,000 (1,148.63 US dollars). Patients in this study spend nearly 16% to 41.7% of the average Indian GNI to buy medicines. Costs of treating PD in India are lower than those in developed nations but are still out of reach for most Indian patients.     

Resource use and costs in a Swedish cohort of patients with Parkinson's disease.

We estimated resource use and costs in patients with Parkinson's disease (PD), thereby providing baseline data for future economic evaluations of therapeutic interventions. Data were collected from medical records of a South Swedish cohort of 127 PD patients during 1 year (1996) and a mailed questionnaire inquiring about cost-related consequences and resource use in 1996 and in 2000. Annual costs were calculated based on prevalence and expressed in SEK (monetary value of the year 2000). Direct health care costs averaged approximately SEK 29,000 ( approximately USD 2,900; EUR 3,200) per patient per year, of which drugs were the most costly component. Nonmedical direct costs were higher than direct health care costs, averaging approximately SEK 43,000 ( approximately USD 4,300; EUR 4,800) per patient per year, and costs due to lost production were approximately SEK 52,000 ( approximately USD 5,200; EUR 5,800) per patient per year. The mean total annual cost for PD in our sample approximated SEK 124,000 ( approximately USD 12,400; EUR 13,800) per patient. These findings are roughly within the same range as estimates from other countries and show that PD causes a considerable societal burden. In addition to other outcomes, evaluations of the economic implications of new therapeutic interventions are highly warranted. In this perspective, the present study provides valuable baseline data.     

Predicting the cost of Parkinson's disease.

The degenerative nature of Parkinson's disease (PD) suggests that it will lead to high levels of resource use. This study measures service use and costs for a representative community sample of PD patients and identifies cost predictors. Patients were identified from general practices and were interviewed twice, separated by a 12-month interval. Demographic and clinical data on patients were collected and 6-month costs were calculated. Regression analysis was used to identify significant baseline predictors of follow-up costs. The annual service costs (baseline and follow-up combined) were 13,804 pounds per person. Formal service costs accounted for 20% of this figure with informal care from families/friends accounting for 80%. The regression model explained 42% of total follow-up costs and significant predictors included gender (with men having higher costs), disability, and depression.     

Mortality from Parkinson's disease: a population-based prospective study (NEDICES)

Most studies of mortality in Parkinson's disease have been clinical studies, yielding results that are not representative of the general population. We assessed the risk of mortality from Parkinson's disease in the Neurological Disorders in Central Spain (NEDICES) study, a prospective population-based study in which Parkinson's disease patients who were not ascertained through medical practitioners were also included. The cohort consisted of 5262 elderly subjects (mean baseline age, 73.0 years), including 81 with Parkinson's disease at baseline (1994-1995). Thirteen-year mortality was assessed. Two thousand seven hundred and one of 5262 subjects (51.3%) died over a median follow-up of 12.0 years (range, 0.04-14.8 years), including 66 of 81 subjects (81.5%) with Parkinson's disease at baseline and 2635 of 5181 subjects (50.8%) without Parkinson's disease at baseline. In an unadjusted Cox model, the hazard ratio of mortality was increased in subjects with Parkinson's disease (hazard ratio, 2.29; 95% confidence interval, 1.80-2.93; P < .001) versus subjects without Parkinson's disease (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, the risk of mortality remained elevated in subjects with Parkinson's disease (hazard ratio, 1.75; 95% CI, 1.32-2.31, P < .001). In additional Cox models, Parkinson's disease patients with dementia had particularly high risks of mortality (adjusted hazard ratio, 2.62; 95% CI, 1.40-4.90; P < .001). In this prospective population-based study, Parkinson's disease was an independent predictor of mortality in the elderly. Parkinson's disease patients with dementia had particularly high risks of mortality.     

Clinical diagnostic criteria for dementia associated with Parkinson's disease.

Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.     

Chemical exposures and Parkinson's disease: a population-based case-control study.

The putative association between pesticide exposures and Parkinson's disease (PD) remains controversial. We identified all subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995, and matched them by age (+/- 1 year) and sex to general population controls. We assessed exposures to chemical products by means of telephone interview with cases, controls, or their proxies (149 cases; 129 controls). Exposure to pesticides related or unrelated to farming was associated with PD in men (odds ratio, 2.4; 95% confidence interval, 1.1-5.4; P = 0.04). The association remained significant after adjustment for education or smoking. Analyses for the other six categories of industrial and household chemicals were all nonsignificant. This population-based study suggests a link between pesticides use and PD that is restricted to men. Pesticides may interact with other genetic or nongenetic factors that are different in men and women.     

Parkinson's disease is associated with hippocampal atrophy.

Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison. There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD.     

Cognitive profile of Parkinson's disease patients: a comparative study between early-onset and late-onset Parkinson's disease

Aim: To investigate the influence of onset age on the occurrence and progression of cognitive dysfunction using neuropsychological tests and the electrophysiological component P300 in both early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) patients. Methods: A cohort of 76 EOPD patients and 166 LOPD patients was recruited for this study. Demographic information and clinical features, including age, disease duration, education level, family history, the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr stage, and depression scores were documented for each patient. The Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale – Revised, Chinese version (WAIS-RC) and Wechsler Memory Scale – Revised, Chinese version (WMS-RC) were used. In addition, P300 was also examined to assess cognitive function. Results: Although EOPD patients had longer disease duration, their cognitive dysfunction progressed more slowly. The MoCA tests revealed that EOPD patients had higher scores in visuospatial function, attention, delayed recall, and orientation than the LOPD patients. The difference between the two groups on the WMS-RC test did not reach significance, whereas the scores in executive function, visuospatial function and attention as measured on the WAIS-RC test were significantly lower in the LOPD group. In addition, P300 latencies were markedly delayed and P300 amplitudes were reduced in the LOPD group. Conclusions: The current findings demonstrated that cognitive dysfunction progressed more slowly in the EOPD group. Although the LOPD patients exhibited shorter disease durations, their cognitive abilities, including executive function, visuospatial function and attention, may have been impaired.     

Restless legs syndrome in Parkinson's disease: a case-controlled study.

Restless legs syndrome (RLS) is a disorder of motor activity with a circadian pattern, occurring frequently in patients with Parkinson's disease (PD). We sought to estimate the prevalence of RLS in Indian PD patients. One hundred twenty-six consecutive PD patients and 128 healthy age- and sex-matched controls were evaluated using a predesigned questionnaire. RLS was present in 10 of 126 cases of PD (7.9%) and 1 of 128 controls (0.8%, P = 0.01). PD patients with RLS were older than those without RLS (63.70 +/- 7.80 years vs. 57.37 +/- 10.04 years; P = 0.05) and had higher prevalence of depression (40% vs. 10.3%; P = 0.023). No demographic factors or factors related to PD correlated with the presence or severity of RLS. RLS is more common among patients with PD than controls. A greater medical recognition of this disorder is needed in view of available effective treatment.     

Estimating the costs of surgical innovations: the case for subthalamic nucleus stimulation in the treatment of advanced Parkinson's disease.

We estimated the current cost of deep brain stimulation surgery targeted on the subthalamic nucleus. The method used was a cost analysis using typical resource use patterns and unit costs from a leading surgical centre, detailed equipment costs from the manufacturer, and sensitivity analysis. Resource use was based on patients with advanced Parkinson's disease. The main outcome measure was the likely total health service costs per patient, including preoperative assessment, surgery, and postoperative management over a 5-year period. The preoperative assessment, surgery, and discounted follow-up costs associated with subthalamic nucleus surgery were estimated at approximately UK Pounds 32,526 per patient over 5 years. Almost 70% of these costs are attributable to the initial costs of the equipment and the likely follow-up and replacement costs of the equipment. These costs will be affected mainly by future equipment costs and their replacement period and are relatively insensitive to preoperative assessment staff costs, length of hospital stay after surgery, and imaging costs. This cost estimate should be of use to researchers, health care managers, policy makers, and surgeons working in this area. Providing an estimate of the cost of this new procedure will provide a baseline for tracking future changes in costs and will assist the production of cost-effectiveness estimates.     

Action fluency in Parkinson's disease: a follow-up study.

The impairment in action fluency task present in Parkinson's disease (PD) patients has been previously interpreted as an indicator of conversion from PD to PD with dementia or as a grammatical deficit for verbs and ascribed to a frontostriatal loop pathophysiology. In the present study, 20 patients with PD without dementia were longitudinally tested with overall cognitive decline scales and semantic, letter, and action fluency tasks in a 24-month follow-up study. In comparison with healthy age-matched controls, PD patients showed a stable and consistent impairment on action fluency without any sign of cognitive decline. Our findings suggest that action fluency task may be an early sign of impairment of frontostriatal circuits in PD and it cannot be considered an indicator of conversion from PD to PD with dementia.     

Risk of Parkinson's disease in patients with hypothyroidism: A nationwide population-based cohort study

IntroductionHypothyroidism has been implicated in many other disease conditions, including neurodegenerative diseases. Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hypothyroidism.MethodsA total of 4725 patients with hypothyroidism and 4725 controls (without hypothyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) of PD incidence rate between patients with hypothyroidism and unaffected controls.ResultsPatients with hypothyroidism had a significantly increased risk of PD compared with unaffected controls (2.00 versus 1.10 per 1,000 person-years, HR: 1.77, 95% CI: 1.13–2.76) after adjusting for age, gender, CCI score, physical comorbidities (brain injury, cerebrovascular disease, hypertension, dyslipidemia, and diabetes mellitus), and duration of levothyroxine use. Also, older age (≥50 vs. <50 - HR:14.83), higher CCI score (CCI score 1–2 & ≥3 vs. 0 - HR: 1.66–1.74), and specific comorbidities (brain injury (HR: 1.78) and cerebrovascular disease (HR: 2.46)) significantly increased the risk of PD after adjusting for the variables mentioned above.ConclusionsPatients with hypothyroidism have an increased risk of developing PD. Other prospective studies that take into account genetic vulnerability and environmental exposures are warranted to confirm their relationship.     

Neural networks associated with quality of life in patients with Parkinson's disease

IntroductionThe neural underpinnings of health-related quality of life in Parkinson's disease remain unclear. This study was conducted to unravel which motor and non-motor symptoms in Parkinson's disease influence health-related quality of life and reveal neural networks most likely linked to it.MethodsComprehensive clinical assessments were conducted for 247 Parkinson's disease patients and image analyses were performed for 181 patients. Clinical scores commonly used to assess various symptoms related to health-related quality of life were investigated. Factor and resting-state functional magnetic resonance imaging analyses were reviewed to reveal health-related quality of life-associated brain networks.ResultsThe Spearman's rank correlation coefficient for the Parkinson's disease Questionnaire-39 summary index was high in the Activities-specific Balance Confidence Scale, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 2, Freezing of Gait Questionnaire, and Self-reported Autonomic Symptoms in Parkinson's disease. Multiple regression and Random Forest regression analyses indicated that health-related quality of life-associated factors were Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 1, Depression Rating Scales, and the above-mentioned scales. The resting-state functional magnetic resonance imaging analysis revealed decreased functional connectivity between the anterior cingulate cortex and right temporo-parietal junction as health-related quality of life worsened.ConclusionFear of falling, daily living activities, gait freezing, and autonomic dysfunction have notable effects on health-related quality of life in Parkinson's disease. Brain networks consisting of the anterior cingulate cortex and temporo-parietal junction may be associated with the emotion-related and social factors of health-related quality of life in Parkinson's disease.     

Excessive daytime sleepiness in patients with Parkinson's disease: a polysomnography study.

To investigate excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD), the reasons for which have not yet been clarified, polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT) were performed in 46 patients with PD, and, in addition, PSG was performed in 30 healthy controls. Assessment included Epworth Sleepiness Score (ESS), Mini-Mental State Examination (MMSE), and Hamilton Test (HT) for depression. Fifty percent of PD patients reported EDS (ESS, 10 +/- 4.5 vs. 6.9 +/- 3.7; P = 0.01). Compared with controls, PD patients as a group had lower sleep efficiency (65 +/- 22 vs. 77 +/- 14; P = 0.03), a longer Stage 2 (73 +/- 12 vs. 67 +/- 12; P = 0.03), and a shorter rapid eye movement stage (8 +/- 8 vs. 17 +/- 8; P < 0.001). Clinical data and sleep characteristics were similar in PD with/without EDS. Of interest, patients treated with clonazepam (CLNZ) had lower EDS than those without CLNZ (ESS, 7.9 +/- 4.7 vs. 11.3 +/- 4.0; P = 0.03). These patients suffered less periodic leg movement during sleep (2.1 +/- 2.7 vs. 12.4 +/- 28; P = 0.04), which might explain the finding. No correlation was found between ESS, MSLT, and all other clinical features analyzed. In PD patients, according to the data obtained, severity of EDS does not depend on any specific clinical factor and the etiology is probably multifactorial. Paradoxically, PD patients treated with CLNZ were less sleepy than patients not treated with CLNZ.