Care of Late-Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. OBJECTIVE: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. METHODS: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. RESULTS: During the 3-month period, the costs were €20,573 (France), €19,959 (Germany), €18,319 (the Netherlands), €25,649 (Sweden), and €12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. CONCLUSION: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Association between longitudinal clinical outcomes in patients with hip fracture and their pre-fracture place of residence.

BACKGROUND: Clinical outcomes of patients with proximal femoral fracture within 1 year after hospitalization are presented. In particular, associations between the patients' clinical status and their pre-fracture residence were evaluated (community-dwelling vs nursing home). METHODS: Patients aged ≥60 years with proximal femoral fractures were included in a prospective, single-centre observational study and followed for 12 months. Patients' clinical status at baseline was compared to their health status at follow-up 12 months later. Several standardized questionnaires were used to evaluate the patients' functional and cognitive capacity (e.g. Lawton Instrumental Activities of Daily Living Scale, Barthel Index, and Mini-Mental State Examination), mobility (timed up-and-go test, Tinetti Test, and Harris Hip Score), quality of life (EuroQol-5 Dimensions index and EuroQol Visual Analogue Scale), and psychological status (Geriatric Depression Scale). RESULTS: This study included 402 patients (mean age: 81.3 ± 8.2 years, 72% women). Patients stayed in hospital for 13.7 ± 6.1 days on average. The comparison of patients' clinical status at baseline and at 12-month follow-up revealed that the Mini-Mental State Examination and Charlson Comorbidity Index remained unchanged (P = 0.527 and P = 0.705), the level of depression (Geriatric Depression Scale) significantly decreased (P < 0.001), and quality of life (EuroQol-5 Dimensions index) diminished (P < 0.001). Although patients' mobility increased after 12 months (P < 0.001 for timed up-and-go test and Harris Hip Score), their functional capacity was significantly reduced (P < 0.001 for Barthel Index and Lawton Instrumental Activities of Daily Living Scale). Nursing home residents showed a significantly higher impairment at baseline than community-dwelling individuals and less improvement in functional and cognitive tests at 12-month follow-up. CONCLUSIONS: Clinical outcomes after hip fracture are significantly associated with patients' pre-fracture residence status. Place of residence as well as functional and cognitive status on admission may lead to differences in functional recovery and affect therapeutic and rehabilitative decision-making.

Cognitive decline in Parkinson's disease: the impact of the motor phenotype on cognition.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. METHODS: Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. RESULTS: Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). CONCLUSION: The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

Prescription of Benzodiazepines and Related Drugs in Patients with Mild Cognitive Deficits and Alzheimer's Disease.

INTRODUCTION: Benzodiazepines and related drugs (BZDR) should be avoided in patients with cognitive impairment. We evaluated the relationship between a BZDR treatment and the health status of patients with Alzheimer's disease (AD). METHODS: Cross-sectional study in 395 AD patients using bivariate and multiple logistic analyses to assess correlations between the prescription of BZDR and patients' characteristics (cognitive and functional capacity, health-related quality of life (HrQoL), neuropsychiatric symptoms). RESULTS: BZDR were used in 12.4% (n=49) of all participants. In bivariate analyses, the prescription was associated with a lower HrQoL, a higher need of care, and the presence of anxiety. Multivariate models revealed a higher risk of BZDR treatment in patients with depression (OR 3.85, 95% CI: 1.45 - 10.27). Community-dwelling participants and those treated by neurologists/psychiatrists had a lower risk of receiving BZDR (OR 0.33, 95% CI: 0.12 - 0.89 and OR 0.16, 95% CI: 0.07 - 0.36). DISCUSSION: The inappropriate use of BZDR conflicts with national and international guidelines. We suggest evaluating indications and treatment duration and improving the knowledge of alternative therapies in healthcare institutions.

Costs of illness in chronic inflammatory demyelinating polyneuropathy in Germany.

INTRODUCTION: Cost of illness studies are essential to estimate societal costs of chronic inflammatory demyelinating polyneuropathy (CIDP) and identify cost-driving factors. METHODS: In total, 108 patients were recruited from 3 specialized neuroimmunological clinics. Costs were calculated for a 3-month period, including direct and indirect costs. The following outcomes were assessed: inflammatory neuropathy cause and treatment disability scale, Mini-Mental State Examination, Beck Depression Inventory, Charlson comorbidity index, EuroQol-5D, World Health Organization quality of life instrument, and socioeconomic status. Univariate and multivariate analyses were applied to identify cost-driving factors. RESULTS: Total quarterly costs were €11,333. Direct costs contributed to 83% of total costs (€9,423), whereas indirect costs accounted for 17% (€1,910) of total costs. The cost of intravenous immunoglobulin (IVIg) was the main determinant of total costs (67%). Reduced health-related quality of life and depressive symptoms were identified as independent predictors of higher total costs. DISCUSSION: CIDP is associated with high societal costs, mainly resulting from the cost of IVIg treatment. Muscle Nerve 58: 681-687, 2018.

Psychometric Properties of an Abbreviated Version of the Apathy Evaluation Scale for Parkinson Disease (AES-12PD).

BACKGROUND: Apathy is a frequent symptom in Parkinson's disease (PD), substantially aggravating the course of PD. Regarding the accumulating evidence of the key role of apathy in PD, time-efficient assessments are useful for fostering progress in research and treatment. The Apathy Evaluation Scale (AES) is widely used for the assessment of apathy across different nosologies. OBJECTIVE: To facilitate the application of the AES in PD, we reduced the AES to two-thirds its length and validated this abbreviated version. DESIGN: Data sets of 339 PD patients of the DEMPARK/LANDSCAPE study without dementia and depression were randomly split into two samples. Data of sample 1 were used to develop a brief version of the AES (AES-12PD). A cross-validation was conducted in sample 2 and in a subsample of 42 PD patients with comorbid dementia and depressive symptomatology. Receiver operating characteristic analysis was applied to determine the optimal cutoff of the AES-12PD as an indicator of apathy. RESULTS: The AES-12PD featured high internal consistency that was better compared to the AES. The abbreviated scale was well differentiated from motor impairment and cognitive deficits. The AES-12PD cutoff of 27/28 was the optimal cutoff for apathy in PD patients without dementia and depression. The cutoff of 25/26 indicated apathy in PD patients with comorbid dementia and depression. CONCLUSION: Results confirm a high internal consistency and good discriminant validity of the AES-12PD. The AES-12PD represents a reliable tool for the efficient assessment of apathy that can be applied in PD patients with and without dementia and depression.

Study protocol: Care of Late-Stage Parkinsonism (CLaSP): a longitudinal cohort study.

BACKGROUND: Parkinson's disease (PD) is a chronic progressive disorder leading to increasing disability. While the symptoms and needs of patients in the early stages of their disease are well characterized, little information is available on patients in the late stage of the disease. METHODS/DESIGN: The Care of Late-Stage Parkinsonism (CLaSP) study is a longitudinal, multicenter, prospective cohort study to assess the needs and provision of care for patients with late stage Parkinsonism and their carers in six European countries (UK, France, Germany, Netherlands, Portugal, Sweden). In addition, it will compare the effectiveness of different health and social care systems. Patients with Parkinsonism with Hoehn and Yahr stage ≥IV in the "On"-state or Schwab and England stage 50% or less are evaluated at baseline and three follow-up time-points. Standardised questionnaires and tests are applied for detailed clinical, neuropsychological, behavioural and health-economic assessments. A qualitative study explores the health care needs and experiences of patients and carers, and an interventional sub-study evaluates the impact of specialist recommendations on their outcomes. DISCUSSION: Through the combined assessment of a range of quantitative measures and qualitative assessments of patients with late stage parkinsonism, this study will provide for the first time comprehensive and in-depth information on the clinical presentation, needs and health care provision in this population in Europe, and lay the foundation for improved outcomes in these patients. TRIAL REGISTRATION: The protocol was registered at ClinicalTrials.gov as NCT02333175 on 07/01/2015.

Antidepressant medication in a German cohort of patients with Alzheimer's disease
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OBJECTIVE: The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design. The patients' clinical characteristics comprised of cognitive status, daily activities, depressive symptoms, further neuropsychiatric symptoms, and health-related quality of life (HrQoL). We conducted multiple logistic regression analyses for the association between the use of antidepressant drugs and the covariates. RESULTS: Approximately 31% of the participants were treated with antidepressant drugs, with a higher chance of being medicated for institutionalized patients (χ2-test: p = 0.010). In the bivariate analyses, the use of antidepressants was significantly associated with higher levels of care, lower cognitive and daily life capacity, higher extent of neuropsychiatric symptoms, and a lower proxy-reported HrQoL. Finally, multiple logistic regression models showed a significantly higher use of antidepressants in patients treated by psychiatrists and neurologists (OR 2.852, 95% CI: 1.223 - 6.652). CONCLUSION: The use of antidepressant drugs in the study population was high, and the suitability of the treatment with antidepressants remains unclear. Participants with diminished cognitive and functional capacity, higher extent of neuropsychiatric symptoms, and those treated by neuropsychiatric specialists were more likely to be treated with antidepressants. The pharmaceutical treatment of patients with these clinical characteristics should be particularly considered in the daily care for dementia patients. Further longitudinal studies should evaluate the appropriateness of indications for antidepressants and the causative direction of correlations with the patients' clinical characteristics.
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Antipsychotic treatment of community-dwelling and institutionalised patients with dementia in Germany.

OBJECTIVE: A restrictive use of antipsychotic drugs in patients with Alzheimer's disease (AD) is recommended due to an increased risk of cerebrovascular events and mortality. We hypothesise that the prescription of antipsychotics is associated with the patients' socio-demographic and clinical status (e.g., dementia severity). METHODS: The prescription of antipsychotics was cross-sectionally evaluated in 272 community-dwelling and 123 institutionalised patients with AD across all severity stages of dementia. The patients' clinical characteristics covered the cognitive status, neuropsychiatric symptoms, daily activities, and quality of life (HrQoL). To determine associations with the use of antipsychotics bivariate and logistic regression analyses were conducted. RESULTS: Totally, 25% of the patients were treated with antipsychotics. significantly less frequently than nursing home inhabitants (15.1% vs. 45.5%). Severely demented patients (MMSE 0-9) received antipsychotics most often (51.5%). Additionally, multiple regression analyses revealed a higher chance of prescription for participants with depressive symptoms (OR 2.3, 95% CI: 1.019-5.160) and those treated by neuropsychiatric specialists (OR 3.4, 95% CI: 1.408-8.328). CONCLUSIONS: Further longitudinal studies are required to assess the appropriateness of indications for antipsychotics and the reasons for a higher use in nursing home inhabitants and patients with severe dementia and depression.

Prevalence, Duration and Severity of Parkinson's Disease in Germany: A Combined Meta-Analysis from Literature Data and Outpatient Samples.

BACKGROUND: Epidemiological data on the prevalence of Parkinson's disease (PD) in Germany are limited. The aims of this study were to estimate the age- and gender-specific prevalence of PD in Germany as well as the severity and illness duration. SUMMARY: A systematic literature search was performed in 5 different databases. European studies were included if they reported age- and gender-specific numbers of prevalence rates of PD. Meta-analytic approaches were applied to derive age- and gender-specific pooled prevalence estimates. Data of 4 German outpatient samples were incorporated to calculate the proportion of patients with PD in Germany grouped by Hoehn and Yahr (HY) stages and disease duration. In the German population, 178,169 cases of PD were estimated (prevalence: 217.22/100,000). The estimated relative illness duration was 40% with less than 5 years, 31% with 5-9 years, and 29% with more than 9 years. The proportions for different HY stages were estimated at 13% (I), 30% (II), 35% (III), 17% (IV), and 4% (V), respectively. Key Message: We provide an up-to-date estimation of age- and gender-specific as well as severity-based prevalence figures for PD in Germany. Further community studies are needed to estimate population-based severity distributions and distributions of non-motor symptoms in PD.

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study.

OBJECTIVE: Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. METHODS: Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. RESULTS: 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. CONCLUSIONS: This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

Cost-effectiveness of neurostimulation in Parkinson's disease with early motor complications.

BACKGROUND: Recent research efforts have focused on the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild-to-moderate PD experiencing motor complications. OBJECTIVES: We assessed the cost utility of subthalamic DBS compared with the best medical treatment for German patients below the age of 61 with early motor complications of PD. METHODS: We applied a previously published Markov model that integrated health utilities based on EuroQoL and direct costs over patients' lifetime adjusted to the German health care payer perspective (year of costing: 2013). Effectiveness was evaluated using the Parkinson's Disease Questionnaire 39 summary index. We performed sensitivity analyses to assess uncertainty. RESULTS: In the base-case analysis, the incremental cost-utility ratio for STN DBS compared to best medical treatment was 22,700 Euros per quality-adjusted life year gained. The time to, and costs for, battery exchange had a major effect on the incremental cost-utility ratios, but never exceeded a threshold of 50,000 Euros per quality-adjusted life year. CONCLUSIONS: Our decision analysis supports the fact that STN DBS at earlier stages of the disease is cost-effective in patients below the age of 61 when compared with the best medical treatment in the German health care system. This finding was supported by detailed sensitivity analyses reporting robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to medical therapy with respect to quality of life for patients with early motor complications, this further analysis has shown its cost-effectiveness. © 2016 International Parkinson and Movement Disorder Society.

Effect of Preexisting Cognitive Impairment on In-Patient Treatment and Discharge Management among Elderly Patients with Hip Fractures.

OBJECTIVE: To examine the influence of cognitive impairment on the functional outcomes and complication rates of patients with hip fracture during in-patient treatment. METHODS: A total of 402 patients who were surgically treated for hip fractures were consecutively enrolled at a single trauma center. The patients were grouped according to their results on the Mini-Mental State Examination (MMSE), i.e., ≥20 points (group I) and ≤19 points (group II). Complication and in-hospital mortality rates as well as postoperative functional outcomes according to the Barthel Index (BI) were compared between the groups. A multivariate regression analysis was performed to control for additional factors. RESULTS: 33% of the patients had MMSE scores ≤19 points. The complication rates were similar between the groups (p > 0.05). Likewise, the overall in-hospital mortality rates were similar between the patients in group I (4.5%) and those in group II (9.8%; ß = 0.218, p < 0.740). Functional outcomes, as assessed by the BI, were lower in group II (ß = -0.266, p < 0.001). The patients in group II were transferred to a rehabilitation clinic less frequently (52.3 vs. 76.0%, p < 0.001). CONCLUSIONS: Patients with lower MMSE scores are at a higher risk for poorer functional outcomes. Perioperative care should focus on the preservation of functional abilities to protect these patients from an additional loss of independence and disadvantageous clinical course.

Impact of Parkinson's disease on the acute care treatment and medium-term functional outcome in geriatric hip fracture patients.

INTRODUCTION: Patients with Parkinson's disease (PD) have a heightened risk of sustaining hip fractures due to disturbed balance and gait insecurity. This study aims to determine the impact of PD on the perioperative course and medium-term functional outcome of patients with hip fractures. MATERIALS AND METHODS: A total of 402 hip fracture patients, aged ≥60 years, were prospectively enrolled. On admission, the American Society of Anesthesiologists score, Mini-Mental Status Examination, and Barthel Index (BI), among other scales, were documented. The Hoehn and Yahr scale was used to assess the severity of PD. The functional outcome was assessed by performance on the BI, Tinetti test (TT), and Timed Up and Go test (TUG) at discharge and at the 6-month follow-up. Additionally, the length of hospitalization, perioperative complications, and discharge management were documented. A multivariate regression analysis was performed to control for influencing factors. RESULTS: A total of 19 patients (4.7%) had a concomitant diagnosis of PD. The functional outcome (BI, TT, and TUG) was comparable between groups (all p > 0.05). Grade II (52.6 vs. 26.1%; OR = 4.304, p = 0.008) and IV complications (15.8 vs. 4.4%; OR = 7.785, p = 0.012) occurred significantly more often among PD patients. While the diagnosis of PD was associated with a significantly longer mean length of hospital stay (ß = 0.119, p = 0.024), the transfer from acute hospital care showed no significant difference (p = 0.246). Patients with an additional diagnosis of PD had inferior results in BI at the 6-month follow-up (p = 0.038). CONCLUSION: PD on hospital admission is not an independent risk factor for in-hospital mortality or an inferior functional outcome at hospital discharge. However, patients with PD are at risk for specific complications and longer hospitalization at the time of transfer from acute care so as for reduced abilities in activities of daily living in the medium term.

Mid- and late-life lifestyle activities as main drivers of general and domain-specific cognitive reserve in individuals with Parkinson's disease: cross-sectional and longitudinal evidence from the LANDSCAPE study.

BACKGROUND: Cognitive reserve (CR) is considered a protective factor for cognitive function and may explain interindividual differences of cognitive performance given similar levels of neurodegeneration, e.g., in Alzheimer´s disease. Recent evidence suggests that CR is also relevant in Parkinson's disease (PD). OBJECTIVE: We aimed to explore the role of life-stage specific CR for overall cognition and specific cognitive domains cross-sectionally and longitudinally in PD. METHODS: The cross-sectional analysis with data from the DEMPARK/LANDSCAPE study included 81 individuals without cognitive impairment (PD-N) and 87 individuals with mild cognitive impairment (PD-MCI). Longitudinal data covered 4 years with over 500 observations. CR was operationalized with the Lifetime of Experiences Questionnaire (LEQ), capturing the complexity of lifestyle activities across distinct life-stages. Cognition was assessed using a comprehensive neuropsychological test battery. RESULTS: Higher LEQ scores, particularly from mid- and late-life, were observed in PD-N compared to PD-MCI [F(1,153) = 4.609, p = .033, ηp2 = 0.029]. They were significantly associated with better cognitive performance (0.200 ≤ ß ≤ 0.292). Longitudinally, linear mixed effect models (0.236 ≤ marginal R2 ≤ 0.441) revealed that LEQ scores were positively related to cognitive performance independent of time. However, the decline in overall cognition and memory over time was slightly more pronounced with higher LEQ scores. CONCLUSIONS: This study emphasizes the association between complex lifestyle activities and cognition in PD. Data indicate that while CR might be related to a delay of cognitive decline, individuals with high CR may experience a more pronounced drop in overall cognition and memory. Future studies will have to replicate these findings, particularly regarding domain-specific effects and considering reverse causal mechanisms.

Preference-based Health status in a German outpatient cohort with multiple sclerosis.

BACKGROUND: To prospectively determine health status and health utility and its predictors in patients with multiple sclerosis (MS). METHODS: A total of 144 MS patients (mean age: 41.0 ± 11.3 y) with different subtypes (patterns of progression) and severities of MS were recruited in an outpatient university clinic in Germany. Patients completed a questionnaire at baseline (n = 144), 6 months (n = 65) and 12 months (n = 55). Health utilities were assessed using the EuroQol instrument (EQ-5D, EQ VAS). Health status was assessed by several scales (Expanded Disability Severity Scale (EDSS), Modified Fatigue Impact Scale (M-FIS), Functional Assessment of MS (FAMS), Beck Depression Inventory (BDI-II) and Multiple Sclerosis Functional Composite (MSFC)). Additionally, demographic and socioeconomic parameters were assessed. Multivariate linear and logistic regressions were applied to reveal independent predictors of health status. RESULTS: Health status is substantially diminished in MS patients and the EQ VAS was considerably lower than that of the general German population. No significant change in health-status parameters was observed over a 12-months period. Multivariate analyses revealed M-FIS, BDI-II, MSFC, and EDSS to be significant predictors of reduced health status. Socioeconomic and socio-demographic parameters such as working status, family status, number of household inhabitants, age, and gender did not prove significant in multivariate analyses. CONCLUSION: MS considerably impairs patients' health status. Guidelines aiming to improve self-reported health status should include treatment options for depression and fatigue. Physicians should be aware of depression and fatigue as co-morbidities. Future studies should consider the minimal clinical difference when health status is a primary outcome.

Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson's disease.

BACKGROUND: Clinical studies employ the Unified Parkinson's Disease Rating Scale (UPDRS) to measure the severity of Parkinson's disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates. METHODS: Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson's disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson's disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R(2), the root mean square error (RMS), the Bayesian information criterion, and Pregibon's link test. Three independent data sets validated the models. RESULTS: The regression analyses resulted in a single best prediction model (R(2): 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models. CONCLUSION: The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.

Naturally occurring autoantibodies against beta-amyloid: investigating their role in transgenic animal and in vitro models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against ß-amyloid (Aß) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aß (NAbs-Aß) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-Aß recognized the mid-/C-terminal end of Aß and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-Aß were able to interfere with Aß peptide toxicity, but NAbs-Aß did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-Aß in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-Aß to dispose of proteins or peptides that are prone to forming toxic aggregates.

Long-Term Cognitive Decline Related to the Motor Phenotype in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. OBJECTIVE: Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). METHODS: Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M = 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year follow-up data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M = 66.10; 68.6% males). RESULTS: Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients were present and we found differences for motor phenotypes in attention (ß= -0.08, SE = 0.003, p < 0.006) and memory functions showing that PIGD-patients deteriorate per months by -0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. CONCLUSION: Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype.

Parkinson's disease and dementia: a longitudinal study (DEMPARK).

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. METHODS/DESIGN: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45-80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients' functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early diagnostic biomarkers and predictors for dementia in PD. RESULTS: The study included 604 PD patients by March 2011; 56.3% were classified as having PD alone, with 30.6% of patients suffering from PD-MCI and 13.1% from PD with dementia. The mean age of the cohort was 68.6 ± 7.9 years, with a mean disease duration of 6.8 ± 5.4 years. There was a preponderance of patients in the earlier Hoehn and Yahr stages. CONCLUSION: The main aim of the study is to characterize the natural progression of cognitive impairment in PD and to identify factors which contribute to the evolution and/or progression of the cognitive impairment. To accomplish this aim we established a large cohort of PD patients without cognitive dysfunction, PD patients with MCI, and PD patients with dementia, to characterize these patients in a standardized manner, using imaging (serial structural MRI), genetic and proteomic methods in order to improve our understanding of the course of the PD process and the development of cognitive dysfunction and dementia in this disease. The inclusion of the DLB patients will start in the second quarter of 2011 in the BMBF-funded follow-up project LANDSCAPE.