The value of cerebrospinal fluid α-synuclein and the tau/α-synuclein ratio for diagnosis of neurodegenerative disorders with Lewy pathology.

BACKGROUND AND PURPOSE: Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are three of the most common neurodegenerative disorders. Up to 20% of these patients have the wrong diagnosis, due to overlapping symptoms and shared pathologies. A cerebrospinal fluid (CSF) biomarker panel for AD is making its way into the clinic, but an equivalent panel for PD and DLB and for improved differential diagnoses is still lacking. Using well-defined, community-based cohorts and validated analytical methods, the diagnostic value of CSF total-α-synuclein (t-α-syn) alone and in combination with total tau (t-tau) in newly diagnosed patients with PD, DLB and AD was determined. METHODS: Cerebrospinal fluid concentrations of t-α-syn were assessed using our validated in-house enzyme-linked immunosorbent assay in 78 PD patients, 20 AD patients, 19 DLB patients and 32 controls. t-tau was measured using a commercial assay. Diagnostic performance was assessed by receiver operating characteristic curve analysis. RESULTS: Compared to controls (mean 517 pg/ml), significantly lower levels of CSF t-α-syn in patients with PD (434 pg/ml, 16% reduction, P = 0.036), DLB (398 pg/ml, 23% reduction, P = 0.009) and AD (383 pg/ml, 26% reduction, P = 0.014) were found. t-α-syn levels did not differ significantly between PD, DLB and AD. The t-tau/t-α-syn ratio showed an improved performance compared to the single markers. CONCLUSION: This is the first study to compare patients with PD, DLB and AD at the time of diagnosis. It was found that t-α-syn can contribute as a teammate with tau in a CSF biomarker panel for PD and DLB, and strengthen the existing biomarker panel for AD.

Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus.

OBJECTIVE: Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels. METHOD: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49). RESULTS: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy. CONCLUSION: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer's disease.

BACKGROUND: Neuropsychiatric symptoms (NPS), such as depression, apathy, agitation, and psychotic symptoms are common in mild cognitive impairment (MCI) and dementia in Alzheimer's disease (AD). Subgroups of NPS have been reported. Yet the relationship of NPS and their subgroups to different stages of cognitive impairment is unclear. Most previous studies are based on small sample sizes and show conflicting results. We sought to examine the frequency of NPS and their subgroups in MCI and different stages of dementia in AD. METHODS: This was a cross-sectional study using data from a Norwegian national registry of memory clinics. From a total sample of 4,571 patients, we included those with MCI or AD (MCI 817, mild AD 883, moderate-severe AD 441). To compare variables across groups ANOVA or χ 2-test was applied. We used factor analysis of Neuropsychiatric Inventory Questionnaire (NPI-Q) items to identify subgroups of NPS. RESULTS: The frequency of any NPS was 87.2% (AD 91.2%, MCI 79.5%; p < 0.001) and increased with increasing severity of cognitive decline. The most frequent NPS in MCI was depression. Apathy was the most frequent NPS in AD across different stages of severity. The factor analysis identified three subgroups in MCI and mild AD, and a fourth one in moderate-severe AD. We labelled the subgroups "depression," "agitation," "psychosis," and "elation." CONCLUSIONS: The frequency of NPS is high in MCI and AD and increases with the severity of cognitive decline. The subgroups of NPS were relatively consistent from MCI to moderate-severe AD. The subgroup elation appeared only in moderate-severe AD.

Psychometric properties of the mutuality scale in Swedish dyads with Parkinson's disease.

OBJECTIVES: The 15-item mutuality scale (MS) has been used in several neurological conditions assessing the quality of relationship associations with negative effects of the caregiving situation. The aim of this study was to translate the original MS into Swedish and assess its psychometric properties in Parkinson's disease (PD). MATERIALS AND METHODS: Following the forward-backward translation method, the scale was evaluated regarding linguistic correctness at a conceptual level and user-friendliness. The scale was filled out by a sample of 50 care dyads where one was having PD. Scale assumptions and scale structure were evaluated using floor/ceiling effect and principal component analyses (PCA) with promax rotation. Internal consistency was evaluated using Cronbach's alpha and mean inter-item correlation coefficients. RESULTS: The Swedish MS was evaluated as user-friendly and relevant by the participants. The scale demonstrated no floor/ceiling effect and showed high internal consistency (α≥0.93) with a mean inter-item correlation coefficient of ≥0.5. Through the PCA, a two factor solution emerged, which accounted for 67% and 64% of the variance of the MS score by PD-partners and PD-patients, respectively. However, some variables were complex and discarded in the final solution. CONCLUSION: Our findings provide initial support of the Swedish MS as a user-friendly and useful instrument with acceptable psychometric properties even though more research is needed to evaluate the existence of subscales.

Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

MMSE and MoCA in Parkinson's disease and dementia with Lewy bodies: a multicenter 1-year follow-up study.

The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used scales to test cognitive impairment in Lewy body disease (LBD), but there is no consensus on which is best suited to assess cognition in clinical practice and most sensitive to cognitive decline. Retrospective cohort study of 265 LBD patients [Parkinson's disease (PD) without dementia (PDnD, N = 197), PD with dementia (PDD, N = 40), and dementia with Lewy bodies (DLB, N = 28)] from an international consortium who completed both the MMSE and MoCA at baseline and 1-year follow-up (N = 153). Percentage of relative standard deviation (RSD%) at baseline was the measure of inter-individual variance, and estimation of change (Cohen's d) over time was calculated. RSD% for the MoCA (21 %) was greater than for the MMSE (13 %) (p = 0.03) in the whole group. This difference was significant only in PDnD (11 vs. 5 %, p < 0.01), but not in PDD (30 vs. 19 %, p = 0.37) or DLB (15 vs. 14 %, p = 0.78). In contrast, the 1-year estimation of change did not differ between the two tests in any of the groups (Cohen's effect <0.20 in each group). MMSE and MoCA are equal in measuring the rate of cognitive changes over time in LBD. However, in PDnD, the MoCA is a better measure of cognitive status as it lacks both ceiling and floor effects.

Antidepressants and mortality risk in a dementia cohort: data from SveDem, the Swedish Dementia Registry.

BACKGROUND: The association between mortality risk and use of antidepressants in people with dementia is unknown. OBJECTIVE: To describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis. METHODS: Study population included 20 050 memory clinic patients from the Swedish Dementia Registry (SveDem) diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during 3-year period before dementia diagnosis were obtained from the Swedish Prescribed Drug Register. Cox regression models were used. RESULTS: During a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis, while 21.6% used antidepressants at some point during a 3-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders and in Alzheimer's disease. CONCLUSION: Antidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.

Neurobiological correlates of depressive symptoms in people with subjective and mild cognitive impairment.

OBJECTIVE: To test the hypothesis that depressive symptoms correlate with Alzheimer's disease (AD) type changes in CSF and structural and functional imaging including hippocampus volume, cortical thickness, white matter lesions, Diffusion tensor imaging (DTI), and fluoro-deoxy-glucose positron emission tomography (FDG-PET) in patient with subjective (SCI) and mild (MCI) cognitive impairment. METHOD: In 60 patients, depressive symptoms were assessed using the Geriatric Depression Scale. The subjects underwent MRI, 18F-FDG PET imaging, and lumbar CSF extraction. RESULTS: Subjects with depressive symptoms (n=24) did not have more pathological AD biomarkers than non-depressed. Uncorrected there were trends towards larger hippocampal volumes (P=0.06), less orbital WM damage measured by DTI (P=0.10), and higher orbital glucose metabolism (P=0.02) in the depressed group. The findings were similar when SCI and MCI were analyzed separately. Similarly, in patients with pathological CSF biomarkers (i.e., predementia AD, n=24), we found that correlations between scores on GDS and CSF Aß42 and P-tau indicated less severe AD-specific CSF changes with increasing depression. CONCLUSION: Depressive symptoms are common in SCI/MCI, but are not associated with pathological imaging or CSF biomarkers of AD. Depression can explain cognitive impairment in SCI/MCI or add to cognitive impairment leading to an earlier clinical investigation in predementia AD.

Influence of age, disease onset and ApoE4 on visual medial temporal lobe atrophy cut-offs.

BACKGROUND: Visual assessment of medial temporal lobe atrophy (MTA; range 0-4, from no atrophy to increasing atrophy of the choroid fissure, temporal horns and hippocampus) is a sensitive radiological marker of Alzheimer's disease (AD). One of the critical elements for visual MTA assessment is the cut-off score that determines deviation from normality. METHODS: In this study, we assessed the sensitivity and specificity of different MTA cut-off scores to classify control subjects, individuals with mild cognitive impairment (MCI) and AD patients from two large independent cohorts, AddNeuroMed and Alzheimer's Disease Neuroimaging Initiative. Of note, we evaluated the effects of clinical, demographic and genetic variables on the classification performance according to the different cut-offs. RESULTS: A cut-off of ≥1.5 based on the mean MTA scores of both hemispheres showed higher sensitivity in classifying patients with AD (84.5%) and MCI subjects (75.8%) who converted to dementia compared to an age-dependent cut-off. The age-dependent cut-off showed higher specificity or ability to correctly identify control subjects (83.2%) and those with MCI who remained stable (65.5%). Increasing age, early-onset disease and absence of the ApoE ε4 allele had a stronger influence on classifications using the ≥1.5 cut-off. Above 75 years of age, an alternative cut-off of ≥2.0 should be applied to achieve a classification accuracy for both patients with AD and control subjects that is clinically useful. CONCLUSION: Clinical, demographic and genetic variables can influence the classification of MTA cut-off scores, leading to misdiagnosis in some cases. These variables, in addition to the differential sensitivity and specificity of each cut-off, should be carefully considered when performing visual MTA assessment.

Efficacy of pain treatment on mood syndrome in patients with dementia: a randomized clinical trial.

BACKGROUND: Depression is common in nursing home (NH) patients with dementia, and often clustered with anxiety and other mood symptoms. An association between pain and depressive symptoms has been reported, but the impact of pain management on depression and other mood symptoms has not been investigated. OBJECTIVE: Secondary analyses of a cluster randomized clinical trial examine the response of dementia-related mood symptoms to a Stepwise Protocol of Treating Pain. METHOD: Three-hundred fifty-two patients with moderate and severe dementia and significant behavioural disturbances, related to 60 clusters (i.e. clusters defined as single independent NH units) in 18 NHs of Western Norway, were included. All patients in the intervention group received individual daily pain treatment with paracetamol, extended release morphine, buprenorphine transdermal patch or pregabaline for 8 weeks, with additional follow-up assessment 4 weeks after completion of the intervention. Clusters randomized to control received usual treatment. A mood cluster consisting of depression, anxiety, sleep disorders, apathy and appetite items from the Neuropsychiatric Inventory-Nursing Home (NPI-NH) was the primary outcome. RESULTS: Analysed by Mann-Whitney U-tests, Stepwise Protocol of Treating Pain conferred significant benefit in treatment of the NPI-NH mood cluster (F = 13.4, df = 1;299, p < 0.001) and depression (F = 2.0, df = 1;301, p = 0.025). Further analyses highlighted improvements in apathy (F = 5.3, df = 1;300, p = 0.017), night-time behaviours (F = 3.1, df = 1;301, p = 0.050), and appetite items (F = 11.6, df = 1;301, p = 0.005), but not irritability (p = 0.092) and anxiety (p = 0.125). CONCLUSION: Mood symptoms including depression significantly improved with pain treatment, emphasizing the importance of more rigorous treatment of pain in agitated people with dementia. Findings have potentially immediate clinical relevance.

Neuropsychiatric symptoms in mild dementia with lewy bodies and Alzheimer's disease.

BACKGROUND/AIMS: To compare neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and dementia with Lewy bodies(DLB). METHODS: Neuropsychiatric symptoms and caregiver distress were assessed using the Neuropsychiatric Inventory (NPI) in mild DLB (n = 57) and AD (n = 126), and compared across the two groups using non-parametric tests. RESULTS: The DLB patients had a higher NPI totalscore (median 24 vs. 11.5, p < 0.005), more numerous symptoms (median 5 vs. 4, p = 0.001) and more clinically significant symptoms (3 vs. 1, p = 0.001). They also had higher item hallucinations (6 vs. 2, p < 0.005) and apathy (7 vs. 5, p = 0.002) subscores. Caregivers scored higher on the NPI total caregiver distress scale (12.5 vs. 6, p = 0.003). CONCLUSIONS: In mild dementia, DLB patients have more neuropsychiatric symptoms and more associated caregiver distress compared with AD.

Clinical trials of dementia with Lewy bodies and Parkinson's disease dementia.

Despite the frequency and importance of dementia associated with Parkinson's disease (PDD) and dementia with Lewy bodies (DLB), there is relatively little evidence on which to base treatment. Evidence from meta-analysis suggests that rivastigmine can improve cognition and functioning in PDD and also reduce risk of falling. There is also evidence supporting its use in DLB. Recent evidence suggests that memantine may also be effective, particularly for PDD, although evidence is more conflicting. Memantine may also improve parkinsonism and dyskinesias. Few clinical trials of cognition in PD without dementia exist, but there is preliminary evidence for atomoxetine, memantine, and piribedil. There is a lack of systematic evidence for the treatment of visual hallucinations and depression in PDD and DLB. In addition, there is a need for studies of whether potentially disease-modifying agents can prevent or delay the progression to dementia in PD.

Cost-effectiveness of memantine in moderate and severe Alzheimer's disease in Norway.

BACKGROUND: The cost-effectiveness of memantine for the treatment of moderate and severe Alzheimer's disease has been assessed in several European countries. Objective of the study was to assess it in Norwegian settings. METHODS: This cost-utility analysis used a Markov modelling approach to simulate the evolution of patients until their need for full-time care (FTC) over a 5-year period. FTC was defined as a patient becoming either dependent or institutionalised. Transition probabilities were estimated using a newly developed predictive equation of time to FTC. Health resource use and utilities were obtained from the Scandinavian Study of Cost and Quality of Life in Alzheimer's Disease study, and mortality was obtained from the Oslo study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine with its alternative in this population, that is no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. The model underwent extensive sensitivity analyses. RESULTS: In Norway, memantine was found to delay the need for FTC by 4.4 weeks compared with standard care and was associated with increased quality-adjusted life years. Memantine was the dominant strategy with cost savings of €3739 (30 041 NOK) per patient. The probability of being the dominant strategy was 98.8%. This result was confirmed across multiple sensitivity analyses. CONCLUSIONS: The model suggests that memantine prolongs time to FTC for no additional cost to the healthcare system and society. It can be regarded as a cost-effective choice in the management of moderate and severe Alzheimer's disease.

Initial prescription of antipsychotics and antidepressants in general practice and specialist care in Norway.

OBJECTIVE: To examine the incidence rates of antipsychotic (AP) and antidepressant (AD) drug treatment in Norway and the proportions initiated in general practice and specialist care respectively. METHOD: Data on all prescriptions of APs and ADs dispensed to the general population in Norway from 1 January 2004 until 31 August 2009 were extracted from the Norwegian Prescription Database. This information was merged with data about general practitioners (GPs) from the Norwegian Regular General Practitioner Scheme. RESULTS: One-year incidence rates per 1000 inhabitants were 3.4 for APs and 8.6 for ADs. GPs initiated 58% of APs and 73% of ADs, while psychiatrists initiated 15% and 6% respectively. Psychiatrists initiated treatment more often among younger patients, and they prescribed relatively newer drugs more commonly than GPs. A large share of incident users did not refill their prescriptions for APs (57%) or ADs (33%). CONCLUSION: GPs have a key role as regards initiating treatment with APs and ADs in Norway, while psychiatrists' influence seems limited, particularly among older patients. Efforts for quality improvement of mental health care need to involve primary health care. In addition, an increased focus from psychiatrists towards the increasingly ageing part of the population seems requisite.

Pain treatment of agitation in patients with dementia: a systematic review.

BACKGROUND: Advancing age is associated with high prevalence of both dementia and pain. Dementia is frequently accompanied by distressing behavioral and psychological symptoms, including agitation and aggression, particularly in nursing home patients. The etiology of agitation is multifactorial. It has been suggested that un-diagnosed and untreated pain may contribute to agitation in people with dementia. If this is correct, individual pain treatment could be of benefit in ameliorating agitation and other behavioral changes in people with dementia. OBJECTIVE: The objective of this paper is to conduct a systematic review of studies of whether pain medication can improve agitation in people with dementia. METHODS: A systematic search of the PubMed and Cochrane databases for the period 1992-2010 was performed, using dementia, agitation, aggression, depression, behavioral disturbances, behavioral and psychological symptoms (BPSD), pain, pain assessment, pain treatment, pain management, and analgesics as search terms. Inclusion criteria were: prospective studies including patients with dementia, interventions focusing on pain reduction, inclusion of a control condition, and outcome measures including agitation or other related behavioral disturbances. RESULTS: Only three controlled trials were identified; all were cross-over trials, and two included small sample sizes (<50). Findings were inconsistent, and although some correlations were reported, these did not support the hypothesis that pain management reduced agitation. CONCLUSION: There is a profound dearth of rigorous studies of the effect of pain treatment in patients with dementia and agitation. The available studies do not support the hypothesis that pain management reduces agitation in nursing-home patients with dementia. Randomized, controlled parallel-group studies are needed.

Efficacy of memantine in PDD and DLB: an extension study including washout and open-label treatment.

OBJECTIVE: This 30-week extension trial was a continuation of the first double-blind randomized controlled trial (RCT) to study memantine in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The objective was to evaluate the presence of recurrence of symptoms upon drug withdrawal. Furthermore, the aim was to explore washout dynamics in order to inform clinical practice. METHODS: Patients were enrolled from psychiatric, memory and neurological outpatient clinics in Norway, Sweden and the UK. The trial comprised a 4-week washout period and a 26-week open-label treatment period. Outcome measures were presence of recurrence of symptom upon drug withdrawal, Clinical Global Impression of Change (CGIC) and modified motor Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: recurrence of symptoms occurred more frequently (p=0.04) in patients receiving memantine (58%) than in patients receiving placebo (25%). There was a significant global deterioration (p=0.0003) during washout within the memantine group as measured by CGIC. The patients seemed to recover during the open-label treatment, however these findings were non-significant. CONCLUSIONS: The findings inform clinical practice that any possible memantine-associated benefits might be rapidly lost after drug withdrawal. The magnitude of deterioration suggests a symptomatic rather than a disease-modifying effect of the drug. Open-label results should merely be considered inspiration for future trials.

Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson's disease: the Norwegian ParkWest study.

OBJECTIVES: We investigated caregiver distress associated with neuropsychiatric problems in patients with newly diagnosed Parkinson's disease (PD). MATERIALS AND METHODS: Persons who were next of kins of 198 patients and 168 healthy individuals completed the Neuropsychiatric Inventory Caregiver Distress Scale. RESULTS: Even at the time of diagnosis PD has a considerable impact on the next of kins' experience of distress. Nearly 50% reported distress, significantly more than in the control group, and more than one-quarter reported moderate severe distress. Except the more rarely reported neuropsychiatric symptoms, apathy was the symptom that most frequently caused caregiver distress in PD patient's next of kin (94.5%), followed by depression (88.2%), anxiety (86.2%) and irritability (83.3%). CONCLUSIONS: The study underlines the importance of focusing on neuropsychiatric aspects in patients and associated caregiver distress even in early PD management.

Health and well-being in care staff and their relations to organizational and psychosocial factors, care staff and resident factors in nursing homes.

OBJECTIVE: The aim of this study is to investigate the association of psychosocial factors and patient factors with stress in care staff in nursing homes. METHODS: In this cross-sectional survey, 197 care staff from 13 dementia wards from four nursing homes in the Stavanger region, Norway, participated. Stress in care staff was measured by Perceived Stress Scale, Hopkins Symptom Check List, and subjective health complaints. Agitation in patients was measured with the Cohen-Mansfield Agitation Inventory. Work-related psychosocial factors were measured by General Nordic Questionnaire for Psychosocial and Social Factors at Work (QPSNordic). Data were analyzed using multivariate regression analyses. RESULTS: Psychosocial factors (QPS Nordic) were significantly associated with all the three outcome measures of stress in care staff, whereas agitation was associated with subjective health complaints only. QPS Nordic subscales significantly associated with stress in care staff were those associated with leadership. CONCLUSIONS: Psychosocial factors were more important predictors of carer stress than patient-related factors such as dementia severity and agitation. The findings provide key background information in the planning of interventions to improve conditions for care staff and ultimately for nursing home residents.

Nursing home structure and association with agitation and use of psychotropic drugs in nursing home residents in three countries: Norway, Austria and England.

BACKGROUND: Understanding the underlying mechanisms and risk factors leading to agitation is crucial to reduce the severity of agitation and increase quality of life. International comparative studies offer special advantages in elucidating environmental risk factors by providing a wider diversity of environmental exposures such as nursing home structures, health care systems and genetic diversity. METHODS: Baseline data for three different intervention studies in Austria (n = 38), England (n = 302) and Norway (n = 163) were combined posthoc. Patients were grouped according to their dementia severity using the global deterioration scale (GDS), functional assessment staging (FAST) and clinical dementia rating (CDR) scales. For the measurement of agitation, the Cohen-Mansfield Agitation Inventory (CMAI) was used. Data analysis was performed using one-way ANOVA, multivariate and linear regression analysis. RESULTS: CMAI scores were available for 503 subjects with dementia. There were significant differences between the nursing home residents in the three countries regarding age, gender and dementia severity (all p values < 0.001). In the multivariate analyses, the level of agitation differed with higher mean scores in the Austrian (mean (SD) score 51.9(21.8)) compared to UK (43.3(16.1)) and Norwegian (41.6(13.2)) nursing homes (p = 0.002). Similarly, the use of psychotropic drugs differed significantly, with a higher proportion of neuroleptics in UK (48%, p < 0.001) and Austrian (52.6%; p = 0.001) compared to Norwegian (19%) nursing homes. CONCLUSION: We found differences in agitation and antipsychotic drug use which are likely related to structural and cultural differences in nursing homes in three European countries. These findings suggest that structural changes can improve quality of care and quality of life for nursing home residents.

Occurrence and risk factors for apathy in Parkinson disease: a 4-year prospective longitudinal study.

BACKGROUND: Apathy is a common but under-recognised behavioural disorder associated with depression and cognitive impairment in patients with Parkinson disease (PD). However, the longitudinal course of apathy in PD has not been studied. OBJECTIVE: To examine the occurrence of and risk factors for apathy over time in a representative sample of patients with PD. METHODS: A sample of 139 patients was drawn from a population-based prevalence study of PD in Rogaland County, Western Norway. Apathy was measured with the Neuropsychiatric Inventory, using a composite score >or=4 to indicate clinically significant apathy. Additional measurements included standardised rating scales for parkinsonism, depression and cognitive impairment. A follow-up evaluation was carried out in 79 patients (78.2% of the survivors) 4 years later. RESULTS: Of the 79 patients included in this study, 29 patients (36.7%) had never had apathy, 11 (13.9%) had persistent apathy, and a further 39 (49.4%) developed apathy during follow-up. At follow-up, patients with apathy were more frequently depressed and demented than never-apathetic patients. Dementia at baseline and a more rapid decline in speech and axial impairment during follow-up were independent risk factors for incident apathy. CONCLUSIONS: Apathy is a persistent behavioural feature in PD with a high incidence and prevalence over time. Progression of motor signs predominantly mediated by non-dopaminergic systems may be a useful preclinical marker for incident apathy in PD.