Uwe Ehrt

A systematic review of prevalence studies of depression in Parkinson's disease: The Prevalence of Depression in PD

Prevalence rates of depressive disorders in Parkinsons disease (PD) vary widely across studies, ranging from 2.7% to more than 90%. The aim of this systematic review was to calculate average prevalences of depressive disorders taking into account the different settings and different diagnostic approaches of studies. Using Medline on Pubmed, a systematic literature search was carried out for studies of depression in Parkinsons disease. A total of 104 articles were included and assessed for quality; 51 articles fulfilled the quality criteria. Multiple publications from the same database were not included in the meta‐analysis. In the remaining 36 articles, the weighted prevalence of major depressive disorder was 17% of PD patients, that of minor depression 22% and dysthymia 13%. Clinically significant depressive symptoms, irrespective of the presence of a DSM defined depressive disorder, were present in 35%. In studies using a (semi) structured interview to establish DSM criteria, the reported prevalence of major depressive disorder was 19%, while in studies using DSM criteria without a structured interview, the reported prevalence of major depressive disorder was 7%. Population studies report lower prevalence rates for both major depressive disorder and the clinically significant depressive symptoms than studies in other settings. This systematic review suggests that the average prevalence of major depressive disorder in PD is substantial, but lower than generally assumed.

Neuropsychiatric symptoms in patients with Parkinson’s disease and dementia: frequency, profile and associated care giver stress

Objective: To explore the profile of neuropsychiatric symptoms in patients with dementia associated with Parkinson’s disease (PDD). Methods: 537 patients with PDD drawn from an international multicentre clinical trial of rivastigmine were assessed using the 10-item Neuropsychiatric Inventory (NPI). A cluster analysis was used to investigate the inter-relationship of NPI items. Associations between the clusters and demographic and clinical variables were analysed. Results: 89% of the patients presented at least one symptom on the NPI, 77% had two or more symptoms and 64% had at least one symptom with a score ⩾4. The most common symptoms were depression (58%), apathy (54%), anxiety (49%) and hallucinations (44%). Patients with more severe dementia and advanced Parkinson’s disease had more neuropsychiatric symptoms. Nearly 60% of the care givers reported at least one NPI symptom to be of at least moderate severe distress. Five NPI clusters were identified: one group with few and mild symptoms (52%); a mood cluster (11%, high scores on depression, anxiety and apathy); apathy (24%; high apathy and low scores on other items); agitation (5%, high score on agitation and high total NPI score); and a psychosis cluster (8%; high scores on delusions and hallucinations). The psychosis and agitation clusters had the lowest Mini-Mental State Examination score and the highest Unified Parkinson’s Disease Rating Scale and care giver distress scores. Conclusion: Neuropsychiatric symptoms are common in patients with PDD. The profile of these symptoms differs from that in other types of dementia. Subgroups with different neuropsychiatric profiles were identified. These subgroups may be associated with distinct neurobiological changes, which should be explored in future studies.

Depression in Parkinson disease--epidemiology, mechanisms and management.

Depression occurs in around 35% of patients with Parkinson disease (PD) and is often persistent. Symptoms of depression can be evident in individuals at the time of diagnosis and might develop in the premotor stage of the disease. The underlying mechanisms of depression in PD are not known in detail, but changes in brain structure, signaling by neurotransmitters, and levels of inflammatory and neurotrophic factors are all suggested to contribute to its development. Psychosocial factors and pain could also have roles in depression. Changes in dopaminergic, noradrenergic and serotonergic systems in patients with PD might help to explain the incidence of depression in these individuals. Antidepressants that have dual serotonergic and noradrenergic effects are the drugs of choice for treating depression in PD. However, antiparkinsonian drugs might have beneficial effects not only on the motor symptoms of disease, but also on a patients mood. Deep brain stimulation can worsen depression in some patients, but a preliminary study has suggested that transcranial magnetic stimulation could improve symptoms of depression. This Review describes the frequency and course of depression in patients with PD. The mechanisms that underlie depression in this disease are also discussed, and the management strategies for these patients are highlighted.

The spectrum of neuropsychiatric symptoms in patients with early untreated Parkinson’s disease

Background: Neuropsychiatric symptoms are common in Parkinson’s disease (PD) and have important clinical consequences for patients, caregivers and society. Few studies of neuropsychiatric symptoms in early untreated PD exist. Objective: To explore the range, clustering and correlates of neuropsychiatric symptoms in an incidence cohort of untreated subjects with PD. Methods: All cases with incident PD identified during a 22 month period in four counties of Western and Southern Norway were included. Standardised criteria were used to diagnose PD. The Neuropsychiatric Inventory (NPI) was administered to 175 PD and 166 healthy control subjects with similar age and sex distributions. Cluster analysis was used to investigate the interrelationship of NPI items. Results: The proportion with any NPI symptoms was higher in PD (56%) than in controls (22%) (p<0.001). Depression (37%), apathy (27%), sleep disturbance (18%) and anxiety (17%) were the most common symptoms. Clinically significant symptoms occurred in 27% of the PD group compared with only 3% in the control group (p<.001). Subjects with clinically significant neuropsychiatric symptoms had more severe parkinsonism than those without. Two neuropsychiatric clusters were identified, one characterised by mood symptoms and one by apathy. Conclusions: Although the majority of patients with early untreated PD do not have clinical significant neuropsychiatric symptoms, these symptoms are more common in patients than in people without PD. Both psychological stress and brain changes associated with PD are likely to contribute to the higher frequencies.

The association between motor subtypes and psychopathology in Parkinson's disease

BACKGROUND In Parkinsons disease (PD) it has been suggested that various motor subtypes are also characterized by a different prevalence and severity of specific non-motor symptoms such as cognitive deterioration, depression, apathy and hallucinations. The aim of this study was to investigate the association between motor subtypes and psychopathology in PD. METHODS An exploratory and confirmatory cluster analysis of motor and psychopathological symptoms was performed with a randomized sample of 173 patients each, stemming from two research databases: one from Stavanger University Hospital and one from Maastricht University Hospital. These databases contained data of standardized assessments of patients with the Unified Parkinsons Disease Rating Scale, the Montgomery-Asberg Depression Rating Scale, and the Mini-Mental State Examination. RESULTS PD patients can be accurately and reliably classified into four different subtypes: rapid disease progression subtype, young-onset subtype, non-tremor-dominant subtype with psychopathology and a tremor-dominant subtype. Cognitive deterioration, depressive and apathetic symptoms, and hallucinations all cluster within the non-tremor-dominant motor subtype, that is characterized by hypokinesia, rigidity, postural instability and gait disorder. CONCLUSIONS This study shows that non-tremor-dominant PD is associated with cognitive deterioration, depression, apathy, and hallucinations, which has implications for future research into the pathophysiology of psychopathology in PD.

Frequency and Case Identification of Dementia with Lewy Bodies Using the Revised Consensus Criteria

Objective: To find the proportion of dementia with Lewy bodies (DLB) in a referral cohort of patients with a first-time diagnosis of mild dementia. Background: The proportion of DLB among the dementia sufferers is not known and the clinical consensus criteria have low sensitivity. We employed the revised DLB criteria to study the proportion with DLB in a community sample of patients with mild dementia. Methods: From March 2005 to March 2007, we included 196 patients from referrals to all geriatric medicine, old age psychiatry and neurology outpatient clinics in Rogaland and Hordaland counties in Western Norway. Standardized clinical instruments and diagnostic criteria were employed. Results: 65% had Alzheimer dementia, 20% DLB (16% probable DLB), 5.6% vascular dementia, 5.6% Parkinson disease with dementia, 2.0% frontotemporal dementia and 1.5% alcoholic dementia. There were no significant differences in the proportion with DLB according to age bands and dementia severity groups. The revised criteria for a clinical diagnosis of DLB increased the proportion of probable DLB by 25% compared to the previous criteria. Conclusion: DLB is common in patients with mild dementia, and is the second most common type of dementia. The introduction of new clinical criteria for DLB leads to an increase in the proportion diagnosed with probable DLB.

Attentional deficits affect activities of daily living in dementia‐associated with Parkinson's disease

Objective: To investigate the effects of attentional deficits on activities of daily living (ADL) in patients with dementia associated with Parkinson’s disease (PDD). Method: 461 patients were assessed neuropsychologically. Factor analyses were used to differentiate attention from other cognitive functions and to differentiate different aspects of ADL functions. The effects of the attentional measure on ADL were examined using sequential multiple regression, controlling for age, sex, education, severity of motor symptoms and other cognitive functions. Results: Three cognitive factors were identified, with one factor emerging as a measure of vigilance and focused attention. This factor predicted different aspects of ADL status even after controlling for motor functions and other cognitive factors. The attention factor was the single strongest cognitive predictor of ADL status, matching the strength of the effects of motor functions on ADL status. Conclusion: Impaired attention is an important determinant of ADL functions in patients with PDD.

Use of drugs with anticholinergic effect and impact on cognition in Parkinson’s disease: A cohort study

Background Cognitive decline is common in Parkinsons disease (PD). Although some of the aetiological factors are known, it is not yet known whether drugs with anticholinergic activity (AA) contribute to this cognitive decline. Such knowledge would provide opportunities to prevent acceleration of cognitive decline in PD. Objective To study whether the use of agents with anticholinergic properties is an independent risk factor for cognitive decline in patients with PD. Methods A community-based cohort of patients with PD (n=235) were included and assessed at baseline. They were reassessed 4 and 8 years later. Cognition was assessed using the Mini-Mental State Examination (MMSE). A detailed assessment of the AA of all drugs prescribed was made, and AA was classified according to a standardised scale. Relationships between cognitive decline and AA load and duration of treatment were assessed using bivariate and multivariate statistical analyses. Results More than 40% used drugs with AA at baseline. During the 8-year follow-up, the cognitive decline was higher in those who had been taking AA drugs (median decline on MMSE 6.5 points) compared with those who had not taken such drugs (median decline 1 point; p=0.025). In linear regression analyses adjusting for age, baseline cognition and depression, significant associations with decline on MMSE were found for total AA load (standardised β=0.229, p=0.04) as well as the duration of using AA drugs (standardised β 0.231, p=0.032). Conclusion Our findings suggest that there is an association between anticholinergic drug use and cognitive decline in PD. This may provide an important opportunity for clinicians to avoid increasing progression of cognitive decline by avoiding drugs with AA. Increased awareness by clinicians is required about the classes of drugs that have anticholinergic properties.

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.

Cortical serotonin 1A receptor levels are associated with depression in patients with dementia with Lewy bodies and Parkinson's disease dementia.

Background: Serotonin 1A receptors (5-HT1A) have not been studied in dementia with Lewy bodies (DLB) or Parkinson’s disease dementia (PDD) patients with depression. Aim: To examine 5-HT1A in DLB and PDD postmortem in relation to depression. Methods: [3H]8-hydroxy-2-dipropylaminotetralin binding to 5-HT1A was determined in temporal cortex (Brodmann areas, BA20 and BA36) from 10 DLB patients, 17 PDD patients and 9 controls. Results: 5-HT1A density was significantly higher in BA36 in combined DLB/PDD patients with depression, but was unaltered in BA20. Conclusion: Higher BA36 5-HT1A density in PDD and DLB patients than in control is dependent on whether the patient had experienced depression during life, not DLB/PDD diagnosis. A 5-HT1A antagonist adjuvant may improve treatment of depression in dementia.