Tore Wentzel-Larsen

Changes in motor subtype and risk for incident dementia in Parkinson's disease

The objective of this study was to assess the temporal relationship between changes in predominant motor symptoms and incident dementia in Parkinsons disease (PD). A community‐based sample of 171 nondemented patients with PD was followed prospectively and examined at baseline and after 4 and 8 years. The motor subtype of Parkinsonism was classified into tremor‐dominant (TD), indeterminate, or postural instability gait difficulty (PIGD) subtype at each visit, based on defined items in the Unified Parkinsons Disease Rating Scale, subscales II and III. Dementia was diagnosed according to DSM‐III‐R criteria, based on clinical interview, cognitive rating scales, and neuropsychological examination. Logistic regression was used to analyze the relationship between subtype of Parkinsonism and dementia. Transition from TD to PIGD subtype was associated with a more than threefold increase in the rate of Mini‐Mental State Examination decline. Compared to patients with persistent TD or indeterminate subtype, the odds ratio for dementia was 56.7 (95% CI: 4.0–808.4; P = 0.003) for patients changing from TD or indeterminate subtype to PIGD subtype, and 80.0 (95% CI: 4.6–1400.1; P = 0.003) for patients with persistent PIGD subtype. Patients with TD subtype at baseline did not become demented until they developed PIGD subtype, and dementia did not occur among patients with persistent TD subtype of Parkinsonism. In a substantial proportion of PD patients who develop postural instability and gait disorder during the course of the disease, this transition is associated with accelerated cognitive decline and highly increased risk for subsequent dementia. These findings raise the question whether PIGD and dementia share common or parallel neuropathology.

Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease.

Background: The relation between dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unknown. Objectives: To compare the cognitive profiles of patients with DLB and PDD, and compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer’s disease). Design: Survey of cognitive features. Setting: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA. Patients: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer’s disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education. Main outcome measures: Dementia rating scale subscores corrected for age. Results: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer’s disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001). Conclusions: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer’s disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer’s disease.

Progression of motor impairment and disability in Parkinson disease: A population-based study

Objective: To investigate risk factors and the rate of progression of motor symptoms and disability in a population-based cohort of patients with Parkinson disease (PD). Methods: In all, 232 patients with PD, derived from a community-based prevalence study, were followed prospectively over an 8-year period. Follow-up examinations were done 4 and 8 years after baseline, and 144 patients participated in at least one follow-up examination. Information on motor function and disability was obtained using the Unified Parkinson Disease Rating Scale (UPDRS), the Hoehn and Yahr staging, and the Schwab and England score. Population-averaged logistic regression models were used to describe annual disease progression and to analyze the influence of potential risk factors on functional decline. Results: We found a similar mean annual decline in the UPDRS motor score and the Hoehn and Yahr staging of 3.1% and 3.2%, respectively. Also the UPDRS Activity of Daily Living (ADL) score and the Schwab and England scale changed similarly, with 3.5% and 3.6% per year, respectively. Age, age at onset, disease duration, and excessive daytime somnolence at baseline were strong and independent predictors of greater impairment in motor function and disability. Cognitive impairment at baseline predicted higher disability and higher Hoehn and Yahr scores. Time by age-at-onset interactions were found for the UPDRS motor score and the Hoehn and Yahr staging. Conclusions: Motor function and disability worsened significantly with time, and to a similar extent. Age, age at onset and disease duration, as well as symptoms thought to be due to involvement of non-dopaminergic brain structures, are predictors of more impaired motor function and disability. However, age at disease onset was the main predictor of motor decline in our cohort, indicating a slower and more restricted pathologic disease process in patients with young-onset PD.

A 12-Year Population-Based Study of Psychosis in Parkinson Disease

OBJECTIVE To investigate the prevalence, incidence, risk factors, and concomitants of Parkinson disease (PD)-associated psychosis (PDP) in a population-based prevalent cohort. DESIGN Prospective longitudinal cohort study. SETTING Community-based study in southwestern Norway. PARTICIPANTS Two hundred thirty community-based PD patients were followed up prospectively for 12 years. Reassessments were conducted at 4 and 8 years and then annually. MAIN OUTCOME MEASURES Severity of PDP was measured by the Unified Parkinson Disease Rating Scale thought disorder (UPDRS-TD) item. Patients with a UPDRS-TD score of 2 or more or those taking antipsychotic drugs owing to psychotic symptoms were categorized at each visit as having PDP. Generalized estimating equations were applied to investigate baseline risk factors for incident PDP and clinical and demographic concomitants of PDP during 12 years. RESULTS By studys end, 137 patients (60%) had developed hallucinations or delusions. The incidence rate of PDP was 79.7 per 1000 person-years. Higher age at onset, higher baseline levodopa-equivalent doses, probable rapid eye movement (REM) sleep behavior disorder at baseline, and follow-up time were independent risk factors of incident PDP. Significant concomitant features of patients with PDP during the 12-year study period were low activities of daily living function (UPDRS II), dementia, high levodopa-equivalent dose, and probable REM sleep behavior disorder. CONCLUSIONS Psychotic symptoms affect most patients with PD, with increased risk in those with higher age at onset, need for high doses of dopaminergic drugs, and probable REM sleep behavior disorder. This risk factor pattern and the observed associations with increased disability and dementia place PDP within a symptom complex signaling a malignant disease course.

Vestibular schwannomas: clinical results and quality of life after microsurgery or gamma knife radiosurgery.

OBJECTIVE:The aim of the present study was to evaluate the overall treatment efficacy (tumor control, facial nerve function, complications) and quality of life for patients treated primarily for unilateral vestibular schwannomas of 30 mm or less, either by microsurgery or by gamma knife (GK) radiosurgery. The results for the two treatment groups are compared with each other, with main emphasis on the long-term quality of life. METHODS:This is a retrospective study of 189 consecutive patients, 86 treated by microsurgery and 103 by gamma knife. The mean observation time was 5.9 years. All patients had a magnetic resonance imaging scan and clinical evaluation performed toward the end of the study. To evaluate the quality of life, we used two standardized questionnaires, the Glasgow Benefit Inventory and Short-Form 36. The questionnaires were sent to the 168 living patients. The reply rate was 83.3%. RESULTS:A total of 79.8% of the patients in the microsurgery group and 94.8% of the GK patients had a good facial nerve function (House-Brackmann Grade 1–2). Hearing was usually lost after microsurgery, whereas the GK patients had preserved hearing, which often became reduced over the years after the treatment. The treatment efficacy, defined as no need for additional treatment, was similar for the two treatment modalities. Quality of life was reduced compared with normative data, being most reduced in the microsurgery group. Some of the quality of life questions showed an association with facial nerve function and sex. CONCLUSION:Posttreatment facial nerve function, hearing, complication rates, and quality of life were all significantly in favor of GK radiosurgery.

Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson’s disease over time

Objective: To examine the occurrence and clinical and demographic correlates of REM sleep behaviour disorder (RBD) in patients with Parkinson’s disease (PD) in a community-based cohort over 8 years. Methods: 231 patients with PD were included in a population-based prevalence study in 1993. Patients were then followed prospectively and reexamined after 4 and 8 years. Semi-structured interviews for information on clinical and demographic data were applied at all study visits. Standardised rating scales of parkinsonism, depression and cognitive impairment were used. The diagnosis of probable RBD (pRBD) was based on a sleep questionnaire. Proportional-odds ordinal logistic regression models for clustered data were used to study the relationship between pRBD and various demographic and clinical variables. Results: 231 patients were evaluated for RBD in 1993 and, after 4 and 8 years, 142 and 89 patients, respectively, were available for re-evaluation. The frequency of pRBD varied from 14.6% to 27% during the study period. Probable RBD was related to male gender, higher dopaminergic treatment and less severe parkinsonism. Conclusion: We found that the frequency of pRBD varied over time and that it is associated with male gender, less parkinsonism and higher levodopa equivalent dose. Our findings indicate that dopaminergic therapy may contribute to the expression of RBD and that RBD is symptomatic in earlier stages of PD.

Is fatigue an independent and persistent symptom in patients with Parkinson disease

Objective: To evaluate if mental fatigue is a symptom that appears independently from other clinical features in patients with Parkinson disease (PD), and to study if fatigue is persistent over time in these patients. Methods: In 1993, 233 patients with PD were included in a community-based study of fatigue and followed prospectively over 8 years. Fatigue was measured by a combination of a seven-point scale and parts of the Nottingham Health Profile (NHP) at baseline and after 4 and 8 years. In addition, the Fatigue Severity Scale (FSS) was used to evaluate fatigue in 2001. Population-averaged logistic regression models for correlated data were performed to study the relationship between fatigue and various demographic and clinical variables. Results: In patients who were followed throughout the 8-year study period, fatigue increased from 35.7% in 1993 to 42.9% in 1997 and 55.7% in 2001. Fatigue was related to disease progression, depression, and excessive daytime sleepiness (EDS). However, the prevalence of fatigue in patients without depression and EDS remained high and increased from 32.1% to 38.9% during the study period. For about 44% of the patients with fatigue the presence of this symptom varied during the study period, as it was persistent in 56% of the patients with fatigue. Conclusions: The authors confirmed the high prevalence of mental fatigue in patients with Parkinson disease (PD). Fatigue is related to other non-motor features such as depression and excessive daytime sleepiness, but cannot be explained by this comorbidity alone. In more than half of the patients mental fatigue is persistent and seems to be an independent symptom that develops parallel to the progressive neurodegenerative disorder of PD.

What predicts mortality in Parkinson disease? A prospective population-based long-term study

Objective: To identify independent risk factors of mortality in a community-based Parkinson disease (PD) cohort during prospective long-term follow-up. Methods: A community-based prevalent sample of 230 patients with PD from southwestern Norway was followed prospectively with repetitive assessments of motor and nonmotor symptoms from 1993 to 2005. Information on vital status until October 20, 2009, was obtained from the National Population Register in Norway. Cox proportional hazards models were applied to identify independent predictors of mortality during follow-up. Chronological age, Unified Parkinsons Disease Rating Scale (UPDRS) motor score, levodopa equivalent dose, probable REM sleep behavior disorder, psychotic symptoms, dementia, and use of antipsychotics were included as time-dependent variables, and age at onset (AAO) and sex as time-independent variables. Results: Of 230 patients, 211 (92%) died during the study period. Median survival time from motor onset was 15.8 years (range 2.2–36.6). Independent predictors of mortality during follow-up were AAO (hazard ratio [HR] 1.40 for 10-years increase, p = 0.029), chronological age (HR 1.51 for 10-years increase, p = 0.043), male sex (HR 1.63, p = 0.001), UPDRS motor score (HR 1.18 for 10-point increase, p < 0.001), psychotic symptoms (HR 1.45, p = 0.039), and dementia (HR 1.89, p = 0.001). Conclusions: This population-based long-term study demonstrates that in addition to AAO, chronological age, motor severity, and dementia, psychotic symptoms independently predict increased mortality in PD. In contrast, no significant impact of antipsychotic or antiparkinsonian drugs on survival was observed in our PD cohort. Early prevention of motor progression and development of psychosis and dementia may be the most promising strategies to increase life expectancy in PD.

Predictors and Course of Health-Related Quality of Life in Parkinson's Disease

We investigated how health related quality of life (HRQL) changes over time in a population‐based cohort of patients with Parkinsons disease (PD), and which factors predict a lower level of HRQL in these patients. Of 227 patients with PD assessed at baseline and followed prospectively, information on HRQL‐status was obtained in 111 subjects 4 years and 82 patients 8 years after inclusion. HRQL was measured by the Nottingham Health Profile (NHP). Analyses were conducted using generalized estimating equation models. The NHP total score (P < 0.001) and scores in all NHP dimensions except for sleep worsened significantly during follow‐up. Steepest slope was found for the domain physical mobility (3.16, 95% CI 2.39–3.92), followed by the domains social isolation (2.22, 95% CI 1.52–2.93) and emotional reactions (1.36, 95% CI 0.74–1.97). In addition to follow‐up time, higher Hoehn and Yahr staging, higher Montgomery and Aasberg Depression Rating Scale scores, and presence of insomnia at baseline were associated with lower levels of overall HRQL during follow‐up. We conclude that PD has an increasing impact on HRQL as the disease progresses. During long‐term follow‐up, deterioration in physical mobility was the most important single factor contributing to decline in HRQL in our cohort, although distress of nonmotor character as a whole outweighed the impact of distress in physical mobility on overall HRQL. More advanced disease, higher severity of depressive symptoms, and presence of insomnia were found to be important and independent predictors of poor HRQL.

Insomnia in Parkinson's disease: frequency and progression over time

Objectives: To examine the development of nocturnal sleeping problems in patients with Parkinson’s disease (PD) over an 8-year period and to study the clinical and demographic correlates of insomnia. Methods: 231 patients were included in a population-based prevalence study in 1993, and re-examined in 1997 and 2001. At all study visits, we applied semi-structured interviews to obtain information on clinical and demographic data, as well as on nocturnal sleeping problems. Standardised rating scales of parkinsonism, depression and cognitive impairment were used. The relationship between insomnia and demographic and clinical variables was analysed using population-averaged logistic regression models for correlated data. 231 patients were included at baseline, 142 were available for re-evaluation in 1997 and 89 patients in 2001. Results: Most nocturnal sleeping problems varied little in prevalence over time, whereas problems related to turning in bed and vivid dreaming or nightmares increased. Insomnia was present in 54–60% of the patients at each of the three study visits and varied considerably in individual patients over time. The presence of insomnia was closely related to disease duration, higher Montgomery–Åsberg Depression Rating Scale scores and female sex. Conclusion: Insomnia is a highly frequent complaint in patients with PD. It fluctuates over time in individual patients, and its origin seems to be multifactorial. Physicians should be aware of the high prevalence of insomnia in patients with PD and should examine their patients for a possible coexisting depression.