D. Aarsland

Cognitive impairment in incident, untreated Parkinson disease The Norwegian ParkWest Study

Background: Little is known regarding the cognitive impairment in subjects with early, drug-naïve Parkinson disease (PD). The aim of this study was to explore the proportion with mild cognitive impairment (MCI) and subtypes in an incidence cohort of untreated PD in Southern and Western Norway. Methods: A total of 196 non-demented, drug-naive patients who were recruited after an extensive search of all new cases of PD in the area and 201 healthy control subjects completed a battery of neuropsychological tests of verbal memory, visuospatial, and attentional-executive functioning. Subjects were classified as MCI if the age- and education-corrected z-score was falling 1.5 standard deviations below the mean for at least one of the cognitive domains. Results: The PD group was more impaired on all neuropsychological tests than controls, but the effect sizes were small. The largest effect size was found for verbal memory. A total of 18.9% of the patients with PD were classified as MCI, with a relative risk of 2.1 (1.2–3.6) in PD compared to the control group. Patients with PD with and without MCI did not differ significantly regarding demographic and motor features. Among PD-MCI patients, nearly two-thirds had a non-amnestic MCI subtype, and one third had an amnestic MCI subtype. Conclusions: The findings demonstrate a twofold increase in the proportion with cognitive impairment in subjects with early, untreated Parkinson disease (PD) compared to controls. This has implications for diagnosis and management of PD. AD = Alzheimer disease; aMCI-MD = amnestic multiple-domain MCI; aMCI-SD = amnestic single-domain MCI; CVLT-2 = California Verbal Learning Test II; IQCode = Informant Questionnaire on Cognitive decline in the elderly; MADRS = Montgomery and Aasberg Depression Rating Scale; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; naMCI-MD = non-amnestic multiple-domain MCI; naMCI-SD = non-amnestic single-domain MCI; PD = Parkinson disease; RR = relative risks; UPDRS = Unified Parkinson’s Disease Rating Scale; VOSP = Visual Object and Space Perception Battery.

Mild cognitive impairment in Parkinson disease: A multicenter pooled analysis

Background: In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies. Objective: The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI. Methods: A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age- and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data. Results: A total of 25.8% of subjects (95% confidence interval [CI] 23.5–28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6–15.3), followed by visuospatial (11.0%; 9.4–13.0) and attention/executive ability impairment (10.1%; 8.6–11.9). Regarding cognitive profiles, 11.3% (9.7–13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0–9.9) as amnestic single-domain, 4.8% (3.8–6.1) as amnestic multiple-domain, and 1.3% (0.9–2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage. Conclusions: MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage.

Mental symptoms in Parkinson's disease are important contributors to caregiver distress

To determine the emotional and social distress of caring for a patient with Parkinsons disease and to explore the impact of motor and mental symptoms in subjects with Parkinsons disease on their caregivers situation.

Dementia and survival in Parkinson disease A 12-year population study

Background: The risk for dementia in Parkinson disease (PD) is high, with important clinical consequences for patients with PD. However, the absolute risk of dementia and how it affects survival in PD are not known. Such questions are important for patients, their families, and service providers but require long-term studies. Methods: This study is a prospective longitudinal cohort study with patients from a prevalence study of PD in Norway. Patients were reassessed 4, 8, 9, 10, 11, and 12 years after prevalence day. A dementia diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria was based on a semistructured caregiver interview, cognitive rating scales, and neuropsychological tests. Progression from PD to PD with dementia and death was modeled using a continuous-time three-state irreversible Markov model. Results: A total of 233 PD patients were included, and 140 patients (60%, 95% CI 54% to 66%) had developed dementia by the end of the study period. The cumulative incidence of dementia steadily increases with age and duration of PD and, conditional on survival, increases to 80% to 90% by age 90 years. Women live with PD longer than men and spend more years with dementia. At age 70 years, a man with PD but no dementia has a life expectancy of 8 years, of which 5 years would be expected to be dementia free and 3 years would be expected to be with dementia. Conclusion: Dementia is a key part of survival in Parkinson disease and must be planned for in services for this condition.

Fluctuations in attention: PD dementia vs DLB with parkinsonism

Background: Marked impairments in and fluctuation of attention are characteristic of dementia with Lewy bodies (DLB). The comparative impairment of these cognitive domains in PD and PD dementia (PD dementia) has not been studied, and is important to the conceptual understanding of parkinsonian dementias. Method: Detailed evaluations of attention and fluctuating attention (Cognitive Drug Research computerized battery) were undertaken in 278 subjects (50 DLB, 48 PD dementia, 50 PD, 80 AD, 50 elderly controls) from the Newcastle dementia register and the Stavanger PD register (controls, PD, and PD dementia patients were recruited from both centers). DLB, AD, PD, and PD dementia were diagnosed using operationalized criteria. Results: Impairments in reaction time, vigilance, and fluctuating attention were comparable in patients with DLB and PD dementia, but were less substantially impaired in patients with DLB without parkinsonism. Patients with PD had significantly greater impairment of cognitive reaction time than elderly controls, and comparable impairments of cognitive reaction time to patients with AD. Patients with PD, however, did not exhibit fluctuation of attention. Conclusion: The profile of attentional impairments and fluctuating attention is similar in PD dementia and DLB with parkinsonism. The current findings do not support the current arbitrary distinctions between these patient groups. Importantly, patients with PD do not experience fluctuating attention.

Differences in neuropathologic characteristics across the Lewy body dementia spectrum

Background: The objective of this comparative neuropathologic study was to determine the extent to which dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are distinct entities or part of a continuum with respect to the duration of parkinsonism. Methods: We evaluated the relationship between cortical α-synuclein pathology, plaques (Consortium to Establish a Registry for Alzheimers Disease [CERAD]), tangles (Braak staging), and cholinergic deficits (choline acetyltransferase in temporal cortex) in 57 prospectively assessed patients (29 DLB, 28 PDD), confirmed at autopsy. The PDD group was divided according to the median duration of parkinsonism prior to dementia. Results: There was an association between longer duration of parkinsonism prior to dementia and less severe cortical α-synuclein pathology (χ2 10.4, df 2, p = 0.006) and lower CERAD plaque scores (χ2 26.6, df 9, p = 0.002), but not Braak staging. These findings were confirmed in a further correlation analysis, which also identified an unexpected correlation between more pronounced cortical cholinergic deficits and longer duration of parkinsonism prior to dementia (R = −0.37, p = 0.04). Conclusion: While there is a clear relationship between the duration of Parkinson disease prior to the onset of dementia and key neuropathologic and neurochemical characteristics, there is a gradation of these differences across the dementia with Lewy bodies/Parkinson disease dementia spectrum and the findings do not support an arbitrary cut-off between the two disorders.

Development of daytime somnolence over time in Parkinson's disease.

Abstract—The authors examined the development over time of excessive daytime sleepiness (EDS) in patients with PD by evaluating EDS among 142 patients in 1993 and 4 years later. Eleven patients were diagnosed with EDS in 1993. In all of these patients, EDS persisted 4 years later. During follow-up, 30 new patients had EDS (6% new patients per year). In 1997, 29% of the patients with PD had EDS. The development of EDS correlated with more advanced disease and dementia.

Mild cognitive impairment in drug-naive patients with PD is associated with cerebral hypometabolism

Objective: To characterize brain metabolic changes associated with mild cognitive impairment (MCI) in drug-naive patients with Parkinson disease (PD) using 18F-fluorodeoxyglucose (FDG) and PET (FDG-PET). Methods: This cross-sectional study included newly diagnosed patients with PD with MCI in single or multiple domain (PD-MCI; n =12) and without MCI (PD-nMCI; n =12), and healthy controls (n =12). The groups were matched for age. Moreover, the patient groups were matched for motor disability. All subjects underwent a FDG-PET study. Cerebral regional relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using regions of interest analysis (ROIs) and voxel-based analysis with statistical parametric mapping. Results: ROIs and voxel-based analyses revealed significant relative hypometabolism in the prefrontal, superior/inferior parietal, and associative occipital cortices as well as in the striatum in patients with PD-MCI relative to controls (p < 0.05) and to a lesser extent in patients with PD-nMCI. In contrast, patients with PD-nMCI did not show significant metabolic changes as compared to controls. Conclusion: MCI in patients with PD is associated with cortical hypometabolism since the earliest stage, independent of therapy or motor disability. The early involvement of posterior cortical region, a pattern shared by advanced stages of PD-MCI and PD with dementia, could represent an early marker of dementia. The relevance of this pattern in predicting prodromal dementia has to be evaluated in longitudinal studies.

Familial Parkinson's disease: a community-based study

Genetic factors seem to be important in the pathogenesis of Parkinsons disease (PD). It is however, still controversial whether these factors also are reflected in a familial aggregation of PD. The aim of this study was to investigate the frequency of PD patients with a positive PD family history compared with two control groups. The included 245u2003PD patients were examined by neurologists and information was obtained through a semi‐structured interview. The patients and the control groups were examined for the frequency of PD and dementia in their families. The 245 patients with PD were included in this study. A positive PD‐family history could be obtained in 53 (21.6%) patients. The frequency was three‐ and four‐fold increased as compared with the control groups (Pu2003<u20030.001). Age at onset of disease was not different among patients with and without PD in the family. The frequency of dementia did not differ in the family of individuals with and without PD (Pu2003>u20030.1). As a conclusion our study of PD in a community based population supports previous reports of a three‐ to fourfold increased risk for PD in the families of patients with the disease. Our results indicate that the familial aggregation of the disease is independent of the age of the proband.

Relationship of cognitive impairment to psychiatric symptoms in multiple sclerosis

Psychiatric and cognitive changes are common in patients with multiple sclerosis (MS), but their relationship has not received much attention. We studied the relationship between psychiatric symptoms and verbal memory, working memory, and mental speed in 78 patients with MS and 40 healthy control subjects using linear regression analyses. The MS group exhibited impaired performance on all cognitive tests. Apathy was associated with intrusions and depression with impaired memory and mental speed. The association between apathy and intrusions supports the hypothesis that lesions in frontal areas or frontal connections contribute to a specific neuropsychiatric syndrome in patients with MS.