Jan Petter Larsen

Risk of dementia in Parkinson's disease: A community-based, prospective study

Objective: To calculate the incidence of and determine possible risk factors for dementia in PD. Background: Dementia has important clinical consequences for patients with PD and their caregivers, but the incidence is unknown. Methods: A population-based cohort of nondemented patients with PD (n = 171) from the county of Rogaland, Norway, was assessed at baseline and 4.2 years later with a comprehensive evaluation of motor, cognitive, and neuropsychiatric symptoms. The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) criteria, based on interview of the patient and a caregiver, cognitive rating scales, and neuropsychologic tests. A representative sample of 3,062 nondemented elderly subjects without PD served as control group. Results: Forty-three patients with PD were demented at follow-up evaluation, equivalent to an incidence rate of 95.3 per 1,000 person-years (95% CI, 68.2 to 122.0). The risk for the development of dementia in patients with PD relative to the control subjects after adjusting for age, sex, and education was 5.9 (95% CI, 3.9 to 9.1). Predictive factors at baseline for dementia in PD in addition to age were Hoehn & Yahr score >2 (OR, 3.4; 95% CI, 1.3 to 8.6) and Mini-Mental State Examination score <29 (OR, 3.3; 95% CI, 1.3 to 8.2). Conclusions: Patients with PD have an almost sixfold increased risk for becoming demented compared with subjects without PD.

Predictors of nursing home placement in Parkinson's disease: a population-based, prospective study.

OBJECTIVES: To examine the rate and predictors of nursing home placement in patients with Parkinsons disease.

Range of neuropsychiatric disturbances in patients with Parkinson’s disease

OBJECTIVES Disturbances of cognition and emotion are common in patients with Parkinson’s disease. Most previous studies of psychopathology in Parkinson’s disease have focused on a single psychiatric diagnosis or condition. The objective of this study was to describe the range of neuropsychiatric symptoms in a representative sample of patients with Parkinson’s disease. METHODS The sample of 139 patients was drawn from an epidemiological study of Parkinson’s disease in Rogaland county, Norway, and represented 93% of those who had survived during the 4 years since the initial assessment. The diagnosis of Parkinson’s disease was based on published criteria. Neuropsychiatric symptoms were assessed using the neuropsychiatric inventory, a caregiver based structured interview, which assesses severity and frequency of 10 psychiatric symptoms present during the past month. RESULTS At least one psychiatric symptom was reported in 61% of the sample. The most common behaviours were depression (38%) and hallucinations (27%), and the least common symptoms were euphoria and disinhibition. The highest mean scores were found for depression, apathy, and hallucinations. Factor analysis showed that hallucinations, delusions, and irritability clustered into one factor, and apathy and anxiety constituted another factor. Psychiatric symptoms were more common among patients living in nursing homes compared with home dwelling patients, and correlated with stage of disease and cognitive impairment, but not with age or duration of disease. No relation to left or right sided parkinsonism was found. CONCLUSION This study emphasises the importance of psychiatric symptoms in Parkinson’s disease, which were present in most patients. Clinicians should focus on the emotional and cognitive disturbances in addition to the motor manifestations of the disease.

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.

The influence of fatigue on health-related quality of life in patients with Parkinson's disease

Objective – To examine the correlation between fatigue and health‐related quality of life (HRQL) in patients with Parkinsons disease (PD). Patients and methods– Sixty‐six patients with idiopathic PD. The patients did not have a depressive mood disorder or cognitive impairment. Fatigue was measured by the Fatigue Severity Scale (FSS). HRQL was measured by the Parkinsons Disease Questionnaire (PDQ‐39) and the Short‐Form 36 (SF‐36). Results– Thirty‐three (50%) of the patients had significant fatigue. Patients with fatigue had a more advanced disease than those without fatigue, measured by the UPDRS scale, including a higher Hoehn and Yahr stage and lower Schwab and England score. Patients with fatigue reported more distress in the dimensions of emotional well‐being and mobility (PDQ‐39) and also had a significantly higher PDQ summary index. On the SF‐36 patients with fatigue reported more problems in the areas of physical functioning, role limitation (physical), social functioning and vitality. Correlations between the FSS and the HRQL scales were highest for the summary index of PDQ‐39 and in the dimensions of ADL, mobility and emotional well‐being (PDQ‐39) and physical functioning, role limitation (physical), social functioning, general health and vitality (SF‐36). Conclusions– PD has a substantial negative impact on HRQL. We found a strong correlation between fatigue and high distress scores on HRQL scales in a population of patients with PD who were not depressed or demented. The diversity of symptoms and high prevalence of non‐motor features, including fatigue, is important to take into account in our efforts to optimize treatment and care for this patient group.

Subtypes of mild cognitive impairment in parkinson's disease: Progression to dementia

The aim of this study was to establish the rate of progression from mild cognitive impairment (MCI) to dementia in patients with Parkinsons disease (PD). PD patients without dementia were recruited in 1997 from an ongoing prospective epidemiological study. The assessment included neurological and psychiatric examinations, a clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM‐III‐R) criteria for dementia, and a battery of neuropsychological tests. PD was diagnosed according to established criteria, dementia was diagnosed according to the DSM‐III‐R criteria, and subtypes of MCI were classified according to modified Petersens criteria. Seventy‐two nondemented PD patients were included. A total of 34 were cognitively intact, whereas 38 were diagnosed with MCI (amnestic, n = 6; single nonmemory domain, n = 17; multiple domains slightly impaired, n = 15). Fifty‐nine patients (82%) completed follow‐up examination 4 years later, and 18 (62%) of the patients with MCI and 6 (20%) of the cognitively intact PD patients were demented (P = 0.001). Single domain nonmemory MCI and multiple domains slightly impaired MCI were associated with later development of dementia (P = 0.003; P = 0.04), whereas amnestic MCI subtype was not (P = 0.76). We conclude that patients with PD and MCI had a higher risk of developing dementia than cognitively intact PD patients, suggesting that MCI in PD is an early manifestation of dementia. However, these findings should be interpreted with caution due to the relatively small number of subjects included in this study.

MRI evaluation of the size and symmetry of the planum temporale in adolescents with developmental dyslexia

MRI technique was used to examine the size and symmetry of the plana temporale in 19 dyslexic students in grade 8 and in carefully matched control subjects. The results demonstrated a high frequency of planum symmetry among the dyslexics (70%) whereas symmetry was observed in only 30% of the control subjects. It was not possible to demonstrate any clear association between symmetry/asymmetry of planum temporale and handedness. Word-reading strategies among the dyslexics and control subjects were investigated with computerized tasks where accuracy and naming latency were recorded. All subjects with pure phonological deficits in reading had symmetrical plana temporale indicating a possible neuroanatomical basis for a characteristic symptom of linguistic processing deficiency in developmental dyslexia.

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.

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.