Dementia is common in patients with Parkinson's disease (PDD). The etiology of PDD is still unclear, but exciting advances have been made in discovering pathogenetic components in Parkinson's disease (PD), implicating the role of genetic factors. It is, however, still controversial whether genetic factors also contribute to the development of dementia in PD. Thus, we investigated the association between development of dementia and a positive family history of PD or dementia in a community-based study of PD in Rogaland County, Norway (n = 219). The patients were followed prospectively with neurological and neuropsychological assessments. Dementia was more common in patients with a strong family association of PD (first-degree relatives > second-degree relatives > no family history; P
Mitochondrial dysfunction, oxidative stress and energy production have been implicated in the etiology of Parkinson's disease (PD). Several agents are under investigation for potential neuroprotective effects including acetyl-l-carnitine (ALC).
To investigate whether low carnitine levels and mutations in the SLC22A5 gene encoding the carnitine transporter are associates with PD risk in the Faroe Islands where the prevalence of both PD and carnitine transporter deficiency (CTD) is high.
We conducted a case-control study with 121 cases and 235 randomly selected controls, matched by gender and age. Blood spots were analyzed for free and total carnitine levels by QUATTRO LC triple quadrupole mass spectrometry (MS/MS) and sequencing performed for five genetic mutations in the SLC22A5 gene with ABI PRISM 3130.
PD cases had significantly lower levels of free and total carnitine levels compared with controls (P??G mutation frequency in the SLC22A5 gene among cases and controls (p?=?.70).
Low carnitine levels seem to be associated with PD, but only in individuals without the c.95A?>?G mutation rendering the carnitine transporter less efficient. Thus, the difference in carnitine levels is not caused by a higher frequency of c.95A?>?G mutation carriers in cases. The cause may be dietary or due to different gut microbiota among cases.
OBJECTIVE: To investigate the frequency of nonfluctuators in a community-based prevalence study of Parkinson's disease (PD) and to describe disability, non-motor problems, and health-related quality of life in patients with PD with and without motor fluctuations, and compare the findings to those of two control groups. METHODS: The study involved 245 patients with PD who were participating in a prevalence study and two control groups (100 healthy elderly individuals and 100 patients with diabetes mellitus [DM]). Data were obtained through neurologic examination and a semistructured interview, and by the use of several questionnaires. RESULTS: In this group of unselected patients with PD, 78% did not experience motor fluctuations. Mean duration of treatment with levodopa was 6.3 years. Patients with motor fluctuations had a lower age at onset of disease, longer duration of disease, and a higher daily levodopa dose than patients without fluctuations. Among the non-fluctuating patients, we found more dementia and a higher age at prevalence day. Disability (assessed by the Unified Parkinson's Disease Rating Scale subscales for activities of daily living and motor function and the Hoehn and Yahr stage) was similar in fluctuators and nonfluctuators. Depression, sleep disturbances, and fatigue were equally frequent in both patient groups. The occurrence of these difficulties was clearly more frequent among non-fluctuating patients with PD than among the control subjects. CONCLUSION: Most patients in the general population who have PD do not experience dose-dependent motor fluctuations. Severity of motor disability and neuropsychiatric manifestations are as important in non-fluctuators as in fluctuators. Patients without motor fluctuations have more depression, sleep disturbances, fatigue, and a poorer health-related quality of life than patients with DM and healthy elderly individuals. This also underlines the importance of developing better management and treatment strategies for this group of patients with PD.
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.
Comment In: Neurology. 2009 Mar 31;72(13):1116-719332688
BACKGROUND: Dementia occurs in the majority of patients with Parkinson's disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. METHODS: Two community-based studies of PD in New York (n=281) and Rogaland county, Norway (n=227) and two population-based groups of healthy elderly from New York (n=180) and Odense, Denmark (n=2414) were followed prospectively for 3-4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. FINDINGS: In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. INTERPRETATION: This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD.
The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss.
To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea.
A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N?=?5?472?745), were included. Data analysis was conducted from June 26 to July 27, 2015.
The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10?000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models.
A total of 5 404 692 individuals were included in the reference population; of these, 22?387 individuals (9812 [43.8%] women; mean [SD] age at diagnosis, 75.9 [10.2] years) received a diagnosis of Parkinson disease during the study period and 68?053 individuals (45 712 [67.2%] women; mean age, 42.2 [16.5] years) were registered as having rosacea. The IRs of Parkinson disease per 10?000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2-fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 [95% CI, 1.67-2.48]), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 [95% CI, 0.97-0.99]).
Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared pathogenic mechanisms involving elevated matrix metalloproteinase activity. The clinical consequences of this association require further study.
Familial aggregation has been described in PD of both early and late onset, but has not been studied in a true population-based sample. Moreover, little is known about its association with disease progression and endophenotypes.
The objectives of this work were to determine familial aggregation of idiopathic PD in a population-based cohort and study the association with clinical endophenotypes and disease progression.
We examined family history data from the Norwegian ParkWest study, a well-characterized, population-based cohort of incident PD patients and age-matched healthy controls. Family data were collected at baseline with a simplified questionnaire (192 cases and 193 controls) and after 3 years of longitudinal follow-up using an extended questionnaire (172 cases and 171 controls).
Compared to the controls, the PD patients had an increased relative risk of having a first-degree relative with PD when using the extended questionnaire (relative risk = 1.988; P = 0.036), but not when using the simplified questionnaire (relative risk = 1.453; P = 0.224). There was no significant difference in age of onset or motor subtype (P = 0.801). However, cases with a family history of PD had reduced progression over 7 years as measured by UPDRS II (P = 0.008) and smaller rate of decrease of MMSE (P = 0.046).
The purpose of this study was to examine the prevalence of fatigue in Parkinson's disease (PD) patients and compare this to the general population. Factors associated with fatigue were investigated by linear regression. Fatigue was assessed by the fatigue questionnaire. The mean age of the 176 PD patients (41% women) was 69 years (range 35-90), and the mean UPDRSIII was 22.3 (SD 11.7). Fatigue levels (means) were significantly higher in PD patients compared with the general population; however, effect sizes were moderate for women for physical and total fatigue indicating clinically significant differences here only. Only female PD patients had more chronic fatigue than the general population. Fatigue was related to characteristics of PD but also to sleep disturbance, depression, and gender. This population-based study demonstrates that fatigue is a common symptom in PD patients, but compared with the general population, clinically significant differences were only found for female PD patients.
Previous twin studies report no heritability of Parkinson's disease (PD) based on cross sectional information. Here, we apply a longitudinal design and re-evaluate cross sectional data in the population-based Swedish Twin Registry (STR) using clinical as well as hospital discharge and cause of death diagnoses. In the longitudinal analyses (based on 46,436 individuals), we identified 542 twins with PD and 65 twins with Parkinsonism. Concordance rates for PD were 11% for monozygotic and 4% for same-sexed dizygotic twin pairs, with a heritability estimate of 34%. Concordance rates for PD or parkinsonism were 13% for monozygotic and 5% for same-sexed dizygotic twin pairs, with a heritability estimate of 40%. In the cross sectional analyses (based on 49,814 individuals), we identified 287 twins with PD and 79 twins with parkinsonism. Concordance rates for PD were 4% for monozygotic and same-sexed dizygotic twin pairs and 0 for opposite-sexed twin pairs. Concordance rates for PD or parkinsonism were somewhat higher but the heritability estimate was nonsignificant. Our longitudinal analyses demonstrate that PD and parkinsonism are modestly heritable.
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.