Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34-0.91; P=.02) or K (OR 0.52; 95% CI 0.30-0.90; P=.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39-0.73; P=.0001). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27-0.71; P=.0009). In addition, SNP 9055A of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22-0.93; P=.03). Our results suggest that ND3 is an important factor in PD susceptibility among white individuals and could help explain the role of complex I in PD expression.
Objective As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson’s disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. Methods The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored. Results The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling=0.95, sexual behavior=0.97, buying=0.87, eating=0.88, punding=0.78, hobbyism=0.93, walkabout=0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling=0.95, sexual behavior=0.96, buying=0.87, eating=0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96% and 94%, respectively. Conclusions Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.
Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). Methods:We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age-and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed.
There is a significant incidence of adverse events associated with the DBS procedure. Nevertheless, DBS is clinically effective in well-selected patients and should be seriously considered as a treatment option for patients with medically refractory movement disorders.
SETTING-Two movement disorders centers at the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center.PARTICIPANTS-A convenience sample of 131 patients with idiopathic PD who were screened for cognitive and psychiatric complications.MEASUREMENTS-Subjects were administered the MoCA and MMSE, and only subjects defined as having a normal age-and education-adjusted MMSE score were included in the analyses (N = 100). As previously recommended in patients without PD, a MoCA score less than 26 was used to indicate the presence of at least mild cognitive impairment (MCI). RESULTS-Mean MMSE andMoCA scores ± standard deviation were 28.8 ± 1.1 and 24.9 ± 3.1, respectively. More than half (52.0%) of subjects with normal MMSE scores had cognitive impairment according to their MoCA score. Impairments were seen in numerous cognitive domains, including memory, visuospatial and executive abilities, attention, and language. Predictors of cognitive impairment on the MoCA using univariate analyses were male sex, older age, lower © 2009, The American Geriatrics Society Address correspondence to Daniel Weintraub, 3615 Chestnut St., Room 330, Philadelphia, PA 19104. E-mail: weintrau@mail.med.upenn.edu. Author Contributions: S.N., A.D.S., J.E.D., A.C., S.S.H., P.J.M., J.W., M.B.S., D.W.: study concept and design, acquisition of subjects and data, analysis and interpretation of data, preparation of data, and preparation of manuscript. T.T.H.: analysis and interpretation of data, preparation of manuscript data, and preparation of manuscript. Impairments in executive function, attention, visuospatial skills, and memory characterize the "typical" cognitive profile in PD, whereas language and praxis are thought to be relatively spared. 3,4,9 The memory impairment associated with PD is classically considered a retrieval deficit (i.e., subcortical memory profile) as opposed to an encoding deficit (i.e., cortical memory profile). NIH Public AccessThere is substantial overlap in the pattern of observed cognitive deficits in PD without dementia and PDD. Studies enrolling both groups of patients have shown qualitatively similar, but quantitatively greater, impairments in patients with PDD in executive function, visuospatial abilities, attention, and psychomotor skills. 10 In longitudinal studies of patients without dementia at baseline, verbal memory deficits 11 and executive or visuospatial impairments 12 have been shown to predict development of PDD on long-term follow-up.Given the aforementioned high prevalence of MCI in PD and its association with future development of dementia, it is important that patients with PD, even those with mild disease, be screened regularly for cognitive impairment. 12 An ideal cognitive screening instrument in PD should be brief, assess a range of cognitive domains, simple to administer, sensitive to the initial stage of cognitive impairment, and unaffected by motor impairment.Few screening instruments have been validated or developed to assess global cognition in PD. The Scales for Outco...
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