PubMed Health⌕ Search

Biomedical subjects

D Masterman

Publications and source records attributed to D Masterman.

10 recordsLinked to original sources
PubMed2001

Complete genomic screen in Parkinson disease: evidence for multiple genes.

CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.

Adult↗
PubMed2001

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.

Age of Onset↗
PubMed2001

Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease.

Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.

Aged↗
PubMed2001

Staged bilateral pallidotomy for treatment of Parkinson disease.

OBJECT: Several investigators have described the motor benefits derived from performing unilateral stereotactic pallidotomy for the treatment of Parkinson disease (PD), but little is known about the efficacy and complication rates of bilateral procedures. The goal of this study was to assess both these factors in 12 patients. METHODS: Eleven patients with medically intractable PD underwent staged bilateral pallidotomy and one patient underwent a simultaneous bilateral procedure. Unilateral pallidotomy resulted in an improvement in the patients' Unified Parkinson Disease Rating Scale (UPDRS) total scores and motor subscores, Hoehn and Yahr stages, and Schwab and England Activities of Daily Living scores. There were no complications. The second procedures were performed 5 to 25 months after the first, and nearly complete 3-month follow-up data are available for eight of these patients. Staged bilateral pallidotomy did result in further improvements in some symptoms, but the patients proved to be less responsive to levodopa. In contrast to outcomes of the initial unilateral pallidotomy, there were significant complications. One patient suffered an acute stroke, two patients suffered delayed infarctions of the internal capsule, four patients had mild-to-moderate worsening of speech and increased drooling, and one patient complained of worsening memory. CONCLUSIONS: Bilateral pallidotomy results in modest benefits but is associated with an increased risk of complications.

Adult↗
PubMed1998

Motor, cognitive, and behavioral performance following unilateral ventroposterior pallidotomy for Parkinson disease.

OBJECTIVE: To evaluate the effects of ventroposterior pallidotomy on motor disability and on behavior and cognition in patients with medically intractable idiopathic Parkinson disease. DESIGN: Detailed motor testing both while receiving and discontinuing levodopa medication, posturography, and neurocognitive and behavioral assessments were performed before and 3 to 6 months after unilateral ventroposterior pallidotomy. SETTING: University-based movement disorder program. PATIENTS: Thirty-two patients without dementia with medically refractory idiopathic Parkinson disease were studied. MAIN OUTCOME MEASURES: Motor function and disability were measured using the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and the Schwab and England Activities of Daily Living Scale. Dynamic balance was measured by sway (amplitude and velocity) using the Chattecx Balance System. Detailed cognitive and behavioral assessments were also performed both before and after surgery. RESULTS: Eighty-three percent of patients experienced improvement of their total Unified Parkinson's Disease Rating Scale score at 3 to 6 months after surgery. Significant improvements were also seen in the contralateral Unified Parkinson's Disease Rating Scale motor subscore (78%) as well as in the contralateral Unified Parkinson's Disease Rating Scale total score both during the on and off period (78% and 79%, respectively). The Hoehn and Yahr stage, Schwab and England Activities of Daily Living Scale score, and dynamic balance when standing on foam also improved following unilateral pallidotomy in many patients. Cognitive performance remained relatively unchanged following surgery with the exception of category fluency, which exhibited a modest decline (P < .04). A significant improvement in depression was found on the Beck Depression Inventory. CONCLUSIONS: Ventroposterior pallidotomy significantly improves motor performance and daily level of function in Parkinson disease. Cognition and behavior are not adversely affected in patients without dementia, and a cognitive screening battery is proposed.

Adult↗
PubMed1998

Assessing the impact of neuropsychiatric symptoms in Alzheimer's disease: the Neuropsychiatric Inventory Caregiver Distress Scale.

OBJECTIVES: To develop an adjunct scale to the Neuropsychiatric Inventory (NPI) for assessing the impact of neuropsychiatric symptoms in Alzheimer's disease (AD) patients on caregiver distress. DESIGN: Cross-sectional descriptive and correlational study. SETTING: University out-patient memory disorders clinics. PARTICIPANTS: Eighty-five AD subjects and their caregivers (54 spouses, 31 children). MEASUREMENTS: The NPI and NPI Caregiver Distress Scale (NPI-D) were used to assess neuropsychiatric symptoms in AD patients and related caregiver distress, respectively. Criterion validity of the NPI-D was examined (N = 69) by comparison with an abridged version of the Relatives' Stress Scale (RSS'), a general measure of caregiver stress, using item clusters that had previously been correlated to behavioral disturbances in demented patients. Test-retest (n = 20) and inter-rater reliability (n = 16) of the NPI-D were also assessed. RESULTS: Test-retest and interrater reliability of the NPI-D were both adequate. Overall, caregiver NPI-D distress ratings were correlated significantly with the RSS' (r = .60, P < .001). RSS' ratings correlated strongly with NPI scores (r = .64, P < .001), even after controlling for degree of cognitive impairment based on the Mini-Mental State Exam (MMSE) score (r = .61). MMSE scores showed a moderate correlation to RSS' ratings (-.30, P = .02), but this association was markedly attenuated when controlling for the degree of neuropsychiatric disturbance based on the NPI score (r = -. 14). NPI-D ratings for 9 of 10 NPI symptom domains correlated most strongly with either NPI symptom severity or total (frequency x severity) scores. Agitation, dysphoria, irritability, delusions, and apathy were the symptoms most often reported to be severely distressing to caregivers. CONCLUSIONS: The NPI-D provides a reliable and valid measure of subjective caregiver distress in relation to neuropsychiatric symptoms measured by the NPI. Neuropsychiatric alterations are more strongly associated than cognitive symptoms to caregiver distress. The NPI-D may be useful in both clinical and research settings for assessing the contribution to caregiver distress of neuropsychiatric symptoms in AD patients.

Aged↗
PubMed1998

Apathy is not depression.

If depression is associated with apathy, then they should be expressed together in different dementia syndromes and should co-occur at varying levels of disease severity. The authors performed a cross-sectional comparison of neuropsychiatric symptoms in 30 Alzheimer's disease, 28 frontotemporal dementia, 40 Parkinson's disease, 34 Huntington's disease, and 22 progressive supranuclear palsy patients, using a standardized rating scale (the Neuropsychiatric Inventory). Apathy did not correlate with depression in the combined sample; apathy (r = -0.40, P < 0.0001), but not depression, correlated with lower cognitive function as measured by the Mini-Mental State Examination. The relationship of apathy to depression also varied across diagnostic groups. Apathy is a specific neuropsychiatric syndrome that is distinct from depression. Distinguishing these two syndromes has therapeutic implications.

Adult↗
PubMedDate not supplied

Telomere shortening in T cells correlates with Alzheimer's disease status.

Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, and therefore serve as markers of a cell's replicative history. In vivo, clonal expansion of T cells during immune responses to both foreign and autoantigens is associated with telomere shortening. To investigate possible immune alterations in Alzheimer's disease (AD) that might impact current vaccine-based therapeutic strategies, we analyzed telomere lengths in immune cell populations from AD patients. Our data show a significant telomere shortening in PBMC from AD versus controls (P=0.04). Importantly, telomere length of T cells, but not of B cells or monocytes, correlated with AD disease status, measured by Mini Mental Status Exam (MMSE) scores (P=0.025). T cell telomere length also inversely correlated with serum levels of the proinflammatory cytokine TNFalpha (a clinical marker of disease status), with the proportion of CD8+ T cells lacking expression of the CD28 costimulatory molecule, and with apoptosis. These findings suggest an immune involvement in AD pathogenesis.

Aged↗