1998 |
Hamilton, Joanne M |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Progressive Executive Decline in Huntingtons Disease @ San Diego State University
DESCRIPTION (Adapted from Applicant's Abstract): The purpose of this project is to identify specific dimensions of cognition that are most sensitive to the functional decline that occurs in Huntington's disease (HD) using neuropsychological tests with known neural substrates. A long- term objective is to utilize the findings to develop a comprehensive is to utilize the findings to develop a comprehensive rating scale of dementia severity that is sensitive to the types of cognitive changes that occur in basal ganglia disorders, such as HD. Specifically, this project seeks to study the progression of executive dysfunction and visuospatial memory deficits in HD gene-carriers. To this end, pre-symptomatic HD gene- carriers (n=20) as well as symptomatic individuals in early and in advanced stages of HD (n=24) will be recruited. Data from these participants will be compared to data collected from age, education, and sex matched, healthy controls (n=44). The specific tests are sensitive to the cognitive changes that occur in the presence of a basal ganglia disorder, and the neural mechanisms underlying these tests are fairly well established. The intent of the study is to correlate the cognitive deterioration inherent in HD with currently used measures of functional capacity, independence, dementia severity, and behavioral abnormalities to determine which cognitive abilities best predict functional decline. Furthermore, analyses will determine whether individuals with HD demonstrate qualitatively different types of errors on the Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks that may provide information on the function of the basal ganglia separate from the frontal cortex. A secondary goal of the study is to determine whether pre- symptomatic, gene-carriers exhibit cognitive deficits as they near their estimated age of onset. The presence or absence of cognitive deficits in HD prior to its neurological diagnosis is a hotly debated topic, and it is hoped that by examining how near to the estimated age of onset these deficits are observed, this study can clarify some of the contradictory findings reported in the literature. Findings may also provide data that can be used to determine when an individual is beginning to exhibit cognitive signs of HD in anticipation of a treatment that may be successful in slowing or stopping the symptoms of this disease.
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2007 — 2010 |
Hamilton, Joanne M |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Visual Cognition in Dementia With Lewy Bodies @ University of California San Diego
[unreadable] DESCRIPTION (provided by applicant): Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia in the elderly, accounting for between 10% and 30% of autopsied cases. Pathological and clinical features of DLB overlap with Alzheimer's disease (AD) and Parkinson's disease (PD), confounding the characterization of the disorder. Accordingly, an international consortium of experts developed diagnostic criteria to improve the antemortem identification of people who likely have the disease. The identification of these core features and the subsequent development of the consensus criteria for the clinical diagnosis of DLB have reportedly improved diagnostic accuracy (i.e., 83% sensitivity and 95% specificity). Yet, as many as 30% of autopsied DLB patients do not exhibit any core features during life. The frequent absence of key criteria necessitates the search for additional means of identifying patients with DLB. Improving diagnostic precision is particularly important since DLB patients may demonstrate a heightened response to cholinesterase inhibitors, may be particularly sensitive to neuroleptic medications, and may experience a different clinical course than patients with PD or AD. Visual cognition is a relatively unexplored domain that may be helpful for delineating clinical changes specific to DLB. Several neuropsychological studies with autopsy-confirmed patients have shown that DLB patients exhibit more severe deficits in visuospatial processing than well-matched AD patients. In fact, visuospatial deficits may be the best indicator of early DLB. However, visuospatial and constructional tests used to assess patients with DLB and AD frequently rely on skills unrelated to visual cognition, such as psychomotor speed, memory, and executive functioning, thus, confounding interpretation of poor performance on these tasks. Tests of basic visual cognition may be better suited for measuring the cognitive and pathological changes specific to DLB because they can be based on the relatively well-understood organization of the visual system. Direct comparisons with AD and PD patients are critical for differentiating the contributions of AD and Lewy body brain pathology in DLB. Because PD and DLB cause extrapyramidal motor signs and psychomotor slowing, excessive visual cognitive deficits in the DLB patients may be attributable to the cognitive, rather than motor, changes of DLB. If DLB and PD patients perform similarly on some of the visual tasks, and worse than AD patients, this pattern would suggest that the deficits result from pathological changes specific to Lewy bodies rather than to shared AD pathology or dementia in general. Detailed analysis and comparison of basic visual cognition in DLB, AD, and PD patients may reveal the components of visual cognition that are more affected by DLB than AD or PD, and may identify sensitive and specific cognitive measures that can effectively distinguish these disorders. [unreadable] [unreadable] [unreadable]
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