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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS049298-01A2
Application #
7195981
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Sutherland, Margaret L
Project Start
2007-09-30
Project End
2011-05-31
Budget Start
2007-09-30
Budget End
2008-05-31
Support Year
1
Fiscal Year
2007
Total Cost
$135,231
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Landy, Kelly M; Salmon, David P; Galasko, Douglas et al. (2015) Motion discrimination in dementia with Lewy bodies and Alzheimer disease. Neurology 85:1376-82
Hamilton, Joanne M; Salmon, David P; Raman, Rema et al. (2014) Accounting for functional loss in Alzheimer's disease and dementia with Lewy bodies: beyond cognition. Alzheimers Dement 10:171-8
Peavy, Guerry M; Salmon, David P; Edland, Steven D et al. (2013) Neuropsychiatric features of frontal lobeýýdysfunction in autopsy-confirmed patients with lewy bodies and ""pure"" Alzheimer disease. Am J Geriatr Psychiatry 21:509-19
Hamilton, Joanne M; Landy, Kelly M; Salmon, David P et al. (2012) Early visuospatial deficits predict the occurrence of visual hallucinations in autopsy-confirmed dementia with Lewy bodies. Am J Geriatr Psychiatry 20:773-81
Hamilton, Joanne M; Salmon, David P; Galasko, Douglas et al. (2008) Visuospatial deficits predict rate of cognitive decline in autopsy-verified dementia with Lewy bodies. Neuropsychology 22:729-37