Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), and Parkinson's disease with dementia (PDD) are neurodegenerative disorders that lead to a global dementia syndrome. Despite differences in the prominence and order of appearance of various clinical characteristics (e.g., dementia, movement disorder, visual hallucinations), the disorders can be quite similar in clinical presentation once dementia is present, making them difficult to clinically differentiate (particularly AD vs. DLB and DLB vs. PDD). Recent evidence suggests that differences in the patterns of cognitive deficits associated with the disorders might aid in distinguishing between them and have some utility in predicting rate of global cognitive decline. Thus, the goal of the proposed project is to determine whether mildly demented DLB, PDD, and AD patients differ in the relative severity of deficits they exhibit on experimental and clinical neuropsychological tests (Study I). Based upon the different distributions of pathological changes associated with the three disorders it is anticipated that semantic knowledge and episodic memory deficits will be most salient in AD, visuospatial processing deficits will be most salient in DLB, and implicit category learning deficits will be most salient in PDD. Furthermore, we will determine whether or not unique patterns of deficits on these tests are maintained over a one-year period (Study II). Previous evidence suggests that the degree of impairment in the most salient cognitive deficit in each disorder predicts the rate of subsequent global cognitive decline. We will address this question by directly comparing the cognitive predictors of decline in three disorders (Studies Illa-c). We anticipate that degree of semantic memory loss (and not the lack of integrity in other cognitive functions) will uniquely predict decline in AD, severity of visuospatial processing deficits will uniquely predict decline in DLB, and degree of category learning impairment will uniquely predict decline in PDD. In exploratory studies (Studies IV-VI), we will examine the relationship between the degree of impairment on the cognitive tests from each domain and the severity of neuropathologic changes in the presumed underlying brain substrate. We anticipate that posterior cortical pathology (e.g., a-synuclein pathology, (3-amyloid and tau pathology, synapse loss) will be associatedwith visuospatial dysfunction and decline (DLB

Public Health Relevance

(Seeinstructions): Identification of differences in the neuropsychological deficits in AD, DLB, and PDD will allow us to better differentiate among the three disorders and facilitate early diagnosis. Validation of cognitive markers that predict subsequent rate of global cognitive decline will improve the accuracy of prognosis and may provide a method to enhance cohorts with rapid decliners for clinical trials of potential disease modifying therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005131-29
Application #
8375271
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
29
Fiscal Year
2012
Total Cost
$176,682
Indirect Cost
$39,190
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Kirson, Noam Y; Scott Andrews, J; Desai, Urvi et al. (2018) Patient Characteristics and Outcomes Associated with Receiving an Earlier Versus Later Diagnosis of Probable Alzheimer's Disease. J Alzheimers Dis 61:295-307
Graves, Lisa V; Holden, Heather M; Van Etten, Emily J et al. (2018) New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3: Clinical Utility in Alzheimer's and Huntington's Disease. J Int Neuropsychol Soc 24:833-841
Fong, Lauren K; Yang, Max M; Dos Santos Chaves, Rodrigo et al. (2018) Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-? clearance in human astrocytes. J Biol Chem 293:11341-11357
Barnes, Josephine; Bartlett, Jonathan W; Wolk, David A et al. (2018) Disease Course Varies According to Age and Symptom Length in Alzheimer's Disease. J Alzheimers Dis 64:631-642
Spencer, Brian; Br├╝schweiler, Sven; Sealey-Cardona, Marco et al. (2018) Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders. Acta Neuropathol 136:69-87
Edmonds, Emily C; Ard, M Colin; Edland, Steven D et al. (2018) Unmasking the benefits of donepezil via psychometrically precise identification of mild cognitive impairment: A secondary analysis of the ADCS vitamin E and donepezil in MCI study. Alzheimers Dement (N Y) 4:11-18
Pottier, Cyril; Zhou, Xiaolai; Perkerson 3rd, Ralph B et al. (2018) Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study. Lancet Neurol 17:548-558
Burke, Shanna L; Maramaldi, Peter; Cadet, Tamara et al. (2018) Decreasing hazards of Alzheimer's disease with the use of antidepressants: mitigating the risk of depression and apolipoprotein E. Int J Geriatr Psychiatry 33:200-211
Weintraub, Sandra; Besser, Lilah; Dodge, Hiroko H et al. (2018) Version 3 of the Alzheimer Disease Centers' Neuropsychological Test Battery in the Uniform Data Set (UDS). Alzheimer Dis Assoc Disord 32:10-17
Qian, Winnie; Fischer, Corinne E; Schweizer, Tom A et al. (2018) Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease. Curr Alzheimer Res 15:187-194

Showing the most recent 10 out of 914 publications