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 #
5P50AG005131-30
Application #
8449633
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
30
Fiscal Year
2013
Total Cost
$163,144
Indirect Cost
$34,039
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Ronquillo, Jay Geronimo; Baer, Merritt Rachel; Lester, William T (2016) Sex-specific patterns and differences in dementia and Alzheimer's disease using informatics approaches. J Women Aging 28:403-11
Ridge, Perry G; Hoyt, Kaitlyn B; Boehme, Kevin et al. (2016) Assessment of the genetic variance of late-onset Alzheimer's disease. Neurobiol Aging 41:200.e13-20
Ringman, John M; Monsell, Sarah; Ng, Denise W et al. (2016) Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database. J Neuropathol Exp Neurol 75:284-90
Besser, Lilah M; Alosco, Michael L; Ramirez Gomez, Liliana et al. (2016) Late-Life Vascular Risk Factors and Alzheimer Disease Neuropathology in Individuals with Normal Cognition. J Neuropathol Exp Neurol 75:955-962
Burke, Shanna L; Maramaldi, Peter; Cadet, Tamara et al. (2016) Neuropsychiatric symptoms and Apolipoprotein E: Associations with eventual Alzheimer's disease development. Arch Gerontol Geriatr 65:231-8
de Wilde, Martijn C; Overk, Cassia R; Sijben, John W et al. (2016) Meta-analysis of synaptic pathology in Alzheimer's disease reveals selective molecular vesicular machinery vulnerability. Alzheimers Dement 12:633-44
John, Samantha E; Gurnani, Ashita S; Bussell, Cara et al. (2016) The effectiveness and unique contribution of neuropsychological tests and the δ latent phenotype in the differential diagnosis of dementia in the uniform data set. Neuropsychology 30:946-960
Bonham, Luke W; Geier, Ethan G; Fan, Chun C et al. (2016) Age-dependent effects of APOE ε4 in preclinical Alzheimer's disease. Ann Clin Transl Neurol 3:668-77
Ting, Simon Kang Seng; Hao, Ying; Chia, Pei Shi et al. (2016) Clinicopathological correlation of psychosis and brain vascular changes in Alzheimer's disease. Sci Rep 6:20858
Valera, Elvira; Masliah, Eliezer (2016) Combination therapies: The next logical Step for the treatment of synucleinopathies? Mov Disord 31:225-34

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