Neurodegenerative diseases including Alzheimer's (AD) and Parkinson's disease (PD) are distressing conditions for those affected and their loved ones, and represent a growing burden on public health funds. These diseases are becoming increasingly prevalent as the population ages. Neuropsychological decline is the hallmark of early AD, and is common in PD. Such symptoms are identified and tracked with neuropsychological tests, which are also important in testing new medications. Recent breakthroughs have led to further understanding of the underlying neurobiology of AD and PD, but how these new findings relate to neuropsychological testing is largely unknown. This project will inform our interpretation of neuropsychological testing in relation to novel neuroimaging and genetic biomarkers of AD and PD. In AD, we will we will study the brain at rest using functional magnetic resonance imaging (fMRI), and learn how the connectivity of the brain's networks relate to neuropsychological testing. We will also use a novel adaptation of a task traditionally used in rodent studies, the Morris Water Maze, and understand this in the context of connectivity at rest during fMRI. Other aspects of the project will involve both AD and PD: we will use a novel method to assess inflammation in the brain, and understand how regional inflammation relates to different types of cognitive impairment. We will also discover how genetic biomarkers of inflammation and AD risk relate to neuropsychology. By gaining better understanding of the correlations of neuropsychology and these novel biomarkers we will be able to inform interpretation of both sets of techniques. Neuropsychology is currently central to the monitoring of novel medications being tested in both diseases, and understanding the neurobiological processes underlying our findings will be central in contributing to the development of new medications. The studies outlined in this project proposal will generate preliminary data to answer further questions about the neuropsychology of these diseases. In combination with a detailed mentoring scheme, the studies proposed here and the experience gained if funded will result in the project leader being a competitive candidate for independent research funding.

Public Health Relevance

Neuropsychological tests are important in diagnosing and tracking cognitive impairment in Alzheimer's and Parkinson's disease. New neuroimaging and genetic tests are showing emerging importance in identifying the underlying brain regions and pathological processes involved in these diseases. The proposed project will investigate the relationships between neuropsychological testing and these new neuroimaging and genetic tests and will provide information important in developing and testing potential new treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM109025-04
Application #
9492791
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Voss, Tiffini; Li, Jerry; Cummings, Jeffrey et al. (2018) Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease. Alzheimers Dement (N Y) 4:173-181
Cordes, Dietmar; Zhuang, Xiaowei; Kaleem, Muhammad et al. (2018) Advances in functional magnetic resonance imaging data analysis methods using Empirical Mode Decomposition to investigate temporal changes in early Parkinson's disease. Alzheimers Dement (N Y) 4:372-386
Zink, Davor N; Miller, Justin B; Caldwell, Jessica Z K et al. (2018) The relationship between neuropsychological tests of visuospatial function and lobar cortical thickness. J Clin Exp Neuropsychol 40:518-527
Cummings, Jeffrey; Lee, Garam; Ritter, Aaron et al. (2018) Alzheimer's disease drug development pipeline: 2018. Alzheimers Dement (N Y) 4:195-214
Miller, Justin B; Shan, Guogen; Lombardo, Joseph et al. (2018) Biomedical informatics applications for precision management of neurodegenerative diseases. Alzheimers Dement (N Y) 4:357-365
Cummings, Jeffrey; Reiber, Carl; Kumar, Parvesh (2018) The price of progress: Funding and financing Alzheimer's disease drug development. Alzheimers Dement (N Y) 4:330-343
Miller, Justin B; Cummings, Jeffrey; Nance, Christin et al. (2018) Neuroscience learning from longitudinal cohort studies of Alzheimer's disease: Lessons for disease-modifying drug programs and an introduction to the Center for Neurodegeneration and Translational Neuroscience. Alzheimers Dement (N Y) 4:350-356
Cummings, Jeffrey (2018) Lessons Learned from Alzheimer Disease: Clinical Trials with Negative Outcomes. Clin Transl Sci 11:147-152
Baer, Michael; Klemetson, Bradley; Scott, Diana et al. (2018) Effects of Fatigue on Balance in Individuals With Parkinson Disease: Influence of Medication and Brain-Derived Neurotrophic Factor Genotype. J Neurol Phys Ther 42:61-71
Ghazi-Saidi, Ladan; Walsh, Ryan R; Shan, Guogen et al. (2018) Biomarkers of Cognitive Impairment: Brain Cortical Thickness, Volumetrics, and Cerebrospinal Fluid. Alzheimer Dis Assoc Disord 32:255-257

Showing the most recent 10 out of 53 publications