This grant is a competitive renewal of prior 5-year grant, in which it was proposed that fMRI during a memory challenge, in combination with information regarding the presence versus absence of APOE-4, would predict future cognitive decline in the elderly. Studies from the prior funding period did indeed show different patterns of brain activation between the two sub-populations of elderly subjects, in areas known to be involved in Alzheimer's disease (hippocampus, parietal cortex, and dorsal prefrontal cortex); further, increased fMRI activity at baseline correlated with cognitive decline measured 2 years later. The renewal application seeks to expand on these findings by conducting longitudinal follow-up of the genotyped-subject groups, with functional and structural MRI, as well as neurocognitive assessments. New subjects will be added to the sample. Novel fMRI memory activation paradigms will be used and new cortical segmentation and unfolding techniques will be used. The goals of this project are to: define the natural history of changes in memory activation for the two subpopulations of elderly individuals (those with and without an APOE-4 allele); predict long-term outcome from baseline fMRI data; and delineate with greater precision the changes in function and structure of the hippocampus that distinguish elderly with an AD risk factor (APOE-4) from elderly without this AD risk factor.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG013308-06
Application #
6196464
Study Section
Special Emphasis Panel (ZRG1-BBBP-4 (01))
Program Officer
Buckholtz, Neil
Project Start
1995-08-10
Project End
2005-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
6
Fiscal Year
2000
Total Cost
$370,959
Indirect Cost
Name
University of California Los Angeles
Department
Pharmacology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Roussotte, Florence F; Siddarth, Prabha; Merrill, David A et al. (2018) In Vivo Brain Plaque and Tangle Burden Mediates the Association Between Diastolic Blood Pressure and Cognitive Functioning in Nondemented Adults. Am J Geriatr Psychiatry 26:13-22
Harrison, Theresa M; McLaren, Donald G; Moody, Teena D et al. (2017) Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease. J Vis Exp :
Burggren, Alison C; Mahmood, Zanjbeel; Harrison, Theresa M et al. (2017) Hippocampal thinning linked to longer TOMM40 poly-T variant lengths in the absence of the APOE ?4 variant. Alzheimers Dement 13:739-748
Harrison, Theresa M; Burggren, Alison C; Small, Gary W et al. (2016) Altered memory-related functional connectivity of the anterior and posterior hippocampus in older adults at increased genetic risk for Alzheimer's disease. Hum Brain Mapp 37:366-80
Merrill, David A; Siddarth, Prabha; Raji, Cyrus A et al. (2016) Modifiable Risk Factors and Brain Positron Emission Tomography Measures of Amyloid and Tau in Nondemented Adults with Memory Complaints. Am J Geriatr Psychiatry 24:729-37
Harrison, Theresa M; Bookheimer, Susan Y (2016) Neuroimaging genetic risk for Alzheimer's disease in preclinical individuals: From candidate genes to polygenic approaches. Biol Psychiatry Cogn Neurosci Neuroimaging 1:14-23
Baerresen, Kimberly M; Miller, Karen J; Hanson, Eric R et al. (2015) Neuropsychological tests for predicting cognitive decline in older adults. Neurodegener Dis Manag 5:191-201
Yushkevich, Paul A; Amaral, Robert S C; Augustinack, Jean C et al. (2015) Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: towards a harmonized segmentation protocol. Neuroimage 111:526-41
Chen, Stephen T; Siddarth, Prabha; Saito, Nathan Y et al. (2014) Psychological well-being and regional brain amyloid and tau in mild cognitive impairment. Am J Geriatr Psychiatry 22:362-9
Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel et al. (2014) Impaired automatization of a cognitive skill in first-degree relatives of patients with schizophrenia. Psychiatry Res 215:294-9

Showing the most recent 10 out of 79 publications