There is wide acceptance that vascular risk factors are the most important modifiable risk factors for AD as well as vascular dementia. This project is designed to add to our understanding of how vascular factors may be associated with very early changes in cognition. Recent work suggests that vascular pathology is associated with decrements in processing resource abilities, whereas losses in hippocampal and cortical grey matter indices are associated with memory declines. Project 1 will combine the extensive psychometric data obtained over 9-15 years from 125 volunteers who are participants in the Long Beach Longitudinal Study (LBLS), R01 AG10569, with vascular and brain structure measures collected at two time points three years apart. Project 1 tests hypotheses that these measures are differentially related to the development of longitudinal declines in memory and other psychometric abilities that represent processing resources, such as working memory. To do this, we will assess the role of demographic predictors, genetic status, vascular risk (blood pressure, BMI, waist circumference, hemoglobin Ale, total cholesterol and HDL), arteriosclerosis (Carotid IMT and indices from retinal AV photography) and MRI indices of vascular brain injury (white matter volume, WMH, infarcts), hippocampal (HC) loss (regional HC volumes), and brain structure (total cortical grey matter) on LBLS longitudinal outcomes of memory: list and text recall;and the processing resources of reasoning (fluid intelligence), speed, working memory, and letter fluency. A three-year follow-up will determine whether additional longitudinal changes covary.

Public Health Relevance

Participants in this long term study may have experienced subtle changes in memory and cognitive resources associated with early pathological indices. Results will inform theories of normal aging as well as models of the adverse effects of vascular changes in initial development of cognitive impairment. Results may suggest that reducing vascular risk may be key to reducing cognitive decline in older adults.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Specialized Center (P50)
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Special Emphasis Panel (ZAG1-ZIJ-4)
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University of Southern California
Los Angeles
United States
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Soosman, Steffan K; Joseph-Mathurin, Nelly; Braskie, Meredith N et al. (2016) Widespread white matter and conduction defects in PSEN1-related spastic paraparesis. Neurobiol Aging 47:201-209
Kammen, Alexandra; Law, Meng; Tjan, Bosco S et al. (2016) Automated retinofugal visual pathway reconstruction with multi-shell HARDI and FOD-based analysis. Neuroimage 125:767-79
Forrester, Sarah N; Gallo, Joseph J; Smith, Gwenn S et al. (2016) Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia. Am J Geriatr Psychiatry 24:117-25
Barnes, Samuel R; Ng, Thomas S C; Montagne, Axel et al. (2016) Optimal acquisition and modeling parameters for accurate assessment of low Ktrans blood-brain barrier permeability using dynamic contrast-enhanced MRI. Magn Reson Med 75:1967-77
Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-9
Kennedy, Richard E; Cutter, Gary R; Wang, Guoqiao et al. (2016) Post Hoc Analyses of ApoE Genotype-Defined Subgroups in Clinical Trials. J Alzheimers Dis 50:1205-15
Crawford, Karen L; Neu, Scott C; Toga, Arthur W (2016) The Image and Data Archive at the Laboratory of Neuro Imaging. Neuroimage 124:1080-3
Finch, Caleb E; Shams, Sara (2016) Apolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice. Trends Neurosci 39:625-37
Halliday, Matthew R; Rege, Sanket V; Ma, Qingyi et al. (2016) Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease. J Cereb Blood Flow Metab 36:216-27
Bilousova, Tina; Miller, Carol A; Poon, Wayne W et al. (2016) Synaptic Amyloid-β Oligomers Precede p-Tau and Differentiate High Pathology Control Cases. Am J Pathol 186:185-98

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