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.
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.
|Schneider, L S; Mangialasche, F; Andreasen, N et al. (2014) Clinical trials and late-stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014. J Intern Med 275:251-83|
|Gatto, Nicole M; Henderson, Victor W; Hodis, Howard N et al. (2014) Components of air pollution and cognitive function in middle-aged and older adults in Los Angeles. Neurotoxicology 40:1-7|
|Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M (2014) Uneven futures of human lifespans: reckonings from Gompertz mortality rates, climate change, and air pollution. Gerontology 60:183-8|
|Villeneuve, Sylvia; Reed, Bruce R; Wirth, Miranka et al. (2014) Cortical thickness mediates the effect of ?-amyloid on episodic memory. Neurology 82:761-7|
|Porsteinsson, Anton P; Drye, Lea T; Pollock, Bruce G et al. (2014) Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA 311:682-91|
|Beecham, Gary W; Hamilton, Kara; Naj, Adam C et al. (2014) Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias. PLoS Genet 10:e1004606|
|Schneider, Lon S (2014) Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease. Alzheimers Dement 10:247-50|
|Escott-Price, Valentina; Bellenguez, Céline; Wang, Li-San et al. (2014) Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PLoS One 9:e94661|
|Cuajungco, Math P; Basilio, Luigi C; Silva, Joshua et al. (2014) Cellular zinc levels are modulated by TRPML1-TMEM163 interaction. Traffic 15:1247-65|
|Jayaraman, Anusha; Christensen, Amy; Moser, V Alexandra et al. (2014) Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats. Endocrinology 155:1398-406|
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