Epidemiologic studies support the finding that cognitive decline is evidenced as early as the fifth decade of life and further, that the estimated prevalence of more marked decline (MCI) for people over 65 years of age is between 10% and 20%. Several lines of evidence point to alterations in white matter as the neural basis of cognitive decline that, in turn, may be the consequence of oxidative stress and inflammation. As a result, by virtue of their anti-inflammatory and antioxidant effects, dietary polyphenols are gaining serious attention as potential candidates to slow, arrest, or perhaps even reverse, age-related cognitive decline. Toward this evolving hypothesis, Curcumin, a natural phenol and member of the ginger family, has been shown to evidence such positive effects and provide a strong rationale to pursue the hypothesis that Curcumin could be an effective therapeutic intervention in age-related cognitive decline. Accordingly, in this project, we will test, for the irst time in a non-human primate model, the hypothesis that the compound, Curcumin (Curcuma longa) will alter the course of age-related cognitive decline using behavioral tasks adapted directly from, or applied to, humans. In addition, we will use established and innovative MRI scanning protocols to assess changes in brain integrity and immunohistochemistry assays to quantify the histopathological markers of damaged myelin. Outcome measures will be assessed against changes in cognitive performance during and at the end of a three-year period. It is hypothesized that monkeys receiving Curcumin will evidence less severe myelin pathology and degeneration, and hence, less age-related cognitive impairment than age-matched controls.

Public Health Relevance

Recent evidence points to oxidative stress and inflammation as a possible cause of the known alteration of forebrain white matter that occurs in normal aging that, in turn, is strongly associated with age-related cognitive decline. By virtue of their well-known anti-inflammatory and antioxidant effects, dietary polyphenols such as Curcumin have been proposed as potential ameliorative compounds that might slow or delay this cognitive change. This project will test the hypothesis that Curcumin will alter the course of age-related cognitive decline by reduction of inflammation and oxidative stress and, in turn, altered myelin, in a non-human primate model.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG043478-01A1
Application #
8578305
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Wagster, Molly V
Project Start
2013-08-15
Project End
2018-05-31
Budget Start
2013-08-15
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$547,957
Indirect Cost
$202,376
Name
Boston University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Moore, Tara L; Bowley, Bethany G E; Shultz, Penny L et al. (2018) Oral curcumin supplementation improves fine motor function in the middle-aged rhesus monkey. Somatosens Mot Res 35:1-10
Moore, Tara L; Bowley, Bethany; Shultz, Penny et al. (2017) Chronic curcumin treatment improves spatial working memory but not recognition memory in middle-aged rhesus monkeys. Geroscience 39:571-584
Valero, M D; Burton, J A; Hauser, S N et al. (2017) Noise-induced cochlear synaptopathy in rhesus monkeys (Macaca mulatta). Hear Res 353:213-223