Sex differences in human brain and cognition are well documented, but it remains unclear whether men and women follow different trajectories of age-related cognitive decline. Identifying predictors of differential cognitive aging between men and women could lead to the development of sex-specific interventions to promote successful cognitive aging in both sexes. Because human cognition is strongly influenced by socio- cultural and environmental factors, studies in nonhuman primate models, for which such confounds can be minimized, can provide considerable insight into the biological bases of sex differences in cognitive aging. This application uses a translational primate model uniquely suited for longitudinal assessments of neurocognitive aging, the common marmoset (Callithrix jacchus). With a lifespan of about 8 years, marmosets can be studied throughout their entire adult lifespan. In addition, they are able to perform complex cognitive tasks and experience age-related brain changes that resemble those of humans. This project will study intact male and female marmosets longitudinally from middle-age to old age. Sex differences and age-related changes will be assessed in monkeys tested annually for four years on a battery of cognitive, emotional and motor tests. Sex differences and age-related changes in brain structure and functional connectivity will also be examined annually using Magnetic Resonance Imaging (MRI) and resting- state functional MRI (fMRI), respectively. Sex differences in dendritic spine density and morphology, hippocampal estradiol levels and -amyloid deposition will be analyzed in the brains of aged monkeys characterized as cognitively impaired or unimpaired. This study should provide invaluable information on the biological correlates of sex and age differences in cognition in a translational primate model followed from middle-age to old age. The data will serve as a fundamental foundation for understanding the role of sex hormones in neurocognitive aging. Ultimately, the project should promote sex-specific approaches to the management of cognitive impairment in older people.

Public Health Relevance

Sex differences in normal cognitive aging and dementia are poorly understood. The proposed studies use a short-lived primate to understand the biological bases of sex differences in cognitive and brain aging. Animals will undergo annual cognitive, behavioral, physiological and noninvasive neuroimaging assessments as they age from middle-age to old age. Analyses of dendritic spine densities, -amyloid deposition and brain-estradiol will also be conducted in aged animals characterized as cognitively impaired or unimpaired. The findings should identify the factors that contribute to differential aging trajectories in men and women and promote the development of sex-specific interventions for successful cognitive aging in each sex.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG046266-03
Application #
9068733
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Wagster, Molly V
Project Start
2014-09-01
Project End
2019-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
153926712
City
Amherst
State
MA
Country
United States
Zip Code
Silver, Michelle; Moore, Constance M; Villamarin, Vanessa et al. (2018) White matter integrity in medication-free women with peripartum depression: a tract-based spatial statistics study. Neuropsychopharmacology 43:1573-1580
Lacreuse, Agn├Ęs; Moore, Constance M; LaClair, Matthew et al. (2018) Glutamine/glutamate (Glx) concentration in prefrontal cortex predicts reversal learning performance in the marmoset. Behav Brain Res 346:11-15
Henninger, Nils; Bouley, James; Sikoglu, Elif M et al. (2016) Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1. Brain 139:1094-105