​Research​

Our long-term goal is to determine how sex, aging, and sex hormones influence vascular and metabolic contributions to dementia and to develop sex-specific therapeutic strategies to improve cognitive function and reduce the burden of dementia. 

Below is a list of current projects.
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Metabolic and hormonal mechanisms of VCID.  Vascular contributions to cognitive impairment and dementia (VCID), is the second leading cause of dementia.  Risk of VCID is significantly increased in metabolically impaired (prediabetic/diabetic) post-menopausal women. We have recently found that menopause impairs metabolic function and exacerbates VCID pathology and cognitive deficits. Further, cognitive impairment induced by menopause can be reversed by increasing estrogen specifically in the brain. Ongoing work is exploring the mechanisms underlying these effects in both VCID and also the context of multiple etiology dementia (vascular + Alzheimer's disease), since up to 80% of those with AD also have underlying VCID that contributes to dementia progression.  This mechanistic insight will facilitate future interventions to decrease the burden of dementia, particularly in the high-risk population of post-menopausal women. This project is funded by an R01 renewal from NINDS.

Influence of female life course factors on Alzheimer's disease. Approximately 2/3 of those with Alzheimer’s disease (AD) are women, the majority of which are post-menopausal and have had prior pregnancy(s).  Pregnancy can induce long-lasting changes in the brain. Further, menopause accelerates mid-life risk factors for AD, by increasing risk for both vascular and metabolic diseases. In collaboration with Dr. Damian Zuloaga's lab, we are assessing the combination of these female life course factors (pregnancy + menopause) on AD. This project is funded by an BrightFocus Foundation Grant.

Influence of male endocrine aging on Alzheimer's disease. Approximately 40% of men over 45 yrs old suffer from low androgen levels.  Endocrine aging in men is characterized age-related declines in androgens (such as testosterone).  Testosterone loss accelerates for AD and cognitive decline. We are currently developing new models of studying male endocrine aging and its impact on AD. This project is funded by an R21 from NIA.

Sex differences in effects of stress on Alzheimer's disease. Psychological stress increases risk for Alzheimer's disease and related dementias.  In a multi-PI collaboration (with Dr. Damian Zuloaga) we are assessing sex differences in the effects of chronic stress in a mouse model of Alzheimer's disease and determining underlying mechanisms.  This project is funded by the AARG-D grant Alzheimer's Association.  We are also assessing effects of adolescent stress on vascular contributions to dementia. This work is funded by PhD student Emily Groom's American Heart Association Predoctoral Fellowship. 

Investigating the functional impact of Alzheimer's disease fisk genes in neuro-vascular interactions. Vascular pathology is found in up to 80% of all Alzheimer's disease cases. In a multi-PI collaboration (with Dr. Sally Temple, Dr. Celeste Karch, Dr. Oscar Harari, Dr. Martin Kampmann, and Dr. Kevin Pumiglia), we are identifying key vascular risk genes for Alzheimer's disease and characterizing their impact on both vascular and cognitive function in several mouse models of Alzheimer's disease. This work is funded by U01 grant from National Institute on Aging as part of the Alzheimer's Disease Sequencing Project (ADSP) Functional Genomics Consortium (FunGen).