Around the world, nearly 7% of older people live with Alzheimer’s disease and related dementia. This prevalence doubles every five years and, in people over 80, reaches 30%-40%. By 2025, the disease rate is projected to triple, according to Amara Ezeamama, an epidemiologist and associate professor in the Michigan State University Department of Psychiatry, a joint department of the colleges of Osteopathic Medicine and Human Medicine.

To help address this growing concern, MSU researchers have been awarded a $4 million grant from the National Institutes of Health. They will study the potential relationship between vitamin D deficiency, gut microbial imbalance and inflammation as contributors to Alzheimer’s disease and related dementia, or ADRD.

The study also seeks to determine whether patients diagnosed with HIV and vitamin D deficiency are at even higher risk of age-related cognitive decline.

In humans, vitamin D supports immune function and regulates thousands of genes via the vitamin D receptor, which can be found on many tissues, organ systems and cells. Of interest are receptors found in brain areas that directly affect cognition.

Cognitive decline is a natural part of aging, but vitamin D deficiency accelerates neuron cell death and progression of ADRD by producing inflammation and oxidative potential. Gut microbial imbalance, which also worsens with age, can accelerate ADRD through the gut-brain axis, affecting intricate immune and endocrine functions that cause additional inflammation in the brain. Patients with HIV already experience lowered immunity and gut issues, so declines in cognition and gut health associated with aging and vitamin D deficiency could create a compounding effect.

With this study, the researchers hope to identify ways to stabilize the gut and address underlying causes of vitamin D deficiency, the severity of inflammation, and an individual’s HIV status.

Led by Ezeamama, the study will be implemented in Uganda, where she has worked since 2018. The multi-department research team from MSU includes Alla Sikorskii, professor, College of Osteopathic Medicine; Ilce Medina Meza, associate professor, Biosystems and Agricultural Engineering and College of Agriculture and Natural Resources; Shannon Manning, MSU Research Foundation Professor, College of Natural Science; and Nicholas Kanaan, Maibach Smiley Professor of Alzheimer’s Research and professor of translational neuroscience, College of Human Medicine.

Additional collaborators represent the Uganda Society for Health Scientists and the Michigan Alzheimer’s Disease Research Center, which is a regional consortium between Michigan State University, the University of Michigan and Wayne State University.

By E. LaClear