Brain Health I NeuroNetwork
doctor pointing to a brain scan

Working to combat cognitive decline and dementia, and preserve brain health.

The Problem

The aging population continues to grow in the United States and worldwide. As we age, our risk of developing cognitive decline and dementia (including Alzheimer’s disease) increases dramatically. Research suggests that cognitive decline is linked to obesity and metabolic dysfunction, including type 2 diabetes. Considering the global epidemic of obesity and metabolic dysfunction, along with the growing aging population, improving brain health – particularly throughout the human lifetime – is increasingly important. 

  • In the United States, approximately 10% of adults 65 years of age or older are living with dementia, and another 22% have mild cognitive impairment. 

  • Cases of dementia worldwide are currently estimated to affect 57 million people, and these numbers are expected to increase. 

brain tractography showing different nerve tracts in a human brain denoted in different colors
Tractography imaging of a human brain

Alzheimer’s disease is the most common form of dementia. 

  • There is no cure for dementia, although some drugs or treatments slow cognitive decline. 

  • While several theories exist, precise dementia causes and mechanisms remain unknown. 

  • Clinical research suggests that specific diets, such as the Mediterranean, DASH, MIND, and ketogenic diets, lower the risk of Alzheimer’s disease in later life. 

  • Studies show that exercise may help prevent or treat cognitive decline and dementia and induce neurogenesis (the birth of new nerve cells) in the brain.
Our brain health program launches
The overarching goal is to understand factors contributing to brain health and develop therapies for dementia, including Alzheimer’s disease. (photo shows the NeuroNetwork for Emerging Therapies in 2009)
members of the NeuroNetwork for Emerging Therapies lab in 2009 members of the NeuroNetwork for Emerging Therapies lab in 2009
Metabolic connections
Discover that brain neurons (cells that transmit signals and form memories) can become nonresponsive to insulin (a molecule that stimulates sugar metabolism).
sugar cubes on a pink cut out of the brain's two hemispheres on a navy background sugar cubes on a pink cut out of the brain's two hemispheres on a navy background
An imaging study
Using a special imaging technique, we found that patients with diabetes and neuropathy have imbalances in the levels of brain neurotransmitters (molecules that transmit brain signals).
neurotransmitters moving between nerve synapses neurotransmitters moving between nerve synapses
Preclinical studies
Demonstrate preclinical mouse models of diabetes develop Alzheimer’s disease pathology in the brain, including changes in tau protein. (photo shows tau protein (blue) in neurons (green))
tau protein (blue) in neurons (green). tau protein (blue) in neurons (green).
Insuline resistance in the brain
Show brains from mouse models of diabetes develop insulin resistance (insensitivity to insulin and sugar metabolism), which is linked to tissue pathology in Alzheimer’s disease and the protein tau.
tau protein (blue) in neurons (green). tau protein (blue) in neurons (green).
Importance of tidying up
Find oxidized cholesterol, which is elevated in diabetes, impairs the function of brain lysosomes (cellular structures that clear debris). If debris is not eliminated, the risk of dementia increases.
Brain stress
We find obesity in mice induces a process called endoplasmic reticulum stress in brains, a cellular response to stress linked to dementia.
Stem cells
Launch our stem cell program for treating dementia and Alzheimer’s disease. (photo shows color imaging of stem cells transplanted into animal model brains)
colored imaging of stem cells transplanted into animal model brains colored imaging of stem cells transplanted into animal model brains
Stem cell successes
Successfully transplant stem cells producing the hormone insulin-like growth factor, which stimulates metabolism and growth, into the brains of Alzheimer’s disease mice. (photo shows stem cells (dark spots) transplanted into an animal model brain)
stem cells shown as dark spots that have been transplanted into an animal model brain stem cells shown as dark spots that have been transplanted into an animal model brain
More discovery related to stem cells
We continue to develop and advance our stem cell program, discovering stem cells expressing insulin-like growth factor I transplanted into brains of Alzheimer’s disease mice enhances memory. (photo is of brain nerve cells derived from stem cells (red))
brain nerve cells derived from stem cells shown in red brain nerve cells derived from stem cells shown in red
Obesity and amyloid precursor protein
Demonstrate obesity also impacts the pathology of another Alzheimer’s disease protein called amyloid precursor protein, and that insulin-like growth factor I prevents this pathology. (photo shows amyloid-beta plaque (red) surrounded by microglia (green))
amyloid beta plaque, shown in red, surrounded by microglia, shown in green amyloid beta plaque, shown in red, surrounded by microglia, shown in green
Metabolic risk factors
Report cognitive performance is impaired in severely obese relative to lean controls and waist circumference (abdominal obesity) is a key metabolic risk factor for cognitive decline.
a doctor measuring the waist of a patient a doctor measuring the waist of a patient
Research support & communication
The Andrea and Lawrence A. Wolfe Brain Health Initiative is launched to support important research related to brain health and healthy brain aging.
Mini Symposium Series
Our 2021 Mini Symposium Series focuses on brain health.
What we eat matters
Demonstrate a diet rich in saturated fats (such as red meat) causes increased body weight and poor nerve function. Conversely, a diet rich in unsaturated fats (such as olive oil and avocado) does not affect nerve function. We connect these observations to mitochondria (the machinery that generates energy in nerves).
Stem cell survival
Use magnetic resonance imaging (MRI) to track the movement of transplanted stem cells in the brains of animal models and show stem cells survive in brains for as long as ten weeks.
CLARiFY study
With new funding from the NIH, launch CLARiFY Diabetes Complications study in partnership with colleagues in Australia. This clinical study followed persons with type 1 diabetes since the 1990s and enhances our understanding of how diabetes control over 30 years impacts brain structure and function. (photo shows tractography of a human brain from the CLARiFY study)
brain tractography showing different nerve tracts in a human brain denoted in different colors brain tractography showing different nerve tracts in a human brain denoted in different colors
Lifestyle interventions
Launch a new NIH-funded project examining effects of diet and exercise on nerve function and brain health in mouse models of obesity, prediabetes, and diabetes.
Metabolic support
Harness power of stem cells to examine how different nerve and supporting glial cells impact brain health and metabolism. (photo shows microglia)
microglia microglia
Novel technology
Identify alterations in brain microglia due to obesity using advanced single-cell RNA sequencing, a novel sequencing technology that examines changes in gene expression at level of individual cells.
Extracellular vesicles
Propose extracellular vesicles may be the missing link between metabolic dysregulation and Alzheimer’s disease due to their ability to propagate Alzheimer’s disease pathology and insulin resistance.
Zambia
Launch the Zambia Cohort for Healthy Aging & Dementia, a population study in Zambia to assess the prevalence of Alzheimer’s and the burden on caregivers.
Zambia collaborators from the Michigan Medicine Zambia Cohort for Healthy Aging and Dementia Zambia collaborators from the Michigan Medicine Zambia Cohort for Healthy Aging and Dementia
Brain Health Initiatives
Heart & Brain

Investigating drivers of decline in both heart and brain health.

Lifestyle Interventions

Growing evidence indicates that changes in diet and exercise can prevent diabetic neuropathy and improve brain health.

CLARiFY Study

Investigating lifelong factors that influence brain health in individuals with Type 1 diabetes, followed for 30 years from childhood diagnosis.

Stem Cells

Special types of cells that can turn into different types of cells in the body, including nerve cells, and have incredible potential in therapies.

Z-CHAD study

Studying the burden of dementia and its risk factors in Zambia to enable the creation of targeted interventions to support patients and their caregivers.

Mini-Brains

Also known as brain organoids, mini-brains are tiny, three-dimensional structures grown from stem cells in cell culture that mimic some features of a real brain and offer exciting research possibilities.

Inflammation & Immunology

While important for recovery, it can be harmful if it lasts too long or happens in healthy tissue, such as peripheral nerves or the brain.

Oligodendrocytes

Metabolic syndrome causes a breakdown in oligodendrocyte function, leading to nerve cell loss and, subsequently, Alzheimer’s disease and related dementias.

Extracellular vesicles

Small, membrane-bound particles released by cells that play a crucial role in cell-to-cell communication.

Mental Health

How diabetes affects mental health.

Pain

Studying pain in neurological conditions to develop effective diagnostic and treatment options.