Dr. Eva Feldman, University of Michigan James W. Albers Distinguished University Professor and Michigan Medicine Russel N. DeJong Professor of Neurology; and Dr. Vijay Viswanathan, M.V. Hospital’s (India) Chief Diabetologist recently laid the groundwork for a population-based study on Alzheimer’s disease (AD) and AD-related dementias (ADRD) in India. The goal is 1000 participants from 4 zones in Chennai and two zones in the nearby Tiruvallur district.

The study aims to determine the metabolic risk factors for neurologic complications and identify lipid classes/species that associate with cognitive impairment and neuropathy in India. They will conduct clinical training for hospital and community-based health care providers to improve the region's AD/ADRD and neuropathy diagnosis and management. Additionally enhanced epidemiologic training will be given to the data collection team for future intervention studies, mentoring for master of social work interns, and ongoing professional development for dedicated grants administrators. The impact will be understanding the metabolic risk factors and underlying mechanisms for AD/ADRD and neuropathy. Further, capacity-building efforts will improve community diagnosis and treatment of AD/ADRD and neuropathy in India.

Why Alzheimer’s in India?

Alzheimer’s disease (AD) affects 50 million people worldwide, with an increase of approximately 10 million patients annually. Current projections are that 82 million will be affected with AD by 2030 and 152 million by 2050. The current prevalence of AD is high in India (3 million people compared to 4 million in the US), and, more importantly, the tripling of the current AD prevalence by 2050 is expected to be driven mainly by the Indian population.

“While AD has been extensively studied in the United States and European populations, much less is known about AD in India,” says Dr. Eva Feldman, a world-renowned neurology professor at the University of Michigan Medical School and director of both the ALS Center of Excellence and the NeuroNetwork for Emerging Therapies. “Socioeconomic, linguistic, geographical, lifestyle and genetic differences between India and other populations strongly suggest that previous results from the US and Europe may not translate to India.”

Alzheimer’s and Neuropathy

Past studies show that type 2 diabetes can be a risk factor for AD, vascular dementia, and other types of dementia. The same cardiovascular problems that increase the risk of type 2 diabetes also can increase the risk of dementia, including obesity, heart disease, or family history of heart disease, impaired blood vessels, circulation problems, high cholesterol, and high blood pressure.

“We will identify patients at risk of developing cognitive deficits that exist with neuropathy,” says Dr. Vijay Viswanathan, who will serve as the person in charge of the study in India and oversee all the aspects of the research collaboration. “It will determine whether central obesity (truncal fat mass), but not general obesity, may be associated with cognitive impairment and neuropathy. We hope to identify other metabolic risk factors and, eventually, improve the quality of life among people with diabetes by preventing or delaying these complications.”

Collaboration Background

The long-range goal of this collaboration is to inform new treatments for AD, related dementias, and neuropathy.

“I first met Dr. Viswanathan in 2014 when he invited me to give a talk at a scientific conference he was organizing on diabetes and its complications,” says Dr. Feldman. “He gave me a tour of his hospital (M.V. Hospital), and we discussed our mutual interest in neuropathy and began to work together the following year.”

The current collaboration with the University of Michigan and the M.V. Hospital for Diabetes in Chennai was established in 2016.  The Chennai Complication Cohort (CCC) was established to better understand the factors underlying neuropathy in India with the idea that central obesity (but not general obesity) associates with neuropathy.

“I am immensely thankful for this collaboration,” adds Dr. Vishwanathan, who has co-authored publications with Dr. Feldman in the past. “My work has focused on diabetes complications, a major problem in India. My ongoing work with Dr. Feldman focuses on phenotyping these people with diabetes and prediabetes.”

The team’s past project recruited 652 Indians for a hospital-based cross-sectional study over three years, which required participants to complete comprehensive metabolic phenotyping and neuropathy outcome measures. That study found a significant association between neuropathy with diabetes and age.

Details of the Chennai Study

Chennai consists of 15 zones comprised of 200 wards. Two zones were selected randomly, consisting of the urban poor (Tondiarpet and Royapuram) and two zones comprised of the urban middle class (Adyar and Teynampet) from which to sample. From the peri-urban Tiruvallur district, there are two randomly selected zones (Gummidipoondi and Ponneri). Recruitment will be equal numbers of men and women and equal numbers in areas representing the urban poor, urban middle class, and peri-urban populations. The urban and peri-urban are intentionally selected zones because metabolic risk factors differ between these communities. Urban communities have a higher prevalence of metabolic risk factors, such as hypertension, whereas peri-urban communities are less likely to be diagnosed and treated appropriately. Moreover, peri-urban communities have lower literacy rates, socioeconomic status, nutritional status, and healthcare access, whereas urban communities have a more sedentary lifestyle.

“In all of these individuals, we will assess their blood sugar levels, lipid levels along with lipidomics, blood pressure, weight, height, measures of central obesity, waist-hip measures, and body mass composition,” adds Dr. Feldman. “We will also assess cognition with a well-established tool, cog state, and neuropathy with our neuropathy screening instruments.”

Dr. Eva Feldman

Dr. Feldman received her MD and PhD degrees from the University of Michigan, completed a neurology residency at the Johns Hopkins Hospital, and returned to University of Michigan for a neuromuscular fellowship. In addition to her active clinical practice in neurology and positions as the James W. Albers Distinguished Professor of Neurology at U-M and Russell N. DeJong Professor of Neurology at Michigan Medicine, Dr. Feldman is currently director of the UM ALS Center of Excellence. She also runs her own 30-scientist laboratory, the NeuroNetwork for Emerging Therapies, and is the principal investigator of two first-ever FDA approved human clinical trials of intraspinal stem cell implantation therapy for ALS. In 2020, she assumed the Chair of the Neurology and Psychiatry Section for the National Academy of Medicine up until this year. Dr. Feldman has published more than 460 original peer-reviewed articles, 70 book chapters, and four books and has had continuous funding from the National Institutes of Health for more than 30 years.

Dr. Vijay Viswanathan

Dr. Vijay Viswanathan has more than 30 years of experience and has several publications that reflect the significant contribution he has made to diabetes research. He is focused on managing the complications of diabetes, especially those that affect the kidneys and feet. His research interest includes the determination of how the metabolic syndrome (MetS) is associated with neuropathy. Dr. Viswanathan is also interested in how obesity relates to neuropathy in Indian populations, as compared to others around the world. Within the M.V. Hospital for Diabetes, he has established a diabetic foot clinic that specializes in preventing the need for amputation.

Dr. Viswanathan earned his MBBS at the University of Madras, his MD in internal medicine from the University of Mangalore, a PhD from MGR Medical University in Madras, and fellowships from the Royal College of Physicians in London, the Royal College of Physicians and Surgeons of Glasgow, and the India College of Physicians.