Targeting Neurophysiology to Treat Agitation in Dementia

Sanjeev Kumar, MD
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)

Co-Principal Investigators

Tarek Rajji, MD, FRCPC
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)
Daniel Blumberger, MD, FRCPC
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)
Zafiris J. Daskalakis, MD, PhD, FRCPC
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)
Benoit H. Mulsant, MD, FRCPC
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)
Bruce G. Pollock, MD, PhD
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)
Reza Zomorrodi, PhD
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)
Corinne E. Fischer, MD, FRCPC
St. Michael's Hospital (Toronto, Ontario, Canada)

Collaborators

Nathan Herrmann, MD, FRCPC
Sunnybrook Research Institute (Toronto, Ontario, Canada)
Year Awarded:
2018
Grant Duration:
July 1, 2018 to June 30, 2021
Disease:
Alzheimer's Disease
Award Amount:
$300,000
Grant Reference ID:
A2018667S
Award Type:
Standard
Award Region:
International
Sanjeev Kumar, MD

Identifying and Targeting Cortical Inhibition Deficits in Agitation/ Aggression due to Alzheimer’s Dementia

Summary

Agitation and aggression affect majority of patients with dementia related to Alzheimer’s disease (AD). Medications used to treat these symptoms are associated with many side effects. In this study we will use magnetic brain stimulation to understand the mechanisms of agitation in AD dementia, and use a non-invasive brain stimulation technique called transcranial direct current stimulation (tDCS) to treat agitation.  If successful, this study will lead to development of a safe and effective treatment for agitation in AD.

Details

The goal of this project is to understand the mechanisms underlying agitation in Alzheimer’s disease (AD) and to explore a new noninvasive brain stimulation intervention (transcranial direct current stimulation, or tDCS) to treat agitation in patients with AD. We will first compare the state of excitation/inhibition in the frontal parts of the brain (dorsolateral prefrontal cortex) in patients with AD and agitation, patients with AD without agitation, and healthy older adults. This will be done using transcranial magnetic stimulation (TMS) combined with electroencephalography. We anticipate that patients with AD and agitation will have abnormalities of excitation and inhibition in their brains. We will then use a noninvasive brain stimulation technique (tDCS) to correct these abnormalities and treat agitation.

The most innovative aspect of the proposal is that this study will be assessing, for the first time, the state of cortical excitability and inhibition in the brain of patients with AD and agitation using TMS combined with electroencephalography. Once this study is successfully completed, it will help identify biological markers of agitation in AD which will stimulate further research in this field. Further, this proposal is, for the first time, investigating the role of tDCS to correct abnormalities of cortical excitability and inhibition and to treat agitation.  If successful, this will lead to larger and more definitive studies of tDCS to treat agitation in AD.  Thus it will be an important step towards developing a safe and effective treatment for agitation in AD to improve the quality of life of patients with AD and their caregivers.

About the Researcher

Dr. Sanjeev Kumar is a geriatric psychiatrist and is the Medical Head of Geriatric Research at the Centre for Addiction and Mental Health (CAMH), Toronto, Canada. He is an assistant professor of psychiatry at the University of Toronto. Dr. Kumar completed his residency in psychiatry at Virginia Tech Carilion School of Medicine followed by a clinical fellowship in geriatric psychiatry at the University of Pittsburgh. He then completed a clinical research fellowship at CAMH and the University of Toronto. Dr. Kumar is a fellow of the Royal College of Physicians and Surgeons of Canada and of the American Psychiatric Association. Dr. Kumar’s research focuses on developing novel biomarkers and treatment interventions for patients with Alzheimer’s disease (AD). He is developing novel neurophysiological markers for the cognitive and behavioral symptoms of AD using transcranial magnetic stimulation (TMS), electroencephalography and brain imaging techniques. He is also exploring the role of novel treatment interventions such as TMS and transcranial direct current stimulation (tDCS) to treat cognitive and neuropsychiatric symptoms of AD. He has been awarded several local, national, and international honors and awards including NARSAD young investigator award and travel awards from Society of Biological Psychiatry and American Psychiatric Association. He has received several peer-reviewed research grants and has published his work in reputed medical journals including JAMA Psychiatry.

Personal Story

Neuroscience has been my passion since early medical school days, and there were a number of personal experiences which shaped my interest in geriatric psychiatry and late life cognitive disorders. I have personally experienced devastating consequences of dementia in my family. I saw my grandfather suffer from dementia during later years of his life.  Further, my background in practice of general medicine, privilege of working with older veterans and inspiration from my mentors during psychiatry residency training strengthened my resolve to care for older adults.  I was fortunate to work with leading researchers in the field of Alzheimer’s disease (AD) during my fellowship in geriatric psychiatry at the University of Pittsburgh and subsequent research training at the University of Toronto. These experiences crystallized my interest in neurophysiology and brain stimulation. I was awarded the NARSAD Young Investigator Award to study the role of transcranial magnetic stimulation for enhancing cognition and neuroplasticity in AD. I was also successful in getting research grants to investigate and treat neuropsychiatric symptoms of dementia. These studies allowed me to further refine my research skills and delve deeper into the field of neuroscience of neurocognitive disorders. I was also fortunate to receive other honors and awards, including a travel fellowship from the National Institute of Health to attend the Summer Research Institute which allowed me to receive mentorship towards developing a successful research career. I deeply appreciate support from the BrightFocus Foundation and its donors for this project, which will help answer vital questions regarding neurophysiology of agitation in AD and help develop a novel treatment intervention which will potentially improve the quality of life of the elderly. Further, I am also extremely grateful to BrightFocus Foundation and its donors for its support because it will help me to further establish myself as an independent scientist and make meaningful contributions towards finding a cure for dementia.

Publications

Kumar, S., Batist, J., Ghazala, Z., Zomorrodi, R.M., Brooks, H., Goodman, M., Blumberger, D.M., Daskalakis, Z.J., Mulsant, B.H. and Rajji, T.K., 2020. Effects of Bilateral Transcranial Direct Current Stimulation on Working Memory and Global Cognition in Older Patients with Remitted Major Depression: A Pilot Randomized Clinical Trial. International Journal of Geriatric Psychiatry. PMID: 32525222 PubMed Icon Google Scholar Icon

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