2024 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Functional Connectivity-Guided rTMS for Personalized Treatment of Apathy

Can noninvasive brain stimulation be individually targeted to treat apathy associated with Alzheimer’s disease? 

Shankar Tumati, Ph.D.
Sunnybrook Research Institute
Toronto, Canada

Background

Alzheimer’s and other dementias are progressive disorders, and individuals often develop neuropsychiatric symptoms such as apathy, as well as memory loss. Apathy can reduce social interaction and lower motivation for disease treatment. In addition, apathy has been linked to accelerated rates of cognitive decline in individuals with dementia. Studies of apathy and dementia, however, are relatively limited, and effective treatments for apathy remain an unaddressed need.

Repeated transcranial magnetic stimulation (rTMS) is a noninvasive technique that shows promise for treating apathy in Alzheimer’s and mild cognitive impairment (MCI, a subtle form of memory loss that may precede Alzheimer’s). rTMS uses magnetic fields to stimulate nerve cells in the brain. Stimulation of a brain region using rTMS is thought to impact brain cell activity in other, connected brain regions. 

The way the nerve cells in certain brain regions communicate with each other is known as functional connectivity. Apathy is associated with changes in functional connectivity between a brain region called the dorsolateral prefrontal cortex (DLPFC) and other brain networks. Dr. Shankar Tumati and colleagues believe that using functional connectivity to guide rTMS to modulate apathy-related brain networks may maximize the treatment’s effectiveness.

Research Plan

Dr. Tumati and colleagues will study functional magnetic resonance imaging (fMRI) brain scans from the Alzheimer’s Disease Neuroimaging Initiative and the COMPASS-ND dataset of the Canadian Consortium of Neurodegeneration in Aging. They will confirm an apathy-specific brain network which includes the DLPFC and other regions to which it is functionally connected. 

Next, the researchers will evaluate personalized DLPFC stimulation sites for the treatment of apathy associated with Alzheimer’s. They will determine personalized rTMS stimulation sites over the DLPFC that are connected to the apathy-associated brain network for each participant. The team will then assess measures of apathy before and after 10 sessions of rTMS treatment.

Impact

This study may support the use of personalized rTMS to treat apathy in individuals with Alzheimer’s or MCI.