Project Details
Description
PROJECT SUMMARY/ABSTRACT
Alzheimer’s Disease (AD) is a neurodegenerative disease that affects over 5 million Americans.
Despite its clinical and public health impact, and the resources invested in treatment development, existing
therapies remain only symptomatic (not disease modifying) and have modest efficacy. Disease models have
traditionally emphasized molecular (maladaptive changes in -amyloid and tau proteins) and cellular
(neurodegeneration) processes. Therefore, treatment development has focused on interventions that engage
these molecular and cellular mechanisms, i.e. pharmacology and immunotherapy. Recent developments in
pathophysiology, biomarker discovery and treatment development have emphasized a physiological approach
to AD, with a focus on gamma oscillations as treatment targets. Critically, evidence in rodents suggests that
engaging these aberrant physiological signatures with 40 Hz light and sound stimulation not only restores
gamma oscillations and improves memory, but it also activates microglia leading to a reduction in amyloid and
tau. Hence, this treatment strategy has the potential to be a disease-modifying therapy, which we are lacking in
AD.
While engaging gamma oscillations with 40Hz light and sound is a viable strategy, using electrical
stimulation to modulate an electrical biological phenomenon should have greater impact. Noninvasive device
neuromodulation technologies have been used as neuroscience tools to probe and study brain physiology in
humans in vivo for decades, and as diagnostic procedures (e.g. TMS for clinical neurophysiology and
presurgical mapping) and therapeutic interventions for neuropsychiatric conditions. tACS is very safe, well
tolerared, cheap to manufacture and portable, making it a potentially home-based therapy. The capacity of
tACS to engage oscillations in the human brain leading to changes in cognition, behavior and perception is
established. That said, given the weak intensity of the electrical currents (e.g. 2mA), tACS may not always
effectively engage or reduce ongoing oscillation in the brain. A more sophisticated and individualized “smart
tACS” approach that uses closed-loop technology by reading the ongoing EEG activity of the patient and
applying the stimulation in phase with the ongoing patient-specific brain activity is now technically possible, and
showing to have greater impact on brain oscillations. We hypothesize that closed-loop tACS at 40 Hz in
patients with AD should be a more effective strategy to engage these abnormal rhythms, and if the results in
rodents translate to humans as early evidence suggests, it may become a much needed disease-modifying
intervention (or at least a safe and cost-effective symptomatic treatment).
Status | Finished |
---|---|
Effective start/end date | 8/15/22 → 4/30/24 |
Funding
- National Institute on Aging: $206,449.00
- National Institute on Aging: $262,718.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.