Matt Euler receives National Institute of Health grant

Congratulations to Matt Euler for receipt of his new NIH RO3 grant.  This grant seeks to develop methods aimed at early identification of individuals at-risk for Alzheimer’s Disease (please see full project details below).  His co-investigators on this grant are Jonathan Butner and Kevin Duff (Neurology). 

Congratulations to Matt and his team!

Task-related EEG Activation as a Biomarker for early Alzheimer’s Disease

The problem: As clinical trials for Alzheimer’s Disease (AD) are moving earlier in the disease spectrum, accurate biomarkers will be needed for in-vivo disease staging and outcome measures. Unfortunately, the existing suite of biomarkers are expensive, technologically sophisticated and resource heavy, and invasive (e.g., advanced neuroimaging or lumbar punctures for amyloid and tau). Although traditional neuropsychological indices are more specific to cognitive status, they may have limits in the early identification of impending AD. Although fMRI has sought to combine the positive attributes of both traditional biomarkers and neuropsychology, concerns persist around its cost and accessibility. Overall, there remains a need for inexpensive, non-invasive, accessible, and easily-implemented AD biomarkers that are sensitive to early disease stages.

A proposed solution: The overall aim of this submission is to examine the translational potential of specific task-related EEG signals (mid-frontal theta power; MFT) as a possible biomarker of Alzheimer’s disease. MFT is an oscillatory neural signal related to controlling complex behavior. MFT, which is centrally-generated in the mid-cingulate cortex, is most strongly elicited when task demands call for behavioral adjustments (e.g., following errors, surprises, or punishments). For that reason, MFT is thought to be elicited under conditions of high cognitive challenge. Therefore, MFT is a compelling potential correlate of mental exertion, which could be over-activated in early AD stages. Practically, since MFT can be measured from as few as three electrodes placed on the scalp, it has considerable promise as an inexpensive, accessible, non-invasive and easily-implemented biomarker for preclinical and early-stage AD.

The specific aims of the proposed research plan are to:

1. Examine group differences in task-related MFT power, across cognitively intact older adults, those with amnestic Mild Cognitive Impairment (MCI), and early AD.

Greater task-related MFT will be associated with more advanced disease states (MFT: early-stage AD > amnestic MCI > healthy seniors).

2. Examine neuropsychological and functional correlates of MFT power across the AD spectrum.

If MFT is sensitive to early AD, it should correlate most strongly with cognitive and functional skills that are affected in earlier disease stages. As such, we expect MFT to correlate most strongly with memory and complex attention, and less so with more general cognitive skills. Likewise, we expect MFT power to relate mostly to complex rather than more basic instrumental activities of daily living.

By achieving these aims, we will inform the translational potential of MFT as a novel biomarker for in-vivo AD staging. This could significantly improve the cost-effectiveness and efficacy of clinical trials, thereby helping to meet the goals of the National Plan to Address Alzheimer’s Disease. Ultimately, the results of this research could culminate in the development of an inexpensive, accessible, and easily-implemented biomarker that will facilitate detection of preclinical and early-stage AD.