OVERVIEW:

Evaluation Of Event-related Potentials As A Method To Diagnose Alzheimer’s Disease

Alzheimer’s disease (AD) currently affects as many as 4.5 individuals in the United States. This represents 1 in 10 adults aged 65 and up to half of all adults by age 85. Although several new drug treatment options have been developed, their effectiveness may be limited by delayed recognition of AD in many patients or confusion with other non-Alzheimer’s dementias. It has long been suspected that earlier treatment may result in more positive treatment outcomes. As a result, considerable attention has been given to efficient and early detection of AD. Much of this work has focused on biomarkers that may be present in individuals who are cognitively intact, but eventually will go on to develop AD.

Our research focuses on using Event-related Potentials (ERPs) as a potential marker/predictor of patients will later be diagnosed with AD. Our program of research is focused on several overlapping areas (1) early detection of AD (2) preclinical detection of AD and prediction of rates of cognitive decline, differential diagnosis of AD from other geriatric syndromes.

RESEARCH QUESTIONS

The purpose of this study is to determine if a new non-invasive ERP screening method can reliably identify subjects who might have Alzheimer’s disease and who should have a more complete diagnostic workup.

STUDY DESIGN AND METHODS

The ERP is a portion of the electroencephalogram (EEG) that reflects a change in electrical brain activity due to a stimulus event or cognitive processing. Such changes occur in amplitude (height) and/or latency (time from stimulus onset to a point of interest). ERPs are characterized by excellent temporal resolution (i.e., millisecond by millisecond) that allows for the tracking of changes in brain activity elicited at the onset of an auditory or visual stimulus.

The ERP methodology is advantageous in that it is safe and non-invasive and provides a very sensitive method for detecting changes in brain activity. The current study will measure electrical activity in the brain (using a portable ERP system, COGNISION™, developed by Neuronetrix, Inc.) while patients and controls are subjected to an auditory stimulus and which may require the completion tasks requiring memory, language processing and/or executive functioning. The recorded brain waves linked to these cognitive tasks will be examined using an advanced statistical methodology to determine how effectively this system can differentiate AD from normal aging.

Up to 50 individuals with mild to moderate AD and 50 age-matched controls will be recruited for the purposes of this study.

The subject ERP tests from each group (AD and controls) will be used to train the COGNISION™ Classifier to differentiate subjects from each group. A standard “leave-one-out cross-validation” (Suykens, 2003) method will be used to determine the statistical power of the COGNISION™ Classifier.

PROCEDURES AND PROTOCOLS

AD participants will be recruited and screened from existing patients at local clinics. A preliminary medical record review will identify patients with an existing diagnosis of dementia (or suspected dementia). Those individuals will then be invited to participate in the study by research staff.

All individuals invited to participate in the study must have had a full diagnostic work-up for dementia according to standard criteria. This should include neuropsychological evaluation and physician evaluation.

Subjects will be interviewed and evaluated by a neurologist and a medical history will be obtained including lab work to include chemistry and CBC studies (i.e., thyroid disease, B12, folate, sed rate, comprehensive chemistry, CBC and differential) as well as any existing images of the brain.

After clarification of diagnostic status, patients with AD will participate in the ERP experiments. Patients with unclear diagnostic status or other dementing disorders (e.g., multi-infarct dementia) will not participate in the ERP phase and will be excluded from the rest of the study after an explanation of their new clinical diagnosis and being referred back to their referring physicians.

The ERP tests will employ relatively brief cognitive tasks requiring verbal memory, language processing, and executive functioning that will be completed while the COGNISION™ System records electrical activity via the scalp. During the tests the participants may be asked to perform certain tasks such as counting or pressing a button in response to a certain sound.