New and Improved Way to Predict MCI on the Horizon?

Pauline Anderson

February 10, 2021

Researchers have uncovered what they believe is a unique brainwave pattern that predicts the risk for mild cognitive impairment (MCI), a frequent precursor to dementia.

The study results suggest a memory test that uses electroencephalography (EEG) can predict transition from normal cognition to amnestic MCI within about 5 years.

Dr Erin Abner

"The findings are a really encouraging signal that there could be a tool in the not too distant future that makes it pretty easy for doctors to take a look at how well their patients' brains are functioning," study investigator Erin L. Abner, PhD, associate professor of epidemiology at the University of Kentucky College of Medicine, Lexington, told Medscape Medical News.

The noninvasive and relatively inexpensive test can easily be set up in clinics, added lead author Yang Jiang, PhD, associate professor in UK Medicine's Department of Behavioral Sciences.

The study was published January 19 in the Journal of Alzheimer's Disease.

Noninvasive, Accessible, Affordable

Deficits in working memory are common early symptoms of dementia. Early pathological changes related to Alzheimer's disease (AD) can be detected using positron emission tomography (PET) or cerebrospinal fluid (CSF), but these methods can be invasive and not always available. EEG, on the other hand, is noninvasive, accessible and affordable.

EEG measures the summations of neural postsynaptic potentials at the scalp. Averaged EEG signals, known as event-related potentials (ERPs), measure synchronized synaptic neural activity associated with a cognitive event (for example memory retrieval).

The study recruited 34 community-dwelling older adults from the University of Kentucky Alzheimer's Disease Center, mean age about 76 years.

At baseline, each participant underwent an EEG recording during a working memory task. During the task, participants were instructed to remember a presented sample target image and then indicate whether each subsequent image was a match or nonmatch to the sample target by pressing a corresponding button.

Researchers recorded EEG and memory performance (percentage accuracy and reaction times in milliseconds) during the working memory task.

Data on the memory task was unavailable for one participant leaving 33 for analysis.

Based on earlier EEG research, investigators examined left frontal sites where significant brainwave differences between cognitively normal and MCI patients were reported during the working memory task.

At the baseline EEG, 14 subjects had a diagnosis of aMCI and 19 had normal cognition (NC). Participants had detailed annual cognitive and clinical assessments.

After a median follow-up of 5.2 years, seven of the 19 baseline NC patients had been diagnosed with incident aMCI.

Early Converters

Compared with participants who had no cognitive decline, converters' baseline memory-related brainwaves were significantly different. Reduced left frontal memory-target related signals at baseline (averaged signals at three left frontal sites) predicted later conversion to aMCI (hazard ratio [HR] 1.47, 95% CI, 1.03 - 2.08).

Dr Yang Jiang

"We found there's a specific left frontal brain wave pattern: if you have it, you convert early; if you don't have it, you continue to be normal," said Jiang. It's common for people with this brain pattern to find it increasingly difficult to pick out their car in a parking lot or to grab the correct luggage at the airport, she added.

As the frontal brainwaves of the seven converters were statistically identical to the 14 patients with aMCI at baseline, this indicates that the signature pattern is present before clinical symptoms or definitive changes in cognitive tests, said Abner.

"This is based on the idea that in Alzheimer's disease and other neurodegenerative diseases that older people get, the pathology is in the brain for many years before there are symptoms."

Identifying people who may already "be on the road to cognitive impairment" is important since interventions such as improving cardiovascular health, encouraging mental activities, and optimally managing medical conditions can help slow cognitive decline, Abner noted.

"The goal is either to prevent dementia entirely or push it down the road as far as we can."

Jiang noted that the memory test is short and takes only about 15-20 minutes and could be done in the doctor's office as part of a physical exam, and maybe even eventually at home. She predicted that a version of the screening test could be in clinical use within a decade.

Abner noted that the EEG test is much more accessible than PET imaging, especially in rural areas.

Another advantage of this test, said Jiang, is that it's visual rather than language-based — so it could be used with patients who don't speak English.

An Emerging Marker

Commenting for Medscape Medical News, Rebecca Edelmayer, PhD, director of scientific engagement, Alzheimer's Association, said the study was "intriguing" although small.

Papers such as the current one "are a nice building block" in terms of developing noninvasive, cost-effective and reliable strategies to predict cognitive decline, said Edelmayer.

EEG is "definitely an emerging marker", she said. She noted that a group of electrophysiology experts associated with the Alzheimer's Association is incorporating this technology into clinical trials "to see how predictive of a biomarker it could be for Alzheimer's disease and other dementias."

However, she emphasized that "it's still very early" and "a lot of work" still needs to be done "to better understand across larger populations how reliable of a marker it is."

She added that EEG also needs to be validated against "more gold standard ways" of identifying brain changes such as imaging technologies, CSF, "or even some of the new blood biomarker tests."

In addition, said Edelmayer, longitudinal studies that look at more than a single time point are "critical" for understanding "when someone might transition from being cognitively unimpaired to cognitively impaired."

The study was supported by the National Institutes of Health as well as the Oak Ridge National Laboratory and UT-Battelle LLC for the US Department of Energy. Abner, Jiang, and Edelmayer have disclosed no relevant financial relationships. One author, Gregory A. Jicha, MD, PhD, reports receiving grants from AbbVie, Biohaven, Eisai, Novartis, and Suven.

J Alzheimers Dis. Published online January 19, 2021. Full text

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