Alzheimer’s Disease Research: Links to Abnormal Vocal Behavior, Epileptiform Activity

According to the Alzheimer’s Association, more than 5 million Americans are currently living with Alzheimer’s Disease—a figure that could more than triple by 2050. Because of the increasing population of people ages 65 and older in the United States, the number of new cases of Alzheimer's and other dementias is projected to grow tremendously and quickly.

Medical researchers, like UCSF Imaging’s Srikantan Nagarajan, PhD, are working to put an end to Alzheimer’s. But first, scientific communities must have a full understanding of the complexities associated with this neurodegenerative disease. Dr. Nagarajan is the director of the Biomagnetic Imaging Laboratory and co-director of the Brain Research Interest Group, where he focuses on the development and refinement of multimodal structural and functional brain imaging and brain computer interfaces for diagnosis and assessment in various patient populations.

He recently co-published two papers on the topic of Alzheimer’s disease to help the scientific and medical communities better understand, diagnose and treat the disease.

The first, Abnormal vocal behavior predicts executive and memory deficits in Alzheimer's disease, was published April 2017 in Neurobiology of Aging. “Speakers respond automatically and rapidly to compensate for brief perturbations of pitch in their auditory feedback,” begins the study’s abstract. “The specific adjustments in vocal output require integration of brain regions involved in speech-motor-control in order to detect the sensory-feedback error and implement the motor correction. Cortical regions involved in the pitch reflex phenomenon are highly vulnerable targets of network disruption in Alzheimer's disease.”

In examining the pitch reflex, degree of behavioral compensation and extent of the adaptive response in patients with Alzheimer’s and an age-matched control group, researchers determined that pitch reflex may serve as as a sensitive behavioral index of impaired prefrontal modulation of sensorimotor integration and of compromised plasticity mechanisms of memory in AD.

The second research article, Incidence and impact of subclinical epileptiform activity in Alzheimer's disease, featured in Annals of Neurology last November, analyzed subclinical epileptiform activity in Alzheimer’s disease with deleterious effects on patient cognition.

The motivation behind the study was a desire to better understand the incidence and consequences of subclinical and epileptiform activity. “Seizures are more frequent in patients with Alzheimer's disease and can hasten cognitive decline. However, the incidence of subclinical epileptiform activity in Alzheimer’s disease and its consequences are unknown.”

Over three years, Dr. Nagarajan’s team studied patients who met criteria for Alzheimer’s but had no history of seizures, and a cognitively normal control group. Through video-electroencephalography (EEG), magnetoencephalography exam with simultaneous EEG, and clinical and cognitive evaluations, the authors determined that extended monitoring detects subclinical epileptiform activity in a substantial proportion of patients with Alzheimer’s disease. They further determines that patients with this indicator are at risk for accelerated cognitive decline and might benefit from antiepileptic therapies. 

Additional research will continue to aid the scientific community in diagnosing and evaluating Alzheimer’s disease and dementia in patients. For more information on Alzheimer’s disease and neuroradiology research at UCSF, please click here.

To learn about Alzheimer's disease assessment and treatment at UCSF, please click here.

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