Primitive Reflexes May Predict Dementia

Primitive or regressive reflexes — known as frontal release signs — later in life were associated with increased dementia risk, a longitudinal study of cognitively normal older adults showed.

In adults with intact cognition, the presence of two or more frontal release signs was associated with a significantly higher risk of progressing to dementia over 7 years (HR 1.78, 95% CI 1.02-3.09), reported Lauren Bojarski, DO, MS, of West Virginia University in Morgantown, and colleagues in JAMA Network Open.

Frontal release signs are present in newborn children and gradually disappear as the brain matures in early life. They include the Myerson sign (an inability to resist blinking when repeatedly tapped between the eyebrows), and grasp, snout, rooting, and palmomental reflexes. Reappearing signs are associated with brain injury or neurodegeneration and can be seen in late-life dementia.

Signs of frontal release are easy to assess and traditionally have been considered part of a standard neurologic exam. While individual signs have shown relatively low sensitivity and specificity for detecting injury or degeneration, a meta-analysis of 29 studies found that people with dementia were up to 16 times more likely to exhibit frontal release signs, with the grasp reflex showing the strongest link.

“As biomarkers become increasingly integrated into the dementia diagnostic pathway, we must remember that clinical acumen remains paramount. A meticulous neurologic examination yields invaluable diagnostic insight, yet we are seeing a concerning decline in the foundational neurology rotations essential for training the next generation of clinicians,” Bojarski said.

“By demonstrating the enduring utility of the clinical exam and prioritizing these bedside skills in medical education, we can ultimately foster greater diagnostic accuracy and therapeutic confidence,” she told MedPage Today.

Bojarski and co-authors followed 873 older adults from the University of Kentucky Alzheimer’s Disease Research Center (ADRC) cohort in Lexington from 2005 to 2024. Participants were cognitively intact (672 participants) or had mild cognitive impairment (201 participants) at baseline; they had a mean age of 76.9 and an average of 16.1 years of education. Most (60.4%) were women.

Follow-up was 7.2 to 7.5 years on average in the cognitively intact group, and 4.0 to 4.4 years in the group with mild cognitive impairment.

Participants had at least two assessments that included standard protocols involving frontal release signs. Each annual evaluation included a medical history, a physical examination, and an extensive battery of neuropsychological tests of cognitive status.

At baseline, participants were classified as positive or negative for frontal release signs; those who had two or more signs were considered positive. In the intact cognition group, 8.8% were positive for frontal release signs; in the group with mild impairment, that proportion was 23.9%.

In the cognitively intact group, 25.4% of people with two or more frontal release signs progressed to dementia compared with 14.5% of people with one or no signs. Models adjusted for baseline age, sex, and education showed that mean scores in memory and executive domains worsened in this group over time.

Among participants with mild impairment at baseline, there was no difference in domains. No significant relationship between frontal release signs and dementia risk emerged.

This study was based on findings from a single ADRC, Bojarski and colleagues acknowledged. The cohort included people with relatively homogenous racial demographics and high education levels.

Frontal release signs can support tests and biomarkers to help determine who might develop dementia, the researchers pointed out. “Classic neurologic examination techniques like checking frontal release are gradually being replaced by sophisticated biomarkers and genetic testing, yet the importance of the neurologic exam for interpreting such biomarkers has never been greater,” observed co-author Gregory Jicha, MD, PhD, of the University of Kentucky.

“We should not lose the art of the neurologic exam, as it adds incredibly to our diagnostic formulation,” Jicha told MedPage Today. “We hope the future generations of neurologists do not simply look at a lab value to diagnose and treat, but rather that they fully examine and understand the patient and their neurologic condition in order to provide optimal care.”