Serotonin levels may play an early role in cognitive decline, according to imaging data from a group of study participants with mild cognitive impairment.

Previous studies have shown a link between a loss of serotonin neurons as part of normal aging and as part of the development of Alzheimer’s disease, wrote Gwenn S. Smith, PhD , of Johns Hopkins University in Baltimore, and her colleagues. However, “it is not known whether serotonin degeneration occurs in the preclinical stages or later in the course of AD,” the researchers said. The researchers used MRI and PET imaging to measure serotonin transporters (SERT) in the brains of 28 adults with mild cognitive impairment (MCI) and 28 healthy controls.

Overall, MCI participants showed significantly lower SERT, compared with the healthy controls; the loss of SERT in the MCI group ranged from 10% to 38%. No significant regions of higher SERT were noted in the MCI group, compared with the controls, and no significant differences were noted in gray matter volume.

The participants were recruited from the community or from the Johns Hopkins University Alzheimer’s Disease Research Center. All of the subjects underwent several evaluations, including the Clinical Dementia Rating Scale and the Mini-Mental State Examination , and mild cognitive impairment was defined as a cognitive decline mainly in the ability to remember sequences or organization, as well as having lower scores on tests such as the California Verbal Learning Test ( Neurobiol Dis. 2017 Sep;105:33-41 ). The average age of the participants was 66 years, and about 45% were women.

The study results were limited by several factors, including lack of arterial blood for quantification purposes and the absence of partial-volume correction in assessing the brain images, reported Dr. Smith, a professor of psychiatry and behavioral sciences at the university, and her colleagues.

However, the findings suggest that “the loss of SERT in MCI may have a substantial impact on brain function and behavior given the widespread distribution of SERT in the brain and the evidence that serotonin modulates other neurotransmitters (glutamate, norepinephrine, dopamine, and acetylcholine) implicated in AD and potentially MCI,” they emphasized.

Based on the findings, next steps for research could include targeting receptors that detect serotonin on message-receiving cells. “The substantially lower SERT in MCI observed in the present study suggests that the serotonin system may represent an important target for prevention and treatment,” the researchers noted.

Dr. Smith has received research funding from the National Institutes of Health and Functional Neuromodulation. This study was supported by the NIH.


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