PET scans reveal link between low serotonin levels and dementia

Written by Kelvin Adu-Darko

A new study carried out by researchers at the Johns Hopkins University (MD, USA) has provided evidence of an association between mild cognitive decline and levels of serotonin. The study, published in Neurobiology of Disease, proposes the use of serotonin receptors as a biomarker to detect cognitive and possible dementia development.
Previous studies have established a correlation between serotonin levels and development of Alzheimer’s disease (AD) or other cognitive defects; but as of yet, no direct cause and effect link have been evidenced.

This current study was influenced by findings from Alena Savonenko et al., which demonstrated that a decrease in serotonergic neurons was linked with the formation of amyloid in mouse brains. The new study follows on from this, investigating this relationship in human patients. Researchers in this new study claim that serotonin deficiency is a contributor to the development of AD rather than a by-product of the disease.

Twenty-eight patients with mild cognitive impairment (MCI) with an average age of 66 years were age-matched with health controls. MRI and PET scans of the brain were used to detect the levels of the serotonin transporter (SERT) in each participant with the aid of radio labelling. The PET scans revealed that individuals with MCI had up to 38% fewer SERTs compared with age-matched healthy controls; no participants in the MCI group had higher SERT levels of in comparison to the control group.

Results from the California Verbal Learning Test – assessing short term memory in participants – also reflected a decrease in cognitive ability. In the test, on a scale from 0 to 80 (0 being the worst and 80 being the best memory ability), it was found that on average, participants with MCI scored 40.5, in comparison to healthy participants who scored an average of 55.8.

The Brief Visuospatial Memory test also demonstrated the participants with mild cognitive impairment scored an average of 12.6 which was lower than 20.0 scored by the healthy control group.

These findings, in addition to a series of other cognitive tests, demonstrate that lower levels of SERTs correlated with the lower cognition scores. The researchers theorize that by finding ways to prevent loss of serotonin or by replacing serotonin losses with a similar neurotransmitter, it may be possible to slow progression of AD and other forms of dementia.

Gwenn Smith of the Johns Hopkins University School of Medicine said: “Now that we have more evidence that serotonin is a chemical that appears affected early in cognitive decline, we suspect that increasing serotonin function in the brain could prevent memory loss from getting worse and slow disease progression.”

The findings from this study could potentially lead to serotonin being used as a biomarker to detect the progression of AD: the researchers say that there are 14 serotonin receptors that could be targeted, with a number of clinical trials already active in this area.

Sources: Smith GS, Barrett FS, Joo JH et al. Molecular imaging of serotonin degeneration in mild cognitive impairment. Neurobiol. Dis. doi:10.1016/j.nbd.2017.05.007 (2017);