Brain Scan Study Adds to Evidence That Lower Brain Serotonin Levels Are Linked to Dementia

BALTIMORE, Md -- August 14, 2017 -- In a study looking at brain scans of people with mild loss of thought and memory ability, researchers report evidence of lower levels of the serotonin transporter.

Previous studies have shown that people with Alzheimer’s disease and severe cognitive decline have severe loss of serotonin neurons, but the studies did not show whether those reductions were a cause or effect of the disease.

The results of the current study of people with very early signs of memory decline suggest that lower serotonin transporters may be drivers of the disease rather than a by-product.

A report on the study, published in the September issue of Neurobiology of Disease, also suggest that finding ways to prevent the loss of serotonin or introducing a substitute neurotransmitter could slow or stop the progression of Alzheimer’s disease and perhaps other dementias.

“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,” said Gwenn Smith, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Serotonin levels that are lower and out of balance with other brain chemicals such as dopamine are well known to significantly impact mood, particularly depression, and drugs that block the brain's reuptake of serotonin are specific treatments for some major forms of depression and anxiety.

Dr. Smith noted that researchers have tried with limited success to treat Alzheimer's disease and cognitive impairment with antidepressants such as SSRIs, which bind to the serotonin transporters. But, since these transporters are at much lower levels in people with Alzheimer's, she speculates that the drugs can’t serve their purpose without their target.

The researchers used brain positron emission tomography (PET) scans to look at levels of serotonin in the brains of people with mild cognitive problems. They recruited participants with community newspaper ads and flyers, as well as from the Johns Hopkins Memory and Alzheimer's Treatment Center. They paired 28 participants with mild cognitive impairment with 28 healthy matched controls. Participants were an average age of 66 years and about 45% were women.

People with mild cognitive impairment were defined as those who have a slight decline in cognition, mainly in memory in terms of remembering sequences or organisation, and who score lower on tests such as the California Verbal Learning Test.

Each participant underwent a magnetic resonance imaging (MR) and PET scan to measure brain structures and levels of the serotonin transporter. During the PET scans, participants were given a chemical labelled with a radioactive carbon.

The researchers found that people with mild cognitive impairment had up to 38% less SERT detected in their brains compared with each of their age-matched healthy controls. And not a single person with mild cognitive impairment had higher levels of SERT compared with their healthy control.

Each participant also underwent learning and memory tests. In the California Verbal Learning Test, on a scale of 0 to 80, with 80 reflecting the best memory, the healthy participants had an average score of 55.8, whereas those with mild cognitive impairment scored an average of 40.5.

With the Brief Visuospatial Memory Test, participants were shown a series of shapes to remember and draw later. From a scale of 0 to 36, with 36 being the top score, healthy people scored an average of 20.0 and those with mild cognitive problems scored an average of 12.6.

The researchers then compared the results from the brain imaging tests for the serotonin transporter to those 2 memory tests, and found that the lower serotonin transporters correlated with lower scores. For example, those people with mild cognitive impairment had 37% lower verbal memory scores and 18% lower levels of SERT in the brain's hippocampus compared with healthy controls.

The researchers are investigating whether PET imaging of serotonin could be a marker to detect progression of disease, whether alone or in conjunction with scans that detect the clumping protein known as amyloid that accumulates in the brains of those with Alzheimer's disease. When it comes to targeting the disease, because of reduced levels of the serotonin transporters, the receptors that detect serotonin on message-receiving cells might be a better option. There are 14 types of serotonin receptors that could be used as possible targets.

SOURCE: Johns Hopkins Medicine
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