Johns Hopkins researchers looked into the brain scans of persons with mild loss of thought and memory and have found that they have significantly low levels of serotonin in their brains. Serotonin is a natural brain chemical that is responsible for several functions including mood, sleep and appetite and also is important for several mental health conditions.

Image Credit: Shidlovski / Shutterstock

There have been studies previously that have shown that persons with Alzheimer's disease and those with severe cognitive decline tend to have lower levels of serotonin. However no studies could quantify or explain the phenomenon and it was unclear if low serotonin caused the disease or the disease caused serotonin levels to drop. This new study on persons with early stages of memory decline showed conclusively that serotonin loss was causing the memory loss rather than the other way round. The study is published in the September issue of the journal Neurobiology of Disease.

The study was published alongside a report that states that if ways could be determined to stop or slow down the loss of serotonin or introducing a substitute chemical into the brain, the progression of Alzheimer’s and other dementias could be stopped.

Gwenn Smith, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and director of geriatric psychiatry and neuropsychiatry at Johns Hopkins University School of Medicine, said that this study gives us the evidence we needed that low serotonin levels are the reason for cognitive decline of the brain. So understandably increasing serotonin function in the brain could be the key to prevent memory loss and also slow the progression of these diseases she explained.

In a normal brain when a message comes via a neuron, the neuron releases serotonin at its end. This is detected by the next neuron receiving the message. Once the message is propagated, there is a serotonin transporter SERT that picks up the serotonin and takes it back to the message-sending neuron. This shows up as the flow of the chemical serotonin. The serotonin neurons and transporters reduce with age in normal persons. As the neurons die with age, the SERTs also reduce in number.

One group of drugs that improve brain serotonin levels are the drugs that block the brain's reuptake of serotonin (known as SSRIs or Selective Serotonin reuptake inhibitors). These drugs are helpful in patients with depression and some forms of anxiety. They can significantly affect mood. According to Smith, with this idea in mind, researchers have already tried to treat Alzheimer’s disease and other diseases of cognitive decline with SSRIs but have met with limited success. But these drugs need adequate number of serotonin transporters or SERTs in the brain to work, she noted, and that was missing among those with cognitive decline. That is probably why SSRIs do not show as much success as expected.

For this study the researchers looked at the brain positron emission tomography (PET) scans of the participants who suffered from mild cognitive problems. These mild cognitive problems usually lead to severe dementias and Alzheimer’s. The participants were recruited using advertisements and flyers and also from the Johns Hopkins Memory and Alzheimer's Treatment Center. There were 28 participants with mild cognitive impairment who were matched to 28 healthy participants for comparison. The participants were all aged around 66 years and 45% of the participating population was female.

Mild cognitive impairment was defined for the study as slight decline in cognition including loss of memory, remembering sequences or organization and those who scored low on California Verbal Learning Test that asked participants to remember related words for example from a shopping list. Average scores of learning and memory tests especially California Verbal Learning Test, on a scale of 0 to 80 showed, average score of 55.8 among healthy participants and average of 40.5 among those with mild cognitive impairment. Another memory test was the Brief Visuospatial Memory Test where the participants were shown a series of shapes and they had to redraw them later from memory. On a scale of 0 to 36, healthy participants scored an average of 20.0 whereas those with mild cognitive problems scored an average of 12.6.

Once diagnosed and grouped, these participants underwent an MRI and PET scan to measure brain structures and levels of the serotonin transporters. To detect the serotonin transporters the patients took a drug that had a radioactive carbon label at a dose low enough to not cause any effect. The chemical went and bound to the serotonin transporter and the PET scanner picked up the radio labels.

Researchers in this study found that people with mild cognitive impairment had up to 38 percent less SERT in their brains compared to their matched healthy controls who were of same age. This means that this loss of the SERTs is more to do with the pathology than with age alone explain the researchers. None of the persons with mild cognitive impairment had higher levels of SERT compared to their healthy control.

The scores of the two memory tests and the PET scan results were compared next. They noted that lower serotonin transporters were associated with lower test scores. According to Smith, there are 14 types of serotonin receptors that could become the potential new targets for drug development in dementia.

Dementia

Dementia or progressive loss of memory and brain functions affects millions worldwide as the number of older people rise. In England there are 570,000 people living with dementia. This rise is expected to continue over the next three decades due to rise of the elderly population and increase in life expectancy.

Usually dementia occurs in people who are 65 or over. It is rarely diagnosed in the under 40s. Dementia may be of different types depending on features and symptoms and severity. Alzheimer’s disease is where small clumps of protein, known as plaques, begin to develop around brain cells. This may lead to severe loss of memory over time. Vascular dementia occurs when there are problems in the blood supply to the brain. The brain does not receive adequate oxygen. Frontotemporal dementia is said to occur when frontal and temporal lobes (two parts of the brain) start shrinking. Dementia with Lewy bodies is another form of dementia where small abnormal structures, known as Lewy bodies, develop inside the brain. There is no cure for dementia. In most patients the symptoms worsen over time.

References