A new systematic review has found that repurposing some drugs currently used for ADHD and depression may offer small improvements in the cognitive symptoms associated with Alzheimer’s disease. The review focuses on a group of drugs developed to stimulate the brain’s noradrenaline system.

Noradrenergic drugs have been used for decades to treat conditions ranging from attention deficit hyperactivity disorder (ADHD) and depression to insomnia and high blood pressure. They work by targeting a neurotransmitter called norepinephrine, which plays a role in a number of cognitive processes, including arousal, attention and memory.

Over the years, as far back as the 1980s, a number of small clinical trials have investigated the effects of noradrenergic drugs on Alzheimer’s. However, the results were generally never convincing enough to be seriously pursued, and other research areas became more popular research targets.

More recently, a number of studies have revived interest in the link between Alzheimer’s disease and the brain’s norepinephrine system. From findings suggesting that the earliest stages of Alzheimer’s neurodegeneration may occur in the locus coeruleus (LC), a brain region responsible for producing norepinephrine, to indications that apathy is an early symptom of the disease, a team of researchers from the United kingdom were inspired to review past research into the effect of noradrenergic drugs on the disease.

The review pooled data from 19 previously published studies involving 1,811 patients. A number of different noradrenergic drugs were examined in the review, including modafinil, mirtazapine and clonidine.

The results revealed that the use of this family of drugs led to small but significant improvements in cognition and large improvements in apathy. The researchers are careful to note the limitations of pooling data from different studies conducted over several decades, but they conclude that there is a good case for a new clinical trial to investigate whether these drugs could be useful as an Alzheimer’s treatment. .

“In patients with dementia or MCI [mild cognitive impairment] caused by Alzheimer’s disease, pharmacotherapies targeting the noradrenergic system can improve cognition and apathy,” the review concluded. “These therapies do not seem to have a beneficial effect on attention or episodic memory. Based on this meta-analysis and the recognition of the importance of the LC-NA system in multiple neurodegenerative diseases, there is a case for further clinical trials of noradrenergic agents in Alzheimer’s disease and other neurodegenerative conditions.

Experts not affiliated with this new review call the findings promising. David Smith of the University of Oxford said the analysis was important and well done, but stressed that these drugs could only slightly improve a patient’s symptoms and did not appear to affect the progression of the disease.

“There was no evidence that the drugs affected disease progression, but they did improve some symptoms, particularly apathy,” Smith said. “A small, probably not clinically significant, improvement in cognitive ability was also found. The report should spur further trials, particularly of combinations of these drugs with other symptomatic treatments.

Sian Gregory of the Alzheimer’s Society said there is currently a lack of treatments for Alzheimer’s patients and anything that can even slightly relieve a patient’s symptoms could be valuable. Gregory called for further clinical trials to investigate the potential of noradrenergic drugs for Alzheimer’s.

“This promising new research may help improve the lives of people living with Alzheimer’s disease in the future, helping to reduce the effects of common symptoms such as memory and thinking problems and improving apathy,” Gregory said. “Since drugs that act on the chemical messenger norepinephrine are already commonly used to treat disorders such as ADHD and depression, clinical trials to evaluate their benefit in people with Alzheimer’s disease should be clear.”

The new study is published in Journal of Neurology, Neurosurgery and Psychiatry.

source: BMJ


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