Medications used to treat conditions such as attention deficit hyperactivity disorder (ADHD) and depression may also improve cognition and decrease apathy in people with Alzheimer’s disease.
The idea that this class of drugs, called noradrenergic drugs, might be useful for treating Alzheimer’s disease dates back to the 1980s. At the time, autopsies of people who had died of Alzheimer’s disease revealed a deterioration of a part of the brainstem called the locus coeruleus (LC). The region produces norepinephrine, a neurotransmitter important for attention, learning, memory, and other cognitive functions. The hope was that because noradrenergic drugs increase norepinephrine levels, they might combat deficits in these functions in people with Alzheimer’s disease.
But after a few small trials that did not lead to convincing results, interest faded, says Michael David of Imperial College London.
Since then, advances in imaging have allowed researchers to measure LC deterioration in living patients and see how this may contribute to their symptoms.
This breakthrough, along with the development of new noradrenergic drugs, prompted David and his colleagues to take a fresh look at these treatments. The researchers collected data from 19 clinical trials that included 1,811 patients with Alzheimer’s disease or related mild cognitive impairment.
They looked at 10 of the studies including 1,300 patients to assess the impact of drugs on general cognitive ability as measured by commonly used assessments. The drugs produced modest improvements over the placebos: The standardized mean difference – a measure that allows researchers to compare results between different types of studies – was 0.14. In comparison, trials of cholinesterase inhibitors, which are commonly prescribed to improve cognition, have a greater impact, with a standardized mean difference of 0.38 in patients with Alzheimer’s disease.
For apathy, the researchers looked at eight trials involving a total of 425 patients. Studies have measured changes in motivation using common scoring systems. Here, noradrenergic drugs produced a significant improvement: the standardized mean difference was 0.45. No effects were found for other symptoms, including attention or restlessness.
Apathy, or loss of motivation, is one of the most common and debilitating symptoms in people with Alzheimer’s disease, David explains. Currently, there are no approved drugs to treat this aspect of the disease.
“If there was a treatment that could improve motivation, especially in patients for whom it’s a very big concern, I think it would be extremely helpful,” says Jim Ray of the University’s MD Anderson Cancer Center. of Texas, who did not participate in the research. . “And I think that’s the potential impact of this release.”
However, more research is needed to determine which of these drug classes would be most effective. The analysis included data on 12 drugs, each with a different impact on the brain. It’s also unclear how their effects may vary across disease stages, Ray says. Clinical trials are underway to answer these questions, but the results won’t be available for a few years, David says.
“Clearly, [these drugs] don’t heal, but people with Alzheimer’s can live a long time,” says David. “So if you can make a difference, especially in the beginning, you have the potential to impact them and their loved ones for years to come.”
Journal reference: Journal of Neurology Neurosurgery and Psychiatry DOI: 10.1136/jnnp-2022-329136
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