Medications used to treat conditions like 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 medications, called noradrenergic drugs, may be useful for treating Alzheimer’s dates to the 1980s. At the time, autopsies of people who had died of Alzheimer’s revealed deterioration in a part of the brainstem called the locus coeruleus (LC). The region produces noradrenaline – a neurotransmitter important for attention, learning, memory and other cognitive functions. The hope was that because noradrenergic drugs increase noradrenaline levels, they could combat deficits in these functions in people with Alzheimer’s.
But, after a few small trials failed to produce convincing results, interest faded, says Michael David from Imperial College London.
Since then, advances in imaging have allowed researchers to measure deterioration of the LC in living patients and see how it may contribute to their symptoms.
This advancement, along with the development of new noradrenergic drugs, spurred David and his colleagues to take a fresh look at these treatments. The researchers collected data from 19 clinical trials that included 1811 patients with either Alzheimer’s disease or the related condition mild cognitive impairment.
They looked at 10 of the studies including 1300 patients to evaluate the drugs’ impact on general cognitive ability as measured by commonly used assessments. The drugs led to modest improvements compared with placebos: the standardised mean difference – a measure that enables researchers to compare outcomes across different types of studies – was .14. In comparison, trials of cholinesterase inhibitors, which are routinely prescribed to improve cognition, have a bigger impact, with a standardised mean difference of .38 in Alzheimer’s patients.
For apathy, the researchers looked at eight trials with a total of 425 patients. The studies measured changes in motivation using common scoring systems. Here, noradrenergic drugs led to significant improvement: the standardised mean difference was .45. No effects were found for other symptoms, including attention or agitation.
Apathy, or the loss of motivation, is one of the most common and debilitating symptoms in people with Alzheimer’s, says David. Currently, no approved medications treat this aspect of the condition.
“If there was a treatment that could improve motivation, particularly in patients where that’s a really big concern, I think that would be extremely useful,” says Jim Ray at the University of Texas MD Anderson Cancer Center, who was not involved in the research. “And I think that’s the potential impact of this publication.”
However, more research is needed to determine which of these class of drugs would be most effective. The analysis included data on 12 medications, each of which impacts the brain differently. It is also unclear how their effects may vary across stages of the disease, says Ray. Clinical trials are underway to answer these questions, but results won’t be available for a few more years, David says.
“Clearly, [these drugs] are not a cure, but people with Alzheimer’s can live for a long time,” says David. “So, if you can make any difference, especially early on, then you have the potential to impact them and their loved ones for quite a few years.”
Journal reference: Journal of Neurology Neurosurgery and Psychiatry , DOI: 10.1136/jnnp-2022-329136
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