One of the primary reasons why Alzheimer’s disease (AD) is so devastating is that it affects multiply brain areas. As more and more neurofibrillary TAU tangles (twisted protein fibers) accumulate in brain cells, they block nutrients from reaching the cells and ultimately cause whole clusters of neurons to die off.
This damage to the brain cells, in turn, produces the infamous symptoms of Alzheimer’s disease, such as memory loss and cognitive decline. But there is one more group of Alzheimer’s symptoms that gets less press - the behavioral kind. These symptoms include depression, apathy, agitation, and even aggression. And they can be just as severe and disruptive to the life of the person with Alzheimer’s and their loved ones as memory loss and cognitive decline.
A clear-cut review study published in July 2022 in the Journal of Neurology Neurosurgery & Psychiatry shows that both cognitive and behavioral symptoms of Alzheimer’s can be improved by treating patients with medications used to treat attention deficit hyperactivity disorder (ADHD).
Let’s begin by clarifying that the types of ADHD medication considered in the analysis are noradrenergic drugs - medications that target a compound called noradrenaline.
And if the word “noradrenaline” rings a bell, you’re not mistaken. Adrenaline is a hormone released by the adrenal glands located on top of both kidneys in response to stress or low blood pressure. That is where we get the term “adrenaline rush.” But when adrenaline travels to the brain, it gets the name nor-adrenaline and turns into a neurotransmitter - a brain chemical used to communicate between nerve cells.
Noradrenaline (also called norepinephrine) is made by specialized noradrenergic nerve cells in the brain as well as the adrenal gland. As a neurotransmitter, norepinephrine plays a huge role in cognition. It aids us to stay focused, improves our ability to learn and memorize new information, and helps us control inappropriate behaviors.
In Alzheimer’s disease, low noradrenaline levels and the loss of neurons that produce norepinephrine are well documented across many brain areas. These disruptions contribute to symptoms often observed in Alzheimer’s disease - from loss of appetite, depression, and sleep disturbances to restlessness, aggression, irritability, and anxiety.
Given that we already have a selection of noradrenergic medications available, researchers have long posited that administering such drugs to people with Alzheimer’s may help reduce AD symptoms.
The study authors examined 19 clinical trials from 1980 to 2021 that used noradrenergic drugs (e.g.atomoxetine, guanfacine, and methylphenidate) in people with Alzheimer’s disease and mild cognitive impairment. These studies involved a total of 1811 participants. The results were examined across two main kinds of symptoms:
The analysis showed that noradrenergic drugs had a small positive effect on general cognition and a large improvement in apathy. And the researchers conclude, “Repurposing of established noradrenergic drugs is most likely to offer effective treatment in Alzheimer’s disease for general cognition and apathy.”
Obviously, using existing medications to treat AD has many advantages. For one, these drugs don’t have to be tested separately for safety and needn’t be approved by the FDA. All the required testing and certification have already been done in the past, which is a massive time saver.
But it's not all rainbows and unicorns. A few more specific questions regarding the use of noradrenergic medications for Alzheimer’s disease are yet to be answered. For instance, we still don’t know which particular patients would benefit from this treatment the most, as well as the specific doses at which noradrenergic drugs should be administered in AD.
H/T: Science Daily
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