The search for a way to treat Alzheimer’s disease has puzzled scientists for decades. This may be why some researchers are shifting their focus slightly, investigating whether treating the systems affected by Alzheimer’s (as opposed to the causes) may better help them find a treatment.
This is exactly what researchers of a new study have shown – finding that drugs normally used to treat ADHD may actually show promise in managing symptoms of Alzheimer’s disease.
The researchers conducted a systematic review which looked at how noradrenergic drugs (commonly used for ADHD) work for managing Alzheimer’s disease symptoms. The review found that taking these drugs improved certain brain functions and other symptoms, such as apathy, in patients with Alzheimer’s disease.
Noradrenergic drugs target the noradrenergic system, which comprises a small part of the brainstem called the locus coeruleus. This area is involved in a broad array of brain functions, such as memory, attention and learning. This system is primarily controlled by a neurotransmitter (a special type of brain cell that sends and receives messages in the brain) called noradrenaline – which also plays an important role in our body’s “fight or flight” response.
The locus coeruleus is also the first recorded brain area to show pathological signs of Alzheimer’s disease. These signs occur in the form of tau tangles. Tau is an important protein that is essential for good brain function. But in people with Alzheimer’s disease, tau proteins accumulate together.
As these tangles build up, they interfere with the noradrenergic system’s ability to keep neurons healthy. Since the noradrenergic system also helps regulate the brain’s immune system, loss of function can lead to neuroinflammation, which is another telltale sign of Alzheimer’s disease.
Problems with the way the noradrenergic system functions have also been seen in other mental health conditions, such as depression, ADHD, and anxiety. This is why noradrenergic treatments may also be prescribed for these disorders. Interestingly, patients with these disorders have higher risk of developing Alzheimer’s.
Symptoms such as depression and anxiety often also appear prior to memory issues in people with Alzheimer’s disease. The presence of depression, anxiety and other mental health issues is also associated with higher risk of premature death in patients with Alzheimer’s.
To conduct their study, the researchers pooled together 19 studies, looking at data from a total of over 1,800 patients. They also looked at a number of different noradrenergic drugs, including those used to treat ADHD and depression.
They found that in the majority of studies, these drugs improved the overall thinking and understanding of people with Alzheimer’s disease. However, they weren’t shown to improve the performance of specific memory functions (such as verbal and episodic memory), executive functions (being able to focus and remember instructions), visuospatial abilities (such as drawing or buttoning a shirt), or agitation.
These drugs were also shown to improve apathy, which is a common symptom of Alzheimer’s. Apathy can greatly reduce quality of life and can advance loss of brain function. Interestingly, a drug used predominantly in treating ADHD, named methylphenidate – better known as Ritalin – was the drug most commonly shown to improve apathy in Alzheimer’s patients.
Overall, this study suggests that noradrenergic drugs can be beneficial for some people with Alzheimer’s disease, so long as the right dosage is used. However, caution should be taken when drawing conclusions, as this is not an experimental study – such as a randomised controlled trial, which would compare the effect of an intervention (such as drug). There was also a lot of variation between the studies included in the review in how they were conducted and their results.
It’s also worth noting that although these drugs were shown to have some benefit for brain function, they can come with a range of side effects. These include heart problems, addiction and, especially when misused, may result in brain changes or psychiatric symptoms, including psychosis-like symptoms such as hallucinations and paranoia. So it will be important for future studies to be conducted further proving the benefits of these drugs – and that the benefits far outweigh any potential risks.
When it comes to the noradrenergic drugs investigated in this study, methylphenidate (Ritalin) has recently been used short term (six months) in a clinical trial and has shown positive results when it comes to apathy. But other drugs investigated in the study, such as the antidepressant mirtazapine, not only showed zero improvement in apathy, but were associated with increased risk of premature death.
While the study didn’t show any improvement in memory issues for people with Alzheimer’s, it has shown us that it may be time to move in a new direction when it comes to treating this disease. Instead of focusing only on potential causes (such as the amyloid and tau hypotheses), research could now benefit from including treatments that target the systems which are involved in different Alzheimer’s symptoms.
The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.