Scientists are discovering that a tiny region deep inside the brain may hold clues to memory loss long before symptoms appear. Even more surprising, medications designed to improve attention could one day help preserve thinking, motivation, and independence in people facing Alzheimer's disease. Here's why researchers are taking a fresh look at an unexpected treatment strategy.
Key Takeaways
Researchers are investigating ADHD medications as a potential Alzheimer's treatment because they increase norepinephrine, a neurotransmitter involved in attention, learning, and memory.
The brain's locus coeruleus may be one of the earliest regions affected by Alzheimer's, making it an exciting target for earlier diagnosis and treatment.
Early studies found improvements in both cognition and motivation, and larger clinical trials are now underway to determine whether these benefits hold up.
A New Alzheimer's Strategy Doesn't Target Amyloid at All
When children don’t pay attention, act impulsively, or are hyperactive, a doctor may diagnose ADHD, or Attention Deficit Hyperactivity Disorder, and prescribe medication to help them have better focus, control their impulses, and feel calmer.
There are a number of drugs available to help both children and adults with ADHD, but one in particular is catching the eye of researchers for its ability to also help people with Alzheimer’s disease.
In the 1980s, pathologists conducting autopsies on people who died of Alzheimer’s witnessed damage to the locus coeruleus, a region of the brainstem that produces norepinephrine, also known as noradrenaline. This neurotransmitter is important for cognitive functions, including attention, learning, and memory. In other words...
Alzheimer's Isn't Just About Memory
Scientists now recognize that Alzheimer's disease affects much more than memory. In many people, the earliest changes involve attention, concentration, decision-making, and the ability to stay focused—functions controlled in part by the brain's noradrenergic system.
Noradrenergic medicines were already available for other purposes to increase the amount of norepinephrine in the brain, so scientists were hopeful that they could help those with Alzheimer’s. However, several small trials failed to yield significant results, and interest waned as a result.
More recently, with the advent of advanced imaging techniques that allow the locus coeruleus to be measured in living patients, scientists have begun to discover the value of ADHD medications in the fight against memory loss.
Modest Cognitive Improvement
Scientists based at Imperial College London, University College London, and the University of Cambridge published a review of the research in the Journal of Neurology, Neurosurgery and Psychiatry. The team analyzed nineteen clinical trials in patients with Alzheimer’s and mild cognitive impairment, settling on ten containing 1,300 patients that met their criteria. They found the ADHD drugs did improve general cognitive ability compared to placebo. The effect was significant but modest, with a standardized mean difference of 0.14. For comparison, cholinesterase-inhibiting drugs - which are sometimes prescribed for Alzheimer’s patients to raise low concentrations of the neurotransmitter acetylcholine to improve memory, attention, and concentration - have a difference of 0.38.
Professor David Smith, Professor Emeritus of Pharmacology, University of Oxford, thought the change with the ADHD medication was “probably not clinically relevant.” But Dr. Andrew Reid, Assistant Professor of Psychology at the University of Nottingham, took a different view. Dr. Reid believes the noradrenergic system “is a promising new avenue of research [because] there is a lot of accumulating evidence that this system is changed very early on in the disease, which is exciting because it suggests a way to identify individuals at risk and treat them much earlier than is currently possible.”
Dr. Reid believes there’s “good evidence” that the effects ADHD drugs have by increasing levels of the neurotransmitter, norepinephrine, can really help patients. But that’s not all. The review also examined the effects of ADHD drugs on what has been described as “the forgotten symptom of dementia,” even though it affects a high number of patients.
The Problem with Lack of Motivation
The London team looked at eight trials with a total of 425 patients to see if the ADHD drugs helped lack of motivation or apathy, a common symptom of dementia.
This time, there was a large improvement with a score of 0.45. This was an important finding because no approved drugs treat this aspect of the condition. Jim Ray at the University of Texas MD Anderson Cancer Center explained, saying, “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, and I think that’s the potential impact of this publication (of the research)."
Michael David at Imperial College London, who led the research, explained, saying, “I think these results certainly show promise with regard to the potential benefits in targeting this neurotransmitter system. “Clearly, [the drugs] are not a cure, but people with Alzheimer’s can live for a long time, 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.”
The London team was so encouraged by the results they’ve already started a trial to see if the ADHD drug guanfacine will help Alzheimer’s patients.
The Guanfacine Trial Is Underway
One of the most anticipated follow-up studies to this research is the NorAD clinical trial, which is evaluating whether the ADHD medication guanfacine can improve attention and thinking in people with Alzheimer's disease when added to standard treatment.
Researchers have completed enrollment, and the scientific community is eagerly awaiting the final results. While it's too early to know whether guanfacine will become part of routine Alzheimer's care, the fact that this large study was undertaken highlights the growing confidence in this new line of research.
What Does This Mean For You?
Today, scientists are looking beyond individual ADHD medications and focusing instead on the entire noradrenergic system—the network of brain cells that relies on norepinephrine for healthy communication.
Rather than asking whether one specific drug works, researchers are also exploring whether restoring this important signaling pathway could help preserve attention, thinking, and other cognitive functions throughout the course of Alzheimer's disease.
This is exciting news. I think the research is promising enough that if I or someone I loved had Alzheimer’s disease, I’d talk to my doctor about these studies and see if he or she would be willing to prescribe an ADHD medication to see if it’s helpful. These drugs do have side effects, but they are usually mild and reportedly resolve after a few weeks as the body adjusts. In my view, patients don’t have anything to lose.
Summary
For years, Alzheimer's research focused primarily on the buildup of amyloid plaques and tau tangles. Now, scientists are exploring another promising target: the brain's noradrenergic system, which relies on the neurotransmitter norepinephrine to regulate attention, learning, memory, and motivation. Damage to the brain's locus coeruleus—one of the earliest regions affected by Alzheimer's—may contribute to many of the disease's cognitive symptoms. A review of clinical trials found that ADHD medications that increase norepinephrine produced modest improvements in overall cognition and even larger improvements in apathy, a common but often overlooked symptom that affects quality of life.
Frequently Asked Questions
Why are scientists studying ADHD medications for Alzheimer's disease?
Many ADHD medications increase norepinephrine, a neurotransmitter that supports attention, learning, memory, and other cognitive functions that decline early in Alzheimer's disease.
What is the locus coeruleus?
The locus coeruleus is a small region deep within the brainstem that produces norepinephrine. Researchers believe it may begin deteriorating years before Alzheimer's symptoms become noticeable.
Did the studies show that ADHD medications improve memory?
The research found modest improvements in overall cognitive function, but the largest benefits were seen in motivation and apathy. More studies are needed to determine how meaningful these improvements are for patients.
What is the NorAD trial?
The NorAD trial is a clinical study evaluating whether the ADHD medication guanfacine can improve attention and thinking in people with Alzheimer's disease when added to standard treatment.
Should people with Alzheimer's ask their doctor about ADHD medications?
These medications are not approved to treat Alzheimer's disease. Anyone interested in this approach should discuss the potential benefits and risks with their healthcare provider before considering off-label treatment.
