ADHD drugs may successfully treat aspects of Alzheimer’s disease

Noradrenergic drugs (including antidepressants and high blood pressure medication) used to treat attention deficit hyperactivity disorder (ADHD) may be able to treat some aspects of Alzheimer’s disease, according to new research.

Researchers looked at data from 1,811 patients across 19 randomised controlled trials focusing on Alzheimer’s disease and mild cognitive impairment between 1980 and 2021. Six of these trials were judged to be ‘good’ quality, seven as ‘fair’, and six as ‘poor’.

The results of 10 of these trials, involving 1300 patients, were pooled for global cognition -orientation/attention, memory, verbal fluency, language and visuospatial ability. This showed a small, but significant, positive effect of noradrenergic drugs on overall cognition, as measured by the Mini-Mental State Exam or the Alzheimer’s Disease Assessment Scale.

The results of 8 clinical trials, involving 425 patients, were then pooled for behaviour and neuropsychiatric symptoms, agitation and apathy. And this showed a large positive effect of noradrenergic drugs on apathy, even after removing outliers to account for differences in trial design and intended outcomes.

How do noradrenergic drugs work?

The researchers say that the findings can be explained by the mechanism of action behind noradrenergic drugs. The drugs target the neurotransmitter noradrenaline, also called norepinephrine, which is released by a network of specialised noradrenergic neurons.

This network is critical for arousal and many cognitive processes, including attention, learning, memory, readiness for action, and suppression of inappropriate behaviours.

Noradrenergic disruption occurs early in Alzheimer’s disease and contributes to the cognitive and neuropsychiatric symptoms that characterise the condition, suggesting that the noradrenergic system would be a good target for drug treatment.

Clinical trials of noradrenergic drugs are now warranted

In light of this new research, experts say that clinical trials of noradrenergic drugs, are now warranted.

• Repurposing of established noradrenergic drugs is most likely to offer effective treatment in Alzheimer’s disease for general cognition and apathy.
• There is a strong rationale for further, targeted clinical trials of noradrenergic treatments in Alzheimer’s disease, say the researchers.

However, they advise that several factors must be considered first. These include appropriate targeting of particular groups of patients and understanding the dose effects of individual drugs and their interactions with other treatments to minimise the cons and maximise the pros of noradrenergic drugs.