London—Could repurposing drugs now used to treat attention-deficit/hyperactivity disorder (ADHD) and other conditions improve some aspects of Alzheimer's disease? A pooled data analysis of the available research suggests that might be the case.
The article published online in the Journal of Neurology Neurosurgery & Psychiatry calls for clinical trials of noradrenergic drugs, which include antidepressants and medicines to treat high blood pressure and ADHD.
UK researchers from Imperial College London and colleagues explained that noradrenergic drugs target the neurotransmitter, noradrenaline (also called norepinephrine), which is released by a network of specialized noradrenergic neurons.
Attention, learning, memory, readiness for action, and suppression of inappropriate behaviors are all affected by that network, which plays a role in arousal and cognitive processes, the authors pointed out.
The study focused on the noradrenergic system because disruption there occurs early in Alzheimer's disease. "This system offers a potential therapeutic target, although noradrenergic treatments are not currently used in clinical practice," the study advised.
The researchers sought to determine if drugs with noradrenergic action could have beneficial effects on cognitive and neuropsychiatric symptoms in Alzheimer's disease. To accomplish this, the study team searched MEDLINE, Embase, and ClinicalTrials.gov databases from 1980 to December 2021 and conducted a meta-analysis.
This study included 19 randomized. controlled trials involving 1,811 patients—six were judged as good quality, seven as fair quality, and six as poor quality.
A meta-analysis of 10 of the studies, which involved 1,300 patients, detected a slight but significant positive effect of noradrenergic drugs on global cognition, which was measured using the Mini-Mental State Examination or Alzheimer's Disease Assessment Scale—Cognitive Subscale (standardized mean difference [SMD]: 0.14, 95% CI: 0.03-0.25, P = .01; I2 = 0%), the authors wrote.
While no significant effect was identified in measures of attention (SMD: 0.01, 95% CI: -0.17-0.19, P = .91; I2 = 0%), the apathy meta-analysis included eight trials (425 patients) and detected a large positive effect of noradrenergic drugs (SMD: 0.45, 95% CI: 0.16-0.73, P = .002; I2 = 58%), according to the researchers, who added, "This positive effect was still present following removal of outliers to account for heterogeneity across studies."
"Repurposing of established noradrenergic drugs is most likely to offer effective treatment in Alzheimer's disease for general cognition and apathy," the researchers concluded. "However, several factors should be considered before designing future clinical trials. These include targeting of appropriate patient subgroups and understanding the dose effects of individual drugs and their interactions with other treatments to minimize risks and maximize therapeutic effects."
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