Noradrenergic drugs may improve cognition, apathy in Alzheimer’s patients

Drugs that target the noradrenergic system may improve cognition and apathy in patients with dementia or mild cognitive impairment caused by Alzheimer’s disease but have little effect on attention or episodic memory, researchers reported.

Michael C. B. David, MBBS, a research fellow and PhD candidate at Imperial College London, and colleagues aimed to assess the efficacy of drugs with principally noradrenergic action on cognition and neuropsychiatric symptoms in patients with AD.

Researchers searched MEDLINE, Embase and ClinicalTrials.gov from 1980 to December 2021 and generated pooled estimates using random effect meta-analyses.

They identified 19 randomized, controlled trials (n = 1,811 patients) and conducted a meta-analysis of 10 studies, which included 1,300 patients and revealed a significant small positive effect of noradrenergic drugs on global cognition (standardized mean difference = 0.14; 95% CI, 0.03-0.25). No significant effect was seen on measures of attention, the authors reported (SMD = 0.01; 95% CI, –0.17 to 0.19).

When measuring apathy via meta-analysis, researchers included eight trials (n = 425 patients) and detected a large positive effect of noradrenergic drugs (SMD = 0.45; 95% CI, 0.16-0.73). This was consistently observed 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,” David and colleagues wrote in the Journal of Neurology, Neurosurgery & Psychiatry. “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.”