Some people with Alzheimer’s develop cognitive and neuropsychiatric symptoms at an early stage due to dysfunction of the locus coeruleus-noradrenergic system. While noradrenergic therapies are not routinely employed in medicine at present, this system represents a promising therapeutic target. The purpose of this study was to evaluate the effectiveness of noradrenergic-primarily acting medications in ameliorating cognitive and neuropsychiatric symptoms in Alzheimer’s disease. From 1980 through December of 2021, the databases MEDLINE, Embase, and ClinicalTrials.gov were combed through. Using meta-analyses with random effects, researchers produced combined estimates. They included 19 randomized controlled trials (1,811 patients), of which 6 were judged as ‘good’ quality, 7 as ‘fair,’ and 6 as ‘poor.’ From a meta-analysis of 10 of these studies (1,300 patients), researchers found that noradrenergic drugs had a small but statistically significant positive effect on global cognition, as assessed by the Mini-Mental State Examination or the Alzheimer’s Disease Assessment Scale—Cognitive Subscale (standardized mean difference (SMD): 0.14, 95% CI: 0.03 to 0.25, P=0.01; I2=0%). There was no statistically significant difference between groups on attention measures (standard deviation [SMD] = 0.01, 95% CI=−0.17 to 0.19, P=0.91; 2=0). An extensive beneficial effect of noradrenergic medications was shown in a meta-analysis of apathy involving eight trials (with a total of 425 patients) (SMD: 0.45, 95% CI: 0.16 to 0.73, P=0.002; I2=58%). The favorable effect remained after trials with extreme results were eliminated to account for heterogeneity. The most promising approach to treating dementia and apathy in Alzheimer’s disease was the repurposing of existing noradrenergic medications. However, before designing future clinical studies, several things should be examined. To minimize potential adverse effects and make the most of therapeutic benefits, it is necessary to consider factors such as the dosing of specific pharmaceuticals and their combinations with other therapies.
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