<title>Abstract</title>
We conducted a randomized placebo-controlled double-blind 24-week trial using <italic>Melissa officinalis</italic> (<italic>M. officinalis</italic>) extract richly containing rosmarinic acid (RA) on patients with mild dementia due to Alzheimer’s disease (AD) with the aim to examine the safety and tolerability (primary endpoint) of RA (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (<italic>n</italic> = 23) diagnosed with mild dementia due to probable AD were randomized to either the placebo or <italic>M. officinalis</italic> extract group. No differences in vital signs or physical and neurologic examination results were detected between the <italic>M. officinalis</italic> and placebo groups. No serious adverse events occurred. There were no significant differences in cognitive measures; however, the mean Neuropsychiatric Inventory Questionnaire (NPI-Q) score improved by 0.5 points in the <italic>M. officinalis</italic> group and worsened by 0.7 points in the placebo group between the baseline and 24-week visit, indicating a significant difference (<italic>P</italic> = 0.012). No significant differences were apparent in disease-related biomarkers between the groups. <italic>M. officinalis</italic> extract containing 500 mg of RA taken daily was safe and well-tolerated by patients with mild dementia due to AD. Our results suggest that RA may help prevent the worsening of AD-related neuropsychiatric symptoms.


<bold>Trial registration:</bold> The registration number for this clinical trial is UMIN000007734 (16/04/2012).