Baseline characteristics of patients with early Alzheimer's disease enrolled in the pivotal trial of low-intensity pulsed ultrasound (LIPUS-AD)

Abstract

Background: We demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy tended to ameliorate cognitive declines in patients with early Alzheimer's disease (AD) in the pilot trial. Thus, we have started the pivotal trial in a randomized, double-blind, placebo-controlled manner (LIPUS-AD). Objective: We here report the clinical characteristics of AD patients enrolled in the trial. Methods: The major inclusion criteria included age 50–90 years of both sex, Clinical Dementia Rating (CDR) global score of 0.5∼1.0 and Japanese version of the Mini-Mental State Examination (MMSE-J) score greater than 20 at screening, positive brain Aβ-PET, and no symptomatic brain hemorrhage, infarction, or edema on brain MRI. Results: A total of 231 subjects were finally enrolled. As compared with the pilot trial, they were characterized by older age and higher prevalence of dyslipidemia. They had lower scores of ADAS-J-cog and Modified Hachinski Ischemic Scale (MHIS), while other cognitive scores were comparable with the pilot trial. Use of cholinesterase inhibitors was less as compared with the pilot trial. APOE ε4 polymorphism is present in 58% of the subjects, including heterozygote in 44% and homozygote in 14%. Brain MRI measurements showed that hippocampus volume was distributed with a peak at 5700–5999 mm 3 without left and right difference, and brain Aβ-PET showed that centiloid scale distributed with a peak at 90–99.9 and standardized uptake value ratio (SUVR) with a peak at 0.7–0.79. There were weak but significant correlations between ADAS-J-cog14 and those brain MRI and Aβ-PET measurements. Conclusions: Clinical characteristics of subjects in the LIPUS-AD trial largely mimic those in the pilot trial, addressing efficacy and safety of the LIPUS therapy in early AD. Clinical Trial Gov. No.: NCT05983575, jRCT No.: jRCT2032230125