👤 Masahiro Akishita

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). We here report the clinical characteristics of AD patients enrolled in the trial. 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. 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. 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. Show less

Argyrophilic grain (AG) is a common neurodegenerative accumulation of 4 repeat tau in dendritic spine. Dementia with grain (DG) is defined as AGs with a sole pathological basis for cognitive decline. As with other multifactorial diseases, DG could result from interactions of environmental and genetic factors. However, the genetic basis of DG is largely unknown. To clarify the genetic architecture of DG pathogenesis, we conducted a genome-wide association study (GWAS) with 214 DG cases versus 12,405 controls. We have identified a candidate locus associated with the risk of DG, the SVIL locus on chromosome 10, with genome-wide significance (rs11595141, P = 4.86 Show less