Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints

Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relevant.We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive complaints.Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.Results Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire cohort.Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−subjects.An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+subjects.Additionally,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−subjects.Conclusion Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment.Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.

Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer＇s Disease

Abstract To date, we still lack disease-modifying thera- pies for Alzheimer＇s disease （AD）. Here, we report that long-term administration of benfotiamine improved the cognitive ability of patients with AD. Five patients with mild to moderate AD received oral benfotiamine （300 mg daily） over 18 months. All patients were examined by positron emission tomography with Pittsburgh compound B （PiB-PET） and exhibited positive imaging with β- amyloid deposition, and three received PiB-PET imaging at follow-up. The five patients exhibited cognitive improve- ment as assayed by the Mini-Mental Status Examination （MMSE） with an average increase of 3.2 points at month 18 of benfotiamine administration. The three patients who received follow-up PiB-PET had a 36.7% increase in the average standardized uptake value ratio in the brain com- pared with that in the first scan. Importantly, the MMSE scores of these three had an average increase of 3 points during the same period. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation. Ourstudy provides new insight to the development of disease- modifying therapy.