Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021
INTRODUCTION We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). METHODS Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. RESULTS The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). DISCUSSION PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.
A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study
Alzheimers Dement. 2020
INTRODUCTION This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild-to-moderate Alzheimer's disease (AD). METHODS Three hundred forty-seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6-week period of weekly conventional PE followed by a 12-month period of monthly low-volume PE), and placebo (sham). RESULTS PE-treated patients performed significantly better than placebo for the co-primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog; P = .06; 66% less decline) scores at month 14. Moderate-AD patients (baseline Mini-Mental State Examination [MMSE] 18-21) scored better on ADCS-ADL (P = .002) and ADAS-Cog (P = .05), 61% less decline both. There were no changes in mild-AD patients (MMSE 22-26). PE-treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR-sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) (P < .0001; 100% less decline) scales. DISCUSSION This trial suggests that PE with albumin replacement could slow cognitive and functional decline in AD, although further studies are warranted.
Impact of erythropoiesis-stimulating agents on morbidity and mortality in patients with heart failure: an updated, post-TREAT meta-analysis
European Journal of Heart Failure. 2010;12((9):):936-42.
AIMS: Randomized clinical trials have suggested that treatment of anaemia with erythropoiesis-stimulating agents (ESAs) in patients with cancer or chronic kidney disease may increase cardiovascular risk. We therefore examined the effect of treating anaemia with an ESA in patients with heart failure in a meta-analysis of randomized clinical trials, including the recently reported TREAT study. METHODS AND RESULTS We performed a systematic review and meta-analysis of all prospective, randomized, controlled studies of ESAs enrolling patients with heart failure and reporting data on mortality or non-fatal heart failure events. Of 10 trials initially identified by our search strategy, we pooled data from 9 placebo-controlled studies enrolling a total of 2039 patients, of whom 1023 (50.2%) were allocated to ESA treatment. The pooled risk ratio for ESA treatment relative to placebo was 1.03 [95% confidence interval (CI): 0.89-1.21, P = 0.68] for overall mortality and 0.95 (95% CI: 0.82-1.10, P = 0.46) for worsening heart failure. CONCLUSIONS The use of ESAs to manage anaemia in patients with heart failure was associated with a neutral effect on both mortality and non-fatal heart failure events. Definitive assessment of the balance of risk and benefit in this population awaits the completion of a randomized clinical trial adequately powered to assess clinical outcomes.