Title : Exploring the impact of anti-tau immunotherapy on cognitive function in Alzheimer's patients: A systematic review and meta-analysis
Abstract:
Introduction: Alzheimer's disease (AD) is a degenerative neurological ailment that impairs memory, thinking, and behavior. The most prevalent cause of dementia in individuals over 65 years of age is protein deposits such as amyloid plaques and tau tangles, which impair cell function and cause cell death. Therapeutic methods targeting tau, including immunotherapies, have emerged as approaches to slowing cognitive decline. This study aimed to examine the therapeutic potential of anti-tau immunotherapies for Alzheimer's disease, focusing on cognitive improvement and associated hazards.
Methods: A comprehensive search of the electronic databases PubMed, Embase, Cochrane Library, Web of Science, and Scopus was conducted using PRISMA principles from inception to March 2024. Quality was assessed using the Cochrane risk-of-bias tool. Treatment efficacy was evaluated using clinically determined cognitive scores, and the risks associated with its use were analysed using Review Manager 5.3.
Results: Eight RCTs were considered for analysis. Clinically assessed cognitive scores such as ADAS-Cog showed no statistically significant improvement in cognition (SMD= -0.71, 95% CI -22.2, 0.80 P value = 0.36, I2=), ADCS-ADL score, which was only calculated in patients who were given passive immunotherapy, favored placebo although the results were not statistically significant (MD= -0.18, 95% CI -1.17, -0.80 P value = 0.72, I2=90%), CDR- SB which also favored placebo (MD= 0.26, 95% CI 0.20, 0.31 P value = <0.00001, I2=39%), and MMSE score, which did not show statistically significant correlation (OR=1.12, 95% CI -0.44, 2.68 P value =0.16, I2=0%). In relation to adverse events, there was no significant difference between the intervention and control groups in terms of arthralgia, headache, hypertension, nasopharyngitis, urinary tract infection, mortality, depression, diarrhea, dizziness, falls, or infusion-related reactions.
Conclusion: Our meta-analysis revealed that neither active nor passive anti-tau immunotherapies enhanced cognitive and functional assessments on clinical scales, but demonstrated a favorable safety profile, underscoring the necessity for rigorous studies, as cognitive scales may be prone to human error. Future trials should employ refined endpoints, sensitive cognitive scales, digital biomarker levels, and MRI findings to effectively assess improvements, while incorporating larger, diverse populations with tailored anti-tau immunotherapies. The success of anti-tau therapy in Alzheimer's disease could influence other tau-related neurodegenerative diseases, broadening its therapeutic relevance.
Keywords: Anti-tau immunotherapy, Active immunotherapy, Passive immunotherapy, Tau protein, Neurodegenerative diseases, Alzheimer’s disease, Dementia treatment.
