Ya-Nan Ou1, Jun-Xia Zhu2, Xiao-He Hou1, Xue-Ning Shen1, Wei Xu1, Qiang Dong2, Lan Tan1, Jin-Tai Yu3. 1. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. 2. Department of Prevention and Health Protection, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 3. Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Abstract
BACKGROUND: The role of infectious agents in the development of Alzheimer's disease (AD) has long been debated, however, uncertainties still persist. OBJECTIVE: We aimed to illuminate the associations between infectious agents and risk of AD comprehensively. METHODS: Studies examining the associations between AD and infectious agents were identified through a systematic search of PubMed, Embase, and Cochrane library. A random-effects meta-analysis was conducted. Publication bias was explored using funnel plot. RESULTS: Fifty-one studies were included in the systematic review, of which forty-seven studies with 108,723 participants and 4,039 AD cases were eligible for meta-analysis. Evidence based on case control studies demonstrated that Chlamydia pneumoniae [odds ratio (OR): 4.39, 95% CI = 1.81-10.67; I2 = 68%)], Human herpes virus-6 (OR: 3.97, 95% CI = 2.04-7.75; I2 = 0%, Epstein-Barr virus (OR:1.45, 95% CI = 1.00-2.08; I2 = 0%), Herpes simplex virus-1 (OR:1.34, 95% CI = 1.02-1.75; I2 = 0%), and the Herpesviridae family (OR:1.41, 95% CI = 1.15-1.74; I2 = 12%) infection were associated with a higher risk of AD. No significant evidence of publication bias was found. CONCLUSION: These findings strengthened the evidence that infection may play an important role in AD. Additional research is required to determine whether treatment strategies targeting infectious diseases to prevent AD are viable in the future.
BACKGROUND: The role of infectious agents in the development of Alzheimer's disease (AD) has long been debated, however, uncertainties still persist. OBJECTIVE: We aimed to illuminate the associations between infectious agents and risk of AD comprehensively. METHODS: Studies examining the associations between AD and infectious agents were identified through a systematic search of PubMed, Embase, and Cochrane library. A random-effects meta-analysis was conducted. Publication bias was explored using funnel plot. RESULTS: Fifty-one studies were included in the systematic review, of which forty-seven studies with 108,723 participants and 4,039 AD cases were eligible for meta-analysis. Evidence based on case control studies demonstrated that Chlamydia pneumoniae [odds ratio (OR): 4.39, 95% CI = 1.81-10.67; I2 = 68%)], Human herpes virus-6 (OR: 3.97, 95% CI = 2.04-7.75; I2 = 0%, Epstein-Barr virus (OR:1.45, 95% CI = 1.00-2.08; I2 = 0%), Herpes simplex virus-1 (OR:1.34, 95% CI = 1.02-1.75; I2 = 0%), and the Herpesviridae family (OR:1.41, 95% CI = 1.15-1.74; I2 = 12%) infection were associated with a higher risk of AD. No significant evidence of publication bias was found. CONCLUSION: These findings strengthened the evidence that infection may play an important role in AD. Additional research is required to determine whether treatment strategies targeting infectious diseases to prevent AD are viable in the future.
Authors: Gabriel A de Erausquin; Heather Snyder; Traolach S Brugha; Sudha Seshadri; Maria Carrillo; Rajesh Sagar; Yueqin Huang; Charles Newton; Carmela Tartaglia; Charlotte Teunissen; Krister Håkanson; Rufus Akinyemi; Kameshwar Prasad; Giovanni D'Avossa; Gabriela Gonzalez-Aleman; Akram Hosseini; George D Vavougios; Perminder Sachdev; John Bankart; Niels Peter Ole Mors; Richard Lipton; Mindy Katz; Peter T Fox; Mohammad Zia Katshu; M Sriram Iyengar; Galit Weinstein; Hamid R Sohrabi; Rachel Jenkins; Dan J Stein; Jacques Hugon; Venetsanos Mavreas; John Blangero; Carlos Cruchaga; Murali Krishna; Ovais Wadoo; Rodrigo Becerra; Igor Zwir; William T Longstreth; Golo Kroenenberg; Paul Edison; Elizabeta Mukaetova-Ladinska; Ekkehart Staufenberg; Mariana Figueredo-Aguiar; Agustín Yécora; Fabiana Vaca; Hernan P Zamponi; Vincenzina Lo Re; Abdul Majid; Jonas Sundarakumar; Hector M Gonzalez; Mirjam I Geerlings; Ingmar Skoog; Alberto Salmoiraghi; Filippo Martinelli Boneschi; Vibuthi N Patel; Juan M Santos; Guillermo Rivera Arroyo; Antonio Caballero Moreno; Pascal Felix; Carla Gallo; Hidenori Arai; Masahito Yamada; Takeshi Iwatsubo; Malveeka Sharma; Nandini Chakraborty; Catterina Ferreccio; Dickens Akena; Carol Brayne; Gladys Maestre; Sarah Williams Blangero; Luis I Brusco; Prabha Siddarth; Timothy M Hughes; Alfredo Ramírez Zuñiga; Joseph Kambeitz; Agustin Ruiz Laza; Norrina Allen; Stella Panos; David Merrill; Agustín Ibáñez; Debby Tsuang; Nino Valishvili; Srishti Shrestha; Sophia Wang; Vasantha Padma; Kaarin J Anstey; Vijayalakshmi Ravindrdanath; Kaj Blennow; Paul Mullins; Emilia Łojek; Anand Pria; Thomas H Mosley; Penny Gowland; Timothy D Girard; Richard Bowtell; Farhaan S Vahidy Journal: Alzheimers Dement (N Y) Date: 2022-09-22
Authors: Avram S Bukhbinder; Yaobin Ling; Omar Hasan; Xiaoqian Jiang; Yejin Kim; Kamal N Phelps; Rosemarie E Schmandt; Albert Amran; Ryan Coburn; Srivathsan Ramesh; Qian Xiao; Paul E Schulz Journal: J Alzheimers Dis Date: 2022 Impact factor: 4.160