Impact of Alzheimer's Disease Co‐Pathology on Shunt Outcomes in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review and Meta‐Analysis

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible condition characterized by gait, cognitive, and urinary impairment and treated with cerebrospinal fluid shunting, yet post-shunt outcomes vary. Coexisting Alzheimer's disease (AD) pathology may contribute to this variability. This systematic review and meta-analysis investigated whether pre-shunt AD co-pathology influences post-shunt outcomes across distinct clinical domains and follow-up durations. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, Embase, Scopus, and Web of Science were searched for studies assessing the impact of pre-shunt AD co-pathology on post-shunt outcomes in iNPH. Studies were included in the meta-analysis if they stratified patients by pre-shunt AD status (iNPH-AD vs. iNPH-nAD) and reported at least one post-shunt outcome compared between groups. Random-effects meta-analyses pooled standardized mean differences across short- (<12 months) and long-term (≥12 months) follow-up. Sixteen studies (n = 1825 patients) were included in the systematic review, with nine (n = 428) eligible for meta-analysis. Pre-shunt AD co-pathology prevalence ranged from 23.9% to 67.6%, and post-shunt follow-up duration ranged from 3 to 60 months. No short-term group differences were observed for cognitive outcomes; however, a significant long-term group effect indicated poorer cognitive recovery in the iNPH-AD group. Gait measures showed short-term group differences favoring the iNPH-nAD group, with no group effects at long-term follow-up, whereas urinary outcomes showed no group differences at any follow-up. AD pathology is not a contraindication to shunting; rather, AD biomarker assessment should be incorporated into the pre-shunt workup, as it can enhance outcome prediction and support tailored postoperative management.