Alzheimer's disease core biomarkers are associated with worse baseline and postoperative cognitive profiles in idiopathic normal pressure hydrocephalus: findings from the Bologna PRO-Hydro study.
Chiara Riccietti, Luisa Sambati, Corrado Zenesini, Simone Baiardi, Maria Sasca Criante, Antonella D'Apolito, David Milletti, Luca Albini-Riccioli, Barbara Polischi, Giovanna Calandra-Buonaura, Elena Magelli, Davide Mascarella, Liliana Mazza, Luca Baldelli, Michelangelo Stanzani-Maserati, Pietro Cortelli, Sabina Cevoli, Giorgio Palandri, Piero Parchi, Giulia Giannini
{"title":"Alzheimer's disease core biomarkers are associated with worse baseline and postoperative cognitive profiles in idiopathic normal pressure hydrocephalus: findings from the Bologna PRO-Hydro study.","authors":"Chiara Riccietti, Luisa Sambati, Corrado Zenesini, Simone Baiardi, Maria Sasca Criante, Antonella D'Apolito, David Milletti, Luca Albini-Riccioli, Barbara Polischi, Giovanna Calandra-Buonaura, Elena Magelli, Davide Mascarella, Liliana Mazza, Luca Baldelli, Michelangelo Stanzani-Maserati, Pietro Cortelli, Sabina Cevoli, Giorgio Palandri, Piero Parchi, Giulia Giannini","doi":"10.1186/s12987-026-00836-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome affecting the elderly. Recent studies have reported a high prevalence of neurodegenerative copathologies in iNPH, particularly Alzheimer's disease (AD). Neuropsychological studies in iNPH sample revealed variable and heterogeneous cognitive profile. Few studies have examined cognitive differences according to neurodegenerative copathology, and none has systematically applied a comprehensive neuropsychological battery while stratifying patients by AD biomarkers both before and after surgery. The main objective of this study was to assess baseline differences in the neuropsychological profile of iNPH patients with and without AD core biomarkers, using a comprehensive neuropsychological battery. The secondary aim was to investigate changes in neuropsychological functions from baseline to short-term postoperative outcomes in the overall sample and in subgroups with and without AD biomarkers.</p><p><strong>Methods: </strong>Patients underwent a standardized inpatient work-up including clinical evaluation, comprehensive neuropsychological assessment, and cerebrospinal fluid (CSF) biomarkers analysis. A multidisciplinary team selected candidates for surgery. An extensive clinical and neuropsychological reassessment was performed six months after surgery.</p><p><strong>Results: </strong>From 2015 to 2025, 226 (97 females) consecutive iNPH patients completed the baseline evaluation. Among these, 102 shunted iNPH patients (46 females) underwent six-month postoperative neuropsychological assessment. The cognitive profile in all individuals revealed deficits in attentive-executive functions with a significant improvement after surgery. Overall, 24.3% of iNPH participants showed a pathological phosphorylated tau/beta-amyloid 1-42 ratio (pTau/Aβ42+). At baseline, pTau/Aβ42+ (n = 53) patients revealed worse neuropsychological performances than those (n = 165) with normal pTau/Aβ ratio (pTau/Aβ42-), with more pronounced memory impairment. At six-month follow-up, the pTau/Aβ42 + group exhibited poorer cognitive outcomes compared to pTau/Aβ42- one, particularly in general cognition, short- and long-term verbal and visuo-spatial memory, and executive functions.</p><p><strong>Conclusions: </strong>Nearly one-quarter of patients exhibited AD core biomarkers positivity. iNPH patients with AD core biomarkers copathology showed an earlier cognitive onset and worse neuropsychological performances at baseline. At follow-up, the pTau/Aβ42 + group demonstrated poorer cognitive outcomes in specific cognitive domains compared to the pTau/Aβ42 - group. These differences in cognitive profiles at baseline and six months after surgery in iNPH patients with AD core biomarker positivity may have clinical relevance.</p>","PeriodicalId":12321,"journal":{"name":"Fluids and Barriers of the CNS","volume":" ","pages":""},"PeriodicalIF":7.2000,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551918/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fluids and Barriers of the CNS","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12987-026-00836-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome affecting the elderly. Recent studies have reported a high prevalence of neurodegenerative copathologies in iNPH, particularly Alzheimer's disease (AD). Neuropsychological studies in iNPH sample revealed variable and heterogeneous cognitive profile. Few studies have examined cognitive differences according to neurodegenerative copathology, and none has systematically applied a comprehensive neuropsychological battery while stratifying patients by AD biomarkers both before and after surgery. The main objective of this study was to assess baseline differences in the neuropsychological profile of iNPH patients with and without AD core biomarkers, using a comprehensive neuropsychological battery. The secondary aim was to investigate changes in neuropsychological functions from baseline to short-term postoperative outcomes in the overall sample and in subgroups with and without AD biomarkers.
Methods: Patients underwent a standardized inpatient work-up including clinical evaluation, comprehensive neuropsychological assessment, and cerebrospinal fluid (CSF) biomarkers analysis. A multidisciplinary team selected candidates for surgery. An extensive clinical and neuropsychological reassessment was performed six months after surgery.
Results: From 2015 to 2025, 226 (97 females) consecutive iNPH patients completed the baseline evaluation. Among these, 102 shunted iNPH patients (46 females) underwent six-month postoperative neuropsychological assessment. The cognitive profile in all individuals revealed deficits in attentive-executive functions with a significant improvement after surgery. Overall, 24.3% of iNPH participants showed a pathological phosphorylated tau/beta-amyloid 1-42 ratio (pTau/Aβ42+). At baseline, pTau/Aβ42+ (n = 53) patients revealed worse neuropsychological performances than those (n = 165) with normal pTau/Aβ ratio (pTau/Aβ42-), with more pronounced memory impairment. At six-month follow-up, the pTau/Aβ42 + group exhibited poorer cognitive outcomes compared to pTau/Aβ42- one, particularly in general cognition, short- and long-term verbal and visuo-spatial memory, and executive functions.
Conclusions: Nearly one-quarter of patients exhibited AD core biomarkers positivity. iNPH patients with AD core biomarkers copathology showed an earlier cognitive onset and worse neuropsychological performances at baseline. At follow-up, the pTau/Aβ42 + group demonstrated poorer cognitive outcomes in specific cognitive domains compared to the pTau/Aβ42 - group. These differences in cognitive profiles at baseline and six months after surgery in iNPH patients with AD core biomarker positivity may have clinical relevance.
期刊介绍：
"Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease.
At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
