Editors' note: Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition

Abstract

High-convexity tight sulci (HCTS) has emerged in the last decade as a radiographic biomarker among cognitively impaired individuals with enlarged subarachnoid spaces, with most of the literature reporting an association with normal pressure hydrocephalus (NPH) and responsiveness to CSF shunting. Using their previously validated, automated imaging analysis of HCTS—which was further validated by a neuroradiologist in this investigation—Drs. Graff-Radford and colleagues explored the relationships between HCTS and various cognitive and radiographic parameters in a cohort of 684 patients aged ≥50 years. Patients with HCTS had more frequent cognitive impairment, subcortical microvascular ischemic disease with lower white matter and cortical volumes, and (most importantly) lower Tau burden. The investigators reported that the lower Tau burden in patients with HCTS indicated that subarachnoid space enlargement could not be related to Alzheimer pathology. Furthermore, the fact that HCTS correlated strongly with less cortical volume (which might otherwise suggest an underlying tauopathy) suggests that this imaging signature could be used to identify a subgroup of cognitively impaired patients without Alzheimer pathology and who may not respond to targeted Alzheimer therapeutics. Drs. Alali and Laticevschi recall their related observations from the Geneva NPH cohort, which further validate HCTS as a radiographic indicator of a nontauopathy condition. Together, these studies typify biomarkers like HCTS as indicators of a nontauopathy state, which could be useful in future clinical trials enrolling patients with neurodegenerative conditions. High-convexity tight sulci (HCTS) has emerged in the last decade as a radiographic biomarker among cognitively impaired individuals with enlarged subarachnoid spaces, with most of the literature reporting an association with normal pressure hydrocephalus (NPH) and responsiveness to CSF shunting. Using their previously validated, automated imaging analysis of HCTS—which was further validated by a neuroradiologist in this investigation—Drs. Graff-Radford and colleagues explored the relationships between HCTS and various cognitive and radiographic parameters in a cohort of 684 patients aged ≥50 years. Patients with HCTS had more frequent cognitive impairment, subcortical microvascular ischemic disease with lower white matter and cortical volumes, and (most importantly) lower Tau burden. The investigators reported that the lower Tau burden in patients with HCTS indicated that subarachnoid space enlargement could not be related to Alzheimer pathology. Furthermore, the fact that HCTS correlated strongly with less cortical volume (which might otherwise suggest an underlying tauopathy) suggests that this imaging signature could be used to identify a subgroup of cognitively impaired patients without Alzheimer pathology and who may not respond to targeted Alzheimer therapeutics. Drs. Alali and Laticevschi recall their related observations from the Geneva NPH cohort, which further validate HCTS as a radiographic indicator of a nontauopathy condition. Together, these studies typify biomarkers like HCTS as indicators of a nontauopathy state, which could be useful in future clinical trials enrolling patients with neurodegenerative conditions.