Do Alzheimer's Disease Biomarkers Impact Normal Pressure Hydrocephalus Lumbar Drain Trial Outcomes

Distinguishing normal pressure hydrocephalus (NPH) from Alzheimer's disease (ad) would aid patient selection for lumbar drain trials (LDT). Cerebrospinal fluid (CSF) ad biomarkers are altered in NPH, limiting interpretation. This study examines the utility of CSF ad biomarkers in predicting gait and cognitive outcomes in patients undergoing LDT.127 patients underwent LDT. CSF ad biomarkers from Mayo Clinic Laboratories (MCL) or Athena Diagnostics were used to classify patients as ad, non-ad, or indeterminate. MCL indeterminate results were further classified as suspected ad, non-ad, or suspected NPH (sNPH) using a derived p-tau threshold (>15 pg/mL & Aß42 <=1026 pg/mL)1. Cognitive improvement was determined using reliable change indices for Trail Making Test A&B and Hopkins Verbal Learning Test-Revised. Physical therapists (PT) utilized the Berg Balance Scale and/or the Timed Up and Go to determine gait improvements. Chi-square tests investigated relationships between diagnostic groups, PT and cognitive improvements, and eventual shunting for the whole sample and then stratified by the two laboratory assays.The sNPH group had the highest percentage of PT (63%-70%) and cognitive (9% -11%) improvement (see Table 1), while the ad group had the lowest (50% and 3%, respectively). The sNPH group underwent shunting more (56%-68%) compared to the ad and non-ad groups (47%). Relationships, however, were not statistically significant (p > 0.05).Patients with sNPH CSF ad biomarker profiles demonstrated clinically meaningful physical improvements and underwent shunting more frequently than those with ad or non-ad biomarker profiles. This highlights the potential for CSF ad biomarkers in predicting NPH treatment response.