Analysis of Alzheimer’s Cerebrospinal Fluid Markers in Idiopathic Normal Pressure Hydrocephalus Pre- and Post-High Volume Lumbar Puncture
Lealani Acosta1, Amanda Puckett1, Anna Pfalzer1
1Vanderbilt University Medical Center
Objective:

 We hypothesized that Alzheimer’s disease (AD) biomarkers in cerebrospinal fluid (CSF) would correlate with performance on cognitive and physical therapy assessments following a high volume lumbar puncture (HVLP) in patients with idiopathic normal pressure hydrocephalus 

Background:

There is inconsistent data correlating AD biomarkers and iNPH in response to HVLP, as evidenced by mixed results in clinical studies. We sought to identify what relationship, if any, was present between AD biomarkers and iNPH assessments.

Design/Methods:
CSF AD biomarkers (total tau [ttau], phosphorylated tau, β-amyloid, amyloid tau index [ATI]) were analyzed in 166 iNPH patients who underwent HVLP. In additio  to biomarkers, we measured changes in cognitive (Montreal Cognitive Assessment, MOCA) and physical therapy assessments (gait scale, time, total gait score) pre- and post-HVLP. 
Results:

ATI was significantly negatively correlated with pre- and post-LP gait scale (pre. r=-.206, p<0.05; post. r=-.252, p<0.01) and total gait score (pre. r= -238, p<0.01; post. r= -.271, p<0.05). Ttau was significantly positively correlated with gait total score pre-HVLP (r=.217, p<0.05) and post-HVLP (r=.209, p<0.05). Interestingly, ttau was positively correlated with the length of time it took for patients to complete gait assessment (r=.184, p<0.05) only pre-HVLP. Scores on the pre- and post- HVLP MOCA were positively correlated with ATI (pre r= .451, p<0.01; post r=.421, p<0.01) and negatively correlated with ttau (pre r= -.349 ,p <0.01, post r= -.377 , p<0.01). No correlations existed between β-amyloid, phosphorylated tau, and gait and cognitive assessments.

Conclusions:

Pre- and post-HVLP measures of ttau and ATI were correlated with gait score and time and MOCA performance. These biomarkers associated with AD were correlated with lower MOCA and worse gait scores in iNPH patients. These findings suggest that AD biomarkers may predict worse performance on cognitive and gait assessments in work-up for iNPH.

10.1212/WNL.0000000000202608