Intracranial Pressure Dynamics and Cerebrospinal Fluid Outflow Resistance in the Elderly: Associations With 10-Year Changes in Cognitive Function and Ventricular Volume

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Abstract
BACKGROUND AND OBJECTIVES: Glymphatic function affects brain health and could be part of the pathophysiology in idiopathic normal-pressure hydrocephalus. Elevated intracranial pressure pulsatility and increased resistance to cerebrospinal fluid (CSF) outflow (R out ) are commonly observed in idiopathic normal-pressure hydrocephalus. Whether such alterations indicate impaired glymphatic function or affect ventricle volumetrics in ordinary elderly is unknown. We investigated the associations between CSF dynamics and changes in cognitive performance, gait, and brain MRI parameters over a 10-year period in a cohort of healthy older adults. METHODS: Twenty-nine subjects (mean age 79 ± 6, range 71-92 years) were investigated with brain MRI, clinical testing, and a CSF infusion test. MRI and clinical testing were repeated after 10 years. An automated software program was used to calculate ventricle volumes, and linear ventricle radiological indices were calculated (Evan's index, callosal angle, and z-Evan's index). CSF dynamic parameters were correlated with longitudinal changes in clinical and MRI parameters. RESULTS: In a multivariable regression model including age, sex, baseline cognitive performance, and CSF dynamic parameters, lower CSF outflow resistance was associated with better cognitive performance after 10 years (standardized β = 0.37, P = .047, n = 29). In a bivariate analysis, outflow resistance had a negative correlation to the difference in cognitive testing score between baseline and follow-up (r = −.44, 95% CI −0.701 to −0.08, P = .017, n = 29, Spearman's rho). CSF dynamic parameters were not associated with changes in gait performance or ventricle volume. Intracranial pressure pulsatility was associated with reduced callosal angle (standardized β = −0.35, P = .02, n = 29) and intracranial pressure with increased z-Evan's index (standardized β = 0.18, P = .003, n = 29). CONCLUSION: Our results provide insight into the complexity of CSF physiology and its possible role in longitudinal change in brain function and structure. Measurement of CSF outflow characteristics hold potential in furthering the understanding of glymphatic performance with regard to change in cognitive function and warrants further investigation.
Funding Information
  • Hjärt-Lungfonden
  • Hjärt-Lungfonden
  • Västerbotten Läns Landsting
  • Stiftelsen för Strategisk Forskning

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