Decreased Cerebrospinal Fluid Flow Is Associated With Cognitive Deficit in Elderly Patients.

Jadwiga Attier-Zmudka,Mo Saffarini,Jeremy Valluy,Anne-Sophie Macaret,Salif Dao,Youcef Douadi,Momar Diouf,Krzysztof Piotr Malinowski,Jean-Marie Sérot,Olivier Balédent

doi:10.3389/fnagi.2019.00087

Abstract

Background: Disruptions in cerebrospinal fluid (CSF) flow during aging could compromise protein clearance from the brain and contribute to the etiology of Alzheimer’s Disease (AD).Objective: To determine whether CSF flow is associated with cognitive deficit in elderly patients (>70 years).Methods: We studied 92 patients admitted to our geriatric unit for non-acute reasons using phase-contrast magnetic resonance imaging (PC-MRI) to calculate their ventricular and spinal CSF flow, and assessed their global cognitive status, memory, executive functions, and praxis. Multivariable regressions with backward selection (criterion p < 0.15) were performed to determine associations between cognitive tests and ventricular and spinal CSF flow, adjusting for depression, anxiety, and cardiovascular risk factors.Results: The cohort comprised 71 women (77%) and 21 (33%) men, aged 84.1 ± 5.2 years (range, 73–96). Net ventricular CSF flow was 52 ± 40 μL/cc (range, 0–210), and net spinal CSF flow was 500 ± 295 μL/cc (range, 0–1420). Ventricular CSF flow was associated with the number of BEC96 figures recognized (β = 0.18, CI, 0.02–0.33; p = 0.025). Spinal CSF flow was associated with the WAIS Digit Span Backward test (β = 0.06, CI, 0.01–0.12; p = 0.034), and categoric verbal fluency (β = 0.53, CI, 0.07–0.98; p = 0.024) and semantic verbal fluency (β = 0.55, CI, 0.07–1.02; p = 0.024).Conclusion: Patients with lower CSF flow had significantly worse memory, visuo-constructive capacities, and verbal fluency. Alterations in CSF flow could contribute to some of the cognitive deficit observed in patients with AD. Diagnosis and treatment of CSF flow alterations in geriatric patients with neurocognitive disorders could contribute to the prevention of their cognitive decline.

Highlights

The cerebrospinal fluid (CSF) is an important part of the central nervous system, as it allows exchange of water, small molecules and proteins between the brain parenchyma and arterial and venous blood (Oreskovic and Klarica, 2010; Brinker et al, 2014), by either passive diffusion or active transport (Oreskovic and Klarica, 2014; Oreskovic et al, 2017b)
Since this CSF flow is important for protein clearance from the brain (Puy et al, 2016), it is possible that impaired CSF flow could be associated with cognitive decline (Coblentz et al, 1973; Sohn et al, 1973; Rubenstein, 1998)
A number of studies suggested that the choroid plexus and the ventricular walls degenerate with the progression of Alzheimer’s disease (AD) (Serot et al, 2000; Balusu et al, 2016; Daouk et al, 2016), but none could determine whether disrupted CSF flow causes cognitive decline, or whether it is a by-product of AD or normal aging

Summary

Introduction

The cerebrospinal fluid (CSF) is an important part of the central nervous system, as it allows exchange of water, small molecules and proteins between the brain parenchyma and arterial and venous blood (Oreskovic and Klarica, 2010; Brinker et al, 2014), by either passive diffusion or active transport (Oreskovic and Klarica, 2014; Oreskovic et al, 2017b). The increase of intracranial pressure during the cardiac cycle causes a flow from the blood and brain interstitial fluid to the CSF, and a net CSF flow toward its extracerebral compartment and venous blood (Oreskovic et al, 2017a) Since this CSF flow is important for protein clearance from the brain (Puy et al, 2016), it is possible that impaired CSF flow could be associated with cognitive decline (Coblentz et al, 1973; Sohn et al, 1973; Rubenstein, 1998). Disruptions in cerebrospinal fluid (CSF) flow during aging could compromise protein clearance from the brain and contribute to the etiology of Alzheimer’s Disease (AD)

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Discussion

Conclusion