INTRACRANIAL FLUIDS DYNAMICS ALTERATIONS AND CORTICAL THICKNESS
Alexandra Vallet1,2, Sylvie Lorthois1, Nicolas Chauveau2, Natalia Del Campo2, Laurent Balardy3, Patrice Peran2, Armelle Lokossou4, Olivier Baledent4, Pierre Payoux2, Eric Schmidt2,3.
- Inst. de Mecanique des Fluides de Toulouse UMR 5502, Toulouse, France
- TONIC UMR 1214, INSERM, Toulouse, France
- University hospital, Toulouse, France
- BIOFLOW EA 7516, Amiens, France
The issue of cortical atrophy is important in normal aging and disease since it is associated with cognitive  and physical impairments . Moreover, cortical atrophy is potentially a relevant biomarker for the early diagnosis of Alzheimer’s disease (AD) [3,4].
Besides, the vascular component is also an integral part of AD and other late-life neurodegenerative diseases. Abnormalities in blood flow appear before accumulation of abnormal proteins in AD . Vascular alterations lead to hypoperfusion, oxidative stress and inflammation, which in turn lead to damage of neurons, glia and myelin, predominantly in the white mater .
Implication of vascular pathologies for gray matter however remains unclear. A recent study  showed that altered cerebral hemodyamics in asymptomatic carotid artery stenosis is associated with cortical thinning. However there is no proven link between vascular pathologies and cortical thinning.
We hypothesize that there is a link between altered cerebral hemodynamics and loss of cortical thickness during brain aging.
The objective of this study is to combine biomechanical and imaging approach in order to assess both fluid dynamics alterations and brain structural modifications and assess the relationship between those two component of brain aging.
The study was based on a cohort of 80 patients suspected of hydrocephalus. All patients complained of gait alteration, urinary difficulties, mild apathy and present ventriculomegaly on brain imaging. They underwent brain MRI with T1 weighted images to quantify cortical thickness and phase contrast images to measure arterial, venous and CSF velocities. Lumbar infusion test was also performed to gauge lumbar pressure, a surrogate marker of intracranial pressure (ICP), and CSF dynamics. The cortical volumetric segmentation was done by an automatic post-processing analysis with FREESURFER. Venous, arterial and CSF velocities were measured from PCMRI with BIOFLOWIMAGE software. ICP and CSF dynamics were extracted form infusion tests. Pearson correlations were calculated between cortical thickness and arterial, venous and CSF velocities, but also ICP and derived indices.
Mean cortical thickness was positively correlated with ICP pulse amplitude (r=0.43, p=0.001), mean ICP (r=0.48, p=0.001) and arterial mean flux (r=0.44, p=0.001).
We observed that cortical thickness is positively correlated with CSF pulsatility and arterial mean flux. This is counter intuitive as pulsatiliy is usually thought  to induce ischemia and brain damage, leading to cortical thinning and reduced cerebral blood flow. This process may be non linear.
The relationship between vascular alterations at the macroscale level and the pathobiology of cortical atrophy needs to be further studied. For that purpose, we are currently developing a biomechanical model of cerebral blood and CSF pulsatility. This model will be used to provide a deeper interpretation of our clinical data.
 Correlation between rates of brain atrophy and cognitive decline in AD. N.C. Fox, R.I. Scahill, W.R. Crum, M.N. Rossor . Neurology May 1999, 52 (8) 1687; DOI: 10.1212/WNL.52.8.1687
 Reduced cerebellar gray matter is a neural signature of physical frailty. Wei‐Ta Chen Kun‐Hsien Chou Li‐Kuo Liu Pei‐Lin Lee Wei‐Ju Lee Liang‐Kung Chen Pei‐Ning Wang Ching‐Po Lin. Hum Brain Mapp. 2015 Sep;36(9):3666-76. doi: 10.1002/hbm.22870
 Early diagnosis of Alzheimer’s disease using cortical thickness: impact of cognitive reserve. Querbes O, Aubry F, Pariente J, Lotterie JA, Démonet JF, Duret V, Puel M, Berry I, Fort JC, Celsis P. Brain. 2009 Aug;132(Pt 8):2036-47. doi: 10.1093/brain/awp105.
 Associations between the Frailty Index and Brain Atrophy: The Treviso Dementia (TREDEM) Registry. Gallucci M, Piovesan C, Di Battista ME. J Alzheimers Dis. 2018;62(4):1623–1634. PMID: 29504533
 Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Iturria-Medina Y, Sotero RC, Toussaint PJ, et al (2016) Nature Communications 7:11934. https://doi.org/10.1038/ncomms11934
 Neuropathology of cerebrovascular diseases. Ferrer I et al. Handb Clin Neurol. 2017;145:79-114.
 Altered cerebral hemodyamics and cortical thinning in asymptomatic carotid artery stenosis. Marshall RS et al. PLoS One. 2017 Dec 14;12(12):e0189727.
 The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility. Wagshul ME, Eide PK, Madsen JR (2011) Fluids and Barriers of the CNS 8:5. https://doi.org/10.1186/2045-8118-8-5