TY - JOUR
T1 - The neurovascular unit and its correlation with cognitive performance in patients with cerebral small vessel disease
T2 - a canonical correlation analysis approach
AU - van Dinther, Maud
AU - Voorter, Paulien H.M.
AU - Zhang, Eleana
AU - van Kuijk, Sander M.J.
AU - Jansen, Jacobus F.A.
AU - van Oostenbrugge, Robert J.
AU - Backes, Walter H.
AU - Staals, Julie
N1 - Funding Information:
This study was supported by the European Union\u2019s Horizon 2020 research and innovation programme \u2018CRUCIAL\u2019 (grant number 848109), NWO (Netherlands Organisation for Scientific Research) (grant number 017.009.048), Hersenstichting (grant number 2013(1)-195) and Stichting de Wijerhorst Foundation.
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/10
Y1 - 2024/10
N2 - Growing evidence indicates an important role of neurovascular unit (NVU) dysfunction in the pathophysiology of cerebral small vessel disease (cSVD). Individually measurable functions of the NVU have been correlated with cognitive function, but a combined analysis is lacking. We aimed to perform a unified analysis of NVU function and its relation with cognitive performance. The relationship between NVU function in the white matter and cognitive performance (both latent variables composed of multiple measurable variables) was investigated in 73 patients with cSVD (mean age 70 ± 10 years, 41% women) using canonical correlation analysis. MRI-based NVU function measures included (1) the intravoxel incoherent motion derived perfusion volume fraction (f) and microvascular diffusivity (D*), reflecting cerebral microvascular flow; (2) the IVIM derived intermediate volume fraction (fint), indicative of the perivascular clearance system; and (3) the dynamic contrast-enhanced MRI derived blood–brain barrier (BBB) leakage rate (Ki) and leakage volume fraction (VL), reflecting BBB integrity. Cognitive performance was composed of 13 cognitive test scores. Canonical correlation analysis revealed a strong correlation between the latent variables NVU function and cognitive performance (r 0.73; p = 0.02). For the NVU, the dominating variables were D*, fint, and Ki. Cognitive performance was driven by multiple cognitive tests comprising different cognitive domains. The functionality of the NVU is correlated with cognitive performance in cSVD. Instead of focusing on individual pathophysiological mechanisms, future studies should target NVU dysfunction as a whole to acquire a coherent understanding of the complex disease mechanisms that occur in the NVU in cSVD. Trial registration: NTR3786 (Dutch Trial Register).
AB - Growing evidence indicates an important role of neurovascular unit (NVU) dysfunction in the pathophysiology of cerebral small vessel disease (cSVD). Individually measurable functions of the NVU have been correlated with cognitive function, but a combined analysis is lacking. We aimed to perform a unified analysis of NVU function and its relation with cognitive performance. The relationship between NVU function in the white matter and cognitive performance (both latent variables composed of multiple measurable variables) was investigated in 73 patients with cSVD (mean age 70 ± 10 years, 41% women) using canonical correlation analysis. MRI-based NVU function measures included (1) the intravoxel incoherent motion derived perfusion volume fraction (f) and microvascular diffusivity (D*), reflecting cerebral microvascular flow; (2) the IVIM derived intermediate volume fraction (fint), indicative of the perivascular clearance system; and (3) the dynamic contrast-enhanced MRI derived blood–brain barrier (BBB) leakage rate (Ki) and leakage volume fraction (VL), reflecting BBB integrity. Cognitive performance was composed of 13 cognitive test scores. Canonical correlation analysis revealed a strong correlation between the latent variables NVU function and cognitive performance (r 0.73; p = 0.02). For the NVU, the dominating variables were D*, fint, and Ki. Cognitive performance was driven by multiple cognitive tests comprising different cognitive domains. The functionality of the NVU is correlated with cognitive performance in cSVD. Instead of focusing on individual pathophysiological mechanisms, future studies should target NVU dysfunction as a whole to acquire a coherent understanding of the complex disease mechanisms that occur in the NVU in cSVD. Trial registration: NTR3786 (Dutch Trial Register).
KW - Cerebral small vessel disease
KW - Cognitive function
KW - Magnetic resonance imaging
KW - Microvascular function
KW - Neurovascular unit
U2 - 10.1007/s11357-024-01235-8
DO - 10.1007/s11357-024-01235-8
M3 - Article
SN - 2509-2715
VL - 46
SP - 5061
EP - 5073
JO - Geroscience
JF - Geroscience
IS - 5
ER -