Small vessel disease burden and functional brain connectivity in mild cognitive impairment

Sofia Marcolini; Jaime D Mondragón; Esther E Bron; Geert J Biessels; Jurgen A H R Claassen; Janne M Papma; Huub Middelkoop; Rudi A J O Dierckx; Ronald J H Borra; Inez H G B Ramakers; Wiesje M van der Flier; Natasha M Maurits; Peter P De Deyn

doi:10.1016/j.cccb.2023.100192

Small vessel disease burden and functional brain connectivity in mild cognitive impairment

Cereb Circ Cogn Behav. 2023 Dec 3:6:100192. doi: 10.1016/j.cccb.2023.100192. eCollection 2024.

Authors

Sofia Marcolini¹, Jaime D Mondragón^{1

2

3}, Esther E Bron⁴, Geert J Biessels⁵, Jurgen A H R Claassen^{6

7}, Janne M Papma^{4

8}, Huub Middelkoop^{9

10}, Rudi A J O Dierckx¹¹, Ronald J H Borra¹¹, Inez H G B Ramakers¹², Wiesje M van der Flier^{13

14}, Natasha M Maurits¹, Peter P De Deyn^{1

15}

Affiliations

¹ Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands.
² Universidad Nacional Autónoma de México, Instituto de Neurobiología, Departamento de Neurobiología Conductual y Cognitiva, Laboratorio de Psicofisiología, Querétaro 76230, Mexico.
³ San Diego State University, Department of Psychology, Life-Span Human Senses Lab, San Diego, California 92182, USA.
⁴ Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam 3015 GD, the Netherlands.
⁵ Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands.
⁶ Department of Geriatrics, Radboud University Medical Center and Donders Institute, Nijmegen 6525 GD, the Netherlands.
⁷ Department of Cardiovascular Sciences, University of Leicester, Leicester LE1 7RH, United Kingdom.
⁸ Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam 3015 GD, the Netherlands.
⁹ Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, Leiden 2316 XC, the Netherlands.
¹⁰ Department of Neurology, Leiden University Medical Centre, Leiden 2333 ZA, the Netherlands.
¹¹ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands.
¹² Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht 6229 ER, the Netherlands.
¹³ Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam 1081 HZ, the Netherlands.
¹⁴ Department of Epidemiology & Data Sciences, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam 1117, the Netherlands.
¹⁵ Laboratory of Neurochemistry and Behavior, University of Antwerp, Antwerp 2610, Belgium.

Abstract

Background: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing.

Method: Functional brain connectivity differences were analyzed between mild cognitive impairment individuals with absent or low (n = 34) and high (n = 34) small vessel disease burden using data from the Parelsnoer Institute, a Dutch multicenter study. Small vessel disease was characterized using an ordinal scale considering: lacunes, microbleeds, perivascular spaces in the basal ganglia, and white matter hyperintensities. Resting state functional MRI data using 3 Tesla scanners was analyzed with group-independent component analysis using the CONN toolbox.

Results: Functional connectivity between areas of the cerebellum and between the cerebellum and the thalamus and caudate nucleus was higher in the absent or low small vessel disease group compared to the high small vessel disease group.

Conclusion: These findings might suggest that functional connectivity of mild cognitive impairment individuals with low or absent small vessel disease burden is more intact than in mild cognitive impairment individuals with high small vessel disease. These brain areas are mainly responsible for motor, attentional and executive functions, domains which in previous studies were found to be mostly associated with small vessel disease markers. Our results support findings on the involvement of the cerebellum in cognitive functioning.

Keywords: Alzheimer's disease; Disease mechanisms; Microvessels; Neurovascular coupling; Risk factors.