Total MRI Small Vessel Disease Burden Correlates with Cognitive Performance, Cortical Atrophy, and Network Measures in a Memory Clinic Population

Article type: Research Article

Authors: Banerjee, Gargi^{a; 1} | Jang, Hyemin^{b; 1} | Kim, Hee Jin^{b; c} | Kim, Sung Tae^d | Kim, Jae Seung^e | Lee, Jae Hong^f | Im, Kiho^g | Kwon, Hunki^h | Lee, Jong Min^h | Na, Duk L.^{b; c} | Seo, Sang Won^{b; c} | Werring, David John^{a; *}

Affiliations: [a] Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK | [b] Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea | [c] Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea | [d] Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea | [e] Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea | [f] Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea | [g] Division of Newborn Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA | [h] Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Professor David J. Werring, UCL Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Russell Square House, 10 - 12 Russell Square, London WC1B 5EH, UK. Tel.: +44 20 3108 7493; Fax: +44 20 7833 8613; E-mail: d.werring@ucl.ac.uk.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Recent evidence suggests that combining individual imaging markers of cerebral small vessel disease (SVD) may more accurately reflect its overall burden and better correlate with clinical measures. Objective:We wished to establish the clinical relevance of the total SVD score in a memory clinic population by investigating the association with SVD score and cognitive performance, cortical atrophy, and structural network measures, after adjusting for amyloid-β burden. Methods:We included 243 patients with amnestic mild cognitive impairment (MCI), Alzheimer’s disease dementia, subcortical vascular MCI, or subcortical vascular dementia. All underwent MR and [11C] PiB-PET scanning and had standardized cognitive testing. Multiple linear regression was used to evaluate the relationships between SVD score and cognition, cortical thickness, and structural network measures. Path analyses were performed to evaluate whether network disruption mediates the effects of SVD score on cortical thickness and cognition. Results:Total SVD score was associated with the performance of frontal (β – 4.31, SE 2.09, p = 0.040) and visuospatial (β – 0.95, SE 0.44, p = 0.032) tasks, and with reduced cortical thickness in widespread brain regions. Total SVD score was negatively correlated with nodal efficiency, as well as changes in brain network organization, with evidence of reduced integration and increasing segregation. Path analyses showed that the associations between SVD score and frontal and visuospatial scores were partially mediated by decreases in their corresponding nodal efficiency and cortical thickness. Conclusion:Total SVD burden has clinical relevance in a memory clinic population and correlates with cognition, and cortical atrophy, as well as structural network disruption.

Keywords: Alzheimer’s disease, cerebral small vessel diseases, cognitive dysfunction, magnetic resonance imaging, positron-emission tomography, vascular dementia

DOI: 10.3233/JAD-170943

Journal: Journal of Alzheimer's Disease, vol. 63, no. 4, pp. 1485-1497, 2018