Multiple Microbleeds are Related to Cerebral Network Disruptions in Patients with Early Alzheimer's Disease

Article type: Research Article

Authors: Heringa, Sophie M.^{a; *} | Reijmer, Yael D.^a | Leemans, Alexander^b | Koek, Huiberdina L.^c | Kappelle, L. Jaap^a | Biessels, Geert Jan^a | on behalf of the Utrecht Vascular Cognitive Impairment (VCI) Study Group¹

Affiliations: [a] Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands | [b] Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands | [c] Department of Geriatrics, University Medical Center Utrecht, Utrecht, The Netherlands

Correspondence: [*] Correspondence to: Sophie M. Heringa, MSc, University Medical Center Utrecht, Department of Neurology G03.232, PO Box 85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 88 75 59488; Fax: +31 30 2542100; E-mail: [email protected].

Note: [1] Members of the Utrecht Vascular Cognitive Impairment Study Group involved in the present study (in alphabetical order by department): University Medical Center Utrecht, the Netherlands, Department of Neurology: E. van den Berg, G.J. Biessels, M. Brundel, W.H. Bouvy, S.M. Heringa, L.J. Kappelle, Y.D. Reijmer; Department of Radiology/Image Sciences Institute: J. de Bresser, H.J.Kuijf, A. Leemans, P.R. Luijten, W.P.Th.M.Mali, M.A. Viergever, K.L. Vincken, J.J.M. Zwanenburg; Department of Geriatrics: H.L. Koek, J.E. de Wit; Hospital Diakonessenhuis Zeist, the Netherlands: M. Hamaker, R. Faaij, M. Pleizier, E. Vriens.

Abstract: Background:Cerebral microbleeds are a manifestation of small vessel disease and are common in patients with Alzheimer’s disease (AD). However, their clinical significance in this condition is uncertain. We hypothesized that microbleeds contribute to disturbances of the cerebral network in AD and as such may affect cognition. Objective:The goal of this study was to examine the relationship between microbleeds and brain networks in patients with amnestic mild cognitive impairment (aMCI) or early AD. Methods:Sixty-seven patients (77.9 ± 7.5 years) with aMCI (n = 29) or early AD (n = 38) underwent cognitive testing and 3Tesla MRI. Microbleeds were rated visually. Diffusion tensor imaging and graph theoretical analysis were used to reconstruct brain networks and to quantify network efficiency for each patient. Network measures were compared between patients without and with ⩾1 microbleeds and between patients without or with ≥3 microbleeds. In secondary analyses, cognitive functioning was compared between groups. Analyses were adjusted for age and gender, and additionally for other markers of small vessel disease and atrophy. Results:Network measures did not differ between patients with ≥1 microbleed (n = 26) and patients without microbleeds (n = 41). However, patients with ≥3 microbleeds (n = 11) showed significant white matter disruptions, longer path length, and less global efficiency than patients without microbleeds, independent of other markers of small vessel disease and atrophy. Cognitive functioning did not differ between patients without microbleeds and patients with ≥1 or ≥3 microbleeds. Conclusion:Multiple microbleeds are related to structural network disruption in patients with early AD, but their direct impact on cognitive functioning appears to be limited.

Keywords: Alzheimer's disease, cerebral amyloid angiopathy, cerebral small vessel disease, cognition, diffusion tensor imaging, magnetic resonance imaging, microbleeds, mild cognitive impairment, network

DOI: 10.3233/JAD-130542

Journal: Journal of Alzheimer's Disease, vol. 38, no. 1, pp. 211-221, 2014