Hippocampal Disconnection in Early Alzheimer's Disease: A 7 Tesla MRI Study

Article type: Research Article

Authors: Wisse, Laura E.M.^{a; b} | Reijmer, Yael D.^{a; c} | ter Telgte, Annemieke^a | Kuijf, Hugo J.^d | Leemans, Alexander^d | Luijten, Peter R.^e | Koek, Huiberdina L.^f | Geerlings, Mirjam I.^b | Biessels, Geert Jan^{a; *} | on behalf of the Utrecht Vascular Cognitive Impairment (VCI) Study Group¹

Affiliations: [a] Department of Neurology, Brain Center Rudolf Magnus, UMC Utrecht, Utrecht, The Netherlands | [b] Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands | [c] J. Philip Kistler Stroke Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA | [d] Image Sciences Institute, UMC Utrecht, Utrecht, The Netherlands | [e] Department of Radiology, UMC Utrecht, Utrecht, The Netherlands | [f] Department of Geriatrics, UMC Utrecht, Utrecht, The Netherlands

Correspondence: [*] Correspondence to: Geert Jan Biessels, MD, PhD, University Medical Center Utrecht, Department of Neurology, G03.232, PO BOX 85500, 3508 GA, Utrecht, The Netherlands. Tel.: +31 88 7559490; 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, L.E.M. Wisse; 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 and Julius Center for Health Sciences and Primary Care, A. Algra, M.I. Geerlings, Y. Van der Graaf, G.E.H.M. Rutten.

Abstract: Background:In patients with Alzheimer’s disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. Objective:We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and parahippocampal cingulum (PHC) microstructure in patients with early AD. Methods:Twenty-five patients with amnestic mild cognitive impairment (aMCI) (n = 15) or early AD (n = 10) and 17 controls underwent 3 tesla diffusion MRI to obtain fractional anisotropy (FA) of the fornix and PHC and 7 tesla MRI to obtain ERC and hippocampal subfield volumes. Linear regression analyses were performed, adjusted for age, gender, and intracranial volume. Results:Fornix FA was significantly lower and subiculum, cornu ammonis (CA) 1, and dentate gyrus &CA4 volume were significantly smaller in patients with MCI or AD as compared to controls. In patients with MCI or AD, fornix FA was positively associated with subiculum volume (β = 0.53, 95% CI 0.10; 0.96), but not with ERC/other subfield volumes. PHC FA was not associated with ERC/subfield volumes. Conclusion:These findings indicate that in early AD subiculum atrophy is associated with lower FA of the fornix, which primarily consists of axons originating in the subiculum. This suggests that degeneration of subicular cell bodies and their axons are related processes in early AD.

Keywords: Alzheimer's disease, diffusion magnetic resonance imaging, fornix, hippocampus, mild cognitive impairment, subiculum

DOI: 10.3233/JAD-142994

Journal: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1247-1256, 2015