Differences in Cortical Thickness in Healthy Controls, Subjects with Mild Cognitive Impairment, and Alzheimer's Disease Patients: A Longitudinal Study

Article type: Research Article

Authors: Julkunen, Valtteri^a | Niskanen, Eini^{a; b} | Koikkalainen, Juha^c | Herukka, Sanna-Kaisa^d | Pihlajamäki, Maija^a | Hallikainen, Merja^d | Kivipelto, Miia^{d; e} | Muehlboeck, Sebastian^f | Evans, Alan C.^f | Vanninen, Ritva^g | Soininen, Hilkka^{a; d; *}

Affiliations: [a] Department of Neurology, Kuopio University Hospital, Kuopio, Finland | [b] Department of Physics, University of Eastern Finland, Kuopio, Finland | [c] VTT Technical Research Centre of Finland, Tampere, Finland | [d] Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland | [e] Aging Research Center, Karolinska Institutet, Stockholm, Sweden | [f] McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University Montreal, PQ, Canada | [g] Department of Radiology, Kuopio University Hospital, Kuopio, Finland

Correspondence: [*] Correspondence to: Hilkka Soininen, MD, PhD, Professor, Department of Neurology, Kuopio University Hospital, P.O.Box 1777, FI-70211, Kuopio, Finland. Tel.: +358 17 173012; Fax: +358 17 173019; E-mail: [email protected].

Abstract: In this study, we analyzed differences in cortical thickness (CTH) between healthy controls (HC), subjects with stable mild cognitive impairment (S-MCI), progressive MCI (P-MCI), and Alzheimer's disease (AD), and assessed correlations between CHT and clinical disease severity, education, and apolipoprotein E4 (APOE) genotype. Automated CTH analysis was applied to baseline high-resolution structural MR images of 145 subjects with a maximum follow-up time of 7.4 years pooled from population-based study databases held in the University of Kuopio. Statistical differences in CTH between study groups and significant correlations between CTH and clinical and demographic factors were assessed and displayed on a cortical surface model. Compared to HC group (n =26), the AD (n = 21) group displayed significantly reduced CTH in several areas of frontal and temporal cortices of the right hemisphere. Higher education and lower MMSE scores were correlated with reduced CTH in the AD group, whereas no significant correlation was found between CDR-SB scores or APOE genotype and CTH. The P-MCI group demonstrated significantly reduced CTH compared to S-MCI in frontal, temporal and parietal cortices even after statistically adjusting for all confounding variables. Ultimately, analysis of CTH can be used to detect cortical thinning in subjects with progressive MCI several years before conversion and clinical diagnosis of AD dementia, irrespective of their cognitive performance, education level, or APOE genotype.

Keywords: Alzheimer's disease, apolipoprotein E, cortical thickness, magnetic resonance imaging, mild cognitive impairment

DOI: 10.3233/JAD-2010-100114

Journal: Journal of Alzheimer's Disease, vol. 21, no. 4, pp. 1141-1151, 2010