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Entorhinal Cortex Thickness Predicts Cognitive Decline in Alzheimer's Disease

Article type: Research Article

Authors: Velayudhan, Lathaa; b; * | Proitsi, Petroulaa | Westman, Ericc | Muehlboeck, J-Sebastiand | Mecocci, Patriziae | Vellas, Brunof | Tsolaki, Magdag | Kłoszewska, Iwonah | Soininen, Hilkkai | Spenger, Christiand | Hodges, Angelaa | Powell, Johna | Lovestone, Simona | Simmons, Andrewa | AddNeuroMed consortium

Affiliations: [a] King's College London, Institute of Psychiatry, London and NIHR Biomedical Research Centre for Mental Health, London, UK | [b] Department of Health Sciences, University of Leicester, Leicester, UK | [c] Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden | [d] Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden | [e] Institute of gerontology and Geriatrics, University of Perugia, Perugia, Italy | [f] INSERM U 558, University of Toulouse, Toulouse, France | [g] 3rd Department of Neurology, Medical School, Aristotle University Thessaloniki, Thessaloniki, Greece | [h] Medical University of Lodz, Lodz, Poland | [i] Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

Correspondence: [*] Correspondence to: Latha Velayudhan, Department of Old Age Psychiatry, King's College London, Institute of Psychiatry, De Crespigny Park, London, UK. Tel.: +44 41 2078480508; Fax: +44 41 2078480625; E-mails: [email protected]; [email protected].

Keywords: Alzheimer's disease, biomarker, cognitive decline, entorhinal cortex, hippocampus, whole brain volume

DOI: 10.3233/JAD-2012-121408

Journal: Journal of Alzheimer's Disease, vol. 33, no. 3, pp. 755-766, 2013

Accepted 27 August 2012
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Published: 10 January 2013
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Abstract

Biomarkers for Alzheimer's disease (AD) based on non-invasive methods are highly desirable for diagnosis, disease progression, and monitoring therapeutics. We aimed to study the use of hippocampal volume, entorhinal cortex (ERC) thickness, and whole brain volume (WBV) as predictors of cognitive change in patients with AD. 120 AD subjects, 106 mild cognitive impairment (MCI), and 99 non demented controls (NDC) from the multi-center pan-European AddNeuroMed study underwent MRI scanning at baseline and clinical evaluations at quarterly follow-up up to 1 year. The rate of cognitive decline was estimated using cognitive outcomes, Mini-Mental State Examination (MMSE) and Alzheimer disease assessment scale–cognitive (ADAS-cog) by fitting a random intercept and slope model. AD subjects had smaller ERC thickness and hippocampal and WBV volumes compared to MCI and NDC subjects. Within the AD group, ERC > WBV was significantly associated with baseline cognition (MMSE, ADAS-cog) and disease severity (Clinical Dementia Rating). Baseline ERC thickness was associated with both longitudinal MMSE and ADAS-cog score changes and WBV with ADAS-cog decline. These data indicate that AD subjects with thinner ERC had lower baseline cognitive scores, higher disease severity, and predicted greater subsequent cognitive decline at one year follow up. ERC is a region known to be affected early in the disease. Therefore, the rate of atrophy in this structure is expected to be higher since neurodegeneration begins earlier. Focusing on structural analyses that predict decline can identify those individuals at greatest risk for future cognitive loss. This may have potential for increasing the efficacy of early intervention.

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