title: Entorhinal cortex thickness predicts cognitive decline in Alzheimer's disease.
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.
authors.affiliation: King's College London, Institute of Psychiatry, London and NIHR Biomedical Research Centre for Mental Health, London, UK. latha.velayudhan@kcl.ac.uk
authors.forename: Latha
authors.initials: L
authors.lastname: Velayudhan
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.forename: J-Sebastian
authors.initials: JS
authors.lastname: Muehlboeck
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.forename: Iwona
authors.initials: I
authors.lastname: Kłoszewska
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Christian
authors.initials: C
authors.lastname: Spenger
authors.forename: Angela
authors.initials: A
authors.lastname: Hodges
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003072:Cognition Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D018728:Entorhinal Cortex / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric
chemical_list: D053327:Apolipoprotein E4; D002800:Cholinesterase Inhibitors