title: Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer's Dementia.
abstract: Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with cognitive impairments and cortical thinning, and begins in medial perirhinal cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction (e.g., semantic object memory impairments) may predate or accompany ERC (i.e., episodic memory) dysfunction in the preclinical course of typical AD. We developed formulae estimating mPRC and ERC integrity (i.e., cortical thickness) using common neuropsychological tests in 31 healthy individuals and 58 early AD patients. These formulae estimated the longitudinal courses of mPRC and ERC functioning in independent groups of 28 optimally healthy individuals who developed AD (NC-AD) over 2.8-13.4 years and 28 pairwise-matched, stable, healthy individuals (NC-NC). Mixed models demonstrated significantly worse NC-AD than NC-NC estimated mPRC and ERC functioning at the earliest observation, 12 years preceding diagnosis, and a significant decline 4 years preceding the AD diagnosis. These findings demonstrate that specific neuropsychological impairments occur early in the course of preclinical AD and that tasks measuring mPRC functioning may serve as additional, powerful markers of preclinical AD.
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix-Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Daniela I
authors.initials: DI
authors.lastname: Hirni
authors.affiliation: Department of Neuroscience and Biomedical Engineering, Aalto University, School of Science, AALTO, Finland.
authors.forename: Sasa L
authors.initials: SL
authors.lastname: Kivisaari
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix-Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Krumm
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix-Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Andreas U
authors.initials: AU
authors.lastname: Monsch
authors.affiliation: Department of Mathematics & Technology, RheinAhrCampus, Remagen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Berres
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix-Platter Hospital, Basel, Switzerland.
authors.forename: Fatma
authors.initials: F
authors.lastname: Oeksuez
authors.affiliation: Department of Radiology, Division of Diagnostic and Interventional Neuroradiology University of Basel Hospital, Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Reinhardt
authors.affiliation: Institute of Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany.|Medical Radiological Institute (MRI), Zurich, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ulmer
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix-Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Reto W
authors.initials: RW
authors.lastname: Kressig
authors.affiliation: University of Basel, Basel, Switzerland.|Department of Radiology, Division of Diagnostic and Interventional Neuroradiology University of Basel Hospital, Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stippich
authors.affiliation: Memory Clinic, University Center for Medicine of Aging Basel, Felix-Platter Hospital, Basel, Switzerland.|University of Basel, Basel, Switzerland.|Centre for Speech, Language and the Brain, Department of Experimental Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Kirsten I
authors.initials: KI
authors.lastname: Taylor
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology*; D018728:Entorhinal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D009483:Neuropsychological Tests; D000071039:Perirhinal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D062706:Prodromal Symptoms; D012660:Semantics
keywords: Episodic memory; longitudinal; neurofibrillary pathology; preclinical cognitive marker; rhinal cortex; semantic memory