Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project: a ‘EuropeanADNIstudy’

• DOI: 10.1111/joim.12482
• Publication Date: 2016-03-05T16:19:45Z
• Authors: S. Galluzzi; M. Marizzoni; C. Babiloni; D. Albani; L. Antelmi; C. Bagnoli; D. Bartres‐Faz; S. Cordone; M. Didic; L. Farotti; U. Fiedler; G. Forloni; N. Girtler; T. Hensch; J. Jovicich; A. Leeuwis; C. Marra; J. L. Molinuevo; F. Nobili; J. Pariente; L. Parnetti; P. Payoux; C. Del Percio; J.‐P. Ranjeva; E. Rolandi; P. M. Rossini; P. Schönknecht; A. Soricelli; M. Tsolaki; P. J. Visser; J. Wiltfang; J. C. Richardson; R. Bordet; O. Blin; G. B. Frisoni
• Keywords: Male; Amyloid beta-Peptide; Genotype; Medizin; tau Proteins; Prodromal AD; Neuropsychological Tests; Spinal Puncture; info:eu-repo/classification/ddc/616.89; ddc:616.89; 03 medical and health sciences; Magnetic resonance imaging; Apolipoproteins E; 0302 clinical medicine; Peptide Fragment; Alzheimer Disease; 616; Internal Medicine; Humans; biomarkers; electroencephalography; magnetic resonance imaging; mild cognitive impairment; prodromal AD; internal medicine; Aged; [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology; Amyloid beta-Peptides; tau Protein; Mild cognitive impairment; Brain; Electroencephalography; Biomarker; Magnetic Resonance Imaging; Peptide Fragments; 3. Good health; biomarkers; electroencephalography; magnetic resonance imaging; mild cognitive impairment; prodromal AD; Biomarkers; Electroencephalography; Magnetic resonance imaging; Mild cognitive impairment; Prodromal AD; Internal Medicine; Neuropsychological Test; Female; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; Biomarkers; Human

AbstractBackgroundIn the field of Alzheimer's disease (AD), the validation of biomarkers for earlyADdiagnosis and for use as a surrogate outcome inADclinical trials is of considerable research interest.ObjectiveTo characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromalADin amnestic mild cognitive impairment (aMCI) patients enrolled in theIMI WP5 PharmaCog (also referred to as the EuropeanADNIstudy).MethodsA total of 147aMCIpatients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid β peptide 1–42 (Aβ42), tau and p‐tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusionMRI) andEEG(with resting‐state and auditory oddball event‐related potential (AO‐ERP) paradigm) biomarkers were evaluated.ResultsProdromalADwas found in 55aMCIpatients defined by low Aβ42 in the cerebrospinal fluid (Aβ positive). Compared to theaMCIgroup with high Aβ42 levels (Aβ negative), Aβ positive patients showed poorer visual (P= 0.001), spatial recognition (P< 0.0005) and working (P= 0.024) memory, as well as a higher frequency ofAPOE4 (P< 0.0005), lower hippocampal volume (P= 0.04), reduced thickness of the parietal cortex (P< 0.009) and structural connectivity of the corpus callosum (P< 0.05), higher amplitude of delta rhythms at rest (P= 0.03) and lower amplitude of posterior cingulate sources ofAO‐ERP(P= 0.03).ConclusionThese results suggest that, inaMCIpatients, prodromalADis characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers inADprogression.