TY - JOUR
T1 - Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project
T2 - A 'European ADNI study'
AU - Galluzzi, Samantha
AU - Marizzoni, Moira
AU - Babiloni, Claudio
AU - Albani, Diego
AU - Antelmi, Luigi
AU - Bagnoli, Cristina
AU - Bartrés-Faz, David
AU - Cordone, Susanna
AU - Didic, Mira
AU - Farotti, L.
AU - Fiedler, Ute
AU - Forloni, Gianluigi
AU - Girtler, Nicola
AU - Hensch, Tilman
AU - Jovicich, Jorge
AU - Leeuwis, A.
AU - Marra, C.
AU - Molinuevo, Jose L.
AU - Nobili, Flavio
AU - Pariente, J.
AU - Parnetti, Lucilla
AU - Payoux, Pierre
AU - Del Percio, Claudio
AU - Ranjeva, Jean Philippe
AU - Rolandi, Elena
AU - Rossini, Paolo Maria
AU - Schönknecht, Peter
AU - Soricelli, Andrea
AU - Tsolaki, Magda
AU - Visser, Pieter J.
AU - Wiltfang, Jens
AU - Richardson, Jill
AU - Bordet, Regis
AU - Blin, Olivier J.
AU - Frisoni, Giovanni Battista
PY - 2016
Y1 - 2016
N2 - Background: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. Objective: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). Methods: A total of 147 aMCI patients 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 diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. Results: Prodromal AD was found in 55 aMCI patients defined by low Aβ42 in the cerebrospinal fluid (Aβ positive). Compared to the aMCI group 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 of APOE4 (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 of AO-ERP (P = 0.03). Conclusion: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.
AB - Background: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. Objective: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). Methods: A total of 147 aMCI patients 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 diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. Results: Prodromal AD was found in 55 aMCI patients defined by low Aβ42 in the cerebrospinal fluid (Aβ positive). Compared to the aMCI group 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 of APOE4 (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 of AO-ERP (P = 0.03). Conclusion: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.
KW - Biomarkers
KW - Electroencephalography
KW - Magnetic resonance imaging
KW - Mild cognitive impairment
KW - Prodromal AD
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U2 - 10.1111/joim.12482
DO - 10.1111/joim.12482
M3 - Article
VL - 279
SP - 576
EP - 591
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
SN - 0954-6820
ER -