THE STUDY WILL BE A TWO-PART RESEARCH PART A and PART A extended: 1. To implement a "common" MRI acquisition protocol in multiple centers across Europe (Pharma-COG partners). 2. Apply the common MRI protocol on phantoms and human subjects to characterize, compare and minimize test-retest variability across the MR sites of WP5 for all the quantitative metrics that will be later assessed on patients. PART B: By collecting clinical, biochemical, neuroimaging, neuropsychological and neurophysiological data in Mild Cognitive Impairment patient, we aim to: 1. To develop a biomarker MATRIX (made of a combination of biological secondary endpoints) which is more sensitive than the changes observed in the loss of hippocampal volume (primary endpoint) and correlate with the neuropsychological progression and conversion (clinical secondary endpoints). 2. To develop a biomarker MATRIX (made of a combination of biological secondary endpoints) at baseline which is more predictive of the loss of hippocampal volume (primary endpoint) and neuropsychological progression (clinical secondary endpoint) in MCI patients. 3. To harmonize the biomarker MATRIX collection and qualify multiple centres across Europe
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
229
All the patients will be divided in two groups based on their Aβ 1-42 levels measured in the cerebro-spinal fluid obtained form a lumbar puncture: in low Aβ1-42 (positive aMCI patients CSFP) and high Aβ1-42 (Negative aMCI patients CSFN). The threshold of Aβ1-42 used to divide the patient will be 500 (ng/L) based on Sjogren criteria (2001). Timeframe of lumbar punctures: every 18 months during 2 years (T0 and T18) or 3 years (T0, T18 and T36).
Université Lille 2, UL2 - Centre d'investigation clinique / Centre de Ressources biologiques 9301 - INSERM - Centre Hospitalier Régional et Universitaire de LILLE
Lille, France
APHM, Hopital de la Timone, Service de Neurologie et Neuropsychologie
Marseille, France
INSERM - CHU Purpan
Toulouse, France
Hospital and Institute of the University of Duisburg and Essen - Department for Psychiatry and Psychotherapy, LVR Hospital Essen
Essen, Germany
University Hospital of Leipzig - Department of Psychiatry
Leipzig, Germany
Aristotle University of Thessaloniki, Greek Association of Alzheimer's disease and related disorders, Thessaloniki, Greece
Thessaloniki, Greece
IRCCS-FBF - Ordine Ospedaliero San Giovanni di Dio, Fatebenefratelli, Istituto di Ricovero e Cura a Carattere Scientifico
Brescia, Provincia Lombardo-Veneta, Italy
Neurofisiologia Clinica IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Padiglione Specialita' piano Fondi
Genoa, Italy
IRCCS Fondazione SDN per la Ricerca e l'Alta Formazione in Diagnostica Nucleare di Napoli
Naples, Italy
Dipartimento di Specialità medico-chirurgiche e Sanità Pubblica, Sezione di Clinica Neurologica, Centro Disturbi della Memoria, Perugia, Italy
Perugia, Italy
...and 3 more locations
Part A: Magnetic Resonance Imagery protocol
The Magnetic Resonance Imagery protocol comprises a localiser or scout run, 4 structural-volumetric MRI sequences (i.e. 2 MP-RAGE, 1 FLAIR and 1 T2\*), a resting state functional MRI acquisition (i.e. rsfMRI), a diffusion tensor scan (i.e. DTI) that will be conducted at the magnetic field strength of 3T and a quantitative assessment of brain perfusion changes with a sequence of Arterial Spin Labelling (i.e. ASL) . The field map will be used for geometric distortion correction of the fMRI data. The main parameter of "efficacy" will be the reliability of the acquired MRI data (in terms of their correct acquisition and limited variability).
Time frame: Two times: One measure at day 1
Part B: Changes of the hippocampal volume
The primary endpoint will be changes of the hippocampal volume between the two groups (differentiated by the level of amyloid β1-42 in the cerebro-spinal fluid) and within the same group over time.
Time frame: 2 or 3 times: every 18 months during 2 or 3 years (T0, T18 and/or T36)
Part B: Clinical assessment
* Mini-Mental State Examination (MMSE) (general cognitive functioning) * Clinical Dementia Rating (CDR) * Medical History * Physical exam * Neurological exams * Hachinski ischemic scale (differentiate Alzheimer's type dementia and multi-infarct dementia) * Geriatric Depression Scale (Depressive symptoms) * Functional Assessment Questionnaire (FAQ) (Activities of daily living) * Neuropsychiatric Inventory Questionnaire (NPI-Q) (Behaviour)
Time frame: Every 6 months (screening, T6, T12, T18, T24, T30 and T36)
Part B: Neuropsychology
* ADAS-COG * Clock Drawing and Copying Test (Executive functions and planning abilities) * Rey Auditory Verbal Test (AVLT) (Memory) * Logical Memory Test I - Immediate Recall (Memory) * Digit Span Forward (Memory) * Digit Span Backward (Memory) * CANTAB Battery (visuospatial functions) * Letter fluency (Language) * Category Fluency (Language) * Boston Naming Test (BNT) (Language) * Trail Making Test (Attention) * Digit Symbol Substitution Test (Processing speed)
Time frame: Every 6 months (screening, T6, T12, T18, T24, T30 and T36)
Part B: Neurophysiology
Electro-Encephalography in several conditions
Time frame: Every 6 months (T0, T6, T12, T18, T24, T30 and T36)
Part B: Magnetic Resonance Imagery and functional MRI
The protocol comprises a localiser or scout run, 2 structural-volumetric MRI sequences (i.e. MPRAGE and FLAIR), one 2D structural analysis (i.e. T2\*) a resting state functional MRI acquisition (i.e. rs-fMRI), a diffusion tensor scan (i.e. DTI) that will be conducted at the magnetic field strength of 3T and a quantitative assessment of brain perfusion changes with a sequence of Arterial Spin Labelling (i.e. ASL only in T18 and T24 timepoints for available patients).
Time frame: Every 6 months (screening, T0, T6, T12, T18, T24, T30 and T36)
Part B: Blood drawing
* ApoE (T0 only) * β amyloid in plasma (T0, T6, T12, T18, T24, T30 and T36) * Plasma and lymphocytes biomarkers (T0, T6, T12, T18, T24, T30 and T36) * PKC conformation (T0 and T18/T36) * amyloid β1-42 binding on erythrocytes (T0 and T18/T36) * Platelet APP-CTF (intracellular APP metabolites)(T0, T6, T12, T18, T24, T30 and T36) * RNA splicing analysis (T0, T6, T12, T18, T24, T30 and T36)
Time frame: Every 6 months
Part B: Actigraphy
Assessment of changes in position and acceleration for up to several weeks providing measures of activity. Additionally, sleep/wake and circadian rhythmicity can objectively be estimated from the recorded data by algorithms.
Time frame: Every 6 months (T0, T6, T12, T18, T24, T30 and T36)
Adverse events
Any changes in the chronicity, severity, action taken, seriousness of a symptom or adverse event will be recorded by a qualified clinician (MD).
Time frame: Every 6 months (T0, T6, T12, T18, T24, T30 and T36)
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