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Longitudinal analysis of the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study : Step 2

English title Longitudinal analysis of the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study : Step 2
Applicant Cavassini Matthias
Number 192777
Funding scheme Project funding (special)
Research institution Service de Médecine Interne Département de Médecine CHUV
Institution of higher education University of Lausanne - LA
Main discipline Internal Medicine
Start/End 01.04.2020 - 31.03.2024
Approved amount 459'520.00
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All Disciplines (3)

Discipline
Internal Medicine
Neurology, Psychiatry
Clinical Pharmacology

Keywords (12)

Large nested project; SHCS; aging; HIV; risk factors; neurocognitive disorders; MRI; Swiss HIV cohort study; HIV associated neurocognitive disorders; cohort; clusters; anticholinergic drugs

Lay Summary (French)

Lead
L'espérance de vie des personnes infectées par le virus d'immunodéficience humaine (VIH) responsable du Syndrome d'Immunodéficience Acquise (SIDA) est, grâce aux traitements antirétroviraux, proche de celle de la population générale. Le VIH infecte le cerveau très tôt après l'infection et peut être responsable de troubles neurocognitifs. Les questions sur la sévérité des troubles cognitifs, les éléments "aggravants" (dépression, alcool, médicaments neurotoxiques), l'évolution au cours des années et les pistes thérapeutiques sont nombreuses. Le projet apporte sa contribution à ce domaine de recherche grâce à une cohorte de plus de 950 volontaires VIH+ participant à l'étude de cohorte VIH suisse, âgés de plus de 45 ans suivis durant 4 ans.
Lay summary

Entre 2013 et 2016, l'étude NAMACO (Neurocognitve Assessment in the Metabolic and Aging Cohort) a recruté 981 patients avec comme objectif principaux de caractériser et comprendre la trajectoire sur 4 ans des patients âgés de plus 45 ans sur le plan de leurs fonctions neurocognitives. Nous avons constaté que 40 % des participants avaient objectivement des atteintes cognitives; ces atteintes étaient presque toujours de faible sévérité. Le VIH était responsable de 27 % des atteintes cognitives; les 13% restant surtout associé à des maladies psychiques (dépression en tête de liste). Nous n'avons pas identifié de traitements antirétroviraux comme associé(s) à un risque accru d'atteinte cognitive. Le suivi neuropsychologique à 2 ans a eu lieu pour les 3/4 des participants et celui à 4 ans se terminera fin 2020. Durant le présent projet nous nous intéresserons aux médicaments non-VIH (surtout les médicaments qui ont une possible toxicité neurologique) comme potentiel responsable d'atteintes cognitives; nous explorerons l'évolution à 2 et 4 ans des performances cognitives et identifierons des facteurs prédictifs de changement; nous analyserons les différents types de virus VIH et explorerons le rôle des virus dans l'étiologie des troubles cognitifs; enfin, pour un sous-groupe de patients qui auront eu une imagerie cérébrale (IRM), nous chercherons à classifier par imagerie les différentes atteintes cognitives et leurs évolutions.

Direct link to Lay Summary Last update: 11.01.2021

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
163348 Longitudinal Neurocognitive Assessment in the Metabolic and Aging Cohort of the Swiss HIV Cohort Study: the NAMACO study 01.01.2016 Project funding (special)
179531 Autologous human induced pluripotent stem cells-derived central nervous system neurons, astrocytes and oligodendrocytes as T cells targets in multiple sclerosis 01.07.2018 Project funding

Abstract

1.SUMMARY Applicant: Matthias Cavassini Co-applicant: Renaud Du Pasquier Partners: Katharine Darling, Catia Marzolini, Roger Kouyos, Laurent Decosterd, Cristina Granziera, Arseny Sokolov and the NAMACO Study Group*Longitudinal analysis of the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study : Step 2 1.SUMMARYNeurocognitive impairment (NCI) in association with human immunodeficiency virus (HIV) has been described since the beginning of the HIV epidemic. What has changed over the past three decades is how NCI is manifest. Prior to antiretroviral therapy (ART), uninhibited viral replication in the central nervous system and profound immune suppression led to severe, irreversible NCI in the form of HIV-associated dementia (HAD). Since the development of highly effective ART, HAD incidence is very low. However, as people with HIV (PWH) age on ART, milder, even asymptomatic, manifestations of NCI have been observed. As the population of older PWH grows, NCI represents an important potential health burden and the race is now on to identify the factors which predispose to NCI and influence its course.Since its inception in 2013, the Neurocognitive Assessment in Metabolic and Aging Cohort (NAMACO) study, with 981 patients recruited from the Swiss HIV Cohort Study, has become one of the largest cohorts in the world set up to examine HIV-associated NCI. The date 2013 is critical as this is described in the literature as the era of modern ART: since 2013, the use of integrase inhibitors has increased and that of ART associated with toxic side effects, including efavirenz, has decreased. Baseline NAMACO study data (at recruitment) have enabled NCI prevalence in Switzerland to be quantified and important clinical questions have been addressed. NAMACO study participants have had a neurocognitive function assessment at two years post-recruitment and a four-year review is almost complete. During this period, much has changed in the NCI field: new terminology; a call for new definitions of NCI stage; and many, surprisingly fundamental, questions remain: how to diagnose NCI, how to treat and how to predict impairment course. In this time, NAMACO has become a high-profile acronym in the field and, with now a high-quality longitudinal database, the study represents a resource for promising collaborations within Switzerland and beyond. The current proposal describes Step 2 of the NAMACO study: the longitudinal analysis of NAMACO study participants, in which we aim to quantify NCI incidence over time and identify predictors of neurocognitive change. Specific aims are:I. to determine the incidence and predictors of change in NCI among NAMACO study patients at four years post-recruitmentII. to investigate the effect of prescribed drugs with anticholinergic and/or sedative activity on neurocognitive function; III. to employ viral genome cluster analysis to examine the role of the virus in NCI aetiology; IV. to develop new deep-learning-based classification of NCI by integrating multicontrast MRI and brain-age information.We believe that this next step will have several important outcomes. It will:1.improve our understanding of the hitherto-neglected influence of non-ART drugs on NCI course;2.highlight possible viral as well as host factors influencing NCI development and course;3.identify novel radiological diagnostic techniques for predicting deterioration in neurocognitive function.The overall aim of this proposal is to use the NAMACO study dataset to examine the longitudinal epidemiology of NCI and associated factors in a population of aging PWH. Our large and highly-characterised cohort population is a resource which will enable us to address matters of debate in the field of NCI, a field which is evolving in real-time. The NAMACO study group*Director: Matthias Cavassini; Co-director: Renaud Du Pasquier; Neuropsychologists: Mélanie Métral, Samanta Simioni, Peter Brugger, Klemens Gutbrod, Andreas U. Monsch, Ursi Kunze, Marianne Schneitter, Isaure Nadin, Severin Früh, Marc Schwind, Riccardo Pignatti, Stefanie Clarke Neurologists: Frédéric Assal, Tobias Derfuss, Sebastian von Arx, Günter Eisele, Leonardo Sacco, Manuel Bertschi, Thomas Hundsberger, Renaud Du Pasquier; Infectious diseases specialists: Alexandra Calmy, Thanh Doco Lecompte, Christoph Hauser, Alexia Cusini, Rainer Weber, Helen Kovari, Barbara Hasse, Philip Tarr, Marcel Stoeckle, Christoph Fux, Enos Bernasconi, Caroline Di Benedetto, Alessandra Bruno, Patrick Schmid, Katharine Darling, Matthias Cavassini; SHCS Data Centre: Alexandra Scherrer; Data Management unit: Alexandra Scherrer, Yannick Vallet, Valérie Sormani; Statistician: Isabella Locatelli Pharmacologist: Laurent Decosterd; Neuro-imaging specialists: Cristina Granziera, Gunnar Krueger, Reto Meuli, Maria Vargas.
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