Clara Sanches, Chloé Stengel, Juliette Godard, Justine Mertz, Marc Teichmann, Raffaella Migliaccio, Antoni Valero-Cabré, FRONTLAB: Fonctions et dysfonctions de systèmes frontaux [ICM Paris] (FRONTlab), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Laboratoire de Linguistique Formelle (LLF), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, Universitat Oberta de Catalunya (UOC), Sorbonne Université, National Reference Center for Rare or Early Onset Dementias, Boston University School of Medicine, FRONTlab - Systèmes frontaux : fonctions et dysfonctions (FRONTlab), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Linguistique Formelle (LLF UMR7110), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Universitat Oberta de Catalunya, Institut du Cerveau, Institute of Memory and Alzheimer's Disease, Laboratoire de Linguistique Formelle (LLF - UMR7110), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Low birth rates and increasing life expectancy experienced by developed societies have placed an unprecedented pressure on governments and the health system to deal effectively with the human, social and financial burden associated to aging-related diseases. At present, ∼24 million people worldwide suffer from cognitive neurodegenerative diseases, a prevalence that doubles every five years. Pharmacological therapies and cognitive training/rehabilitation have generated temporary hope and, occasionally, proof of mild relief. Nonetheless, these approaches are yet to demonstrate a meaningful therapeutic impact and changes in prognosis. We here review evidence gathered for nearly a decade on non-invasive brain stimulation (NIBS), a less known therapeutic strategy aiming to limit cognitive decline associated with neurodegenerative conditions. Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation, two of the most popular NIBS technologies, use electrical fields generated non-invasively in the brain to long-lastingly enhance the excitability/activity of key brain regions contributing to relevant cognitive processes. The current comprehensive critical review presents proof-of-concept evidence and meaningful cognitive outcomes of NIBS in eight of the most prevalent neurodegenerative pathologies affecting cognition: Alzheimer’s Disease, Parkinson’s Disease, Dementia with Lewy Bodies, Primary Progressive Aphasias (PPA), behavioral variant of Frontotemporal Dementia, Corticobasal Syndrome, Progressive Supranuclear Palsy, and Posterior Cortical Atrophy. We analyzed a total of 70 internationally published studies: 33 focusing on Alzheimer’s disease, 19 on PPA and 18 on the remaining neurodegenerative pathologies. The therapeutic benefit and clinical significance of NIBS remains inconclusive, in particular given the lack of a sufficient number of double-blind placebo-controlled randomized clinical trials using multiday stimulation regimes, the heterogeneity of the protocols, and adequate behavioral and neuroimaging response biomarkers, able to show lasting effects and an impact on prognosis. The field remains promising but, to make further progress, research efforts need to take in account the latest evidence of the anatomical and neurophysiological features underlying cognitive deficits in these patient populations. Moreover, as the development ofin vivobiomarkers are ongoing, allowing for an early diagnosis of these neuro-cognitive conditions, one could consider a scenario in which NIBS treatment will be personalized and made part of a cognitive rehabilitation program, or useful as a potential adjunct to drug therapies since the earliest stages of suh diseases. Research should also integrate novel knowledge on the mechanisms and constraints guiding the impact of electrical and magnetic fields on cerebral tissues and brain activity, and incorporate the principles of information-based neurostimulation.