scholarly journals Past, Present, and Future of Non-invasive Brain Stimulation Approaches to Treat Cognitive Impairment in Neurodegenerative Diseases: Time for a Comprehensive Critical Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Clara Sanches ◽  
Chloé Stengel ◽  
Juliette Godard ◽  
Justine Mertz ◽  
Marc Teichmann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Brain Stimulation ◽  
Critical Review ◽  
Cognitive Rehabilitation ◽  
Financial Burden ◽  
Cortical Atrophy ◽  
Non Invasive ◽  
The Impact

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 of in vivo biomarkers 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.

Non-invasive brain stimulation to assess and modulate neuroplasticity in Alzheimer's disease

2011 ◽  
Vol 21 (5) ◽  
pp. 703-716 ◽  
Author(s):  
Paulo Sérgio Boggio ◽  
Claudia Aparecida Valasek ◽  
Camila Campanhã ◽  
Ana Carolina Alem Giglio ◽  
Nathalia Ishikawa Baptista ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Stimulation ◽  
Non Invasive

scholarly journals Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer’s disease

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Ryan J. Bevan ◽  
Tim R. Hughes ◽  
Pete A. Williams ◽  
Mark A. Good ◽  
B. Paul Morgan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Brain Pathology ◽  
Cell Degeneration ◽  
Non Invasive

AbstractNeuronal dendritic and synaptic pruning are early features of neurodegenerative diseases, including Alzheimer’s disease. In addition to brain pathology, amyloid plaque deposition, microglial activation, and cell loss occur in the retinas of human patients and animal models of Alzheimer’s disease. Retinal ganglion cells, the output neurons of the retina, are vulnerable to damage in neurodegenerative diseases and are a potential opportunity for non-invasive clinical diagnosis and monitoring of Alzheimer’s progression. However, the extent of retinal involvement in Alzheimer’s models and how well this reflects brain pathology is unclear. Here we have quantified changes in retinal ganglion cells dendritic structure and hippocampal dendritic spines in three well-studied Alzheimer’s mouse models, Tg2576, 3xTg-AD and APPNL-G-F. Dendritic complexity of DiOlistically labelled retinal ganglion cells from retinal explants was reduced in all three models in an age-, gender-, and receptive field-dependent manner. DiOlistically labelled hippocampal slices showed spine loss in CA1 apical dendrites in all three Alzheimer’s models, mirroring the early stages of neurodegeneration as seen in the retina. Morphological classification showed that loss of thin spines predominated in all. The demonstration that retinal ganglion cells dendritic field reduction occurs in parallel with hippocampal dendritic spine loss in all three Alzheimer’s models provide compelling support for the use of retinal neurodegeneration. As retinal dendritic changes are within the optical range of current clinical imaging systems (for example optical coherence tomography), our study makes a case for imaging the retina as a non-invasive way to diagnose disease and monitor progression in Alzheimer’s disease.

scholarly journals Patient-Tailored, Home-Based Non-invasive Brain Stimulation for Memory Deficits in Dementia Due to Alzheimer's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Lucie Bréchet ◽  
Wanting Yu ◽  
Maria Chiara Biagi ◽  
Giulio Ruffini ◽  
Margaret Gagnon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Stimulation ◽  
Controlled Trial ◽  
Memory Deficits ◽  
Human Studies ◽  
Cognitive Disability ◽  
Brain Disorder ◽  
Non Invasive ◽  
Home Based

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that can cause dementia (Alzheimer's disease-related dementia, ADRD) with growing cognitive disability and vast physical, emotional, and financial pressures not only on the patients but also on caregivers and families. Loss of memory is an early and very debilitating symptom in AD patients and a relevant predictor of disease progression. Data from rodents, as well as human studies, suggest that dysregulation of specific brain oscillations, particularly in the hippocampus, is linked to memory deficits. Animal and human studies demonstrate that non-invasive brain stimulation (NIBS) in the form of transcranial alternating current stimulation (tACS) allows to reliably and safely interact with ongoing oscillatory patterns in the brain in specific frequencies. We developed a protocol for patient-tailored home-based tACS with an instruction program to train a caregiver to deliver daily sessions of tACS that can be remotely monitored by the study team. We provide a discussion of the neurobiological rationale to modulate oscillations and a description of the study protocol. Data of two patients with ADRD who have completed this protocol illustrate the feasibility of the approach and provide pilot evidence on the safety of the remotely-monitored, caregiver-administered, home-based tACS intervention. These findings encourage the pursuit of a large, adequately powered, randomized controlled trial of home-based tACS for memory dysfunction in ADRD.

scholarly journals On Colour, Category Effects, and Alzheimer’s Disease: A Critical Review of Studies and Further Longitudinal Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
F. Javier Moreno-Martínez ◽  
Inmaculada C. Rodríguez-Rojo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Critical Review ◽  
Naming Task ◽  
Object Processing ◽  
Semantic Level ◽  
Colour Category ◽  
A Minor ◽  
Category Effects ◽  
The Impact

The role of colour in object recognition is controversial; in this study, a critical review of previous studies, as well as a longitudinal study, was conducted. We examined whether colour benefits the ability of Alzheimer’s disease (AD) patients and normal controls (NC) when naming items differing in colour diagnosticity: living things (LT) versus nonliving things (NLT). Eleven AD patients were evaluated twice with a temporal interval of 3 years; 26 NC were tested once. The participants performed a naming task (colour and greyscale photographs); the impact of nuisance variables (NVs) and potential ceiling effects were also controlled. Our results showed that (i) colour slightly favoured processing of items with higher colour diagnosticity (i.e., LT) in both groups; (ii) AD patients used colour information similarly to NC, retaining this ability over time; (iii) NVs played a significant role as naming predictors in all the participants, relegating domain to a minor plane; and (iv) category effects (better processing of NLT) were present in both groups. Finally, although patients underwent semantic longitudinal impairment, this was independent of colour deterioration. This finding provides better support to the view that colour is effective at the visual rather than at the semantic level of object processing.

scholarly journals Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases

2021 ◽  
Author(s):  
Anita Monteverdi ◽  
Fulvia Palesi ◽  
Alfredo Costa ◽  
Paolo Vitali ◽  
Anna Pichiecchio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Functional Connectivity ◽  
Neurodegenerative Diseases ◽  
Frontotemporal Dementia ◽  
Neural Mass Model ◽  
Brain Dynamics ◽  
The Impact ◽  
Lateral Sclerosis

Brain pathologies are based on microscopic changes in neurons and synapses that reverberate into large scale networks altering brain dynamics and functional states. An important yet unresolved issue concerns the impact of patients excitation/inhibition profiles on neurodegenerative diseases including Alzheimer's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. In this work we used a simulation platform, The Virtual Brain, to simulate brain dynamics in healthy controls and in Alzheimer's disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis patients. The brain connectome and functional connectivity were extracted from 3T-MRI scans and The Virtual Brain nodes were represented by a Wong-Wang neural mass model endowing an explicit representation of the excitatory/inhibitory balance. The integration of cerebro-cerebellar loops improved the correlation between experimental and simulated functional connectivity, and hence The Virtual Brain predictive power, in all pathological conditions. The Virtual Brain biophysical parameters differed between clinical phenotypes, predicting higher global coupling and inhibition in Alzheimer's disease and stronger NMDA (N-methyl-D-aspartate) receptor-dependent excitation in Amyotrophic Lateral Sclerosis. These physio-pathological parameters allowed an advanced analysis of patients' state. In backward regressions, The Virtual Brain parameters significantly contributed to explain the variation of neuropsychological scores and, in discriminant analysis, the combination of The Virtual Brain parameters and neuropsychological scores significantly improved discriminative power between clinical conditions. Eventually, cluster analysis provided a unique description of the excitatory/inhibitory balance in individual patients. In aggregate, The Virtual Brain simulations reveal differences in the excitatory/inhibitory balance of individual patients that, combined with cognitive assessment, can promote the personalized diagnosis and therapy of neurodegenerative diseases.

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