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Proposal of a Special Issue On: Basic, Translational and Clinical Research on Dementia

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 18837

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Department of Pharmacy, Health Science and Nutrition, University of Calabria, 87036 Rende, CS, Italy
Interests: pharmacology; neurotherapeutics; brain ischemia; glaucoma; pain; herbal medicines
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Guest Editor
German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany
Interests: Alzheimer; dementia; epigenetics; aging
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Guest Editor
Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, Italy
Interests: basic and translational research; neurotherapeutics; neurorehabilitation; dementia; pain; migraine; natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The global impact of dementia is increasingly worrisome and up to 90% of dementia patients in low- and middle-income countries is not diagnosed with further delays in diagnosis due to the pandemic during which these fragile population pays the highest price.

Alzheimer’s disease (AD) is the most common accounting for about two-thirds of all cases, but mixed forms of dementia are being increasingly recognized, making dementia a public health priority. These different forms may at least in part be explained through progressive alterations of the epigenome that may contribute to the decrease of cognitive abilities with advancing age.

Indeed, there is little doubt that AD is a multifactorial disease, which involves diverse pathogenic mechanisms and will probably require combinatorial therapies. Although many pathological factors, such as accumulation of protein aggregates of amyloid-beta (Aβ) and tau, have been identified, their role in combination with other factors, at different disease stages, requires further clarification. A comprehensive understanding of the complex disease mechanisms, the identification of early disease markers aided by ultrastructural magnetic resonance imaging are necessary to develop more effective treatments.

Although multiple failures of phase III trials with agents targeting Aβ had initially been disappointing, the accelerated approval of mAbs has recently renewed the interest in targeting Aβ. The gain of information from the real-world data on these neurotherapeutics may anticipate that further development of clinical trials in AD will be prompted.

Accordingly, we would like to invite contributions from basic, translational and clinical research on dementia in the form of original, narrative or systematic reviews on each of the above-named topics.

Prof. Dr. Giacinto Bagetta
Dr. Daniele Bano
Dr. Damiana Scuteri
Guest Editors

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Keywords

  • dementia
  • Alzheimer’s disease
  • amyloid-beta
  • tau protein

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Published Papers (13 papers)

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Research

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11 pages, 875 KiB  
Article
Constitutive NOS Production Is Modulated by Alzheimer’s Disease Pathology Depending on APOE Genotype
by Chiara Giuseppina Bonomi, Alessandro Martorana, Denise Fiorelli, Marzia Nuccetelli, Fabio Placidi, Nicola Biagio Mercuri and Caterina Motta
Int. J. Mol. Sci. 2024, 25(7), 3725; https://doi.org/10.3390/ijms25073725 - 27 Mar 2024
Viewed by 471
Abstract
Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer’s disease (AD). We aimed to explore the relationship between amyloid pathology and NO dynamics by comparing the cerebrospinal fluid (CSF) levels [...] Read more.
Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer’s disease (AD). We aimed to explore the relationship between amyloid pathology and NO dynamics by comparing the cerebrospinal fluid (CSF) levels of nNOS and eNOS of 8 healthy controls (HC) and 27 patients with a clinical diagnosis of Alzheimer’s disease and isolated CSF amyloid changes, stratified according to APOE ε genotype (APOE ε3 = 13, APOE ε4 = 14). Moreover, we explored the associations between NOS isoforms, CSF AD biomarkers, age, sex, cognitive decline, and blood–brain barrier permeability. In our cohort, both eNOS and nNOS levels were increased in APOE ε3 with respect to HC and APOE ε4. CSF eNOS inversely correlated with CSF Amyloid-β42 selectively in carriers of APOE ε3; CSF nNOS was negatively associated with age and CSF p-tau only in the APOE ε4 subgroup. Increased eNOS could represent compensative vasodilation to face progressive Aβ-induced vasoconstriction in APOE ε3, while nNOS could represent the activation of NO-mediated plasticity strategies in the same group. Our results confirm previous findings that the APOE genotype is linked with different vascular responses to AD pathology. Full article
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17 pages, 4092 KiB  
Article
Altered Extracellular Vesicle miRNA Profile in Prodromal Alzheimer’s Disease
by Caterina Visconte, Chiara Fenoglio, Maria Serpente, Paola Muti, Andrea Sacconi, Marta Rigoni, Andrea Arighi, Vittoria Borracci, Marina Arcaro, Beatrice Arosio, Evelyn Ferri, Maria Teresa Golia, Elio Scarpini and Daniela Galimberti
Int. J. Mol. Sci. 2023, 24(19), 14749; https://doi.org/10.3390/ijms241914749 - 29 Sep 2023
Cited by 2 | Viewed by 1306
Abstract
Extracellular vesicles (EVs) are nanosized vesicles released by almost all body tissues, representing important mediators of cellular communication, and are thus promising candidate biomarkers for neurodegenerative diseases like Alzheimer’s disease (AD). The aim of the present study was to isolate total EVs from [...] Read more.
Extracellular vesicles (EVs) are nanosized vesicles released by almost all body tissues, representing important mediators of cellular communication, and are thus promising candidate biomarkers for neurodegenerative diseases like Alzheimer’s disease (AD). The aim of the present study was to isolate total EVs from plasma and characterize their microRNA (miRNA) contents in AD patients. We isolated total EVs from the plasma of all recruited subjects using ExoQuickULTRA exosome precipitation solution (SBI). Subsequently, circulating total EVs were characterized using Nanosight nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. A panel of 754 miRNAs was determined with RT-qPCR using TaqMan OpenArray technology in a QuantStudio 12K System (Thermo Fisher Scientific). The results demonstrated that plasma EVs showed widespread deregulation of specific miRNAs (miR-106a-5p, miR-16-5p, miR-17-5p, miR-195-5p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-296-5p, miR-30b-5p, miR-532-3p, miR-92a-3p, and miR-451a), some of which were already known to be associated with neurological pathologies. A further validation analysis also confirmed a significant upregulation of miR-16-5p, miR-25-3p, miR-92a-3p, and miR-451a in prodromal AD patients, suggesting these dysregulated miRNAs are involved in the early progression of AD. Full article
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10 pages, 2048 KiB  
Article
Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP
by Carmela Belardo, Serena Boccella, Michela Perrone, Antimo Fusco, Andrea Maria Morace, Federica Ricciardi, Roozbe Bonsale, Ines ELBini-Dhouib, Francesca Guida, Livio Luongo, Giacinto Bagetta, Damiana Scuteri and Sabatino Maione
Int. J. Mol. Sci. 2023, 24(18), 14399; https://doi.org/10.3390/ijms241814399 - 21 Sep 2023
Viewed by 1081
Abstract
Transient global amnesia, both persistent and transient, is a very common neuropsychiatric syndrome. Among animal models for amnesia and testing new drugs, the scopolamine test is the most widely used for transient global amnesia (TGA). This study examined the scopolamine-induced deficits in working [...] Read more.
Transient global amnesia, both persistent and transient, is a very common neuropsychiatric syndrome. Among animal models for amnesia and testing new drugs, the scopolamine test is the most widely used for transient global amnesia (TGA). This study examined the scopolamine-induced deficits in working memory, discriminative memory, anxiety, and motor activity in the presence of intranasal PEA-OXA, a dual antagonist of presynaptic α2 and H3 receptors. Male C57BL/6 mice were treated with intraperitoneal scopolamine (1 mg/kg) with or without pre-treatment (15 min) or post-treatment (15 min) with intranasal PEA-OXA (10 mg/kg). It was seen that scopolamine induced deficits of discriminative and spatial memory and motor deficit. These changes were associated with a loss of synaptic plasticity in the hippocampal dentate gyrus: impaired LTP after lateral entorhinal cortex/perforant pathway tetanization. Furthermore, hippocampal Ach levels were increased while ChA-T expression was reduced following scopolamine administration. PEA-OXA either prevented or restored the scopolamine-induced cognitive deficits (discriminative and spatial memory). However, the same treatment did not affect the altered motor activity or anxiety-like behavior induced by scopolamine. Consistently, electrophysiological analysis showed LTP recovery in the DG of the hippocampus, while the Ach level and ChoA-T were normalized. This study confirms the neuroprotective and pro-cognitive activity of PEA-OXA (probably through an increase in the extracellular levels of biogenic amines) in improving transient memory disorders for which the available pharmacological tools are obsolete or inadequate and not directed on specific pathophysiological targets. Full article
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18 pages, 861 KiB  
Article
Monocytes in the Characterization of Pain in Palliative Patients with Severe Dementia—A Pilot Study
by Hugo Ribeiro, Raquel Alves, Joana Jorge, Ana Cristina Gonçalves, Ana Bela Sarmento-Ribeiro, Manuel Teixeira-Veríssimo, José Paulo Andrade and Marília Dourado
Int. J. Mol. Sci. 2023, 24(13), 10723; https://doi.org/10.3390/ijms241310723 - 27 Jun 2023
Viewed by 1316
Abstract
In assessing and managing pain, when obtaining a self-report is impossible, therapeutic decision-making becomes more challenging. This study aimed to investigate whether monocytes and some membrane monocyte proteins, identified as a cluster of differentiation (CD), could be potential non-invasive peripheral biomarkers in identifying [...] Read more.
In assessing and managing pain, when obtaining a self-report is impossible, therapeutic decision-making becomes more challenging. This study aimed to investigate whether monocytes and some membrane monocyte proteins, identified as a cluster of differentiation (CD), could be potential non-invasive peripheral biomarkers in identifying and characterizing pain in patients with severe dementia. We used 53 blood samples from non-oncological palliative patients, 44 patients with pain (38 of whom had dementia) and 0 without pain or dementia (controls). We evaluated the levels of monocytes and their subtypes, including classic, intermediate, and non-classic, and characterized the levels of specific phenotypic markers, namely CD11c, CD86, CD163, and CD206. We found that the relative concentrations of monocytes, particularly the percentage of classic monocytes, may be a helpful pain biomarker. Furthermore, the CD11c expression levels were significantly higher in patients with mixed pain, while CD163 and CD206 expression levels were significantly higher in patients with nociceptive pain. These findings suggest that the levels of monocytes, particularly the classic subtype, and their phenotype markers CD11c, CD163, and CD206 could serve as pain biomarkers in patients with severe dementia. Full article
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13 pages, 1405 KiB  
Article
A Targeted Mass Spectrometry Approach to Identify Peripheral Changes in Metabolic Pathways of Patients with Alzheimer’s Disease
by Pierluigi Reveglia, Carmela Paolillo, Antonella Angiolillo, Gabriella Ferretti, Ruggero Angelico, Rossana Sirabella, Gaetano Corso, Carmela Matrone and Alfonso Di Costanzo
Int. J. Mol. Sci. 2023, 24(11), 9736; https://doi.org/10.3390/ijms24119736 - 04 Jun 2023
Cited by 2 | Viewed by 1500
Abstract
Alzheimer’s disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a [...] Read more.
Alzheimer’s disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology. Full article
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Review

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23 pages, 898 KiB  
Review
The Metabolic Impact of Nonalcoholic Fatty Liver Disease on Cognitive Dysfunction: A Comprehensive Clinical and Pathophysiological Review
by Mauro Giuffrè, Nicola Merli, Maura Pugliatti and Rita Moretti
Int. J. Mol. Sci. 2024, 25(6), 3337; https://doi.org/10.3390/ijms25063337 - 15 Mar 2024
Viewed by 773
Abstract
Nonalcoholic fatty liver disease (NAFLD) exponentially affects the global healthcare burden, and it is currently gaining increasing interest in relation to its potential impact on central nervous system (CNS) diseases, especially concerning cognitive deterioration and dementias. Overall, scientific research nowadays extends to different [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) exponentially affects the global healthcare burden, and it is currently gaining increasing interest in relation to its potential impact on central nervous system (CNS) diseases, especially concerning cognitive deterioration and dementias. Overall, scientific research nowadays extends to different levels, exploring NAFLD’s putative proinflammatory mechanism of such dysmetabolic conditions, spreading out from the liver to a multisystemic involvement. The aim of this review is to analyze the most recent scientific literature on cognitive involvement in NAFLD, as well as understand its underlying potential background processes, i.e., neuroinflammation, the role of microbiota in the brain–liver–gut axis, hyperammonemia neurotoxicity, insulin resistance, free fatty acids, and vitamins. Full article
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24 pages, 1343 KiB  
Review
Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review
by Maria Tiziana Corasaniti, Giacinto Bagetta, Pierluigi Nicotera, Sabatino Maione, Paolo Tonin, Francesca Guida and Damiana Scuteri
Int. J. Mol. Sci. 2024, 25(2), 1264; https://doi.org/10.3390/ijms25021264 - 19 Jan 2024
Viewed by 1235
Abstract
The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches. Several drugs belonging to different classes [...] Read more.
The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches. Several drugs belonging to different classes were suggested to be effective in managing Alzheimer’s disease (AD) by means of autophagy induction. Useful autophagy inducers in AD should be endowed with a direct, measurable effect on autophagy, have a safe tolerability profile, and have the capability to cross the blood–brain barrier, at least with poor penetration. According to the PRISMA 2020 recommendations, we propose here a systematic review to appraise the measurable effectiveness of autophagy inducers in the improvement of cognitive decline and neuropsychiatric symptoms in clinical trials and retrospective studies. The systematic search retrieved 3067 records, 10 of which met the eligibility criteria. The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile. Differences in sample power, intervention, patients enrolled, assessment, and measure of outcomes prevents generalization of results. Moreover, the domain of behavioral symptoms was found to be less investigated, thus prompting new prospective studies with homogeneous design. PROSPERO registration: CRD42023393456. Full article
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13 pages, 302 KiB  
Review
MRI and Clinical Biomarkers Overlap between Glaucoma and Alzheimer’s Disease
by Alessio Martucci, Francesca Di Giuliano, Silvia Minosse, Giulio Pocobelli, Carlo Nucci and Francesco Garaci
Int. J. Mol. Sci. 2023, 24(19), 14932; https://doi.org/10.3390/ijms241914932 - 05 Oct 2023
Cited by 1 | Viewed by 1562
Abstract
Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways [...] Read more.
Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways and disruption of brain network organization have been reported using advanced neuroimaging techniques. The brain structural changes at the level of the areas implied in processing visual information could justify the discrepancy between signs and symptoms and underlie the analogy of this disease with neurodegenerative dementias, such as Alzheimer’s disease, and with the complex group of pathologies commonly referred to as “disconnection syndromes.” This review aims to summarize the current state of the art on the use of advanced neuroimaging techniques in glaucoma and Alzheimer’s disease, highlighting the emerging biomarkers shared by both diseases. Full article
19 pages, 701 KiB  
Review
Anti-NMDA and Anti-AMPA Receptor Antibodies in Central Disorders: Preclinical Approaches to Assess Their Pathological Role and Translatability to Clinic
by Guendalina Olivero, Alessandra Roggeri and Anna Pittaluga
Int. J. Mol. Sci. 2023, 24(19), 14905; https://doi.org/10.3390/ijms241914905 - 05 Oct 2023
Viewed by 1487
Abstract
Autoantibodies against NMDA and AMPA receptors have been identified in the central nervous system of patients suffering from brain disorders characterized by neurological and psychiatric symptoms. It has been demonstrated that these autoantibodies can affect the functions and/or the expression of the targeted [...] Read more.
Autoantibodies against NMDA and AMPA receptors have been identified in the central nervous system of patients suffering from brain disorders characterized by neurological and psychiatric symptoms. It has been demonstrated that these autoantibodies can affect the functions and/or the expression of the targeted receptors, altering synaptic communication. The importance to clarify, in preclinical models, the molecular mechanisms involved in the autoantibody-mediated effects has emerged in order to understand their pathogenic role in central disorders, but also to propose new therapeutic approaches for preventing the deleterious central consequences. In this review, we describe some of the available preclinical literature concerning the impact of antibodies recognizing NMDA and AMPA receptors in neurons. This review discusses the cellular events that would support the detrimental roles of the autoantibodies, also illustrating some contrasting findings that in our opinion deserve attention and further investigations before translating the preclinical observations to clinic. Full article
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25 pages, 886 KiB  
Review
Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies
by Francesca R. Buccellato, Marianna D’Anca, Gianluca Martino Tartaglia, Massimo Del Fabbro, Elio Scarpini and Daniela Galimberti
Int. J. Mol. Sci. 2023, 24(18), 13900; https://doi.org/10.3390/ijms241813900 - 09 Sep 2023
Cited by 5 | Viewed by 3473
Abstract
In an ever-increasing aged world, Alzheimer’s disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are [...] Read more.
In an ever-increasing aged world, Alzheimer’s disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies are aimed to mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) and the N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, the best approaches for managing the disease seem to combine pharmacological and non-pharmacological therapies to stimulate cognitive reserve. Over the last twenty years, a number of drugs have been discovered acting on the well-established biological hallmarks of AD, deposition of β-amyloid aggregates and accumulation of hyperphosphorylated tau protein in cells. Although previous efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT) for the treatment of AD, aducanumab, a monoclonal antibody (mAb) designed against Aβ plaques and oligomers in 2021, and in January 2023, the FDA granted accelerated approval for a second monoclonal antibody, Lecanemab. This review describes ongoing clinical trials with DMTs and non-pharmacological therapies. We will also present a future scenario based on new biomarkers that can detect AD in preclinical or prodromal stages, identify people at risk of developing AD, and allow an early and curative treatment. Full article
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19 pages, 684 KiB  
Review
Antiseizure Medications in Alzheimer’s Disease from Preclinical to Clinical Evidence
by Francesca Bosco, Lorenza Guarnieri, Vincenzo Rania, Ernesto Palma, Rita Citraro, Maria Tiziana Corasaniti, Antonio Leo and Giovambattista De Sarro
Int. J. Mol. Sci. 2023, 24(16), 12639; https://doi.org/10.3390/ijms241612639 - 10 Aug 2023
Cited by 3 | Viewed by 1179
Abstract
Alzheimer’s disease (AD) and epilepsy are common neurological disorders in the elderly. A bi-directional link between these neurological diseases has been reported, with patients with either condition carrying almost a two-fold risk of contracting the other compared to healthy subjects. AD/epilepsy adversely affects [...] Read more.
Alzheimer’s disease (AD) and epilepsy are common neurological disorders in the elderly. A bi-directional link between these neurological diseases has been reported, with patients with either condition carrying almost a two-fold risk of contracting the other compared to healthy subjects. AD/epilepsy adversely affects patients’ quality of life and represents a severe public health problem. Thus, identifying the relationship between epilepsy and AD represents an ongoing challenge and continuing need. Seizures in AD patients are often unrecognized because they are often nonconvulsive and sometimes mimic some behavioral symptoms of AD. Regarding this, it has been hypothesized that epileptogenesis and neurodegeneration share common underlying mechanisms. Targeted treatment to decrease epileptiform activity could represent a valuable strategy for delaying the neurodegenerative process and related cognitive impairment. Several preclinical studies have shown that some antiseizure medications (ASMs) targeting abnormal network hyperexcitability may change the natural progression of AD. However, to date, no guidelines are available for managing seizures in AD patients because of the paucity of randomized clinical trials sufficient for answering the correlated questions. Future AD clinical studies are mandatory to update clinicians about the symptomatic treatment of seizures in AD patients and recognize whether ASM therapy could change the natural progression of the disease, thereby rescuing cognitive performance. Full article
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26 pages, 3039 KiB  
Review
Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review
by Paula M. Loveland, Jenny J. Yu, Leonid Churilov, Nawaf Yassi and Rosie Watson
Int. J. Mol. Sci. 2023, 24(15), 12116; https://doi.org/10.3390/ijms241512116 - 28 Jul 2023
Cited by 2 | Viewed by 1594
Abstract
Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson’s disease dementia) and, secondly, identify alterations in [...] Read more.
Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson’s disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development. Full article
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16 pages, 651 KiB  
Review
I Feel! Therefore, I Am from Pain to Consciousness in DOC Patients
by Francesco Riganello, Paolo Tonin and Andrea Soddu
Int. J. Mol. Sci. 2023, 24(14), 11825; https://doi.org/10.3390/ijms241411825 - 23 Jul 2023
Viewed by 1077
Abstract
Pain assessment and management in patients with disorders of consciousness (DOC) is a challenging and important aspect of care, with implications for detecting consciousness and promoting recovery. This narrative review explores the role of pain in consciousness, the challenges of pain assessment, pharmacological [...] Read more.
Pain assessment and management in patients with disorders of consciousness (DOC) is a challenging and important aspect of care, with implications for detecting consciousness and promoting recovery. This narrative review explores the role of pain in consciousness, the challenges of pain assessment, pharmacological treatment in DOC, and the implications of pain assessment when detecting changes in consciousness. The review discusses the Nociception Coma Scale and its revised version, which are behavioral scales used to assess pain in DOC patients, and the challenges and controversies surrounding the appropriate pharmacological treatment of pain in these patients. Moreover, we highlight recent evidence suggesting that an accurate pain assessment may predict changes in the level of consciousness in unresponsive wakefulness syndrome/vegetative state patients, underscoring the importance of ongoing pain management in these patients. Full article
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