Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical, and Translational Neuropsychiatry—Second Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 32822

Special Issue Editors


E-Mail Website1 Website2
Guest Editor
1. Department of Psychology, University of Turin, Turin, Italy
2. Center for Studies and Research in Cognitive Neuroscience, Department of Psychology, University of Bologna, Bologna, Italy
Interests: NIBS techniques; TMS; skin conductance; heart rate variability; fear conditioning; fear learning; learning; neuropsychology; prefrontal cortex; amygdala; hippocampus; anxiety; depression; working memory; PTSD; skin conductance responses; psychophysiology; error-related negativity; EEG; tDCS; Alzheimer’s disease; PIT; stress-related disorders; Parkinson’s disease; resilience; memory; neurologic patients; cognitive decisions; fMRI; translational and molecular psychiatry
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Guest Editor
Danube Neuroscience Research Laboratory, HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos krt. 113, H-6725 Szeged, Hungary
Interests: depression; anxiety; dementia pain; and their comorbidities nature; and translational research in neurological diseases and psychiatric disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurodegeneration is the progressive atrophy and subsequent functional loss of neurons responsible for the pathogenesis of neurodegenerative diseases and psychiatric disorders. This degenerative change of neurons may take place on molecular, cellular, histological, functional, and organizational levels; may initiate in the prodromal stage during the early gestational period in neurodevelopmental disorders; and may progress to the progression and exacerbation of neuropsychiatric symptoms in mental illnesses. It is particularly important to understand degenerative changes in the neural correlates of consciousness and pay attention to the cognitive and emotional domains in the development of neuropsychiatric disorders. Thus, probing neurodegenerative changes is of great importance for susceptibility detection, understanding pathogenesis and progression, and discovering novel therapeutic targets. Moreover, many branches of neuroscience can help us understand the underlying biological factors and neural computations behind brain impairments, neurodegeneration, and psychiatric disorders, as well as determine where and how to focus on research and treatment. Currently, most neurodegenerative diseases lack effective disease-modifying treatments, highlighting the urgent need for new and effective therapeutic strategies. In recent years, noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial electric current stimulation (TES), have been developed for both diagnostic and therapeutic purposes in patients with neurodegenerative disorders. These techniques have been shown to have meaningful cognitive outcomes in various neurodegenerative diseases, and their mechanistic approach aims to modulate local and spread-out effects via structural connectivity to rebalance the abnormal activity levels between different brain regions. Importantly, NIBS has been linked to the induction of neuroplasticity, which refers to the ability of the brain to reorganize by forming new neural connections throughout life. By stimulating the brain and promoting the formation of new neural connections, NIBS may help improve the symptoms and functional outcomes in conditions such as neurodegenerative diseases.

This Special Issue highlights the most recent advances in experimental, clinical, and translational research in the field of neuropsychiatry, focusing on neurodegeneration and neural correlates of the development of cognitive impairment and psychiatric emotional disturbance. We invite authors to contribute comprehensive review and original research articles focusing on (but not limited to) the following:

  • Etiology, pathogenesis, and mechanisms of progression;
  • Early diagnosis, including biomarkers, bioimaging, and biosensors;
  • Prophylactic, disease-modifying, and therapeutic strategies and novel targets;
  • Novel drug discovery and development, naturally driven biomedicines, natural bioactive molecules, and vaccines;
  • Preclinical in vitro and animal models;
  • Bench-to-bedside translational research;
  • Bedside-to-bench translational research;
  • Noninvasive brain stimulation (NIBS) to diagnosis and treatment of neurodegenerative and psychiatric disorders.

Dr. Simone Battaglia
Dr. Masaru Tanaka
Guest Editors

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Keywords

  • Alzheimer’s disease
  • Parkinson’s disease
  • aging decline
  • mild cognitive impairment
  • multiple sclerosis
  • stroke
  • psychiatric disorders
  • depressive disorder
  • bipolar disorder
  • post-traumatic stress disorder
  • anxiety disorder
  • schizophrenia
  • somatic symptom disorder
  • autism spectrum disorder
  • hyperactive attention deficit disorder
  • learning disabilities
  • acquired brain damage
  • altered cognitive processes
  • brain functional impairment
  • neurocognitive disorders
  • cognitive, behavioral, and functional disorders
  • acquired trauma
  • brain plasticity and connectivity
  • non-invasive brain stimulation
  • diagnosis and treatment
  • functional evidence of altered cognition and connectivity

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Related Special Issue

Published Papers (12 papers)

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Research

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17 pages, 2147 KiB  
Article
Predictive Accuracy of a Clinical Model for Carriage of Pathogenic/Likely Pathogenic Variants in Patients with Dementia and a Positive Family History at PUMCH
by Jialu Bao, Yuyue Qiu, Tianyi Wang, Li Shang, Shanshan Chu, Wei Jin, Wenjun Wang, Yuhan Jiang, Bo Li, Yixuan Huang, Bo Hou, Longze Sha, Yunfan You, Yuanheng Li, Meiqi Wu, Yutong Zou, Yifei Wang, Li Huo, Ling Qiu, Qi Xu, Feng Feng, Chenhui Mao, Liling Dong and Jing Gaoadd Show full author list remove Hide full author list
Biomedicines 2025, 13(5), 1235; https://doi.org/10.3390/biomedicines13051235 - 19 May 2025
Viewed by 349
Abstract
Background and Objectives: Identifying carriers of Pathogenic/Likely Pathogenic Variants in patients with dementia is crucial for risk stratification, particularly in individuals with a family history. This study developed and validated a clinical prediction model using whole-exome sequencing-confirmed cohorts. Methods: A total of 601 [...] Read more.
Background and Objectives: Identifying carriers of Pathogenic/Likely Pathogenic Variants in patients with dementia is crucial for risk stratification, particularly in individuals with a family history. This study developed and validated a clinical prediction model using whole-exome sequencing-confirmed cohorts. Methods: A total of 601 Chinese patients with dementia and a family history were enrolled at Peking Union Medical College Hospital, with 476 in a retrospective derivation cohort and 125 in a temporal validation cohort. Predictive factors included age at onset, APOE ε4 status, and family history characteristics. Model performance was assessed using discrimination and calibration metrics. Results: In the derivation cohort (median age at onset 66 years), 10.3% carried Pathogenic/Likely Pathogenic Variants. Among patients with dementia, those with age at onset < 55 years (OR 2.56, p = 0.0098), more than two affected relatives (OR 3.32, p = 0.0039), parental disease history (OR 4.72, p = 0.015), and early-onset cases in the family (OR 2.61, p = 0.0096) were positively associated with Pathogenic/Likely Pathogenic Variant carriage, whereas APOE ε4 carriage was inversely associated (OR 0.36, p = 0.0041). The model achieved an area under the curve of 0.776 (95% CI, 0.701–0.853) in the derivation cohort and 0.781 (95% CI, 0.647–0.914) in the validation cohort (median age at onset 58 years), with adequate calibration. Conclusions: This model demonstrated strong predictive performance for Pathogenic/Likely Pathogenic Variant carriage, supporting its clinical utility in guiding genetic testing. Further research is needed to refine the model. Full article
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18 pages, 3460 KiB  
Article
Brain Structural Alterations Underlying Mood-Related Deficits in Schizophrenia
by Margherita Biondi, Marco Marino, Dante Mantini and Chiara Spironelli
Biomedicines 2025, 13(3), 736; https://doi.org/10.3390/biomedicines13030736 - 18 Mar 2025
Viewed by 739
Abstract
Background/Objectives: Schizophrenia (SZ) is a complex psychiatric disorder characterized by neurodegenerative processes, but the structural brain alterations associated with its progression remain poorly understood. This study investigated structural brain changes in SZ, particularly in the fronto-temporal and limbic regions, and explored their relationship [...] Read more.
Background/Objectives: Schizophrenia (SZ) is a complex psychiatric disorder characterized by neurodegenerative processes, but the structural brain alterations associated with its progression remain poorly understood. This study investigated structural brain changes in SZ, particularly in the fronto-temporal and limbic regions, and explored their relationship with symptom severity, with a focus on mood- and emotion-related symptoms. Methods: We analyzed structural MRI data from 74 SZ patients and 91 healthy controls (HCs) using voxel-based morphometry (VBM) to compare whole-brain grey matter volumes (GMVs). The analysis focused on the fronto-temporal and limbic regions, and correlations between GMV and symptom severity were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Generalized Psychopathology (GP) scale. Results: SZ patients exhibited significant reductions in GMV in the fronto-temporal and limbic regions, including the dorsolateral prefrontal cortex (dlPFC) and the temporal pole, compared to HCs. Notably, a significant positive association was found between GMV in the right inferior temporal gyrus (ITG) and the severity of generalized psychopathology, as well as with anxiety, depression, mannerisms, and unusual thought content. Further post hoc analysis identified a specific cluster of mood-related symptoms contributing to the GP scale, which correlated with GMV changes in the right ITG. Conclusions: Our findings provide new evidence of structural brain alterations in SZ, particularly in the fronto-temporal and limbic regions, suggesting a progressive neurodegenerative pattern. The role of the right ITG in mood- and emotion-related symptoms requires further exploration, as it could offer insights into SZ pathophysiology and aid in distinguishing SZ from other mood-related disorders. Full article
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15 pages, 1096 KiB  
Article
The Impact of Urodynamic Findings on Fatigue and Depression in People with Multiple Sclerosis
by Anke K. Jaekel, Julius Watzek, Jörn Nielsen, Anna-Lena Butscher, John Bitter, Marthe von Danwitz, Pirmin I. Zöhrer, Franziska Knappe, Ruth Kirschner-Hermanns and Stephanie C. Knüpfer
Biomedicines 2025, 13(3), 601; https://doi.org/10.3390/biomedicines13030601 - 1 Mar 2025
Viewed by 924
Abstract
Background: Fatigue and depression are common symptoms of multiple sclerosis (MS) that severely impair quality of life. The factors influencing both are of increasing interest for establishing therapeutic synergisms. Correlations between the symptoms of neurogenic lower urinary tract dysfunction (NLUTD), fatigue, and [...] Read more.
Background: Fatigue and depression are common symptoms of multiple sclerosis (MS) that severely impair quality of life. The factors influencing both are of increasing interest for establishing therapeutic synergisms. Correlations between the symptoms of neurogenic lower urinary tract dysfunction (NLUTD), fatigue, and depression have been described, but the impact of pathological urodynamic study (UDS) findings has not been investigated to date. Method: This retrospective, observational study correlated UDS findings of 274 people with MS (PwMS), prospectively collected between February 2017 and September 2021, with scores on the Fatigue Scale for Motor and Cognitive Functions and the German version of the Centre for Epidemiologic Studies Depression Scale. The effects of abnormal UDS on the FSMC and ADS scores were examined. Abnormal UDS was defined as follows: first desire to void (FDV) < 100 mL, strong desire to void < 250 mL (SDV), abnormal sensation, detrusor overactivity, detrusor–sphincter dyssynergia, reduced cystometric bladder capacity < 250 mL (MCBC), and compliance < 20 mL/cm H2O (Clow). Results: PwMS with Clow (mean difference 3.21, 95% CI 0.25; 6.17, p = 0.036) or FDV < 100 mL (mean difference 2.61, 95% CI 0.1; 5.12, p = 0.041) had significantly higher FSMC mean values than those without. PwMS with MCBC < 250 mL (relative risk 1.06, 95% CI 1.02; 1.1, p = 0.006) or Clow (relative risk 1.06, 95% CI 1.02; 1.1, p = 0.004) had an increased risk of clinically relevant fatigue. No effects were found for depression. Conclusions: PwMS with NLUTD have higher FSMC scores and an increased risk of fatigue in our retrospective study. The assessment of prospective longitudinal data regarding the effect of successfully treated NLUTD on fatigue is important for utilising therapeutic synergisms for improved quality of life in PwMS. Full article
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16 pages, 638 KiB  
Article
Machine Learning for Early Detection of Cognitive Decline in Parkinson’s Disease Using Multimodal Biomarker and Clinical Data
by Raziyeh Mohammadi, Samuel Y. E. Ng, Jayne Y. Tan, Adeline S. L. Ng, Xiao Deng, Xinyi Choi, Dede L. Heng, Shermyn Neo, Zheyu Xu, Kay-Yaw Tay, Wing-Lok Au, Eng-King Tan, Louis C. S. Tan, Ewout W. Steyerberg, William Greene and Seyed Ehsan Saffari
Biomedicines 2024, 12(12), 2758; https://doi.org/10.3390/biomedicines12122758 - 3 Dec 2024
Viewed by 2246
Abstract
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease, primarily affecting the middle-aged to elderly population. Among its nonmotor symptoms, cognitive decline (CD) is a precursor to dementia and represents a critical target for early risk assessment and diagnosis. Accurate [...] Read more.
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease, primarily affecting the middle-aged to elderly population. Among its nonmotor symptoms, cognitive decline (CD) is a precursor to dementia and represents a critical target for early risk assessment and diagnosis. Accurate CD prediction is crucial for timely intervention and tailored management of at-risk patients. This study used machine learning (ML) techniques to predict the CD risk over five-year in early-stage PD. Methods: Data from the Early Parkinson’s Disease Longitudinal Singapore (2014 to 2018) was used to predict CD defined as a one-unit annual decrease or a one-unit decline in Montreal Cognitive Assessment over two consecutive years. Four ML methods—AutoScore, Random Forest, K-Nearest Neighbors and Neural Network—were applied using baseline demographics, clinical assessments and blood biomarkers. Results: Variable selection identified key predictors of CD, including education year, diastolic lying blood pressure, diastolic standing blood pressure, systolic lying blood pressure, Hoehn and Yahr scale, body mass index, phosphorylated tau at threonine 181, total tau, Neurofilament light chain and suppression of tumorigenicity 2. Random Forest was the most effective, achieving an AUC of 0.93 (95% CI: 0.89, 0.97), using 10-fold cross-validation. Conclusions: Here, we demonstrate that ML-based models can identify early-stage PD patients at high risk for CD, supporting targeted interventions and improved PD management. Full article
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12 pages, 648 KiB  
Article
Exploring Cognitive Impairments Associated with Primary Open-Angle Glaucoma and Exfoliation Glaucoma
by Yoichi Kadoh, Suguru Kubota, Soichiro Shimomine and Masaki Tanito
Biomedicines 2024, 12(8), 1706; https://doi.org/10.3390/biomedicines12081706 - 1 Aug 2024
Cited by 1 | Viewed by 1394
Abstract
This study explored the link between different types of glaucoma and cognitive function in a cohort of 620 Japanese patients. Participants were categorized into primary open-angle glaucoma (PG), exfoliation glaucoma (EG), and non-glaucomatous control groups. The findings revealed a significant decline in cognitive [...] Read more.
This study explored the link between different types of glaucoma and cognitive function in a cohort of 620 Japanese patients. Participants were categorized into primary open-angle glaucoma (PG), exfoliation glaucoma (EG), and non-glaucomatous control groups. The findings revealed a significant decline in cognitive function as indicated by the Mini-Cog test in the EG group (mean ± SD: 4.0 ± 1, 95% CI: 3.9 to 4.2) compared to the PG group (4.4 ± 0.1, 4.3 to 4.5, p < 0.0001). Levels of fingertip measured advanced glycation end-products (AGEs) were significantly higher in the EG group (mean ± SD: 0.45 ± 0.006, 95% CI: 0.44 to 0.46) compared to the PG group (0.43 ± 0.004, 0.42 to 0.44, p = 0.0014). Although the multivariate analysis initially showed no direct association between glaucoma types and Mini-Cog scores, the EG group exhibited higher age and intraocular pressure (IOP) compared to the PG group. Further analysis revealed that high levels of AGEs were associated with cognitive decline and decreased mean visual fields in the EG group. Age was identified as a cofounding factor in these associations. An inverse correlation was observed between the accumulation of AGEs and skin carotenoid levels. Early detection of cognitive decline in glaucoma patients could enable timely intervention to preserve visual fields. Fingertip measurements of skin carotenoids and AGEs offer promising potential as non-invasive, straightforward diagnostic tools that could be widely adopted for monitoring ophthalmic and cognitive health in glaucoma patients. Full article
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15 pages, 319 KiB  
Article
Platelet Levels of Brain-Derived Neurotrophic Factor in Adults with Autism Spectrum Disorder: Is There a Specific Association with Autism Spectrum Psychopathology?
by Barbara Carpita, Benedetta Nardi, Chiara Bonelli, Lavinia Pascariello, Gabriele Massimetti, Ivan Mirko Cremone, Stefano Pini, Lionella Palego, Laura Betti, Gino Giannaccini and Liliana Dell’Osso
Biomedicines 2024, 12(7), 1529; https://doi.org/10.3390/biomedicines12071529 - 10 Jul 2024
Cited by 1 | Viewed by 1530
Abstract
To date, although several studies have investigated the circulating levels of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorder (ASD), only a few authors have addressed their evaluation in adults. Furthermore, an important limitation of these studies lies in the fact [...] Read more.
To date, although several studies have investigated the circulating levels of brain-derived neurotrophic factor (BDNF) in children with autism spectrum disorder (ASD), only a few authors have addressed their evaluation in adults. Furthermore, an important limitation of these studies lies in the fact that circulating BDNF is stored in platelets and released into the circulation when needed. To the best of our knowledge, a very limited number of studies have related peripheral BDNF values to platelet counts, and yet no study has evaluated intra-platelet BDNF levels in adults with ASD. In this framework, the aim of the present work is to pave the way in this field and evaluate platelet BNDF levels in adult ASD patients, as well as their correlation with autistic symptoms and related psychopathological dimensions. We recruited 22 ASD and 22 healthy controls, evaluated with the Adult autism subthreshold spectrum (AdAS Spectrum), the Social Anxiety Spectrum—self report (SHY-SR), the Trauma and loss spectrum—self report (TALS-SR), the Work and Social Adjustment Scale (WSAS), and the Mood Spectrum—self report for suicidality. Intra-platelet BDNF levels were also assessed. The results highlighted lower BDNF levels in the ASD group; moreover, AdAS Spectrum and WSAS total score as well as AdAS Spectrum Restricted interest and rumination, WSAS Private leisure activities, TALS-SR Arousal, and SHY-SR Childhood domains were significant negative predictors of platelet BDNF levels. Full article

Review

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28 pages, 1451 KiB  
Review
Minor Visual Phenomena in Lewy Body Disease: A Systematic Review
by Elettra Capogna, Virginia Pollarini, Alessia Quinzi, Lucia Guidi, Luisa Sambati, Maria Sasca Criante, Elena Mengoli, Annalena Venneri, Raffaele Lodi, Caterina Tonon and Micaela Mitolo
Biomedicines 2025, 13(5), 1152; https://doi.org/10.3390/biomedicines13051152 - 9 May 2025
Viewed by 580
Abstract
Minor visual phenomena (MVP), such as visual illusions, pareidolias, feeling of presence, and passage hallucinations, are often experienced by patients with Lewy Body Disease (LBD), in addition to complex visual hallucinations (VH), even in the early stages of the disease. This systematic review [...] Read more.
Minor visual phenomena (MVP), such as visual illusions, pareidolias, feeling of presence, and passage hallucinations, are often experienced by patients with Lewy Body Disease (LBD), in addition to complex visual hallucinations (VH), even in the early stages of the disease. This systematic review aimed to provide an up-to-date literature review of the occurrence and prevalence of MVP in LBD and to assess their potential associations both with VH and visuoperceptual and visuospatial deficits. A systematic literature search was carried out in PubMed, Web of Science, APA PsycInfo, Scopus, and Cochrane Library, and a total of 44 articles were included. The included studies showed significant variability in the occurrence of MVP in the LBD population and in the assessment methods used, such as standardized scales (e.g., the noise pareidolia test), semi-structured interviews (e.g., the North-East Visual Hallucinations Interview), and clinical descriptions. Similarly to VH, MVP appears to be highly specific to LBD, helping in differential diagnosis from Alzheimer’s Disease. The overall relationship between MVP, VH, and visuoperceptual/visuospatial deficits remains unclear. Some studies found that MVP (especially pareidolic responses and presence of hallucinations) was positively correlated with VH, yet it is challenging to determine whether MVP can be considered a precursor of future VH development. Negative associations were reported between MVP (especially pareidolias) and visuoperceptual/visuospatial abilities. However, it is not clear whether these deficits serve as independent, exclusive factors in MVP occurrence or if they interact with VH as a contributing component. Gaining insight into the occurrence of these phenomena could prove beneficial for differential diagnosis, prognosis, and prediction of treatment outcomes in patients with LBD. Full article
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26 pages, 1370 KiB  
Review
Relationship Between Depression and Neurodegeneration: Risk Factor, Prodrome, Consequence, or Something Else? A Scoping Review
by Dario Papa, Alessandro Ingenito, Alessandro von Gal, Maria Francesca De Pandis and Laura Piccardi
Biomedicines 2025, 13(5), 1023; https://doi.org/10.3390/biomedicines13051023 - 23 Apr 2025
Viewed by 581
Abstract
Background: The link between depression and neurodegeneration is complex and unclear. It is debated whether depression is a risk factor, a prodrome, a consequence, or unrelated. Objectives: This review examines these possibilities to clarify their connection, focusing primarily on Alzheimer’s disease, [...] Read more.
Background: The link between depression and neurodegeneration is complex and unclear. It is debated whether depression is a risk factor, a prodrome, a consequence, or unrelated. Objectives: This review examines these possibilities to clarify their connection, focusing primarily on Alzheimer’s disease, vascular dementia, Parkinson’s disease, and other highly comorbid neurodegenerative diseases. Methods: Eligibility criteria: The studies included in this review focused on neurodegenerative diseases with high comorbidity with depression, published in peer-reviewed English-language journals, providing empirical evidence on the link between the two conditions or theoretical frameworks that point to other studies. Non-human studies and those irrelevant to this connection were excluded. Source of evidence: AI-supported tools identified relevant articles. Results: Most studies suggest depression may contribute to neurodegeneration, but clinical, neuroimaging, and longitudinal evidence also support its role as a prodrome or consequence, indicating a bidirectional relationship. Conclusions: Despite extensive research, the connection remains unclear, highlighting the need for further investigation into underlying mechanisms and interdependencies, focusing on longitudinal studies by examining causality. Full article
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23 pages, 691 KiB  
Review
Hallmarks of Brain Plasticity
by Yauhen Statsenko, Nik V. Kuznetsov and Milos Ljubisaljevich
Biomedicines 2025, 13(2), 460; https://doi.org/10.3390/biomedicines13020460 - 13 Feb 2025
Viewed by 3465
Abstract
Cerebral plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions between genetic and environmental influences, and structural–functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Studies on brain [...] Read more.
Cerebral plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions between genetic and environmental influences, and structural–functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Studies on brain plasticity have important practical implications. The molecular characteristics of changes in brain plasticity may reveal disease course and the rehabilitative potential of the patient. Neurological disorders are linked with numerous cerebral non-coding RNAs (ncRNAs), in particular, microRNAs; the discovery of their essential role in gene regulation was recently recognized and awarded a Nobel Prize in Physiology or Medicine in 2024. Herein, we review the association of brain plasticity and its homeostasis with ncRNAs, which make them putative targets for RNA-based diagnostics and therapeutics. New insight into the concept of brain plasticity may provide additional perspectives on functional recovery following brain damage. Knowledge of this phenomenon will enable physicians to exploit the potential of cerebral plasticity and regulate eloquent networks with timely interventions. Future studies may reveal pathophysiological mechanisms of brain plasticity at macro- and microscopic levels to advance rehabilitation strategies and improve quality of life in patients with neurological diseases. Full article
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37 pages, 2898 KiB  
Review
Vascular Impairment, Muscle Atrophy, and Cognitive Decline: Critical Age-Related Conditions
by Enzo Pereira de Lima, Masaru Tanaka, Caroline Barbalho Lamas, Karina Quesada, Claudia Rucco P. Detregiachi, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Virgínia Maria Cavallari Strozze Catharin, Marcela Vialogo Marques de Castro, Edgar Baldi Junior, Marcelo Dib Bechara, Bruna Fidencio Rahal Ferraz, Vitor Cavallari Strozze Catharin, Lucas Fornari Laurindo and Sandra Maria Barbalho
Biomedicines 2024, 12(9), 2096; https://doi.org/10.3390/biomedicines12092096 - 13 Sep 2024
Cited by 18 | Viewed by 8710
Abstract
The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the muscle mass reduction seen in sarcopenia and the decline in neuronal function characteristic of neurodegeneration. Our limited understanding [...] Read more.
The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the muscle mass reduction seen in sarcopenia and the decline in neuronal function characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient outcomes. This study emphasizes the complex interplay between vascular dysfunction, muscle degeneration, and cognitive decline, highlighting the necessity for multidisciplinary treatment approaches. Advances in this domain promise improved diagnostic accuracy, more effective therapeutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population. Full article
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16 pages, 1156 KiB  
Review
P-tau217 as a Reliable Blood-Based Marker of Alzheimer’s Disease
by Roy Lai, Brenden Li and Ram Bishnoi
Biomedicines 2024, 12(8), 1836; https://doi.org/10.3390/biomedicines12081836 - 13 Aug 2024
Cited by 3 | Viewed by 7859
Abstract
Amyloid plaques and tau tangles are the hallmark pathologic features of Alzheimer’s disease (AD). Traditionally, these changes are identified in vivo via cerebrospinal fluid (CSF) analysis or positron emission tomography (PET) scans. However, these methods are invasive, expensive, and resource-intensive. To address these [...] Read more.
Amyloid plaques and tau tangles are the hallmark pathologic features of Alzheimer’s disease (AD). Traditionally, these changes are identified in vivo via cerebrospinal fluid (CSF) analysis or positron emission tomography (PET) scans. However, these methods are invasive, expensive, and resource-intensive. To address these limitations, there has been ongoing research over the past decade to identify blood-based markers for AD. Despite the challenges posed by their extremely low concentrations, recent advances in mass spectrometry and immunoassay techniques have made it feasible to detect these blood markers of amyloid and tau deposition. Phosphorylated tau (p-tau) has shown greater promise in reflecting amyloid pathology as evidenced by CSF and PET positivity. Various isoforms of p-tau, distinguished by their differential phosphorylation sites, have been recognized for their ability to identify amyloid-positive individuals. Notable examples include p-tau181, p-tau217, and p-tau235. Among these, p-tau217 has emerged as a superior and reliable marker of amyloid positivity and, thus, AD in terms of accuracy of diagnosis and ability for early prognosis. In this narrative review, we aim to elucidate the utility of p-tau217 as an AD marker, exploring its underlying basis, clinical diagnostic potential, and relevance in clinical care and trials. Full article
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19 pages, 772 KiB  
Review
Molecular Changes in the Ischemic Brain as Non-Invasive Brain Stimulation Targets—TMS and tDCS Mechanisms, Therapeutic Challenges, and Combination Therapies
by Aleksandra Markowska and Beata Tarnacka
Biomedicines 2024, 12(7), 1560; https://doi.org/10.3390/biomedicines12071560 - 13 Jul 2024
Cited by 4 | Viewed by 2463
Abstract
Ischemic stroke is one of the leading causes of death and disability. As the currently used neurorehabilitation methods present several limitations, the ongoing research focuses on the use of non-invasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial direct [...] Read more.
Ischemic stroke is one of the leading causes of death and disability. As the currently used neurorehabilitation methods present several limitations, the ongoing research focuses on the use of non-invasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). NIBS methods were demonstrated to modulate neural excitability and improve motor and cognitive functioning in neurodegenerative diseases. However, their mechanisms of action are not fully elucidated, and the clinical outcomes are often unpredictable. This review explores the molecular processes underlying the effects of TMS and tDCS in stroke rehabilitation, including oxidative stress reduction, cell death, stimulation of neurogenesis, and neuroprotective phenotypes of glial cells. A highlight is put on the newly emerging therapeutic targets, such as ferroptotic and pyroptotic pathways. In addition, the issue of interindividual variability is discussed, and the role of neuroimaging techniques is investigated to get closer to personalized medicine. Furthermore, translational challenges of NIBS techniques are analyzed, and limitations of current clinical trials are investigated. The paper concludes with suggestions for further neurorehabilitation stroke treatment, putting the focus on combination and personalized therapies, as well as novel protocols of brain stimulation techniques. Full article
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