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Brain Sciences Jun 2024Interoceptive dysfunctions are increasingly implicated in a number of physical and mental health conditions. Accordingly, there is a pertinent need for therapeutic... (Review)
Review
The Utility of Heartrate and Heartrate Variability Biofeedback for the Improvement of Interoception across Behavioural, Physiological and Neural Outcome Measures: A Systematic Review.
Interoceptive dysfunctions are increasingly implicated in a number of physical and mental health conditions. Accordingly, there is a pertinent need for therapeutic interventions which target interoceptive deficits. Heartrate and heartrate variability biofeedback therapy (HR(V)-BF), interventions which train individuals to regulate their cardiovascular signals and constrain these within optimal parameters through breathing, could enhance the functioning of interoceptive pathways via stimulation of the vagus nerve. Consequently, this narrative systematic review sought to synthesise the current state of the literature with regard to the potential of HR(V)-BF as an interoceptive intervention across behavioural, physiological and neural outcome measures related to interoception. In total, 77 papers were included in this review, with the majority using physiological outcome measures. Overall, findings were mixed with respect to improvements in the outcome measures after HR(V)-BF. However, trends suggested that effects on measures related to interoception were stronger when resonance frequency breathing and an intense treatment protocol were employed. Based on these findings, we propose a three-stage model by which HR(V)-BF may improve interoception which draws upon principles of interoceptive inference and predictive coding. Furthermore, we provide specific directions for future research, which will serve to advance the current knowledge state.
PubMed: 38928579
DOI: 10.3390/brainsci14060579 -
Tau Protein Accumulation Trajectory-Based Brain Age Prediction in the Alzheimer's Disease Continuum.Brain Sciences Jun 2024Clinical cognitive advancement within the Alzheimer's disease (AD) continuum is intimately connected with sustained accumulation of tau protein pathology. The biological...
Clinical cognitive advancement within the Alzheimer's disease (AD) continuum is intimately connected with sustained accumulation of tau protein pathology. The biological brain age and its gap show great potential for pathological risk and disease severity. In the present study, we applied multivariable linear support vector regression to train a normative brain age prediction model using tau brain images. We further assessed the predicted biological brain age and its gap for patients within the AD continuum. In the AD continuum, evaluated pathologic tau binding was found in the inferior temporal, parietal-temporal junction, precuneus/posterior cingulate, dorsal frontal, occipital, and inferior-medial temporal cortices. The biological brain age gaps of patients within the AD continuum were notably higher than those of the normal controls ( < 0.0001). Significant positive correlations were observed between the brain age gap and global tau protein accumulation levels for mild cognitive impairment ( = 0.726, < 0.001), AD ( = 0.845, < 0.001), and AD continuum ( = 0.797, < 0.001). The pathologic tau-based age gap was significantly linked to neuropsychological scores. The proposed pathologic tau-based biological brain age model could track the tau protein accumulation trajectory of cognitive impairment and further provide a comprehensive quantification index for the tau accumulation risk.
PubMed: 38928575
DOI: 10.3390/brainsci14060575 -
Brain Sciences Jun 2024This study introduces Multi-Threshold Recurrence Rate Plots (MTRRP), a novel methodology for analyzing dynamic patterns in complex systems, such as those influenced by...
This study introduces Multi-Threshold Recurrence Rate Plots (MTRRP), a novel methodology for analyzing dynamic patterns in complex systems, such as those influenced by neurodegenerative diseases in brain activity. MTRRP characterizes how recurrence rates evolve with increasing recurrence thresholds. A key innovation of our approach, Recurrence Complexity, captures structural complexity by integrating local randomness and global structural features through the product of Recurrence Rate Gradient and Recurrence Hurst, both derived from MTRRP. We applied this technique to resting-state EEG data from patients diagnosed with Alzheimer's Disease (AD), Frontotemporal Dementia (FTD), and age-matched healthy controls. The results revealed significantly higher recurrence complexity in the occipital areas of AD and FTD patients, particularly pronounced in the Alpha and Beta frequency bands. Furthermore, EEG features derived from MTRRP were evaluated using a Support Vector Machine with leave-one-out cross-validation, achieving a classification accuracy of 87.7%. These findings not only underscore the utility of MTRRP in detecting distinct neurophysiological patterns associated with neurodegenerative diseases but also highlight its broader applicability in time series analysis, providing a substantial tool for advancing medical diagnostics and research.
PubMed: 38928565
DOI: 10.3390/brainsci14060565 -
Brain Sciences May 2024Protein kinase C (PKC) is a diverse enzyme family crucial for cell signalling in various organs. Its dysregulation is linked to numerous diseases, including cancer,... (Review)
Review
Protein kinase C (PKC) is a diverse enzyme family crucial for cell signalling in various organs. Its dysregulation is linked to numerous diseases, including cancer, cardiovascular disorders, and neurological problems. In the brain, PKC plays pivotal roles in synaptic plasticity, learning, memory, and neuronal survival. Specifically, PKC's involvement in Alzheimer's Disease (AD) pathogenesis is of significant interest. The dysregulation of PKC signalling has been linked to neurological disorders, including AD. This review elucidates PKC's pivotal role in neurological health, particularly its implications in AD pathogenesis and chronic alcohol addiction. AD, characterised by neurodegeneration, implicates PKC dysregulation in synaptic dysfunction and cognitive decline. Conversely, chronic alcohol consumption elicits neural adaptations intertwined with PKC signalling, exacerbating addictive behaviours. By unravelling PKC's involvement in these afflictions, potential therapeutic avenues emerge, offering promise for ameliorating their debilitating effects. This review navigates the complex interplay between PKC, AD pathology, and alcohol addiction, illuminating pathways for future neurotherapeutic interventions.
PubMed: 38928554
DOI: 10.3390/brainsci14060554 -
Brain Sciences May 2024R4Alz is utilized for the early detection of minor neurocognitive disorders. It was designed to assess three main dimensions of cognitive-control abilities:...
UNLABELLED
R4Alz is utilized for the early detection of minor neurocognitive disorders. It was designed to assess three main dimensions of cognitive-control abilities: working-memory capacity, attentional control, and executive functioning.
OBJECTIVES
To reveal the cognitive-control dimensions that can differentiate between adults and older adults with healthy cognition, people with subjective cognitive impairment, and people diagnosed with mild cognitive impairment by examining the factorial structure of the R4Alz tool.
METHODS
The study comprised 404 participants: (a) healthy adults (n = 192), (b) healthy older adults (n = 29), (c) people with SCI (n = 74), and (d) people diagnosed with MCI (n = 109). The R4Alz battery was administered to all participants, including tests that assess short-term memory storage, information processing, information updating in working memory, and selective, sustained and divided attention), task/rule-switching, inhibitory control, and cognitive flexibility.
RESULTS
A two-factorial structural model was confirmed for R4Alz, with the first factor representing "fluid intelligence (FI)" and the second factor reflecting "executive functions (EF)". Both FI and EFs discriminate among all groups.
CONCLUSIONS
The R4Alz battery presents sound construct validity, evaluating abilities in FI and EF. Both abilities can differentiate very early cognitive impairment (SCI) from healthy cognitive aging and MCI.
PubMed: 38928548
DOI: 10.3390/brainsci14060548 -
Brain Sciences May 2024This work aimed to study the Village Test (VT) in a group of patients with Alzheimer's disease (AD) and compare the results with those of a group of patients with mild...
BACKGROUND
This work aimed to study the Village Test (VT) in a group of patients with Alzheimer's disease (AD) and compare the results with those of a group of patients with mild cognitive impairment (MCI) and controls.
METHODS
A total of 50 patients with AD, 28 patients with MCI, and 38 controls were evaluated. All participants underwent the VT and an extensive neuropsychological evaluation.
RESULTS
The mean ages of the participants were 74.4 years for those with AD, 74 for those with MCI, and 70.2 for the controls. The AD group built smaller and essential villages with a scarce use of pieces, a poor use of dynamic pieces, and scarce use of human figures. All constructions were often concentrated in the center of the table.
CONCLUSIONS
The villages built by the AD group represent a cognitive and affective coarctation and indicate a sense of existential disorientation and isolation. The VT is a useful aid for getting in touch with the inner emotional and existential states of patients with AD, and it could represent a complementary screening tool for orienting cognitive impairment diagnoses.
PubMed: 38928524
DOI: 10.3390/brainsci14060523 -
Brain Sciences May 2024Excessive and prolonged alcohol use can have long-term severe neurological consequences. The mechanisms involved may be complicated; however, new evidence seems to... (Review)
Review
Excessive and prolonged alcohol use can have long-term severe neurological consequences. The mechanisms involved may be complicated; however, new evidence seems to indicate the involvement of iron accumulation and neuroinflammation. Prolonged alcohol consumption has been linked to the accumulation of iron in specific regions of the brain. Evidence suggests that excess iron in the brain can trigger microglia activation in response. This activation leads to the release of pro-inflammatory cytokines and reactive oxygen species, which can cause damage to neurons and surrounding brain tissue. Additionally, iron-induced oxidative stress and inflammation can disrupt the blood-brain barrier, allowing immune cells from the periphery to infiltrate the brain. This infiltration can lead to further neuroinflammatory responses. Inflammation in the brain subsequently disrupts neuronal networks, impairs synaptic plasticity, and accelerates neuronal cell death. Consequently, cognitive functions such as memory, attention, and decision-making are compromised. Additionally, chronic neuroinflammation can hasten the development and progression of neurodegenerative diseases, further exacerbating cognitive impairment. Therefore, alcohol could act as a trigger for iron-induced neuroinflammation and cognitive decline. Overall, the mechanisms at play here seem to strongly link alcohol with cognitive decline, with neuroinflammation resulting from alcohol-induced iron accumulation playing a pivotal role.
PubMed: 38928521
DOI: 10.3390/brainsci14060520 -
International Journal of Molecular... Jun 2024The 5xFAD transgenic mouse model widely used in Alzheimer's disease (AD) research recapitulates many AD-related phenotypes with a relatively early onset and aggressive... (Review)
Review
The 5xFAD transgenic mouse model widely used in Alzheimer's disease (AD) research recapitulates many AD-related phenotypes with a relatively early onset and aggressive age-dependent progression. Besides developing amyloid peptide deposits alongside neuroinflammation by the age of 2 months, as well as exhibiting neuronal decline by the age of 4 months that intensifies by the age of 9 months, these mice manifest a broad spectrum of behavioural impairments. In this review, we present the extensive repertoire of behavioural dysfunctions in 5xFAD mice, organised into four categories: motor skills, sensory function, learning and memory abilities, and neuropsychiatric-like symptoms. The motor problems, associated with agility and reflex movements, as well as balance and coordination, and skeletal muscle function, typically arise by the time mice reach 9 months of age. The sensory function (such as taste, smell, hearing, and vision) starts to deteriorate when amyloid peptide buildups and neuroinflammation spread into related anatomical structures. The cognitive functions, encompassing learning and memory abilities, such as visual recognition, associative, spatial working, reference learning, and memory show signs of decline from 4 to 6 months of age. Concerning neuropsychiatric-like symptoms, comprising apathy, anxiety and depression, and the willingness for exploratory behaviour, it is believed that motivational changes emerge by approximately 6 months of age. Unfortunately, numerous studies from different laboratories are often contradictory on the conclusions drawn and the identification of onset age, making preclinical studies in rodent models not easily translatable to humans. This variability is likely due to a range of factors associated with animals themselves, housing and husbandry conditions, and experimental settings. In the forthcoming studies, greater clarity in experimental details when conducting behavioural testing in 5xFAD transgenic mice could minimise the inconsistencies and could ensure the reliability and the reproducibility of the results.
Topics: Animals; Alzheimer Disease; Disease Models, Animal; Mice, Transgenic; Mice; Humans; Behavior, Animal; Memory; Amyloid beta-Peptides
PubMed: 38928472
DOI: 10.3390/ijms25126766 -
International Journal of Molecular... Jun 2024Stroke is one of the leading causes of death. It not only affects adult people but also many children. It is estimated that, every year, 15 million people suffer a... (Review)
Review
Stroke is one of the leading causes of death. It not only affects adult people but also many children. It is estimated that, every year, 15 million people suffer a stroke worldwide. Among them, 5 million people die, while 5 million people are left permanently disabled. In this sense, the research to find new treatments should be accompanied with new therapies to combat neuronal death and to avoid developing cognitive impairment and dementia. Phytocannabinoids are among the compounds that have been used by mankind for the longest period of history. Their beneficial effects such as pain regulation or neuroprotection are widely known and make them possible therapeutic agents with high potential. These compounds bind cannabinoid receptors CB and CB. Unfortunately, the psychoactive side effect has displaced them in the vast majority of areas. Thus, progress in the research and development of new compounds that show efficiency as neuroprotectors without this psychoactive effect is essential. On the one hand, these compounds could selectively bind the CB receptor that does not show psychoactive effects and, in glia, has opened new avenues in this field of research, shedding new light on the use of cannabinoid receptors as therapeutic targets to combat neurodegenerative diseases such as Alzheimer's, Parkinson's disease, or stroke. On the other hand, a new possibility lies in the formation of heteromers containing cannabinoid receptors. Heteromers are new functional units that show new properties compared to the individual protomers. Thus, they represent a new possibility that may offer the beneficial effects of cannabinoids devoid of the unwanted psychoactive effect. Nowadays, the approval of a mixture of CBD (cannabidiol) and Δ-THC (tetrahydrocannabinol) to treat the neuropathic pain and spasticity in multiple sclerosis or purified cannabidiol to combat pediatric epilepsy have opened new therapeutic possibilities in the field of cannabinoids and returned these compounds to the front line of research to treat pathologies as relevant as stroke.
Topics: Humans; Receptor, Cannabinoid, CB2; Receptor, Cannabinoid, CB1; Ischemic Stroke; Animals; Cannabidiol; Neuroprotective Agents
PubMed: 38928415
DOI: 10.3390/ijms25126708 -
International Journal of Molecular... Jun 2024Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only... (Review)
Review
Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies to treat Alzheimer's disease are approved, dozens are in the testing phase, and one was withdrawn, and the other halted, likely due to efficacy issues. However, these outcomes should have been evident since these antibodies cannot enter the brain sufficiently due to the blood-brain barrier (BBB) protectant. However, all products can be rejuvenated by binding them with transferrin, preferably as smaller fragments. This model can be tested quickly and at a low cost and should be applied to bapineuzumab, solanezumab, crenezumab, gantenerumab, aducanumab, lecanemab, donanemab, cinpanemab, and gantenerumab, and their fragments. This paper demonstrates that conjugating with transferrin does not alter the binding to brain proteins such as amyloid-β (Aβ) and α-synuclein. We also present a selection of conjugate designs that will allow cleavage upon entering the brain to prevent their exocytosis while keeping the fragments connected to enable optimal binding to proteins. The identified products can be readily tested and returned to patients with the lowest regulatory cost and delays. These engineered antibodies can be manufactured by recombinant engineering, preferably by mRNA technology, as a more affordable solution to meet the dire need to treat neurodegenerative disorders effectively.
Topics: Humans; Neurodegenerative Diseases; Protein Engineering; Transferrin; Blood-Brain Barrier; Amyloid beta-Peptides; Antibodies, Monoclonal; Animals; alpha-Synuclein; Alzheimer Disease; Brain
PubMed: 38928395
DOI: 10.3390/ijms25126683