Previous
Depression is associated with executive cognitive deficits which are not well explored and treated. Such deficits have a significant impact on remission and recurrence. To understand the neurocognitive mechanisms of executive processes, a literature search was conducted using bibliographic databases in neuroscience and cognitive sciences: PubMed, ScienceDirect, EBSCOhost, and PsyArxiv, combining search terms: “depression”, “executive functions”, and “specific brain event-related potentials”. The theoretical review focuses on experiments using electrophysiological techniques, non-invasive tools with high temporal resolution. Depression shows alterations in brain activity linked with cognition: P3 diminished amplitudes and prolonged latencies, indicating executive attentional dysfunction; similar activity characterizes mismatch negativity (MMN), reflecting difficulties for change detection, voluntary effort, and mental shifting. Besides, depression tends to increase N1 latencies related with discrimination, and amplitudes of loudness dependence of auditory evoked potentials (LDAEP), suggesting inhibitory control’s deficits. Regarding feedback processing, the alterations of error-related negativity (ERN), correct response negativity (CRN), and error positivity (Pe), at anterior cingulate cortex (ACC), and frontal regions, are related with troubles for error awareness, cognitive control, and error monitoring in depression. Lastly, the ability to interpret coherently the information value of negative feedback (NF), and a propensity to commit perseverative and non-perseverative errors, need further investigation. Depressive individuals commit both errors on more occasions than controls, what seems to relate with fronto-striatal networks’ alterations, producing visual attention deficits and difficulties for inhibiting incoming information. Results show a variety of brain and executive cognitive components that are impaired under depression, although further research may clarify controversies resulting from depression heterogeneity and methodology used.
Depression is associated with executive cognitive deficits which are not well explored and treated. Such deficits have a significant impact on remission and recurrence. To understand the neurocognitive mechanisms of executive processes, a literature search was conducted using bibliographic databases in neuroscience and cognitive sciences: PubMed, ScienceDirect, EBSCOhost, and PsyArxiv, combining search terms: “depression”, “executive functions”, and “specific brain event-related potentials”. The theoretical review focuses on experiments using electrophysiological techniques, non-invasive tools with high temporal resolution. Depression shows alterations in brain activity linked with cognition: P3 diminished amplitudes and prolonged latencies, indicating executive attentional dysfunction; similar activity characterizes mismatch negativity (MMN), reflecting difficulties for change detection, voluntary effort, and mental shifting. Besides, depression tends to increase N1 latencies related with discrimination, and amplitudes of loudness dependence of auditory evoked potentials (LDAEP), suggesting inhibitory control’s deficits. Regarding feedback processing, the alterations of error-related negativity (ERN), correct response negativity (CRN), and error positivity (Pe), at anterior cingulate cortex (ACC), and frontal regions, are related with troubles for error awareness, cognitive control, and error monitoring in depression. Lastly, the ability to interpret coherently the information value of negative feedback (NF), and a propensity to commit perseverative and non-perseverative errors, need further investigation. Depressive individuals commit both errors on more occasions than controls, what seems to relate with fronto-striatal networks’ alterations, producing visual attention deficits and difficulties for inhibiting incoming information. Results show a variety of brain and executive cognitive components that are impaired under depression, although further research may clarify controversies resulting from depression heterogeneity and methodology used.
DOI: https://doi.org/10.37349/en.2025.100696
This article belongs to the special issue Novel Therapeutic Approaches for the Treatment of Depression
Spinal myelopathies, characterized by neurological deficits due to spinal compression in the spinal column, are increasingly common in the aging population. Although spinal myelopathies commonly present with sensory and motor deficits, they also manifest with life-debilitating enteric dysfunction associated with increased gastroparesis, constipation, bloating, abdominal pain, neurogenic bowel disease, and bladder and bowel incontinence. That said, the effects of spinal myelopathies on enteric gastrointestinal (GI) function are still poorly understood. This review aims to summarize existing literature concerning spinal myelopathies and their effect on the GI system, including the relevant anatomy and physiology of the nervous systems, etiology of various spinal cord injuries, clinical manifestations, current diagnosis and treatment strategies, and ongoing research concerning the gut-brain-spinal axis. The autonomic nervous system contributes to GI innervation through enteric reflex arcs and communication with the central nervous system (CNS) via spinal nerves. When spinal cord damage occurs, enteric reflex arcs, autonomic regulation, and gut-brain-spinal axis can become impaired, leading to GI symptoms. Etiologies of spinal myelopathies occur at all spinal levels. Spinal myelopathy includes inflammatory processes, such as multiple sclerosis and infection, and non-inflammatory processes, such as spondylosis, degenerative disc disease, tumors, and traumatic spinal cord injuries. Diagnosis modalities include imaging, particularly MRI, and functional assessments, such as high-resolution anorectal manometry and colonic transit studies. Enteric dysfunction treatment includes non-pharmacological, pharmacological, neuromodulatory interventions, and surgery. These strategies encompass lifestyle modifications, laxatives, prosecretory agents, 5HT4 agonists, vagus nerve stimulation, sympathetic nerve stimulation, colostomy, and ileostomy. Despite these treatment options, ongoing research with pudendal nerve stimulation, transanal irrigation, mesenchymal stem cells, and the relationship between the gut microbiome and gut-brain-spinal nerve axis may be beneficial in understanding spinal cord myelopathy-related enteric dysfunction, diagnosis, and treatment, ultimately improving clinical outcomes and quality of life for those who are affected.
Spinal myelopathies, characterized by neurological deficits due to spinal compression in the spinal column, are increasingly common in the aging population. Although spinal myelopathies commonly present with sensory and motor deficits, they also manifest with life-debilitating enteric dysfunction associated with increased gastroparesis, constipation, bloating, abdominal pain, neurogenic bowel disease, and bladder and bowel incontinence. That said, the effects of spinal myelopathies on enteric gastrointestinal (GI) function are still poorly understood. This review aims to summarize existing literature concerning spinal myelopathies and their effect on the GI system, including the relevant anatomy and physiology of the nervous systems, etiology of various spinal cord injuries, clinical manifestations, current diagnosis and treatment strategies, and ongoing research concerning the gut-brain-spinal axis. The autonomic nervous system contributes to GI innervation through enteric reflex arcs and communication with the central nervous system (CNS) via spinal nerves. When spinal cord damage occurs, enteric reflex arcs, autonomic regulation, and gut-brain-spinal axis can become impaired, leading to GI symptoms. Etiologies of spinal myelopathies occur at all spinal levels. Spinal myelopathy includes inflammatory processes, such as multiple sclerosis and infection, and non-inflammatory processes, such as spondylosis, degenerative disc disease, tumors, and traumatic spinal cord injuries. Diagnosis modalities include imaging, particularly MRI, and functional assessments, such as high-resolution anorectal manometry and colonic transit studies. Enteric dysfunction treatment includes non-pharmacological, pharmacological, neuromodulatory interventions, and surgery. These strategies encompass lifestyle modifications, laxatives, prosecretory agents, 5HT4 agonists, vagus nerve stimulation, sympathetic nerve stimulation, colostomy, and ileostomy. Despite these treatment options, ongoing research with pudendal nerve stimulation, transanal irrigation, mesenchymal stem cells, and the relationship between the gut microbiome and gut-brain-spinal nerve axis may be beneficial in understanding spinal cord myelopathy-related enteric dysfunction, diagnosis, and treatment, ultimately improving clinical outcomes and quality of life for those who are affected.
DOI: https://doi.org/10.37349/en.2025.100695
This article belongs to the special issue Enteric Neuro-Gliopathies: Ready for Prime Time?
Alzheimer’s disease, the main cause of dementia worldwide, is a slowly progressive neurodegenerative disorder. This disease involves a diversity of etiophatogenic processes as it is not only a genetic but also a biological and environmental disease. Owing to that complexity, nowadays there is no efficacious treatment for this disorder. The major Alzheimer’s disease clinical indications include extracellular senile plaques of amyloid-β protein, intracellular hyperphosphorylated τ neurofibrillary tangles, uncommon neuroinflammatory response, oxidative stress, and synaptic and neuronal dysfunction. The evaluation of the neuroprotective potential of new compounds is imperative. As natural products, like phenolic compounds, exhibit several bioactivities, it is urgent to test them and evaluate their inhibition of each clinical indication of Alzheimer’s disease. If phenolic compounds target more than one Alzheimer’s disease pathogenic mechanism (multi-target drug ligands), they will have the potential of becoming a leading Alzheimer’s disease treatment. Thus, this review analyzes, for each Alzheimer’s disease clinical indication, the scaffolds of several phenolic compounds leading to the highest activity with the objective to find phenolic compounds active against all the clinical indications. It was concluded that compounds presenting scaffolds like rugosin E or isocorilagin show potential in combating Alzheimer’s disease.
Alzheimer’s disease, the main cause of dementia worldwide, is a slowly progressive neurodegenerative disorder. This disease involves a diversity of etiophatogenic processes as it is not only a genetic but also a biological and environmental disease. Owing to that complexity, nowadays there is no efficacious treatment for this disorder. The major Alzheimer’s disease clinical indications include extracellular senile plaques of amyloid-β protein, intracellular hyperphosphorylated τ neurofibrillary tangles, uncommon neuroinflammatory response, oxidative stress, and synaptic and neuronal dysfunction. The evaluation of the neuroprotective potential of new compounds is imperative. As natural products, like phenolic compounds, exhibit several bioactivities, it is urgent to test them and evaluate their inhibition of each clinical indication of Alzheimer’s disease. If phenolic compounds target more than one Alzheimer’s disease pathogenic mechanism (multi-target drug ligands), they will have the potential of becoming a leading Alzheimer’s disease treatment. Thus, this review analyzes, for each Alzheimer’s disease clinical indication, the scaffolds of several phenolic compounds leading to the highest activity with the objective to find phenolic compounds active against all the clinical indications. It was concluded that compounds presenting scaffolds like rugosin E or isocorilagin show potential in combating Alzheimer’s disease.
DOI: https://doi.org/10.37349/en.2025.100693
This article belongs to the special issue Alzheimer's Disease
DOI: https://doi.org/10.37349/en.2025.100694
This article belongs to the special issue Alzheimer's Disease
All living beings, from microorganisms to plants, animals, and humans, require iron as an essential micronutrient for their lives. However, iron overload can constitute a scenario prone to damage to the organism, including oxidative stress, deterioration of cellular and subcellular membranes, and thus leading to cell death. This process involves unrestricted lipid peroxidation caused by the generation of reactive oxygen species (ROS) because of an abrupt increase in free Fe2+ in the cytoplasm, all of which leads to subsequent membrane damage and iron-dependent cell death, now known as “ferroptosis”. This process can be induced by convulsive stress, and conversely, inducing seizures, and in both situations under a context of neuroinflammation. In this critical review, we will highlight the most relevant aspects of this recently described mechanism, which has been studied little in epilepsy, its impact on the prognosis of the disease, and its effects on the development of central and/or peripheral comorbidities, including SUDEP (sudden unexpected death in epilepsy).
All living beings, from microorganisms to plants, animals, and humans, require iron as an essential micronutrient for their lives. However, iron overload can constitute a scenario prone to damage to the organism, including oxidative stress, deterioration of cellular and subcellular membranes, and thus leading to cell death. This process involves unrestricted lipid peroxidation caused by the generation of reactive oxygen species (ROS) because of an abrupt increase in free Fe2+ in the cytoplasm, all of which leads to subsequent membrane damage and iron-dependent cell death, now known as “ferroptosis”. This process can be induced by convulsive stress, and conversely, inducing seizures, and in both situations under a context of neuroinflammation. In this critical review, we will highlight the most relevant aspects of this recently described mechanism, which has been studied little in epilepsy, its impact on the prognosis of the disease, and its effects on the development of central and/or peripheral comorbidities, including SUDEP (sudden unexpected death in epilepsy).
DOI: https://doi.org/10.37349/en.2025.100692
This article belongs to the special issue Advances in Epilepsy Research
Ectonucleoside triphosphate diphosphohydrolases (ENTPDases), members of the cluster of differentiation 39 (CD39) family, are key regulators of purinergic signaling through the hydrolysis of tri and diphosphate nucleotides. These enzymes are expressed on the cell surface, extracellular environment, or within intracellular organelles such as the Golgi apparatus. ENTPDases play critical roles in modulating immune responses, inflammation, and neuroinflammation by controlling extracellular nucleotide availability in mammals. Moreover, they contribute to adenosine-mediated signaling in cooperation with 5’-nucleotidases (CD73). Pathogenic microorganisms also express ENTPDases, manipulating host purinergic signaling, suppressing adenosine triphosphate (ATP)-driven inflammation, and promoting immune evasion via increased adenosine production. Pathogenic parasites also express ENTPDases, manipulating host purinergic signaling, suppressing ATP-driven inflammation, and promoting immune evasion via increased adenosine production. Given their involvement in infection and inflammatory diseases, ENTPDases have emerged as promising pharmacological targets. This review comprehensively analyzes the ENTPDases from mammals and pathogenic parasites, emphasizing their role in purinergic signaling and their potential as therapeutic targets. While ENTPDase inhibitors hold promise for modulating inflammation and infection, their clinical translation faces challenges, including selectivity, off-target effects, and systemic alterations in purinergic homeostasis. Addressing these concerns through targeted drug delivery, allosteric modulation, and improved inhibitor specificity is crucial for therapeutic advancements.
Ectonucleoside triphosphate diphosphohydrolases (ENTPDases), members of the cluster of differentiation 39 (CD39) family, are key regulators of purinergic signaling through the hydrolysis of tri and diphosphate nucleotides. These enzymes are expressed on the cell surface, extracellular environment, or within intracellular organelles such as the Golgi apparatus. ENTPDases play critical roles in modulating immune responses, inflammation, and neuroinflammation by controlling extracellular nucleotide availability in mammals. Moreover, they contribute to adenosine-mediated signaling in cooperation with 5’-nucleotidases (CD73). Pathogenic microorganisms also express ENTPDases, manipulating host purinergic signaling, suppressing adenosine triphosphate (ATP)-driven inflammation, and promoting immune evasion via increased adenosine production. Pathogenic parasites also express ENTPDases, manipulating host purinergic signaling, suppressing ATP-driven inflammation, and promoting immune evasion via increased adenosine production. Given their involvement in infection and inflammatory diseases, ENTPDases have emerged as promising pharmacological targets. This review comprehensively analyzes the ENTPDases from mammals and pathogenic parasites, emphasizing their role in purinergic signaling and their potential as therapeutic targets. While ENTPDase inhibitors hold promise for modulating inflammation and infection, their clinical translation faces challenges, including selectivity, off-target effects, and systemic alterations in purinergic homeostasis. Addressing these concerns through targeted drug delivery, allosteric modulation, and improved inhibitor specificity is crucial for therapeutic advancements.
DOI: https://doi.org/10.37349/en.2025.100691
Aim:
Natural products possess diverse pharmacological properties that are effective and safe for treating and managing amnesia; however, there is little or no scientific proof for most of their claims. This study evaluates the efficacy of Lecaniodiscus cupanioide-supplemented diets (LCSD) and Alchornea cordifolia-supplemented diets (ACSD) on scopolamine-induced amnesia in male rats. Roots of L. cupanioide and A. cordifolia were obtained and used to formulate 10% and 20% supplemented diets.
Methods:
Experimental animals were orally pre-fed LCSD and ACSD for 14 days before the induction of amnesia via single i.p. (intraperitoneal) administration of scopolamine (2 mg/kg body weight). Experimental animals were subjected to a Y-maze test to evaluate cognitive performance before experiment termination. The activities of hippocampal key enzymes linked to cognitive function were determined.
Results:
The result of the Y-maze showed that the induction of amnesia significantly (p < 0.001) reduced spatial memory function, which was protected against LCSD and ACSD pre-treated rats. Also, pre-treatment with supplemented diets inhibited the significant (p < 0.01) aggravation of monoamine oxidase, arginase, tumor necrosis factor-α, malonaldehyde, myeloperoxidase, acetylcholinesterase, and butyrylcholinesterase concentrations, and the significant (p < 0.05) depletion of dopamine, nitric oxide, interleukin-6, total thiol, and non-protein thiol concentrations, in comparison with that observed with amnesic-induced untreated rats. Comparatively, LCSD was more effective in preventing neuronal enzymatic imbalances, while ACSD was more effective in avoiding antioxidant status depletion.
Conclusions:
Conclusively, this study established that the supplemented diets possess potent anti-amnesic and neuroprotective abilities. Furthermore, this study recommends supplemented diets as a dietary intervention for preventing and managing amnesic conditions.
Aim:
Natural products possess diverse pharmacological properties that are effective and safe for treating and managing amnesia; however, there is little or no scientific proof for most of their claims. This study evaluates the efficacy of Lecaniodiscus cupanioide-supplemented diets (LCSD) and Alchornea cordifolia-supplemented diets (ACSD) on scopolamine-induced amnesia in male rats. Roots of L. cupanioide and A. cordifolia were obtained and used to formulate 10% and 20% supplemented diets.
Methods:
Experimental animals were orally pre-fed LCSD and ACSD for 14 days before the induction of amnesia via single i.p. (intraperitoneal) administration of scopolamine (2 mg/kg body weight). Experimental animals were subjected to a Y-maze test to evaluate cognitive performance before experiment termination. The activities of hippocampal key enzymes linked to cognitive function were determined.
Results:
The result of the Y-maze showed that the induction of amnesia significantly (p < 0.001) reduced spatial memory function, which was protected against LCSD and ACSD pre-treated rats. Also, pre-treatment with supplemented diets inhibited the significant (p < 0.01) aggravation of monoamine oxidase, arginase, tumor necrosis factor-α, malonaldehyde, myeloperoxidase, acetylcholinesterase, and butyrylcholinesterase concentrations, and the significant (p < 0.05) depletion of dopamine, nitric oxide, interleukin-6, total thiol, and non-protein thiol concentrations, in comparison with that observed with amnesic-induced untreated rats. Comparatively, LCSD was more effective in preventing neuronal enzymatic imbalances, while ACSD was more effective in avoiding antioxidant status depletion.
Conclusions:
Conclusively, this study established that the supplemented diets possess potent anti-amnesic and neuroprotective abilities. Furthermore, this study recommends supplemented diets as a dietary intervention for preventing and managing amnesic conditions.
DOI: https://doi.org/10.37349/en.2025.100690
This article belongs to the special issue Medicinal Plants and Bioactive Phytochemicals in Neuroprotection
The choroid plexus, pivotal for cerebrospinal fluid (CSF) regulation and blood-CSF barrier function, becomes a focal point for primary central nervous system lymphoma (PCNSL). This article delves into a case of this uncommon presentation, highlighting diagnostic challenges, treatment complexities, and post-treatment outcomes. A 30-year-old Lebanese patient with mild headaches and vomiting was initially diagnosed with vasculitis but later confirmed through endoscopic biopsy to have diffuse large B-cell lymphoma of the choroid plexus. Treatment with intravenous methotrexate, intrathecal cytarabine, rituximab, and radiotherapy led to gradual neurological improvement. Treatment strategies, aligned with PCNSL standards, include intravenous methotrexate, intrathecal cytarabine, rituximab, and radiotherapy, leading to gradual neurological improvement post-treatment. Prognostic factors, such as age and specific brain area involvement, guide tailored treatment plans. This report emphasizes the need for a multidisciplinary approach, increased awareness, and ongoing research for optimal outcomes in PCNSL cases involving the choroid plexus.
The choroid plexus, pivotal for cerebrospinal fluid (CSF) regulation and blood-CSF barrier function, becomes a focal point for primary central nervous system lymphoma (PCNSL). This article delves into a case of this uncommon presentation, highlighting diagnostic challenges, treatment complexities, and post-treatment outcomes. A 30-year-old Lebanese patient with mild headaches and vomiting was initially diagnosed with vasculitis but later confirmed through endoscopic biopsy to have diffuse large B-cell lymphoma of the choroid plexus. Treatment with intravenous methotrexate, intrathecal cytarabine, rituximab, and radiotherapy led to gradual neurological improvement. Treatment strategies, aligned with PCNSL standards, include intravenous methotrexate, intrathecal cytarabine, rituximab, and radiotherapy, leading to gradual neurological improvement post-treatment. Prognostic factors, such as age and specific brain area involvement, guide tailored treatment plans. This report emphasizes the need for a multidisciplinary approach, increased awareness, and ongoing research for optimal outcomes in PCNSL cases involving the choroid plexus.
DOI: https://doi.org/10.37349/en.2025.100689
CD36 is a transmembrane protein that plays a role in various biological processes, including oxidized low-density lipoprotein and fatty acid uptake as well as regulatory control for inflammation signaling. Its robust expression in monocytes and macrophages associated with its ability to translocate fatty acids linked this scavenger receptor to foam cell formation and atherosclerosis. In the context of ischemic stroke, CD36 has been shown to contribute to brain injury and inflammation. Preclinical studies have demonstrated that CD36 expression increases in the brain after stroke and that inhibiting CD36 can reduce infarction size and improve neurological outcomes in animal models. These findings suggest that CD36 may be a potential therapeutic target for ischemic stroke. However, no clinical trials addressing CD36 and acute ischemic stroke are registered in the American or European databases. This review will discuss the relationship between CD36 and ischemic stroke and present some clinical findings in patients with single nucleotide polymorphisms of the CD36 gene.
CD36 is a transmembrane protein that plays a role in various biological processes, including oxidized low-density lipoprotein and fatty acid uptake as well as regulatory control for inflammation signaling. Its robust expression in monocytes and macrophages associated with its ability to translocate fatty acids linked this scavenger receptor to foam cell formation and atherosclerosis. In the context of ischemic stroke, CD36 has been shown to contribute to brain injury and inflammation. Preclinical studies have demonstrated that CD36 expression increases in the brain after stroke and that inhibiting CD36 can reduce infarction size and improve neurological outcomes in animal models. These findings suggest that CD36 may be a potential therapeutic target for ischemic stroke. However, no clinical trials addressing CD36 and acute ischemic stroke are registered in the American or European databases. This review will discuss the relationship between CD36 and ischemic stroke and present some clinical findings in patients with single nucleotide polymorphisms of the CD36 gene.
DOI: https://doi.org/10.37349/en.2025.100688
This article belongs to the special issue Cerebral Ischemia, Genetics, Comorbidities, Risk Factors and New Therapeutic Options for Neurorestoration
Aim:
To report the incidence, characteristics, and prognosis of spontaneous intracerebral hemorrhage (ICH) in North Karelia Central Hospital Primary Stroke Center (PSC).
Methods:
All patients admitted with ICH to North Karelia Central Hospital between January 1, 2021, and August 8, 2023, were identified from the center’s prospectively updated stroke care database. Post-hospital care data on outcomes were retrospectively updated between May 27 and June 5, 2024.
Results:
During the entire study period, we identified altogether 56 ICH patients, of whom two thirds were men. The mean annual incidence of 2021–2022 was 12.3/100,000, and in the population 19–49 years of age, 1.8/100,000. Three months after the stroke, 50% of the patients were functionally independent. In-hospital mortality was 5%, and altogether 11 patients (20%) died during the follow-up (mean 1.72 years). In multivariate analyses, diabetes was associated with mortality [hazard ratio: 3.50, 95% confidence interval (CI): 1.02–11.95], and age was associated with functional outcome in three-month follow-up (odds ratio: 1.060, 95% CI: 1.015–1.107). New-onset epilepsy was diagnosed in three patients (6%) during the follow-up (mean: 1.84 years).
Conclusions:
Short-term functional outcome of ICH was mostly favorable, continuing long-term trends of improving outcomes after stroke. Efficacy of multiple interventions care bundle in the treatment of ICH in a PSC-level hospital, a shift of using direct oral anticoagulants (DOACs) instead of warfarin, and improved health status of elderly citizens could be contributing to the better outcome.
Aim:
To report the incidence, characteristics, and prognosis of spontaneous intracerebral hemorrhage (ICH) in North Karelia Central Hospital Primary Stroke Center (PSC).
Methods:
All patients admitted with ICH to North Karelia Central Hospital between January 1, 2021, and August 8, 2023, were identified from the center’s prospectively updated stroke care database. Post-hospital care data on outcomes were retrospectively updated between May 27 and June 5, 2024.
Results:
During the entire study period, we identified altogether 56 ICH patients, of whom two thirds were men. The mean annual incidence of 2021–2022 was 12.3/100,000, and in the population 19–49 years of age, 1.8/100,000. Three months after the stroke, 50% of the patients were functionally independent. In-hospital mortality was 5%, and altogether 11 patients (20%) died during the follow-up (mean 1.72 years). In multivariate analyses, diabetes was associated with mortality [hazard ratio: 3.50, 95% confidence interval (CI): 1.02–11.95], and age was associated with functional outcome in three-month follow-up (odds ratio: 1.060, 95% CI: 1.015–1.107). New-onset epilepsy was diagnosed in three patients (6%) during the follow-up (mean: 1.84 years).
Conclusions:
Short-term functional outcome of ICH was mostly favorable, continuing long-term trends of improving outcomes after stroke. Efficacy of multiple interventions care bundle in the treatment of ICH in a PSC-level hospital, a shift of using direct oral anticoagulants (DOACs) instead of warfarin, and improved health status of elderly citizens could be contributing to the better outcome.
DOI: https://doi.org/10.37349/en.2025.100687
Neuropathic pain, defined by the International Association for the Study of Pain as “pain caused by a lesion or disease of the somatosensory system”, has an estimated prevalence of 7–9.2% in the general population and is associated with poorer health-related quality of life than other types of pain. Diagnosis can be improved by the use of diagnostic algorithms, but treatment remains rather unsatisfactory, with only 30–40% of patients achieving an acceptable response. Some authors have suggested that the poor results in the treatment of neuropathic pain may be related to the different mechanisms present in each patient and have tried to correlate them with clinical characteristics in order to evaluate possible targeted treatments. This approach has been used in some studies evaluating the response to specific pharmacotherapies in clusters of patients, with encouraging results but still limited applicability to clinical practice. In this narrative review, we attempt to analyse the literature suggesting possible pathogenetic mechanisms manifested along the nociceptive pathway due to a lesion or disease of the nervous system; aware of the limitations of exploring such a wide field, we look for conditions that could be targeted by the available pharmacological or interventional treatment options. Functional changes may occur in the nociceptive system from the periphery to the cerebral cortex, in particular in the nociceptive terminals, along the first-order neuron and the dorsal root ganglion, at the first synapses, or at supraspinal levels. Clinical assessment is the first step in the study of anatomical and functional changes; the diagnostic hypothesis should be confirmed, if possible, by instrumental studies or diagnostic blocks or procedures to guide an individualised therapeutic algorithm from less to more invasive treatments.
Neuropathic pain, defined by the International Association for the Study of Pain as “pain caused by a lesion or disease of the somatosensory system”, has an estimated prevalence of 7–9.2% in the general population and is associated with poorer health-related quality of life than other types of pain. Diagnosis can be improved by the use of diagnostic algorithms, but treatment remains rather unsatisfactory, with only 30–40% of patients achieving an acceptable response. Some authors have suggested that the poor results in the treatment of neuropathic pain may be related to the different mechanisms present in each patient and have tried to correlate them with clinical characteristics in order to evaluate possible targeted treatments. This approach has been used in some studies evaluating the response to specific pharmacotherapies in clusters of patients, with encouraging results but still limited applicability to clinical practice. In this narrative review, we attempt to analyse the literature suggesting possible pathogenetic mechanisms manifested along the nociceptive pathway due to a lesion or disease of the nervous system; aware of the limitations of exploring such a wide field, we look for conditions that could be targeted by the available pharmacological or interventional treatment options. Functional changes may occur in the nociceptive system from the periphery to the cerebral cortex, in particular in the nociceptive terminals, along the first-order neuron and the dorsal root ganglion, at the first synapses, or at supraspinal levels. Clinical assessment is the first step in the study of anatomical and functional changes; the diagnostic hypothesis should be confirmed, if possible, by instrumental studies or diagnostic blocks or procedures to guide an individualised therapeutic algorithm from less to more invasive treatments.
DOI: https://doi.org/10.37349/en.2025.100686
This article belongs to the special issue Neuropathic Pain
Aim:
This study is to better understand how the transient ion transport activity of touch receptors could change the graded potential to stimulate an action potential firing.
Methods:
The latest transmembrane-electrostatically localized protons/cations charges (TELC) theory is employed for numerical analysis to calculate the neural touch signal transduction responding time required to fire an action potential spike.
Results:
A neural action potential spike was constructed successfully using newly developed time-dependent TELC-based neural transmembrane potential integral equations (Equations 5, 6, and 7). The results explicated that the TELC curve has an inverse relationship with neural transmembrane potential since its curve appears as an inverse mirror image to the action potential spike. Based on the TELC density at resting membrane potential of –70 mV calculated to be 3,900 (excess protons + cations) per μm2 and that at the stimulation threshold level (–55 mV) calculated to be 3,100 (excess protons + cations) per μm2 on extracellular membrane surface, the neural touch signal transduction responding time from PIEZO channel ion conduction to reduce the TELC density to the stimulation level of 3,100 TELC per μm2 has now, for the first time, been calculated for action potential firing.
Conclusions:
The activity of a single or a few PIEZO channels may be sufficient to generate a “graded potential” to trigger an action potential spike firing. With a high number (200–300) of PIEZO channels activated by touch, it can generate the required “graded potential” to reach the stimulation threshold level (–55 mV) within a neural touch signal transduction time as fast as 0.3 ms. The calculated neural touch signal transduction responding time (e.g., 0.3 ms) may have fundamental implications not only for neuroscience but also for other science and technology fields such as bioengineering and sports physiology.
Aim:
This study is to better understand how the transient ion transport activity of touch receptors could change the graded potential to stimulate an action potential firing.
Methods:
The latest transmembrane-electrostatically localized protons/cations charges (TELC) theory is employed for numerical analysis to calculate the neural touch signal transduction responding time required to fire an action potential spike.
Results:
A neural action potential spike was constructed successfully using newly developed time-dependent TELC-based neural transmembrane potential integral equations (Equations 5, 6, and 7). The results explicated that the TELC curve has an inverse relationship with neural transmembrane potential since its curve appears as an inverse mirror image to the action potential spike. Based on the TELC density at resting membrane potential of –70 mV calculated to be 3,900 (excess protons + cations) per μm2 and that at the stimulation threshold level (–55 mV) calculated to be 3,100 (excess protons + cations) per μm2 on extracellular membrane surface, the neural touch signal transduction responding time from PIEZO channel ion conduction to reduce the TELC density to the stimulation level of 3,100 TELC per μm2 has now, for the first time, been calculated for action potential firing.
Conclusions:
The activity of a single or a few PIEZO channels may be sufficient to generate a “graded potential” to trigger an action potential spike firing. With a high number (200–300) of PIEZO channels activated by touch, it can generate the required “graded potential” to reach the stimulation threshold level (–55 mV) within a neural touch signal transduction time as fast as 0.3 ms. The calculated neural touch signal transduction responding time (e.g., 0.3 ms) may have fundamental implications not only for neuroscience but also for other science and technology fields such as bioengineering and sports physiology.
DOI: https://doi.org/10.37349/en.2025.100685
Aim:
Cognitive complaints are frequent among cancer patients. These issues can significantly affect the patient’s quality of life and are linked to a higher risk of developing dementia. However, their occurrence does not consistently correlate with measurable objective cognitive dysfunction, which contributes to their negligence in oncological care. Thus, this study aimed to examine the relationship between subjective and objective measures of cognitive function in patients without CNS involvement in a developing context.
Methods:
A cross-sectional study was conducted with 50 patients aged 18 and above shortly after diagnosis of non-CNS cancer but before any systematic treatment at a tertiary hospital in Gauteng. The patients completed a self-perceived cognitive impairment (PCI) assessment, and the mini-Montreal Cognitive Assessment (mini-MoCA) as an objective measure of cognition. Correlational analyses were conducted to examine the relationship between self-perceived cognitive problems and performance on the mini-MoCA.
Results:
The results of the study revealed the presence of both self-perceived cognitive problems and objective cognitive impairments among the study cohort. There was a small non-significant association between self-PCI and the objective measure of cognitive impairment on the mini-MoCA, rs(43) = 0.220, P = 0.147. Notably, only the memory sub-domain showed a significant but moderate positive association with self-PCI, rs(43) = 0.325, P = 0.029.
Conclusions:
This study offers initial evidence of both subjective and objective cognitive impairment in non-CNS cancer patients before treatment in a resource-constrained setting. While there was a small non-significant association between global objective cognitive impairment and patients’ PCIs, a significant moderate association was revealed between the memory sub-domain and PCI. These results underscore the need for thorough cognitive assessment before treatment, as both the presence of cognitive impairment and patients’ perceptions of it can influence treatment compliance and everyday functioning.
Aim:
Cognitive complaints are frequent among cancer patients. These issues can significantly affect the patient’s quality of life and are linked to a higher risk of developing dementia. However, their occurrence does not consistently correlate with measurable objective cognitive dysfunction, which contributes to their negligence in oncological care. Thus, this study aimed to examine the relationship between subjective and objective measures of cognitive function in patients without CNS involvement in a developing context.
Methods:
A cross-sectional study was conducted with 50 patients aged 18 and above shortly after diagnosis of non-CNS cancer but before any systematic treatment at a tertiary hospital in Gauteng. The patients completed a self-perceived cognitive impairment (PCI) assessment, and the mini-Montreal Cognitive Assessment (mini-MoCA) as an objective measure of cognition. Correlational analyses were conducted to examine the relationship between self-perceived cognitive problems and performance on the mini-MoCA.
Results:
The results of the study revealed the presence of both self-perceived cognitive problems and objective cognitive impairments among the study cohort. There was a small non-significant association between self-PCI and the objective measure of cognitive impairment on the mini-MoCA, rs(43) = 0.220, P = 0.147. Notably, only the memory sub-domain showed a significant but moderate positive association with self-PCI, rs(43) = 0.325, P = 0.029.
Conclusions:
This study offers initial evidence of both subjective and objective cognitive impairment in non-CNS cancer patients before treatment in a resource-constrained setting. While there was a small non-significant association between global objective cognitive impairment and patients’ PCIs, a significant moderate association was revealed between the memory sub-domain and PCI. These results underscore the need for thorough cognitive assessment before treatment, as both the presence of cognitive impairment and patients’ perceptions of it can influence treatment compliance and everyday functioning.
DOI: https://doi.org/10.37349/en.2025.100684
“Functional” gut disorders are clinical conditions frequently encountered in clinical practice, often characterized by abnormalities of the intestinal sensory and motor functions. Although traditionally believed not harboring organic abnormalities, some of these disorders have been demonstrated to have more or less subtle involvement of the enteric nervous system. This involvement has been especially documented for enteric glial cells, even though other elements may be involved. Given the pivotal role of enteric glial cells in gut pathophysiology and their evident abnormalities in some disorders of gut-brain interaction, it may be time to reconsider their role and recognize them as an important pathophysiological factor in these conditions. Thus, due to the prominent neuronal and glial involvement in some clinically severe forms, it is proposed that at least some of the “functional” gut disorders should be reclassified as enteric neuro-gliopathies.
“Functional” gut disorders are clinical conditions frequently encountered in clinical practice, often characterized by abnormalities of the intestinal sensory and motor functions. Although traditionally believed not harboring organic abnormalities, some of these disorders have been demonstrated to have more or less subtle involvement of the enteric nervous system. This involvement has been especially documented for enteric glial cells, even though other elements may be involved. Given the pivotal role of enteric glial cells in gut pathophysiology and their evident abnormalities in some disorders of gut-brain interaction, it may be time to reconsider their role and recognize them as an important pathophysiological factor in these conditions. Thus, due to the prominent neuronal and glial involvement in some clinically severe forms, it is proposed that at least some of the “functional” gut disorders should be reclassified as enteric neuro-gliopathies.
DOI: https://doi.org/10.37349/en.2025.100683
This article belongs to the special issue Enteric Neuro-Gliopathies: Ready for Prime Time?
Alzheimer’s disease (AD), the term “dementia”, describes a specific neuropathology together with the development and progression of age-related cognitive and functional loss. Formononetin is naturally occurring isoflavone recognized for its potential health benefits, anti-oxidant, anti-inflammatory, anti-cancer, and anti-apoptotic properties. Neurodegenerative disorders arise from the gradual loss of function and eventual death of nerve cells in the brain or peripheral nervous system. Astragalus membranaceus is a traditional plant with a variety of pharmacological and biochemical properties, including antiviral, anti-hyperglycaemic, and immunomodulatory effects. Moreover, the expression of membrane-bound and soluble receptor for advanced glycation end products (RAGE) is enhanced in the AD brain due to increased levels of soluble and insoluble amyloid-beta (Aβ) peptides. Additionally, in inflammatory circumstances, leukocytes’ firm attachment and transmigration to endothelial cells are regulated by intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Formononetin also possesses anti-bacterial, anti-inflammatory, anti-cancer, anti-oxidant, and estrogenic activity. Formononetin has emerged as a promising agent in the modulation of mediators involved in neurodegenerative disease. Formononetin might modulate nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway to potentiate the anti-Alzheimer’s activity. Additionally, formononetin might inhibit the Aβ/RAGE interaction which further inactivates the activity of extracellular signal regulated kinase (ERK), Janus kinase (JNK) signaling pathway that results in the reduction of nuclear translocation of nuclear factor kappa B (NF-κB) and also reduces the cytokines level to ameliorate AD. It might inhibit the ICAM, VCAM, and THP-1 proteins. Therefore, this compound offers potential therapeutic benefits by reducing cytokine levels to ameliorate AD. This review article is designed to explore the mechanistic interplay underlying the anti-Alzheimer’s effect of A. membranaceus, especially formononetin.
Alzheimer’s disease (AD), the term “dementia”, describes a specific neuropathology together with the development and progression of age-related cognitive and functional loss. Formononetin is naturally occurring isoflavone recognized for its potential health benefits, anti-oxidant, anti-inflammatory, anti-cancer, and anti-apoptotic properties. Neurodegenerative disorders arise from the gradual loss of function and eventual death of nerve cells in the brain or peripheral nervous system. Astragalus membranaceus is a traditional plant with a variety of pharmacological and biochemical properties, including antiviral, anti-hyperglycaemic, and immunomodulatory effects. Moreover, the expression of membrane-bound and soluble receptor for advanced glycation end products (RAGE) is enhanced in the AD brain due to increased levels of soluble and insoluble amyloid-beta (Aβ) peptides. Additionally, in inflammatory circumstances, leukocytes’ firm attachment and transmigration to endothelial cells are regulated by intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Formononetin also possesses anti-bacterial, anti-inflammatory, anti-cancer, anti-oxidant, and estrogenic activity. Formononetin has emerged as a promising agent in the modulation of mediators involved in neurodegenerative disease. Formononetin might modulate nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway to potentiate the anti-Alzheimer’s activity. Additionally, formononetin might inhibit the Aβ/RAGE interaction which further inactivates the activity of extracellular signal regulated kinase (ERK), Janus kinase (JNK) signaling pathway that results in the reduction of nuclear translocation of nuclear factor kappa B (NF-κB) and also reduces the cytokines level to ameliorate AD. It might inhibit the ICAM, VCAM, and THP-1 proteins. Therefore, this compound offers potential therapeutic benefits by reducing cytokine levels to ameliorate AD. This review article is designed to explore the mechanistic interplay underlying the anti-Alzheimer’s effect of A. membranaceus, especially formononetin.
DOI: https://doi.org/10.37349/en.2025.100682
This article belongs to the special issue Medicinal Plants and Bioactive Phytochemicals in Neuroprotection
Glioma is a highly aggressive brain cancer associated with significant mortality. Despite advances in diagnostic and therapeutic strategies, the prognosis for glioma patients remains poor due to limited diagnostic accuracy and monitoring capabilities. Translocator protein (TSPO) is a mitochondrial protein implicated in various cancers, including glioma, where it plays a significant role in cell survival, proliferation, and chemo-resistance. This review article aimed to comprehensively analyze the role of TSPO in glioma, particularly its potential applications in enhancing diagnostic methods and therapeutic strategies. Molecular imaging techniques have emerged as promising tools for non-invasive diagnosis, disease progression monitoring, and treatment selection of gliomas. A comprehensive literature review was conducted to explore TSPO’s expression patterns, biological functions, and applications in molecular imaging. Studies utilizing positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and other imaging modalities were included. TSPO is overexpressed in glioma cells, particularly in high-grade tumors, correlating with tumor aggressiveness and patient prognosis. TSPO-targeted imaging agents demonstrate high specificity and sensitivity for glioma detection, positioning TSPO as a promising marker for accurate diagnosis and therapeutic monitoring. Future studies should focus on optimizing TSPO imaging protocols, validating their clinical utility, and exploring combined imaging modalities to improve diagnostic precision.
Glioma is a highly aggressive brain cancer associated with significant mortality. Despite advances in diagnostic and therapeutic strategies, the prognosis for glioma patients remains poor due to limited diagnostic accuracy and monitoring capabilities. Translocator protein (TSPO) is a mitochondrial protein implicated in various cancers, including glioma, where it plays a significant role in cell survival, proliferation, and chemo-resistance. This review article aimed to comprehensively analyze the role of TSPO in glioma, particularly its potential applications in enhancing diagnostic methods and therapeutic strategies. Molecular imaging techniques have emerged as promising tools for non-invasive diagnosis, disease progression monitoring, and treatment selection of gliomas. A comprehensive literature review was conducted to explore TSPO’s expression patterns, biological functions, and applications in molecular imaging. Studies utilizing positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and other imaging modalities were included. TSPO is overexpressed in glioma cells, particularly in high-grade tumors, correlating with tumor aggressiveness and patient prognosis. TSPO-targeted imaging agents demonstrate high specificity and sensitivity for glioma detection, positioning TSPO as a promising marker for accurate diagnosis and therapeutic monitoring. Future studies should focus on optimizing TSPO imaging protocols, validating their clinical utility, and exploring combined imaging modalities to improve diagnostic precision.
DOI: https://doi.org/10.37349/en.2025.100681
This article belongs to the special issue Current Approaches to Malignant Tumors of the Nervous System
Neuropathic pain (NP) is a significant global health challenge, affecting an estimated 7–10% of the population. Painful diabetic neuropathy (PDN), a severe complication of diabetes, impacts approximately one in every three diabetic patients. With the rising global prevalence of diabetes, PDN is projected to become an increasingly urgent health concern. Current treatments for PDN often provide inadequate pain relief and are associated with adverse side effects, emphasizing the need for safe and effective therapeutic options. This review examines the limitations of existing pharmacological therapies for PDN and presents the sigma-1 receptor (S1R) as a promising therapeutic target. We explore the biological role of S1R, its implication in NP and PDN, its structural biology, and the expanding preclinical and clinical evidence supporting its potential. Furthermore, we present evidence for various S1R antagonists in addressing NP and PDN, with a particular focus on E-52862 and [18F]FTC-146. These compounds represent first-in-class ligands for therapeutic and diagnostic applications, respectively, marking significant advances in the development of S1R antagonists. This review underscores the potential of S1R antagonism as a strategy for developing more effective treatments for PDN, with the ability to significantly improve patient outcomes.
Neuropathic pain (NP) is a significant global health challenge, affecting an estimated 7–10% of the population. Painful diabetic neuropathy (PDN), a severe complication of diabetes, impacts approximately one in every three diabetic patients. With the rising global prevalence of diabetes, PDN is projected to become an increasingly urgent health concern. Current treatments for PDN often provide inadequate pain relief and are associated with adverse side effects, emphasizing the need for safe and effective therapeutic options. This review examines the limitations of existing pharmacological therapies for PDN and presents the sigma-1 receptor (S1R) as a promising therapeutic target. We explore the biological role of S1R, its implication in NP and PDN, its structural biology, and the expanding preclinical and clinical evidence supporting its potential. Furthermore, we present evidence for various S1R antagonists in addressing NP and PDN, with a particular focus on E-52862 and [18F]FTC-146. These compounds represent first-in-class ligands for therapeutic and diagnostic applications, respectively, marking significant advances in the development of S1R antagonists. This review underscores the potential of S1R antagonism as a strategy for developing more effective treatments for PDN, with the ability to significantly improve patient outcomes.
DOI: https://doi.org/10.37349/en.2025.100680
This article belongs to the special issue Neuropathic Pain
The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on a global scale. One of the main molecular mechanisms responsible for the development of Neuro-PASC, in individuals of all ages, is the formation and inadequate proteolysis/clearance of phase-separated amyloid crystalline aggregates—a hallmark feature of aging-related neurodegenerative disorders. Amyloidogenesis during viral infection and persistence is a natural, inevitable, protective defense response that is exacerbated by SARS-CoV-2. Acting as chemical catalyst, SARS-CoV-2 accelerates hydrophobic collapse and the heterogeneous nucleation of amorphous amyloids into stable β-sheet aggregates. The clearance of amyloid aggregates is most effective during slow wave sleep, when high levels of adenosine triphosphate (ATP)—a biphasic modulator of biomolecular condensates—and melatonin are available to solubilize amyloid aggregates for removal. The dysregulation of mitochondrial dynamics by SARS-CoV-2, in particular fusion and fission homeostasis, impairs the proper formation of distinct mitochondrial subpopulations that can remedy challenges created by the diversion of substrates away from oxidative phosphorylation towards glycolysis to support viral replication and maintenance. The subsequent reduction of ATP and inhibition of melatonin synthesis during slow wave sleep results in incomplete brain clearance of amyloid aggregates, leading to the development of neurological manifestations commonly associated with age-related neurodegenerative disorders. Exogenous melatonin not only prevents mitochondrial dysfunction but also elevates ATP production, effectively augmenting the solubilizing effect of the adenosine moiety to ensure the timely, optimal disaggregation and clearance of pathogenic amyloid aggregates in the prevention and attenuation of Neuro-PASC.
The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on a global scale. One of the main molecular mechanisms responsible for the development of Neuro-PASC, in individuals of all ages, is the formation and inadequate proteolysis/clearance of phase-separated amyloid crystalline aggregates—a hallmark feature of aging-related neurodegenerative disorders. Amyloidogenesis during viral infection and persistence is a natural, inevitable, protective defense response that is exacerbated by SARS-CoV-2. Acting as chemical catalyst, SARS-CoV-2 accelerates hydrophobic collapse and the heterogeneous nucleation of amorphous amyloids into stable β-sheet aggregates. The clearance of amyloid aggregates is most effective during slow wave sleep, when high levels of adenosine triphosphate (ATP)—a biphasic modulator of biomolecular condensates—and melatonin are available to solubilize amyloid aggregates for removal. The dysregulation of mitochondrial dynamics by SARS-CoV-2, in particular fusion and fission homeostasis, impairs the proper formation of distinct mitochondrial subpopulations that can remedy challenges created by the diversion of substrates away from oxidative phosphorylation towards glycolysis to support viral replication and maintenance. The subsequent reduction of ATP and inhibition of melatonin synthesis during slow wave sleep results in incomplete brain clearance of amyloid aggregates, leading to the development of neurological manifestations commonly associated with age-related neurodegenerative disorders. Exogenous melatonin not only prevents mitochondrial dysfunction but also elevates ATP production, effectively augmenting the solubilizing effect of the adenosine moiety to ensure the timely, optimal disaggregation and clearance of pathogenic amyloid aggregates in the prevention and attenuation of Neuro-PASC.
DOI: https://doi.org/10.37349/en.2025.100678
DOI: https://doi.org/10.37349/en.2025.100679
Aim:
Alzheimer’s disease (AD) is associated with several electrophysiological biomarkers. These biomarkers are associated with global decline in cognition and a diagnosis of AD. However, a specific electrophysiological biomarker is not characterized as normal-functioning older adults convert to AD. The longitudinal retrospective study was conducted to describe an electrophysiological biomarker indicator for AD as normal-functioning older adults convert to a diagnosis in the AD continuum over a 2-year period.
Methods:
The study was conducted with 54 community-residing older adults, ranging from normal functioning to a diagnosis of AD. All initial and follow-up electrophysiological evaluations were completed in the New York University Brain Research Laboratories, and overall decline assessments with the Global Deterioration Scale (GDS) were completed in the New York University Aging and Dementia Research Center. Data included measurements from the GDS and raw resting-state electroencephalogram (rsEEG), which was transformed into quantitative EEG (qEEG) data. Data analysis consisted of descriptive statistics and a Kruskal-Wallis test. The level of significance was 0.05 with a moderate effect size. Topographic brain images displayed electrophysiological biomarkers.
Results:
A consistently increasing rsEEG theta frequency (P ≤ 0.01) occurred as normal-functioning older adults converted to AD across all GDS stages from the frontal to posterior regions with the progressive global decline. No discernible consistent electrophysiological changes were observed for rsEEG delta, alpha, or beta frequencies over all GDS stages. The GDS stages differed at baseline and follow-up (P ≤ 0.01). The rsEEG theta frequency increased with the progressive global decline across the GDS stages.
Conclusions:
The consistently increasing rsEEG theta frequency may be an electrophysiological biomarker indicator for AD from normal functioning to a diagnosis within the AD continuum. This biomarker will enhance the assessment of the risk, onset, and progression of AD and potentially inform the treatment of AD.
Aim:
Alzheimer’s disease (AD) is associated with several electrophysiological biomarkers. These biomarkers are associated with global decline in cognition and a diagnosis of AD. However, a specific electrophysiological biomarker is not characterized as normal-functioning older adults convert to AD. The longitudinal retrospective study was conducted to describe an electrophysiological biomarker indicator for AD as normal-functioning older adults convert to a diagnosis in the AD continuum over a 2-year period.
Methods:
The study was conducted with 54 community-residing older adults, ranging from normal functioning to a diagnosis of AD. All initial and follow-up electrophysiological evaluations were completed in the New York University Brain Research Laboratories, and overall decline assessments with the Global Deterioration Scale (GDS) were completed in the New York University Aging and Dementia Research Center. Data included measurements from the GDS and raw resting-state electroencephalogram (rsEEG), which was transformed into quantitative EEG (qEEG) data. Data analysis consisted of descriptive statistics and a Kruskal-Wallis test. The level of significance was 0.05 with a moderate effect size. Topographic brain images displayed electrophysiological biomarkers.
Results:
A consistently increasing rsEEG theta frequency (P ≤ 0.01) occurred as normal-functioning older adults converted to AD across all GDS stages from the frontal to posterior regions with the progressive global decline. No discernible consistent electrophysiological changes were observed for rsEEG delta, alpha, or beta frequencies over all GDS stages. The GDS stages differed at baseline and follow-up (P ≤ 0.01). The rsEEG theta frequency increased with the progressive global decline across the GDS stages.
Conclusions:
The consistently increasing rsEEG theta frequency may be an electrophysiological biomarker indicator for AD from normal functioning to a diagnosis within the AD continuum. This biomarker will enhance the assessment of the risk, onset, and progression of AD and potentially inform the treatment of AD.
DOI: https://doi.org/10.37349/en.2025.100677
This article belongs to the special issue Alzheimer's Disease
