Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer’s Disease DOI Open Access
Jialin Li, Alireza Ebrahimi, Afia B. Ali

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5169 - 5169

Published: May 9, 2024

Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities daily living', the most prevalent type dementia being Alzheimer's disease (AD), accounting for about 80% diagnosed cases. AD is associated an increased risk comorbidity other conditions such hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, depression well mortality in late life. For example, up 70% patients are affected by anxiety. As aging major factor AD, this represents huge global burden ageing populations. Over last 10 years, efforts have been made recognize complexity understand aetiology pathophysiology biomarkers early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors glutamate receptor regulators, limited they work targeting symptoms, only more recent FDA-approved drugs designed target amyloid-β protein aim slowing down progression disease. However, these may help temporarily, cannot stop or reverse disease, do not act reducing NPS AD. The first-line options management selective serotonin reuptake inhibitors/selective noradrenaline (SSRIs/SNRIs) monoaminergic system; however, rational drug choices anxiety disorders since GABAergic system has prominent role their development. Considering overall failures side effects currently available medication, there unmet need rationally therapies In review, we summarize current status therapy highlight novel angles future our ongoing alleviate cognitive deficits devastating

Language: Английский

Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression DOI Creative Commons
S. Meftah, Jian Gan

Frontiers in Synaptic Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 9, 2023

The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, loss is, to date, one of the main biological correlates cognitive decline disease. This occurs prior neuronal with ample evidence that synaptic dysfunction precedes this, in support idea failure is crucial stage disease pathogenesis. two pathological hallmarks abnormal aggregates amyloid or tau proteins, have had demonstrable effects on physiology animal cellular models There also growing these proteins may synergistic effect neurophysiological dysfunction. Here, we review some findings alterations what know from models. First, briefly summarize human suggest synapses are altered, including how this relates network activity. Subsequently, considered, highlighting mouse pathology role play dysfunction, either isolation examining pathologies interact specifically focuses function observed models, typically measured using electrophysiology calcium imaging. Following loss, it would be impossible imagine not alter oscillatory activity brain. Therefore, discusses underpin aberrant patterns seen patients. Finally, an overview key directions considerations field covered. includes current therapeutics targeted at but methods modulate rescue patterns. Other important future avenues note include non-neuronal cell types such as astrocytes microglia, mechanisms independent will certainly continue for foreseeable future.

Language: Английский

Citations

74
Prescribing in Older People DOI
David G. Le Couteur, Sarah N. Hilmer, Nicholas Glasgow

et al.

Published: April 10, 2025

Prescribing medications to older people is difficult due comorbidity, limited evidence for efficacy, increased risk of adverse drug reactions, polypharmacy, and altered pharmacokinetics. This article describes the principles underlying clinical geriatric pharmacology including approaches evaluating benefit, adjusting dose age related pharmacokinetic changes. The challenge general practitioner balance an incomplete base efficacy in frail, against problems reactions without denying potentially valuable pharmacotherapeutic interventions.

Language: Английский

Citations

62
Pathogenesis, Diagnostics, and Therapeutics for Alzheimer's Disease: Breaking the Memory Barrier DOI Creative Commons

Pushpa Tryphena Kamatham,

Rashi K. Shukla, Dharmendra Kumar Khatri

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102481 - 102481

Published: Sept. 3, 2024

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % all cases. It affects millions people worldwide. AD poses a substantial economic burden on societies healthcare systems. progressive neurodegenerative disorder characterized by cognitive decline, memory loss, impaired daily functioning. As prevalence continues to increase, understanding its pathogenesis, improving diagnostic methods, developing effective therapeutics have become paramount. This comprehensive review delves into intricate mechanisms underlying AD, explores current state techniques, examines emerging therapeutic strategies. By revealing complexities this aims contribute growing body knowledge surrounding devastating disease.

Language: Английский

Citations

22
Mathematical models on Alzheimer's disease and its treatment: A review DOI

Mitali Maji,

Subhas Khajanchi

Physics of Life Reviews, Journal Year: 2025, Volume and Issue: 52, P. 207 - 244

Published: Jan. 10, 2025

Language: Английский

Citations

3
Glucose Metabolism, Neural Cell Senescence and Alzheimer’s Disease DOI Open Access
Qianqian Wang,

Linyan Duan,

Xingfan Li

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4351 - 4351

Published: April 14, 2022

Alzheimer’s disease (AD), an elderly neurodegenerative disorder with a high incidence and progressive memory decline, is one of the most expensive, lethal, burdening diseases. To date, pathogenesis AD has not been fully illustrated. Emerging studies have revealed that cellular senescence abnormal glucose metabolism in brain are early hallmarks AD. Moreover, disturbance patients may precede amyloid-β deposition or Tau protein phosphorylation. Thus, metabolic reprogramming targeting senescent microglia astrocytes be novel strategy for intervention treatment. Here, we recapitulate relationships between neural cell (e.g., insulin signaling, lactate metabolism) We then discuss potential perspective towards intervention, providing theoretical basis further exploration therapeutic approach toward

Language: Английский

Citations

60
Thymoquinone: Review of Its Potential in the Treatment of Neurological Diseases DOI Creative Commons
Faheem Hyder Pottoo,

Abdallah Mohammad Ibrahim,

Ali Alammar

et al.

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(4), P. 408 - 408

Published: March 27, 2022

Thymoquinone (TQ) possesses anticonvulsant, antianxiety, antidepressant, and antipsychotic properties. It could be utilized to treat drug misuse or dependence, those with memory cognitive impairment. TQ protects brain cells from oxidative stress, which is especially pronounced in memory-related regions. exhibits antineurotoxin characteristics, implying its role preventing neurodegenerative disorders such as Alzheimer's disease Parkinson's disease. TQ's antioxidant anti-inflammatory properties protect damage inflammation. Glutamate can trigger cell death by causing mitochondrial malfunction the formation of reactive oxygen species (ROS). Reduction ROS production explain effects neuroinflammation. help prevent glutamate-induced apoptosis suppressing malfunction. Several studies have demonstrated inhibiting Toll-like receptors (TLRs) some inflammatory mediators, leading reduced inflammation neurotoxicity. did not show any signs dopaminergic neuron loss after treatment various animals. has been shown clinical block acetylcholinesterase (AChE) activity, increases acetylcholine (ACh). As a result, fresh memories are programmed preserve effects. Treatment linked better outcomes decreased side than other drugs.

Language: Английский

Citations

52
Panax Ginseng in the treatment of Alzheimer's disease and vascular dementia DOI Creative Commons
Zhiyong Wang, Zhen Zhang, Jiangang Liu

et al.

Journal of Ginseng Research, Journal Year: 2023, Volume and Issue: 47(4), P. 506 - 514

Published: March 21, 2023

Dementia has become one of the most important diseases threatening human health. Alzheimer's disease (AD) and vascular dementia (VaD) have highest incidence rates among types dementia, but until now, therapeutic methods been limited. Panax ginseng used in China for thousands years to treat modern medical studies found that it contains multiple active components, such as ginsenosides, polysaccharides, amino acids, volatile oils polyacetylenes, many which effects treating AD VaD. Studies ginsenosides multitarget regulation synaptic plasticity cholinergic system, inhibition Aβ aggravation tau hyperphosphorylation, anti-neuroinflammation, anti-oxidation anti-apoptosis effects. Other components ginseng, gintonin, oligosaccharides, polysaccharides proteins, also on The effectiveness ginseng-containing Chinese medicine compounds confirmed by clinical basic investigations In this review, we summarized potential related mechanisms VaD provide some examples further studies.

Language: Английский

Citations

38
Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer’s and Parkinson’s diseases DOI Creative Commons
Elizabeth M. Rhea,

Alice Babin,

P. C. Thomas

et al.

Tissue Barriers, Journal Year: 2023, Volume and Issue: 12(4)

Published: Dec. 14, 2023

Background A number of peptide incretin receptor agonists (IRAs) show promise as therapeutics for Alzheimer's disease (AD) and Parkinson's (PD). Transport across the blood–brain barrier (BBB) is one way IRAs to act directly within brain. To determine which are high priority candidates treating these disorders, we have studied their brain uptake pharmacokinetics.

Language: Английский

Citations

27
The impact of diabetes in cognitive impairment: A review of current evidence and prospects for future investigations DOI Creative Commons
Nicholas Aderinto, Gbolahan Olatunji, Muili Abdulbasit

et al.

Medicine, Journal Year: 2023, Volume and Issue: 102(43), P. e35557 - e35557

Published: Oct. 27, 2023

Cognitive impairment in individuals with diabetes represents a multifaceted and increasingly prevalent health concern. This review critically examines the current evidence regarding intricate relationship between cognitive decline. It highlights existing knowledge on impact of function, spanning from mild to dementia, including vascular Alzheimer dementia. The underscores need for standardized diagnostic paradigm explores research gaps, such as implications younger populations various types. Furthermore, this emphasizes relevance diabetes-related comorbidities, hypertension dyslipidemia, influencing advocates comprehensive, interdisciplinary approach, integrating insights neuroscience, endocrinology, immunology elucidate mechanistic underpinnings impairment. second part outlines prospective directions opportunities. longitudinal studies understand disease progression better identifies critical windows vulnerability. search accurate biomarkers predictive factors is paramount, encompassing genetic epigenetic considerations. Personalized approaches tailored interventions are essential addressing substantial variability outcomes among diabetes.

Language: Английский

Citations

26
Detecting Early Cognitive Decline in Alzheimer’s Disease with Brain Synaptic Structural and Functional Evaluation DOI Creative Commons
Samo Ribarič

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 355 - 355

Published: Jan. 26, 2023

Early cognitive decline in patients with Alzheimer's (AD) is associated quantifiable structural and functional connectivity changes the brain. AD dysregulation of Aβ tau metabolism progressively disrupt normal synaptic function, leading to loss synapses, decreased hippocampal density early atrophy. Advances brain imaging techniques living have enabled transition from clinical signs symptoms-based diagnosis biomarkers-based diagnosis, techniques, quantitative EEG, body fluids sampling. The hippocampus has a central role semantic episodic memory processing. This function critically dependent on intrahippocampal connections many cortical regions, including perirhinal entorhinal cortex, parahippocampal association regions temporal parietal lobes, prefrontal cortex. Therefore, reflected altered intrinsic networks (aka large-scale networks), memory, default mode, salience networks. narrative review discusses recent critical issues related detecting AD-associated markers high-risk or neuropsychologically diagnosed subjective impairment mild impairment.

Language: Английский

Citations

24