Curr Alzheimer Res [JOURNAL]
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200 papers
The Postoperative Effects of Anesthesia Exposure on Cognitive Decline in Older Adults: A Narrative Review.
Willoughby-Dudley KA, Darwin ML, Davalos DB
Curr Alzheimer Res · 2024 · PMID 38623985 · Publisher ↗
BACKGROUND: As modern medicine continues to make strides in effective surgical treatments, we must also consider the critical impact of anesthesia on neuropsychological outcomes. Recent evidence suggests that anesthesia...
BACKGROUND: As modern medicine continues to make strides in effective surgical treatments, we must also consider the critical impact of anesthesia on neuropsychological outcomes. Recent evidence suggests that anesthesia exposure may be a risk factor for postoperative cognitive decline and the eventual development of dementia. OBJECTIVES: To explore the vulnerability of the aging brain in the context of anesthesia exposure in surgery, studies will be reviewed, and pertinent findings will be highlighted and explored to better understand risks and possible factors that need to be considered when contemplating surgery. METHODS: A narrative review was conducted using a combination of MEDLINE and APA PsycINFO databases to shed light on themes across studies assessing general trends regarding the influence of anesthesia on postoperative cognitive decline. RESULTS: A search of relevant literature identified 388 articles. Excluding results outside the parameters of this study, the review includes quality assessments for 24 articles. CONCLUSION: While findings are inconclusive, suggestions for further investigation into the relationship between anesthesia exposure and increased risk for postoperative cognitive decline are discussed, in addition to factors that may allow for greater informed disclosure of potential risks of anesthesia in older adults.
Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology.
Kalyaanamoorthy S, Opare SK, Xu X … +2 more , Ganesan A, Rao PPN
Curr Alzheimer Res · 2024 · PMID 38623984 · Publisher ↗
Microtubule-Associated Protein Tau (also known as tau) has been shown to accumulate into paired helical filaments and neurofibrillary tangles, which are known hallmarks of Alzheimer's disease (AD) pathology. Decades of r...
Microtubule-Associated Protein Tau (also known as tau) has been shown to accumulate into paired helical filaments and neurofibrillary tangles, which are known hallmarks of Alzheimer's disease (AD) pathology. Decades of research have shown that tau protein undergoes extensive post-translational modifications (PTMs), which can alter the protein's structure, function, and dynamics and impact the various properties such as solubility, aggregation, localization, and homeostasis. There is a vast amount of information describing the impact and role of different PTMs in AD pathology and neuroprotection. However, the complex interplay between these PTMs remains elusive. Therefore, in this review, we aim to comprehend the key post-translational modifications occurring in tau and summarize potential connections to clarify their impact on the physiology and pathophysiology of tau. Further, we describe how different computational modeling methods have helped in understanding the impact of PTMs on the structure and functions of the tau protein. Finally, we highlight the tau PTM-related therapeutics strategies that are explored for the development of AD therapy.
Comprehensive Insights into Pathophysiology of Alzheimer's Disease: Herbal Approaches for Mitigating Neurodegeneration.
Sen D, Rathee S, Pandey V … +2 more , Jain SK, Patil UK
Curr Alzheimer Res · 2024 · PMID 38623983 · Publisher ↗
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, the exact etiology remains elusive. This review...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, the exact etiology remains elusive. This review explores the multifaceted pathophysiology of AD, focusing on key hypotheses such as the cholinergic hypothesis, hyperphosphorylated Tau Protein and Amyloid β hypothesis, oxidative stress hypothesis, and the metal ion hypothesis. Understanding these mechanisms is crucial for developing effective therapeutic strategies. Current treatment options for AD have limitations, prompting the exploration of alternative approaches, including herbal interventions. Cholinesterase inhibitors, targeting the cholinergic hypothesis, have shown modest efficacy in managing symptoms. Blocking Amyloid β (Aβ) and targeting hyperphosphorylated tau protein are under investigation, with limited success in clinical trials. Oxidative stress, implicated in AD pathology, has led to the investigation of antioxidants. Natural products, such as , and have demonstrated antioxidant properties, along with anti-inflammatory effects, offering potential neuroprotective benefits. Several herbal extracts, including and , have shown promise in preclinical studies. Compounds like Huperzine A, Melatonin, and Bryostatin exhibit neuroprotective effects through various mechanisms, including cholinergic modulation and anti-inflammatory properties. However, the use of herbal drugs for AD management faces limitations, including standardization issues, variable bioavailability, and potential interactions with conventional medications. Additionally, the efficacy and safety of many herbal products remain to be established through rigorous clinical trials. This review also highlights promising natural products currently in clinical trials, such as Resveratrol and Homotaurine, and their potential impact on AD progression. DHA, an omega-3 fatty acid, has shown cognitive benefits, while Nicotine is being explored for its neuroprotective effects. In conclusion, a comprehensive understanding of the complex pathophysiology of AD and the exploration of herbal interventions offer a holistic approach for managing this devastating disease. Future research should address the limitations associated with herbal drugs and further evaluate the efficacy of promising natural products in clinical settings.
Evaluation and Characterization of Modified K114 Method to Localize Plaques in Rodent and Plaques and Tangles in Human Brain Tissue.
Padala S, Setti S, Raymick J … +2 more , Hanig J, Sarkar S
Curr Alzheimer Res · 2024 · PMID 38566375 · Publisher ↗
BACKGROUND: A plethora of studies has shown the utility of several chemical dyes due to their affinity to bind Aβ to enable visualization of plaques under light or fluorescence microscope, and some of them showed affinit...
BACKGROUND: A plethora of studies has shown the utility of several chemical dyes due to their affinity to bind Aβ to enable visualization of plaques under light or fluorescence microscope, and some of them showed affinity to bind neurofibrillary tangles (NFT) as well. However, only a few of them have the propensity to bind both senile plaques (SP) and NFT simultaneously. OBJECTIVE: In our current study, we aimed to modify the K114 dye and the staining procedure to substantially improve the staining of amyloid plaques in both human and rodent brains and neurofibrillary tangles in the human brain. METHODS: We modified the K114 solution and the staining procedure using Sudan Black as a modifier. Additionally, to evaluate the target of the modified K114, we performed double labeling of K114 and increased Aβ against three different epitopes. We used 5 different antibodies to detect phosphorylated tau to understand the specific targets that modified K114 binds. RESULTS: Dual labeling using hyperphosphorylated antibodies against AT8, pTau, and TNT1 revealed that more than 80% hyperphosphorylated tau colocalized with tangles that were positive for modified K114, whereas more than 70% of the hyperphosphorylated tau colocalized with modified K114. On the other hand, more than 80% of the plaques that were stained with Aβ MOAB-2 were colocalized with modified K114. CONCLUSION: Our modified method can label amyloid plaques within 5 min in the rat brain and within 20 min in the human brain. Our results indicated that modified K114 could be used as a valuable tool for detecting amyloid plaques and tangles with high contrast and resolution relative to other conventional fluorescence markers.
Disruptions of Gut Microbiota are Associated with Cognitive Deficit of Preclinical Alzheimer's Disease: A Cross-Sectional Study.
Yu B, Wan G, Cheng S … +9 more , Wen P, Yang X, Li J, Tian H, Gao Y, Zhong Q, Liu J, Li J, Zhu Y
Curr Alzheimer Res · 2024 · PMID 38529601 · Publisher ↗
BACKGROUND: Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients. OBJECTIVE: The study aimed to explore changes in gut m...
BACKGROUND: Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients. OBJECTIVE: The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances. METHODS: This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators. RESULTS: Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including , and , were screened based on the best classification model (HC and MCI) having intergroup differences. is associated with better performance in multiple cognitive scores and several serum indicators. showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ). CONCLUSION: The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.
Current Progress on Central Cholinergic Receptors as Therapeutic Targets for Alzheimer's Disease.
Nagori K, Pradhan M, Sharma M … +3 more , Ajazuddin, Badwaik HR, Nakhate KT
Curr Alzheimer Res · 2024 · PMID 38529600 · Publisher ↗
Acetylcholine (ACh) is ubiquitously present in the nervous system and has been involved in the regulation of various brain functions. By modulating synaptic transmission and promoting synaptic plasticity, particularly in...
Acetylcholine (ACh) is ubiquitously present in the nervous system and has been involved in the regulation of various brain functions. By modulating synaptic transmission and promoting synaptic plasticity, particularly in the hippocampus and cortex, ACh plays a pivotal role in the regulation of learning and memory. These procognitive actions of ACh are mediated by the neuronal muscarinic and nicotinic cholinergic receptors. The impairment of cholinergic transmission leads to cognitive decline associated with aging and dementia. Therefore, the cholinergic system has been of prime focus when concerned with Alzheimer's disease (AD), the most common cause of dementia. In AD, the extensive destruction of cholinergic neurons occurs by amyloid-β plaques and tau protein-rich neurofibrillary tangles. Amyloid-β also blocks cholinergic receptors and obstructs neuronal signaling. This makes the central cholinergic system an important target for the development of drugs for AD. In fact, centrally acting cholinesterase inhibitors like donepezil and rivastigmine are approved for the treatment of AD, although the outcome is not satisfactory. Therefore, identification of specific subtypes of cholinergic receptors involved in the pathogenesis of AD is essential to develop future drugs. Also, the identification of endogenous rescue mechanisms to the cholinergic system can pave the way for new drug development. In this article, we discussed the neuroanatomy of the central cholinergic system. Further, various subtypes of muscarinic and nicotinic receptors involved in the cognition and pathophysiology of AD are described in detail. The article also reviewed primary neurotransmitters that regulate cognitive processes by modulating basal forebrain cholinergic projection neurons.
Plant Soup Formulations Show Cholinesterase Inhibition Potential in the Prevention of Alzheimer's Disease.
Gajowniczek-Ałasa D, Szwajgier D, Baranowska-Wójcik E
Curr Alzheimer Res · 2024 · PMID 38523524 · Publisher ↗
BACKGROUND: As the cholinesterase theory is a prominent hypothesis underlying our current understanding of Alzheimer's disease (AD), the goal of this study was to compose functional vegan lunchtime soups with potential h...
BACKGROUND: As the cholinesterase theory is a prominent hypothesis underlying our current understanding of Alzheimer's disease (AD), the goal of this study was to compose functional vegan lunchtime soups with potential health benefits in the prevention of AD (in the context of cholinesterase inhibition). MATERIALS AND METHODS: The potential of 36 edible plant raw materials in terms of acetyl- and butyrylcholinesterase inhibition was investigated using a 96-well microplate reader. The most promising ingredients were combined to obtain 18 palatable vegetable soup recipes with 6 dominant flavor, appearance, and aroma variants. To shortlist candidates for in-depth analysis and potential consideration in industrial production, our team performed a sensory analysis of the soups. RESULTS: The white boletus soup exhibited the highest potential for cholinesterase inhibition, further bolstered by the inclusion of other ingredients known for their elevated capacity to inhibit both AChE and BChE. Ingredients such as blackthorn (), garlic, and white potato contributed significantly to this inhibitory effect (nearly 100% of AChE inhibition). Notably, intriguing results were also observed for asparagus soup, despite the fact that the inhibitory potential of asparagus itself is negligible compared to other raw materials. The success of the asparagus soup lies in the meticulous selection of various ingredients, each contributing to its overall effectiveness. It was observed that mushroom soups scored the highest in this respect, while the team members' response to nettle soup was the least favorable. CONCLUSION: The outcomes of our study should serve as a catalyst for further exploration of this important research domain. Our current research focuses on deeper insights into the potential of comprehensive meal options. Furthermore, the synergy/antagonism/non-interaction between respective soup ingredients as well as elements of individual soups' chemical composition is a very interesting topic currently under our intensive scientific investigation.
Beyond Conventional Therapies: Molecular Dynamics of Alzheimer's Treatment through CLOCK/BMAL1 Interactions.
Haskologlu IC, Erdag E, Sehirli AO … +2 more , Uludag O, Abacioglu N
Curr Alzheimer Res · 2024 · PMID 38509675 · Publisher ↗
BACKGROUND: Alzheimer's Disease (AD) represents a neurodegenerative disorder characterized by cognitive and behavioral impairments significantly hindering social and occupational functioning. Melatonin, a hormone pivotal...
BACKGROUND: Alzheimer's Disease (AD) represents a neurodegenerative disorder characterized by cognitive and behavioral impairments significantly hindering social and occupational functioning. Melatonin, a hormone pivotal in regulating the body's intrinsic circadian rhythm, also acts as a catalyst in the breakdown of beta-amyloid deposits, offering a promising therapeutic approach for AD. The upregulation of Brain and Muscle ARNT-Like 1 (Bmal1) gene expression, stimulated by melatonin, emerges as a potential contributor to AD intervention. Current pharmacological interventions, such as FDA-approved cholinesterase inhibitors and the recently authorized monoclonal antibody, Lecanemab, are utilized in AD management. However, the connection between these medications and Bmal1 remains insufficiently explored. OBJECTIVE: This study aims to investigate the molecular effects of FDA-endorsed drugs on the CLOCK: Bmal1 dimer. Furthermore, considering the interactions between melatonin and Bmal1, this research explores the potential synergistic efficacy of combining these pharmaceutical agents with melatonin for AD treatment. METHODS: Using molecular docking and MM/PBSA methodologies, this research determines the binding affinities of drugs within the Bmal1 binding site, constructing interaction profiles. RESULTS: The findings reveal that, among FDA-approved drugs, galanthamine and donepezil demonstrate notably similar binding energy values to melatonin, interacting within the Bmal1 binding site through analogous amino acid residues and functional groups. CONCLUSION: A novel therapeutic approach emerges, suggesting the combination of melatonin with Lecanemab as a monoclonal antibody therapy. Importantly, prior research has not explored the effects of FDA-approved drugs on Bmal1 expression or their potential for synergistic effects.
Research Progress of Mitophagy in Alzheimer's Disease.
Yao J, Kan B, Dong Z … +1 more , Tang Z
Curr Alzheimer Res · 2024 · PMID 38482617 · Publisher ↗
The prevalence of Alzheimer's disease (AD) is increasing as the elderly population, which hurts elderly people's cognition and capacity for self-care. The process of mitophagy involves the selective clearance of ageing a...
The prevalence of Alzheimer's disease (AD) is increasing as the elderly population, which hurts elderly people's cognition and capacity for self-care. The process of mitophagy involves the selective clearance of ageing and impaired mitochondria, which is required to preserve intracellular homeostasis and energy metabolism. Currently, it has been discovered that mitophagy abnormalities are intimately linked to the beginning and progression of AD. This article discusses the mechanism of mitophagy, abnormal mitophagy, and therapeutic effects in AD. The purpose is to offer fresh perspectives on the causes and remedies of AD.
Drug Design for Alzheimer's Disease: Biologics . Small Molecules.
Weaver DF
Curr Alzheimer Res · 2024 · PMID 38468530 · Publisher ↗
There shall probably be no "magic bullet" for Alzheimer's; rather, we should be pursuing a "magic shotgun blast" that will target multiple complementary therapeutic receptors. Although protein misfolding/oligomerization...
There shall probably be no "magic bullet" for Alzheimer's; rather, we should be pursuing a "magic shotgun blast" that will target multiple complementary therapeutic receptors. Although protein misfolding/oligomerization will probably be one of these targets, this alone is insufficient and will require the co-administration of other therapeutic entities engaging targets, such as immunopathy, gliopathy, mitochondriopathy, synaptotoxicity or others. Although polypharmacy is emerging as the preferred therapeutic route, many questions remain unanswered. Should this be a cocktail of biologics, a concoction of small molecules, or a judicious combination of both? Biologics and small molecule drugs display both strengths and weaknesses. When addressing a disease as complex and globally important as Alzheimer's, there should be room for the continuing development of both of these therapeutic classes. Each has much to offer, and when used with their advantages and disadvantages in clear focus, an ultimate solution will probably require contributions from both.
A Review on the Use of Modern Computational Methods in Alzheimer's Disease-Detection and Prediction.
De A, Mishra TK, Saraf S … +2 more , Tripathy B, Reddy SS
Curr Alzheimer Res · 2024 · PMID 38468529 · Publisher ↗
Discoveries in the field of medical sciences are blooming rapidly at the cost of voluminous efforts. Presently, multidisciplinary research activities have been especially contributing to catering cutting-edge solutions t...
Discoveries in the field of medical sciences are blooming rapidly at the cost of voluminous efforts. Presently, multidisciplinary research activities have been especially contributing to catering cutting-edge solutions to critical problems in the domain of medical sciences. The modern age computing resources have proved to be a boon in this context. Effortless solutions have become a reality, and thus, the real beneficiary patients are able to enjoy improved lives. One of the most emerging problems in this context is Alzheimer's disease, an incurable neurological disorder. For this, early diagnosis is made possible with benchmark computing tools and schemes. These benchmark schemes are the results of novel research contributions being made intermittently in the timeline. In this review, an attempt is made to explore all such contributions in the past few decades. A systematic review is made by categorizing these contributions into three folds, namely, First, Second, and Third Generations. However, priority is given to the latest ones as a handful of literature reviews are already available for the classical ones. Key contributions are discussed vividly. The objectives set for this review are to bring forth the latest discoveries in computing methodologies, especially those dedicated to the diagnosis of Alzheimer's disease. A detailed timeline of the contributions is also made available. Performance plots for certain key contributions are also presented for better graphical understanding.
Nanostructured Lipid Carriers of Donepezil Hydrochloride for the Treatment of Alzheimer's Disease.
Tekade A, Susar R, Kulkarni G … +2 more , Surwade S, Gaikwad A
Curr Alzheimer Res · 2024 · PMID 38445703 · Publisher ↗
BACKGROUND: Alzheimer's Disease (AD) is a long-term brain disorder that worsens over time. A cholinesterase inhibitor called Donepezil HCl (DNZ) is used to treat and control AD. Due to its failure to reach the appropriat...
BACKGROUND: Alzheimer's Disease (AD) is a long-term brain disorder that worsens over time. A cholinesterase inhibitor called Donepezil HCl (DNZ) is used to treat and control AD. Due to its failure to reach the appropriate concentration in the brain cells, its efficacy upon oral administration is limited, and thus investigation of alternative administration route is necessary. OBJECTIVE: The objective of this study was to develop donepezil HCl-loaded Nanostructured Lipid Carriers (NLCs) that can bypass the blood-brain barrier and thus be directly delivered to the brain through the nasal route. This method improves availability at the site of action, reduces the negative effects of oral medication, and ensures an expedited commencement of action. METHODS: High-pressure homogenization and ultrasonication were used to formulate NLCs. Glyceryl Monostearate (GMS) as a solid lipid, Tween 80 as a surfactant, and Poloxamer 407 as a cosurfactant were used. In this study, argan oil was employed as a liquid lipid as well as a penetration enhancer. RESULTS: The chosen NLCs displayed a particle size of 137.34 ± 0.79 nm, a PDI of 0.365 ± 0.03, and a zeta potential of -10.4 mV. The selected formulation showed an entrapment efficiency of 84.05 ± 1.30% and a drug content of 77.02 ± 0.23%. The concentration of the drug in the brain after intravenous and intranasal administration of DNZ NLCs at 1 h was found to be 0.490 ± 0.007 and 4.287 ± 0.115, respectively. Thus, the concentration of DNZ achieved in the brain after intranasal administration of DNZ NLCs was approximately 9 times more than the concentration when administered by intravenous route. CONCLUSION: The DNZ-loaded NLCs, when administered via nasal route, showed markedly improved drug availability in the brain, suggesting an efficient drug delivery strategy to treat Alzheimer's disease.
Multimodal Gamma Stimulation Improves Activity but not Memory in Aged Tgf344-AD Rats.
Bentley JH, Broussard JI
Curr Alzheimer Res · 2024 · PMID 38445702 · Publisher ↗
BACKGROUND: Multimodal sensory gamma stimulation is a treatment approach for Alzheimers disease that has been shown to improve pathology and memory in transgenic mouse models of Alzheimer's. Because rats are closer to hu...
BACKGROUND: Multimodal sensory gamma stimulation is a treatment approach for Alzheimers disease that has been shown to improve pathology and memory in transgenic mouse models of Alzheimer's. Because rats are closer to humans in evolution, we tested the hypothesis that the transgenic rat line bearing human APP and PS1, line TgF344-AD, would be a good supplemental candidate to test the efficacy of this treatment. Current therapy approaches under investigation seek to utilize the immune response to minimize or degrade the accumulation of β-amyloid plaque load in mouse models designed to overexpress Aβ. However, many of these models lack some of the hallmarks of Alzheimer's disease, such as hyperphosphorylated tau and neuronal cell loss. The TgF344-AD transgenic rat model is a good candidate to bridge the gap between mouse models and clinical efficacy in humans. OBJECTIVE: The objective of this study was to use multimodal gamma stimulation at light and auditory modalities simultaneously to test whether this enhances memory performance as measured by the object location task and the spontaneous alternation task. METHODS: In our study, we designed and built a low-cost, easy-to-construct multimodal light and sound gamma stimulator. Our gamma stimulation device was built using an Arduino microcontroller, which drives lights and a speaker at the gamma frequency. We have included in this paper our device's parts, hardware design, and software architecture for easy reproducibility. We then performed an experiment to test the effect of multimodal gamma stimulation on the cognitive performance of fourteen-month-old TgF344-AD rats. Rats were randomly assigned to either an experimental group that received gamma stimulation or a control group that did not. Performance in a Novel Object Location (NOL) task and spontaneous alternation task was evaluated in both groups before and after the treatment. RESULTS: Multimodal gamma stimulation did not improve memory compared to unstimulated TgF344-AD rats. However, the gamma-stimulated rats did spend significantly more time exploring objects in the novel location task than the unstimulated rats. In the spontaneous alternation task, gamma-stimulated rats exhibited significantly greater exploratory activity than unstimulated controls. CONCLUSION: Multimodal gamma stimulation did not enhance memory performance in the object location task or the spontaneous alternation task. However, in both tasks, the treatment group had improved measures of exploratory activity relative to the untreated group. We conclude that several limitations could have contributed to this mixed effect, including aging complications, different animal models, or light cycle effects.
Exploring Potential of Nano-formulations in the Treatment of Alzheimer's Disease through Nasal Route.
Tekade A, Kadam P, Jagdale S … +4 more , Surwade S, Gaikwad A, Pawar P, Shinde R
Curr Alzheimer Res · 2024 · PMID 38425107 · Publisher ↗
Alzheimer's disease, a progressive neurodegenerative disorder, severely impacts cognitive function and daily living. The current treatment provides only symptomatic relief, and thus, disease-modifying therapies targeting...
Alzheimer's disease, a progressive neurodegenerative disorder, severely impacts cognitive function and daily living. The current treatment provides only symptomatic relief, and thus, disease-modifying therapies targeting underlying causes are needed. Although several potential therapies are in various stages of clinical trials, bringing a new Alzheimer's drug to market remains challenging. Hence, researchers are also exploring monoclonal antibodies, tau protein inhibitors, and anti-inflammatory drugs as treatment options. Conventionally designed dosage forms come with limitations like poor absorption, first-pass metabolism, and low bioavailability. They also cause systemic adverse effects because these designed systems do not provide target-specific drug delivery. Thus, in this review, the authors highlighted the current advancements in the development of intranasal nanoformulations for the treatment of Alzheimer's disease. This strategy of delivering anti-Alzheimer drugs through the nasal route may help to target the drug exactly to the brain, achieve rapid onset of action, avoid first-pass metabolism, and reduce the side effects and dose required for administration. Delivering drugs to the brain through the nasal route for treating Alzheimer's disease is crucial due to the limited efficacy of existing treatments and the profound impact of the disease on patients and their families. Thus, by exploring innovative approaches such as nose-to-brain drug delivery, it is possible to improve the quality of life for individuals living with Alzheimer's and alleviate its societal burden.
Estimating Dementia Onset: AT(N) Profiles and Predictive Modeling in Mild Cognitive Impairment Patients.
Platero C, Tohka J, Strange B
Curr Alzheimer Res · 2024 · PMID 38425106 · Publisher ↗
BACKGROUND: Mild Cognitive Impairment (MCI) usually precedes the symptomatic phase of dementia and constitutes a window of opportunities for preventive therapies. OBJECTIVES: The objective of this study was to predict th...
BACKGROUND: Mild Cognitive Impairment (MCI) usually precedes the symptomatic phase of dementia and constitutes a window of opportunities for preventive therapies. OBJECTIVES: The objective of this study was to predict the time an MCI patient has left to reach dementia and obtain the most likely natural history in the progression of MCI towards dementia. METHODS: This study was conducted on 633 MCI patients and 145 subjects with dementia through 4726 visits over 15 years from Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A combination of data from AT(N) profiles at baseline and longitudinal predictive modeling was applied. A data-driven approach was proposed for categorical diagnosis prediction and timeline estimation of cognitive decline progression, which combined supervised and unsupervised learning techniques. RESULTS: A reduced vector of only neuropsychological measures was selected for training the models. At baseline, this approach had high performance in detecting subjects at high risk of converting from MCI to dementia in the coming years. Furthermore, a Disease Progression Model (DPM) was built and also verified using three metrics. As a result of the DPM focused on the studied population, it was inferred that amyloid pathology (A+) appears about 7 years before dementia, and tau pathology (T+) and neurodegeneration (N+) occur almost simultaneously, between 3 and 4 years before dementia. In addition, MCI-A+ subjects were shown to progress more rapidly to dementia compared to MCI-A- subjects. CONCLUSION: Based on proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicated that only a single cerebrospinal fluid sample is necessary during the prodromal phase of AD. Prediction from MCI into dementia and its timeline can be achieved exclusively through neuropsychological measures.
Handwriting Markers for the Onset of Alzheimer's Disease.
Chernov Y
Curr Alzheimer Res · 2024 · PMID 38424434 · Publisher ↗
INTRODUCTION: Alzheimer's disease has an impact on handwriting (AD). Numerous researchers reported that fact. Therefore, examining handwriting characteristics could be a useful way to screen for AD. The aim of the articl...
INTRODUCTION: Alzheimer's disease has an impact on handwriting (AD). Numerous researchers reported that fact. Therefore, examining handwriting characteristics could be a useful way to screen for AD. The aim of the article is to present the reliability and effectiveness of the AD-HS tool. METHODS: Most of the existing studies examine either linguistic manifestations of writing or certain motor functions. However, handwriting is a complex of cognitive and motor activities. Since the influence of AD on handwriting is individual, it is important to analyze the complete set of handwriting features. The AD-HS instrument is based on this principle. Validation of the AD-HS instrument for revealing cognitive impairment in AD-diagnosed persons in comparison to the control group. The study is based on the evaluation of free handwritten texts. AD-HS includes 40 handwriting and 2 linguistic features of handwritten texts. It is based on the standard protocol for handwriting analysis. The cumulative evaluation of all features builds a quantitative AD-Indicator (ADI) as a marker of possible AD conditions. The analyzed experiment includes 53 AD-diagnosed persons and a control group of 192 handwriting specimens from the existing database. RESULTS: AD-HS shows a distinct difference in evaluated ADI for the participants (the mean value equals 0.49) and the control group (the mean value equals 0.28). CONCLUSION: The handwriting marker of AD could be an effective supplement instrument for earlier screening. It is also useful when traditional biomarkers and neurological tests could not be applied. AD-HS can accompany therapy as an indication of its effect on a person.
Proton Pump Inhibitors and Cognitive Health: Review on Unraveling the Dementia Connection and Co-morbid Risks.
Khan Z, Mehan S, Saifi MA … +3 more , Gupta GD, Narula AS, Kalfin R
Curr Alzheimer Res · 2024 · PMID 38424433 · Full text
Dementia, an international health issue distinguished by the impairment of daily functioning due to cognitive decline, currently affects more than 55 million people worldwide, with the majority residing in low-income and...
Dementia, an international health issue distinguished by the impairment of daily functioning due to cognitive decline, currently affects more than 55 million people worldwide, with the majority residing in low-income and middle-income countries. Globally, dementia entails significant economic burdens in 2019, amounting to a cost of 1.3 trillion US dollars. Informal caregivers devote considerable hours to providing care for those affected. Dementia imposes a greater caregiving and disability-adjusted life-year burden on women. A recent study has established a correlation between prolonged Proton Pump Inhibitor (PPI) usage and dementia, in addition to other neurodegenerative conditions. PPIs are frequently prescribed to treat peptic ulcers and GERD (gastroesophageal reflux disease) by decreasing stomach acid secretion. They alleviate acid-related symptoms through the inhibition of acid-secreting H-K ATPase. In a number of observational studies, cognitive decline and dementia in the elderly have been linked to the use of PPIs. The precise mechanism underlying this relationship is unknown. These drugs might also alter the pH of brain cells, resulting in the accumulation of amyloid-beta (Aβ) peptides and the development of Alzheimer's disease (AD). Despite the compelling evidence supporting the association of PPIs with dementia, the results of studies remain inconsistent. The absence of a correlation between PPI use and cognitive decline in some studies emphasizes the need for additional research. Chronic PPI use can conceal underlying conditions, including cancer, celiac disease, vitamin B12 deficiency, and renal injury, highlighting dementia risk and the need for further investigations on cognitive health.
Association Between Cannabis Use and Subjective Cognitive Decline: Findings from the Behavioral Risk Factor Surveillance System (BRFSS).
Chen Z, Wong R
Curr Alzheimer Res · 2024 · PMID 38409714 · Publisher ↗
BACKGROUND: Cannabis consumption has rapidly increased in the United States due to more states legalizing non-medical and medical use. There is limited research, however, investigating whether cannabis may be associated...
BACKGROUND: Cannabis consumption has rapidly increased in the United States due to more states legalizing non-medical and medical use. There is limited research, however, investigating whether cannabis may be associated with cognitive function, particularly across multiple dimensions of cannabis use. OBJECTIVE: The objective of this study was to examine whether cannabis consumption reason, frequency, and method are associated with subjective cognitive decline (SCD). METHODS: Data were obtained from 4,744 U.S. adults aged 45 and older in the 2021 Behavioral Risk Factor Surveillance System (BRFSS). SCD was a self-reported increase in confusion or memory loss in the past year. Odds of SCD by cannabis use reason, frequency, and methods (e.g., smoke, eat, vaporize) were examined using multiple logistic regression after imputing missing data, applying sampling weights, and adjusting for sociodemographic, health, and substance use covariates. RESULTS: Compared to non-users, non-medical cannabis use was significantly associated with 96% decreased odds of SCD (aOR=0.04, 95% CI=0.01-0.44, p<.01). Medical (aOR=0.46, 95% CI=0.06-3.61, p=.46) and dual medical and non-medical use (aOR=0.30, 95% CI=0.03-2.92, p=.30) were also associated with decreased odds of SCD, although not significant. Cannabis consumption frequency and method were not significantly associated with SCD. CONCLUSION: The reason for cannabis use, but not frequency and method, is associated with SCD. Further research is needed to investigate the mechanisms that may contribute to the observed associations between non-medical cannabis use and decreased odds of SCD.
Antipsychotics in Alzheimer's Disease: Current Status and Therapeutic Alternatives.
Maziero MP, Rocha NP, Teixeira AL
Curr Alzheimer Res · 2023 · PMID 38409713 · Publisher ↗
Psychosis and hyperactive behaviors, such as agitation and wandering, affect a significant proportion of patients with Alzheimer's disease (AD). These symptoms are often treated with antipsychotics, usually in an off-lab...
Psychosis and hyperactive behaviors, such as agitation and wandering, affect a significant proportion of patients with Alzheimer's disease (AD). These symptoms are often treated with antipsychotics, usually in an off-label approach. This mini-review provides an updated perspective on the pharmacological approach for the neuropsychiatric symptoms (NPS) in AD. The results of new studies have provided a better understanding of AD-related NPS management, but high-quality evidence still needs to be obtained. Herein, we argue for a more cautious approach to the use of antipsychotics in AD and highlight the importance of exploring alternative treatments for NPS. By doing so, we can ensure that patients with AD receive optimal care that is both effective and safe.
Alzheimer's Disease and Suicide: An Integrative Literature Review.
Rodrigues JFR, Rodrigues LP, de Araújo Filho GM
Curr Alzheimer Res · 2024 · PMID 38409712 · Publisher ↗
INTRODUCTION: Suicide has been described in patients with Alzheimer's disease. Some promising medications for treating Alzheimer's disease have had their studies suspended because they increase the risk of suicide. Under...
INTRODUCTION: Suicide has been described in patients with Alzheimer's disease. Some promising medications for treating Alzheimer's disease have had their studies suspended because they increase the risk of suicide. Understanding the correlations between suicide and Alzheimer's disease is essential in an aging world. METHODS: A search was carried out on electronic websites (PubMed and Scielo) using the MeSH Terms "suicide" and "Alzheimer" (1986-2023). Of a total of 115 articles, 26 were included in this review. RESULTS: Depression and the allele ε4 of Apolipoprotein (APOE4) were demonstrated to be the main risk factors for suicide in patients with Alzheimer's disease. CONCLUSION: Adequately delineating which elderly people are vulnerable to suicide is important so that new treatments for Alzheimer's disease can be successful. This review showed a need for new studies to investigate the interface between Alzheimer's disease and suicide.
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