Curr Alzheimer Res [JOURNAL]
Sun
200 papers
Acetyl-L-Carnitine Aids in Preservation of Cholinergic Neurons and Memory in the Model of Alzheimer's Disease.
Bolshakova OI, Slobodina AD, Slepneva EE … +1 more , Sarantseva SV
Curr Alzheimer Res · 2024 · PMID 39716786 · Publisher ↗
BACKGROUND: The lack of effective therapy for the treatment of Alzheimer's disease demands both the search for new drugs and the reconsideration of already known substances currently used in other areas of medicine. off...
BACKGROUND: The lack of effective therapy for the treatment of Alzheimer's disease demands both the search for new drugs and the reconsideration of already known substances currently used in other areas of medicine. offers the potential to model features of Alzheimer's disease, study disease mechanisms, and conduct drug screening. OBJECTIVES: The purpose of this work was to analyze the neuroprotective properties of the drug "carnicetine", which is an acetylated form of the natural low molecular weight compound L-carnitine. The drug is able to cross the blood-brain barrier and is currently used as a means of improving cellular metabolism. METHODS: Using tissue-specific drivers, direct expression of amyloid beta peptide (42 amino acids) was exhibited in certain groups of neurons in the brain, namely in dopaminergic and cholinergic neurons. The effect of acetyl-L-carnitine (carnicetine) on the death of these neurons and the memory of flies was analyzed. RESULTS: The expression of amyloid beta peptide in dopaminergic or cholinergic neurons resulted in neurodegeneration of cholinergic neurons in the brain and memory impairment. The use of carnicetine added to animal food made it possible to treat these disorders. At the same time, no effect on dopaminergic neurons was noted. CONCLUSION: The data obtained confirmed the neuroprotective properties of the drug under study, demonstrating its participation in the restoration of the cholinergic system and the feasibility of using carnicetine for the treatment of Alzheimer's disease.
Quantitative Proteomic Analysis of APP/PS1 Transgenic Mice.
Wang J, Wang X, An Z … +6 more , Wang X, Wang Y, Lu Y, Qiu M, Liu Z, Tan Z
Curr Alzheimer Res · 2024 Dec · PMID 39623717 · Publisher ↗
BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) de...
BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD. OBJECTIVE: The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD. METHODS: To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts. RESULTS: Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks. CONCLUSIONS: This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.
The Potential Role of Enrichment Environment on Plasticity in Alzheimer's Disease Models: Insights About Therapeutic Approaches.
Neves RC, Figueiredo RC, Faria-Melibeu AC
Curr Alzheimer Res · 2024 · PMID 39623716 · Publisher ↗
Alzheimer's Disease (AD) is characterized by synapse loss and neurodegeneration, which leads to cognitive and psychiatric symptoms. Researchers worldwide have been studying therapeutic approaches aiming to induce plastic...
Alzheimer's Disease (AD) is characterized by synapse loss and neurodegeneration, which leads to cognitive and psychiatric symptoms. Researchers worldwide have been studying therapeutic approaches aiming to induce plasticity and neuroprotection once AD has no cure and the existing treatments are limited. Environmental Enrichment (EE) is a change in housing conditions that promotes increased cognitive stimulus. Studies have demonstrated that EE acts as a plasticity modulator in several conditions and experimental models. In this review, we analyze and discuss the potential role of EE on plasticity modulation in different animal models but primarily on AD models. The data were extracted from the PubMed and ScienceDirect databases. The EE was shown to induce plasticity. LTP and behavior were enhanced in animals under different conditions, such as the AD model. The mechanisms were related to the glutamatergic system and excitatory/ inhibitory balance. Moreover, many studies have evidenced that EE promotes the upregulation of BDNF and the synaptic proteins SYN and PSD95. These data also suggest a neuroprotective function performed by EE in different contexts, such as aging and AD. Therefore, an enriched environment can be a target of new therapeutic approaches that aim to induce neuroplasticity and neuroprotection against AD.
Molecular Signatures and Clinical Significance of Notch Signaling Pathway in Peripheral Blood of Patients with Alzheimer's Disease.
Jia D, He T, Sun L … +2 more , Wang Q, Yu H
Curr Alzheimer Res · 2024 · PMID 39620329 · Publisher ↗
INTRODUCTION: Alzheimer's Disease (AD) is the most common neurodegenerative disease, and timely and effective diagnosis is essential for the prevention and treatment of AD. Peripheral blood is readily available, inexpens...
INTRODUCTION: Alzheimer's Disease (AD) is the most common neurodegenerative disease, and timely and effective diagnosis is essential for the prevention and treatment of AD. Peripheral blood is readily available, inexpensive, and non-invasive, making it an ideal substrate for screening diagnostic biomarkers. METHOD: The Notch signaling pathway is closely related to AD, so genes related to the Notch signaling pathway may be candidate diagnostic biomarkers for AD. Here, we have performed an integrated analysis of peripheral blood cells transcriptomics from two AD cohorts (GSE63060: Ctrl = 104, MCI = 80, AD = 145; GSE63061: Ctrl = 134, MCI = 109, AD = 139) to reveal the expression levels of 16 Notch signals involving 100 genes. RESULT: The results have shown the changes in Notch signaling-related genes to be highly consistent in both AD cohorts. Bioinformatics analysis has found Differentially Expressed Genes (DEGs) related to Notch signaling to mainly play important roles in Alzheimer's disease, the Notch signaling pathway, and the C-type lectin receptor signaling pathway. Multiple machine learning analyses have revealed IKBKB, HDAC2, and PIK3R1 to exhibit good diagnostic value in both AD cohorts and that they may be ideal biomarkers for early diagnosis of AD. CONCLUSION: This study has provided a comprehensive description of the molecular signatures of the Notch signaling pathway in AD peripheral blood and a potential diagnostic model for AD clinical screening.
Impact of the COVID-19 Pandemic on People with Dementia and their Caregivers: A Multiphase Observational Study from India.
Arshad F, Hurzuk S, Tiwari M … +12 more , Varghese F, Hoskeri RM, Paplikar A, Goyal S, Dhiren SR, Ganeshbhai PV, Ansari MF, Komaravolu S, Kammammettu C, Thomas PT, Rao GN, Alladi S
Curr Alzheimer Res · 2024 · PMID 39601170 · Publisher ↗
INTRODUCTION: The COVID-19 pandemic has had multifaceted and enduring impacts on people with dementia and their caregivers; however, our understanding of the long-term outcomes remains limited. We aimed to explore the lo...
INTRODUCTION: The COVID-19 pandemic has had multifaceted and enduring impacts on people with dementia and their caregivers; however, our understanding of the long-term outcomes remains limited. We aimed to explore the long-term effects of the COVID-19 pandemic on cognitive symptoms and vaccination rates in people living with dementia. METHODS: This study was conducted as a part of a longitudinal study design in two specialized hospitals in South India. In this study, patients with dementia and their caregivers assessed in earlier phases ('period of lockdown with phased relaxations - phase-I' and 'cluster of cases transmission phase - phase-II') were telephonically interviewed. We adopted a quantitative approach to understand disease progression during the three-year course of the pandemic. Changes in cognition and disease severity were measured using the Clinical Dementia Rating (CDR) scale. In brief, semistructured interviews were carried out with caregivers of people with dementia to gain insights into vaccination rates. Data obtained from the current study (phase III) were compared against phase I data, which served as the baseline. Among the 72 participants contacted in the current phase, 59 (81·9%) could be reevaluated for dementia severity and vaccination status, whereas 13 (18·0%) had died. Among the 59 participants, 33 (55·9%) had severe dementia (CDR 3). This is in contrast to phases I and II, when 17·6% and 19·2% of the participants, respectively, were classified as CDR 3. RESULTS: A significant difference in dementia severity between the two phases (phases I and III) was observed. In addition, we observed vaccination hesitancy among caregivers of patients with dementia. This study would provide valuable insights into the long-term impact of the COVID-19 pandemic on the cognitive outcomes and vaccination status of patients with dementia. CONCLUSION: This overall longitudinal study has compared dementia severity between different phases throughout the pandemic, with implications for future studies to tailor home-based support and healthcare interventions in order to meet these evolving needs.
Transforming Alzheimer's Digital Caregiving through Large Language Models.
Kim S, Han DY, Bae J
Curr Alzheimer Res · 2024 · PMID 39592896 · Publisher ↗
INTRODUCTION/OBJECTIVE: Alzheimer's Disease and Related Dementias (AD/ADRD) present significant caregiving challenges, with increasing burdens on informal caregivers. This study examines the potential of AI-driven Large...
INTRODUCTION/OBJECTIVE: Alzheimer's Disease and Related Dementias (AD/ADRD) present significant caregiving challenges, with increasing burdens on informal caregivers. This study examines the potential of AI-driven Large Language Models (LLMs) in developing digital caregiving strategies for AD/ADRD. The objectives include analyzing existing caregiving education materials (CEMs) and mobile application descriptions (MADs) and aligning key caregiving tasks with digital functions across different stages of disease progression. METHODS: We analyzed 38 CEMs from the National Library of Medicine's MedlinePlus, along with associated hyperlinked web resources, and 57 MADs focused on AD digital caregiving. Using ChatGPT 3.5, essential caregiving tasks were extracted and matched with digital functionalities suitable for each stage of AD progression, while also highlighting digital literacy requirements for caregivers. RESULTS: The analysis categorizes AD caregiving into 4 stages-Pre-Clinical, Mild, Moderate, and Severe-identifying key tasks, such as behavior monitoring, daily assistance, direct supervision, and ensuring a safe environment. These tasks were supported by digital aids, including memory- enhancing apps, Global Positioning System (GPS) tracking, voice-controlled devices, and advanced GPS tracking for comprehensive care. Additionally, 6 essential digital literacy skills for AD/ADRD caregiving were identified: basic digital skills, communication, information management, safety and privacy, healthcare knowledge, and caregiver coordination, highlighting the need for tailored training. CONCLUSION: The findings advocate for an LLM-driven strategy in designing digital caregiving interventions, particularly emphasizing a novel paradigm in AD/ADRD support, offering adaptive assistance that evolves with caregivers' needs, thereby enhancing their shared decision-making and patient care capabilities.
A Cross-Sectional Study on the Association between Physical Activity and Cognitive Function Among Community-Dwelling Older Adults in Tianjin.
Wang T, Duan K, Cai X … +6 more , Chen Q, Zu L, Liu L, Wu X, Li C, Ma F
Curr Alzheimer Res · 2024 · PMID 39592895 · Publisher ↗
BACKGROUND: The association between physical activity (PA) and cognitive function remains controversial, and the impact of gender on this association remains underexplored. Therefore, this study aimed to investigate the...
BACKGROUND: The association between physical activity (PA) and cognitive function remains controversial, and the impact of gender on this association remains underexplored. Therefore, this study aimed to investigate the association between PA and cognitive function and to explore whether this association was modified by gender among older adults. METHODS: In 2016, a cluster sampling method was used to select community-dwelling older adults aged 65 and above. PA was assessed using the International Physical Activity Questionnaire-Short Form and classified as low, middle, and high. Cognitive function was assessed using the revised Chinese version of the Wechsler Adult Intelligence Scale. The multiple linear regression model was used to explore the association between PA and cognitive function and to assess whether this association differs by gender. RESULTS: A total of 676 participants with a mean age of 73.63 ± 6.39 were included. The multiple linear regression analysis showed that higher PA was significantly statistically associated with higher Full Intelligence Quotient (FIQ), Performance Intelligence Quotient (PIQ), and verbal Intelligence Quotient (VIQ) scores (P<0.05). Among the WAIS-RC subtests, higher PA was significantly statistically associated with higher scores of the similarity subtest, picture completion subtest, and picture arrangement subtest (P<0.05). In the gender subgroup analysis, higher PA was significantly statistically associated with higher FIQ and PIQ scores (P<0.05), but no significant association was found with VIQ scores (P>0.05) in the male group, while in the female group, there was no significant statistical association between higher PA and FIQ, PIQ, or VIQ scores (P>0.05). CONCLUSION: Higher PA was significantly statistically associated with better cognitive function (P<0.05). In the male group, PA was significantly statistically associated with cognitive function, whereas no comparable association was found in the female group.
Correlations between SHBG, Sex Hormones, Inflammation, and Neurocognitive Decline in Alzheimer's Disease: A Retrospective Study.
Jin J, Lu L, Hua K … +3 more , Fang L, Li X, Li W
Curr Alzheimer Res · 2024 · PMID 39592894 · Full text
BACKGROUND: Alzheimer's Disease (AD) is characterized by a progressive neurodegenerative process leading to cognitive decline and functional impairment. Endocrine factors, particularly sex hormones and their binding prot...
BACKGROUND: Alzheimer's Disease (AD) is characterized by a progressive neurodegenerative process leading to cognitive decline and functional impairment. Endocrine factors, particularly sex hormones and their binding proteins, play a critical role in AD pathophysiology. Understanding the relationship between these factors and AD is essential for developing targeted interventions. OBJECTIVE: To investigate the potential links between sex hormone binding globulin (SHBG) levels, sex hormone profiles, inflammatory markers, and neurocognitive decline in patients with AD. METHODS: A retrospective case-control investigation was conducted with 110 AD patients who were admitted to our hospital from January 2021 to December 2023, and the patients were classified into either a mild neurocognitive impairment group (n=59) or a moderate to severe neurocognitive impairment group (n=51) according to their cognitive function. Correlation and regression analyses were conducted to examine relationships between variable factors. RESULTS: The study revealed a significant neurocognitive decline in AD patients with lower Mini-- Mental State Examination (MMSE) and higher AD Assessment Scale-Cognitive Subscale (ADAS- Cog) scores in the moderate to severe neurocognitive impairment group compared to the mild neurocognitive impairment group. Additionally, the moderate to severe neurocognitive impairment group significantly increased for SHBG, estradiol, progesterone inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β)). It decreased for follicle-stimulating hormone (FSH) and luteinizing hormone (LH)]. Moreover, significant positive correlations were found between SHBG levels and ADAS-Cog scores, and significant negative correlations were found between SHBG levels and MMSE scores. FSH showed significant negative correlations with the MMSE score, while certain inflammatory markers demonstrated significant correlations with neurocognitive abilities. The correlation between sex hormones and inflammatory factors is weak. FSH, LH, SHBG, CRP, IL-6, TNF-α, and IL-1β are risk factors for neurocognitive impairment, while E2 and P are protective factors. CONCLUSION: The study provides evidence of significant correlations between SHBG levels, sex hormone profiles, inflammatory markers, and neurocognitive decline in AD patients.
Associations between Physical Performance Tests with Cognitive Changes: The Moderating Effect of Cognitive Status.
Lim ZH, Yu J, Kuparasundram S … +2 more , Mahendran R, Ng TKS
Curr Alzheimer Res · 2024 · PMID 39572921 · Publisher ↗
INTRODUCTION/OBJECTIVE: Age-related cognitive decline has been linked with risk factors, including physical performance. Prior studies investigating such associations were typically conducted in clinical settings within...
INTRODUCTION/OBJECTIVE: Age-related cognitive decline has been linked with risk factors, including physical performance. Prior studies investigating such associations were typically conducted in clinical settings within Western populations with a frequent focus on late neurocognitive diagnostic stages (i.e., Alzheimer's disease), reducing their generalizability to the Asian population and early neurocognitive stages. To address these knowledge gaps, our study investigated longitudinal associations between physical performance measures at baseline and cognitive change in global cognition, executive functioning (EF) based and non-executive functioning (non- EF) based cognitive domains within the Singaporean population. The moderating role of early neurocognitive status, namely mild cognitive impairment (MCI) and cognitively normal (CN), was also examined. METHODS: This paper examined data from 347 participants (CN = 284; MCI = 63) who participated in the Community Health and Intergenerational (CHI) study at baseline and follow-up. Data from a neurocognitive battery and three physical performance tests, namely the timed-up and go (TUG), fast gait speed (FGS) and 30-second chair-stand test (30s-CST), were analysed using multivariate linear regression models. RESULTS: Only one significant association between FGS scores and cognitive change in Semantic Fluency was observed; other associations were not significant. Cognitive status also significantly moderated associations between TUG/30s-CST tasks with several neurocognitive tests. CONCLUSION: The lack of significant longitudinal associations between baseline physical performance measures and cognitive change differed from findings in the literature. Nevertheless, the moderating role of cognitive status further highlighted the need to account for cognitive status when exploring such associations within a heterogeneous group of older adults without dementia.
Age-Related Differences in the Association between Life's Essential 8 and Cognition in Cognitively Normal Adults: The CABLE Study.
Tang L, Ma LZ, Cheng-Kun S … +3 more , Guo R, Tan L, Tan MS
Curr Alzheimer Res · 2024 · PMID 39572920 · Publisher ↗
BACKGROUND: This study investigated the relationship between Life's Essential 8 (LE8), a recently updated lifestyle-related health factor, and cognition across multiple life stages. METHODS: We enrolled 1098 cognitively...
BACKGROUND: This study investigated the relationship between Life's Essential 8 (LE8), a recently updated lifestyle-related health factor, and cognition across multiple life stages. METHODS: We enrolled 1098 cognitively normal participants from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. We investigated the interactions between age and LE8 on cognition. Multiple linear regression models were utilized to explore the relationship between the LE8 total scores and its two subscales scores with cognition in the total sample, as well as in the mid-age (≤65 years) and the late-age (>65 years) subgroups. In addition, mediation analyses were performed to explore the biologically plausible pathways between LE8 and cognition. RESULTS: There was a significant interaction effect between age and LE8 total scores on MOCA score (P = 0.030). The mid-age subgroup showed a positive correlation between LE8 total scores and CM-MMSE (β = 0.110, P = 0.005) and MOCA (β = 0.112, P = 0.005) scores. However, no significant associations were found in the late-age subgroup. In the mid-age subgroup, CSF p-tau partially mediated the relationship between LE8 total scores and its two subscales and cognition, with a mediation proportion ranging from 6% to 12%. CONCLUSION: Our findings revealed that the association of the LE8 total scores with MOCA and CM-MMSE scores were significant in mid-age adults rather than late-age adults, indicating that the association might be age-specific and emphasizing the importance of lifestyle interventions in mid-life.
Identifying the Role of Oligodendrocyte Genes in the Diagnosis of Alzheimer's Disease through Machine Learning and Bioinformatics Analysis.
Yan C, Chen L, Yinhui Y … +1 more , Yazhen S
Curr Alzheimer Res · 2024 · PMID 39506420 · Publisher ↗
BACKGROUND: Due to the heterogeneity of Alzheimer's disease (AD), the underlying pathogenic mechanisms have not been fully elucidated. Oligodendrocyte (OL) damage and myelin degeneration are prevalent features of AD path...
BACKGROUND: Due to the heterogeneity of Alzheimer's disease (AD), the underlying pathogenic mechanisms have not been fully elucidated. Oligodendrocyte (OL) damage and myelin degeneration are prevalent features of AD pathology. When oligodendrocytes are subjected to amyloid-beta (Aβ) toxicity, this damage compromises the structural integrity of myelin and results in a reduction of myelin-associated proteins. Consequently, the impairment of myelin integrity leads to a slowdown or cessation of nerve signal transmission, ultimately contributing to cognitive dysfunction and the progression of AD. Consequently, elucidating the relationship between oligodendrocytes and AD from the perspective of oligodendrocytes is instrumental in advancing our understanding of the pathogenesis of AD. OBJECTIVE: Here, an attempt is made in this study to identify oligodendrocyte-related biomarkers of AD. METHODS: AD datasets were obtained from the Gene Expression Omnibus database and used for consensus clustering to identify subclasses. Hub genes were identified through differentially expressed genes (DEGs) analysis and oligodendrocyte gene set enrichment. Immune infiltration analysis was conducted using the CIBERSORT method. Signature genes were identified using machine learning algorithms and logistic regression. A diagnostic nomogram for predicting AD was developed and validated using external datasets and an AD model. A small molecular compound was identified using the eXtreme Sum algorithm. RESULTS: 46 genes were found to be significantly correlated with AD progression by examining the overlap between DEGs and oligodendrocyte genes. Two subclasses of AD, Cluster A, and Cluster B, were identified, and 9 signature genes were identified using a machine learning algorithm to construct a nomogram. Enrichment analysis showed that 9 genes are involved in apoptosis and neuronal development. Immune infiltration analysis found differences in immune cell presence between AD patients and controls. External datasets and RT-qPCR verification showed variation in signature genes between AD patients and controls. Five small molecular compounds were predicted. CONCLUSION: It was found that 9 oligodendrocyte genes can be used to create a diagnostic tool for AD, which could help in developing new treatments.
Molecular Mechanisms of GFAP and PTPRC in Alzheimer's Disease: An Analysis of Neuroinflammatory Response and Progression.
Huang J, Pang X, Yang H … +5 more , Gao C, Wang D, Sun Y, Taishi Y, Pang C
Curr Alzheimer Res · 2024 · PMID 39482922 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD) is a complex neurological disorder that progressively worsens. Although its exact causes are not fully understood, new research indicates that genes related to non-neuronal cells ch...
INTRODUCTION: Alzheimer's disease (AD) is a complex neurological disorder that progressively worsens. Although its exact causes are not fully understood, new research indicates that genes related to non-neuronal cells change significantly with age, playing key roles in AD's pathology. METHOD: This study focuses on a protein network centered on Glial Fibrillary Acidic Protein (GFAP) and Protein Tyrosine Phosphatase Receptor Type C (PTPRC). The Key Findings of this Study Include: 1. A significant correlation was observed between GFAP and PTPRC expression throughout AD progression, which links closely with clinical phenotypes and suggests their role in AD pathology. 2. A molecular network centered on GFAP and PTPRC, including Catenin Beta 1 (CTNNB1) and Integrin Beta 2 (ITGB2), showed distinct changes in interactions, highlighting its regulatory role in AD. 3. Analysis of GSE5281 data revealed a decline in the interaction strength within this network, pointing to potential desynchronization as a biomarker for AD. 4. SVM diagnostic models comparing GFAP expression and coupling values confirmed this desynchronization, suggesting it worsens with AD progression. RESULT: Based on these findings, it is hypothesized that as AD progresses, the GFAP- and PTPRCcentered molecular framework undergoes significant changes affecting key biological pathways. These changes disrupt immune regulation and cellular functions, increasing immune cell activation and inflammation in the brain. This may impair neuronal communication and synaptic functionality, exacerbating AD's pathology. CONCLUSION: To verify these findings, Support Vector Machine (SVM) diagnostic models and correlation analyses were used to examine changes in this network, indicating that its dysregulation significantly affects AD progression.
Analysis of Alzheimer's Disease-Related Mortality Rates Among the Elderly Populations Across the United States: An Analysis of Demographic and Regional Disparities from 1999 to 2020.
Khan AH, Ijaz E, Ubaid B … +4 more , Eddaki I, Edhi M, Shah MN, Perry G
Curr Alzheimer Res · 2024 · PMID 39444182 · Publisher ↗
INTRODUCTION: Alzheimer's Disease (AD) is the leading cause of dementia and a significant public health concern, characterized by high incidence, mortality, and economic burden. This study analyzes the mortality patterns...
INTRODUCTION: Alzheimer's Disease (AD) is the leading cause of dementia and a significant public health concern, characterized by high incidence, mortality, and economic burden. This study analyzes the mortality patterns and demographic disparities in Alzheimer's disease-related deaths among the elderly population in the United States from 1999 through 2020. METHODS: Alzheimer's disease mortality data for individuals 65 and older were obtained from the CDC WONDER database, utilizing ICD-10 codes G30.0, G30.1, G30.8, and G30.9 for identification. Demographic and regional variables included age, gender, race/ethnicity, place of death, urban- rural status, and geographic region. Crude death rates (CR) and age-adjusted mortality rates (AAMR) per 100,000 individuals were calculated. Joinpoint Regression Program 5.0.2 was used to analyze trends, calculating Annual Percentage Changes (APCs) and Average Annual Percentage Changes (AAPCs). RESULTS: From 1999 to 2020, 1,852,432 deaths were attributed to AD among individuals aged 65 and older. The AAMR increased from 128.8 in 1999 to 254.3 in 2020, with an AAPC of 2.99% (95% CI = 2.61-3.48). The age-adjusted mortality rate (AAMR) was higher in females (218.5) than in males (163.5). Among racial and ethnic groups, non-Hispanic whites had the highest AAMR, followed by Non-Hispanic Blacks and Hispanics. Regionally, the West reported the highest AAMR, while the Northeast recorded the lowest. Most deaths occurred in nursing homes (57.3%), with a significant portion also occurring at decedents' homes (22.4%). CONCLUSION: AD mortality rates in the U.S. have risen significantly, with notable disparities across age, gender, race, and geographic regions. These findings highlight the need for targeted interventions and research to address the growing burden of AD, particularly among the most affected demographic groups.
Correlations between Cerebrospinal Fluid Biomarkers and Gray Matter Atrophy in Alzheimer's and Behavioural Variant Frontotemporal Dementia.
Scianatico G, Manippa V, Zaca D … +4 more , Jovicich J, Tafuri B, Rivolta D, Logroscino G
Curr Alzheimer Res · 2024 · PMID 39440732 · Publisher ↗
INTRODUCTION: Distinguishing between frontotemporal dementia (FTD) and Alzheimer's disease (AD) in their early stages remains a significant clinical challenge. Cerebrospinal fluid (CSF) biomarkers (total Tau, phosphoryla...
INTRODUCTION: Distinguishing between frontotemporal dementia (FTD) and Alzheimer's disease (AD) in their early stages remains a significant clinical challenge. Cerebrospinal fluid (CSF) biomarkers (total Tau, phosphorylated Tau, and beta-amyloid) are promising candidates for identifying early differences between these conditions. This study investigates the relationship between grey matter density and CSF markers in the behavioural variant of frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). METHOD: CSF and 3D T1-weighted magnetic resonance (MR) images were acquired from 14 bvFTD patients, 15 AD patients, and 13 cognitively normal (CN) matched subjects. The CSF markers and their relative ratios (total Tau/beta-amyloid, phosphorylated Tau/beta-amyloid) were compared across the three groups. Voxel-based morphometry (VBM) was performed to characterize the anatomical changes in bvFTD and AD patients compared to CN subjects. Grey matter density maps were obtained by automatic segmentation of 3.0 Tesla 3D T1-Weighted MR Images, and their correlation with CSF markers and relative ratios was investigated. RESULTS: Results demonstrated that, as compared to CN subjects, AD patients are characterised by higher CSF total Tau levels and lower beta-amyloid levels; however, beta-amyloid and relative ratios discriminated AD from bvFTD. In addition, AD and bvFTD patients showed different patterns of atrophy, with AD exhibiting more central (temporal areas) and bvFTD more anterior (frontal areas) atrophy. A correlation was found between grey matter density maps and CSF marker concentrations in the AD group, with total Tau and phosphorylated Tau levels showing a high association with low grey matter density in the left superior temporal gyrus. CONCLUSION: Overall, while bvFTD lacks a CSF marker profile, CSF beta-amyloid levels are useful for differentiating AD from bvFTD. Furthermore, MR structural imaging can contribute significantly to distinguishing between the two pathologies.
Capgras Syndrome in Dementia: A Systematic Review of Case Studies.
Margariti C, Mircea MT
Curr Alzheimer Res · 2024 · PMID 39411962 · Publisher ↗
BACKGROUND: In an ageing population, dementia has become an imminent healthcare emergency. Capgras syndrome, the most common delusion of misidentification (DMS), is frequently found alongside dementia. Previous research...
BACKGROUND: In an ageing population, dementia has become an imminent healthcare emergency. Capgras syndrome, the most common delusion of misidentification (DMS), is frequently found alongside dementia. Previous research showed that Capgras syndrome has significant negative effects on people living with dementia and their carers due to its complex presentation and impact on their lives. This qualitative systematic review explores the evidence base of the effective management and treatment of Capgras syndrome in dementia. AIMS: As per our knowledge, this is the first systematic review exploring the symptomatology of Capgras syndrome across different types of dementia. Additionally, it aims to identify the treatments used and their efficacy. METHODS: Four databases (EMBASE, MEDLINE, PsycINFO, and CINHAL) were screened in March, 2023. Twenty-six studies met the inclusion criteria and were included in the review. Thematic analysis was performed to explore and synthesise the qualitative findings of the studies. RESULTS: Three conceptual themes were identified: diagnostic tools, Capgras syndrome symptomatology, and Capgras syndrome treatment. Results showed that Capgras syndrome in dementia is not diagnosed and treated in a standardised manner. Following the pharmacological intervention, 28% of cases showed resolution of symptoms, and another 28% experienced improvement. However, 7% of cases reported worsening symptoms, and 10.7% experienced no change. While some patients had positive outcomes with specific medications, others either did not respond or experienced a deterioration of their condition. CONCLUSION: The results highlight that there is no single treatment approach for Capgras syndrome in people living with dementia. This underscores the need for person-centred care, where treatment is tailored to individual needs. The review also reveals a heavy reliance on antipsychotic medications and a noticeable lack of psychosocial interventions. Given the limited benefits and significant risks associated with antipsychotics, future research should prioritise developing and testing psychosocial approaches. Additionally, establishing standardised diagnostic criteria and consistent outcome measures for Capgras syndrome in dementia is crucial for evaluating treatment effectiveness and improving care.
Corrigendum to: Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid.
Chakrabarti S, Jana M, Roy A … +1 more , Pahan K
Curr Alzheimer Res · 2024 · PMID 39404116 · Publisher ↗
In the online version of the article, a change was made in Figure 1 of the article titled "Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid", published in Current Alzheimer Research, 2018,...
In the online version of the article, a change was made in Figure 1 of the article titled "Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid", published in Current Alzheimer Research, 2018, 15(10), 894-904. The author informed the publisher that an incorrect image was provided for Figure 1. The correct image was from the P-CREB experiment of Figure 5 [1]. Now, the revised Figure 1 has been updated in the article, and it can be found online at: https://www.eurekaselect.com/article/90209.
Cortical Thickness and Complexity in aMCI Patients: Altered Pattern Analysis and Early Diagnosis.
Tao M, Xie Z, Chen P … +2 more , Xu X, Wang P
Curr Alzheimer Res · 2024 · PMID 39318217 · Publisher ↗
BACKGROUND: Amnestic Mild Cognitive Impairment (aMCI) is a prodromal phase of Alzheimer's disease. Although recent studies have focused on cortical thickness as a key indicator, cortical complexity has not been exhaustiv...
BACKGROUND: Amnestic Mild Cognitive Impairment (aMCI) is a prodromal phase of Alzheimer's disease. Although recent studies have focused on cortical thickness as a key indicator, cortical complexity has not been exhaustively investigated. OBJECTIVES: To investigate the altered patterns of cortical features in aMCI patients and their correlation with memory function for early identification. METHODS: 25 aMCI patients and 54 normal controls underwent neuropsychological assessments and 3D-T1 MRI scans. Cortical thickness and complexity measures were calculated using CAT12 software. Differences between groups were analyzed using two-sample t-tests, and multiple linear regression was employed to identify features associated with memory function. A support vector machine (SVM) model was constructed using multidimensional structural indicators to evaluate diagnostic performance. RESULTS: aMCI patients exhibited extensive reductions in cortical thickness ( <0.05), with complexity reduction predominantly in the left parahippocampal, entorhinal, rostral anterior cingulate, fusiform, and orbitofrontal (<0.05). Cortical indicators exhibited robust correlations with auditory verbal learning test (AVLT) scores. Specifically, the fractal dimension of the left medial orbitofrontal region was independently and positively associated with AVLT-short delayed score (r=0.348, p=0.002), while the gyrification index of the left rostral anterior cingulate region showed independent positive correlations with AVLT-long delayed and recognition scores (r=0.408, p=0.000; r=0.332, p=0.003). Finally, the SVM model integrating these cortical features achieved an AUC of 0.91, with 82.28% accuracy, 76% sensitivity, and 85.19% specificity. CONCLUSION: Cortical morphological indicators provide important neuroimaging evidence for the early diagnosis of aMCI. Integrating multiple structural indicators significantly improves diagnostic accuracy.
Post-Hoc Assessment of Cognitive Efficacy in Alzheimer's Disease Using a Latent Growth Mixture Model in AMBAR, a Phase 2B Randomized Controlled Trial.
Ayasse ND, Stewart WF, Lipton RB … +2 more , Gomez-Ulloa D, Runken MC
Curr Alzheimer Res · 2024 · PMID 39318022 · Publisher ↗
BACKGROUND: Disease progression in Alzheimer's Dementia (AD) is typically characterized by accelerated cognitive and functional decline, where heterogeneous trajectories can impact the observed treatment response. METHOD...
BACKGROUND: Disease progression in Alzheimer's Dementia (AD) is typically characterized by accelerated cognitive and functional decline, where heterogeneous trajectories can impact the observed treatment response. METHODS: We hypothesized that unobserved heterogeneity could obscure treatment benefits in AD. The effect of unobserved heterogeneity was empirically quantified within the Alzheimer's Management By Albumin Replacement (AMBAR) phase 2b trial data. The ADAS-Cog 12 cognition endpoint was reanalyzed in a 2-class latent growth mixture model initially fit to the treatment arm. The model with the best fit was then applied across both treatment arms to a larger (n=1000) simulated dataset that was representative of AMBAR trial cognitive data. RESULTS: Two classes of patients were observed: a stable cognitive trajectory class and a highly variable class. Removal of the latter (n=48, 22%) from the analysis and refitting efficacy models comparing the stable class to full placebo yielded significant treatment efficacy on cognition (p=0.007, Cohen's D=-0.4). Comparison of the stable class of each arm within the simulated dataset revealed a significant difference in treatment efficacy favoring the simulated stable treatment arm. CONCLUSION: This post hoc exploratory analysis suggests that prespecified strategies for addressing unobserved heterogeneity may yield improved effect detection in AD trials. The generalizability of the analytic strategy is limited by latent stratification in only the treatment arm, a requirement given the small placebo arm in AMBAR. This limitation was partially addressed by the simulation modeling.
Microglial Circadian Rhythms and Neurodegenerative Diseases.
Xia Y
Curr Alzheimer Res · 2024 · PMID 39313894 · Publisher ↗
Abstract loading — click title to view on PubMed.
Multifunctional Tasks and an Energy Crisis are Crucial Players in Determining the Vulnerability of the Entorhinal Cortex to Early Damage in Alzheimer's Disease.
Sivanesan S, Howell MD, Kaushik V … +3 more , Jayakumar R, Pari SM, Goyal P
Curr Alzheimer Res · 2024 · PMID 39279693 · Publisher ↗
Alzheimer's disease (AD) is a devastating neurological disorder that affects synaptic transmission between neurons. Several theories and concepts have been postulated to explain its etiology and pathogenesis. The disease...
Alzheimer's disease (AD) is a devastating neurological disorder that affects synaptic transmission between neurons. Several theories and concepts have been postulated to explain its etiology and pathogenesis. The disease has no cure, and the drugs available to manage AD symptoms provide only modest benefits. It originates in the brain's entorhinal cortex (EC), with tau pathology that poses overt symptoms for decades and then spreads to other connected areas and networks to cause severe cognitive decline. Despite decades of research, the reason why the EC is the first region to be affected during AD pathophysiology remains unknown. The EC is well connected with surrounding areas to support the brain's structural and functional integrity, participate in navigation, working memory, memory consolidation, olfaction, and olfactory-auditory coordination. These actions require massive energy expenditure, thus, the EC is extremely vulnerable to severe hypometabolism and an energy crisis. The crucial events/factors that make the EC vulnerable to pathological sequelae more than other brain regions have not been thoroughly explored. An in- -depth analysis of available research on the role of the EC in AD could provide meaningful insights into the susceptibility of this region and its role in propagating AD. In this review article, we highlight how the functional complexities of the EC account for its vulnerability to AD.
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