Dementia is a syndrome in which there is deterioration in memory, behavior, and the ability to perform everyday activities. Alzheimer's disease and vascular dementia are the most common forms of dementia. There is evidence supporting the hypothesis that inflammatory and immune mechanisms are involved in dementia. Microglia, the resident macrophage tissues in the central nervous system, play a significant role in neuroinflammation and play an important role in amyloid-β clearance in the brain, and impaired microglial clearance of amyloid-β has also been shown to be involved in the pathogenesis of Alzheimer's disease. However, there is also abundant evidence that microglia have harmful actions in dementia. Once activated, they can mediate uptake at neuronal synapses. They can also exacerbate tau pathology and secrete deleterious inflammatory factors that can directly or indirectly damage neurons. Thus, depending on the stage of the disease, microglia can act both protectively and detrimentally. Therefore, it is still necessary to continue with studies to better understand the role of microglia in the pathology of dementia. Currently available drugs can only improve cognitive symptoms, have no impact on progression and are not curative, so identifying and studying new therapeutic approaches is important. Considering the role played by microglia in this pathology, it has been pointed out as a possible therapeutic approach. This manuscript aims to address the relationship between microglia and dementia and how this relationship could be used for therapeutic purposes.
痴呆症是一种记忆力、行为和日常活动能力退化的综合症。阿尔茨海默病和血管性痴呆是最常见的痴呆形式。有证据支持炎症和免疫机制与痴呆症有关的假设。小胶质细胞是中枢神经系统中的常驻巨噬细胞组织，在神经炎症中发挥着重要作用，并在清除脑内淀粉样蛋白-β的过程中扮演重要角色，小胶质细胞清除淀粉样蛋白-β的能力受损也被证明与阿尔茨海默病的发病机制有关。然而，也有大量证据表明，小胶质细胞在痴呆症中具有有害作用。小胶质细胞一旦被激活，就会介导神经元突触的吸收。它们还能加剧 tau 病理学，并分泌有害的炎症因子，直接或间接损害神经元。因此，根据疾病的不同阶段，小胶质细胞既能起到保护作用，也能起到损害作用。因此，仍有必要继续开展研究，以更好地了解小胶质细胞在痴呆症病理中的作用。目前可用的药物只能改善认知症状，对病情发展没有影响，也不能治愈疾病，因此确定和研究新的治疗方法非常重要。考虑到小胶质细胞在这一病理过程中所扮演的角色，有人指出它是一种可能的治疗方法。本手稿旨在探讨小胶质细胞与痴呆症之间的关系，以及如何将这种关系用于治疗目的。
{"title":"Microglia as a Possible Alternative Therapeutic for Dementia.","authors":"Jessica Sarahi Alavez-Rubio, Teresa Juarez-Cedillo","doi":"10.3233/ADR-230112","DOIUrl":"10.3233/ADR-230112","url":null,"abstract":"<p><p>Dementia is a syndrome in which there is deterioration in memory, behavior, and the ability to perform everyday activities. Alzheimer's disease and vascular dementia are the most common forms of dementia. There is evidence supporting the hypothesis that inflammatory and immune mechanisms are involved in dementia. Microglia, the resident macrophage tissues in the central nervous system, play a significant role in neuroinflammation and play an important role in amyloid-β clearance in the brain, and impaired microglial clearance of amyloid-β has also been shown to be involved in the pathogenesis of Alzheimer's disease. However, there is also abundant evidence that microglia have harmful actions in dementia. Once activated, they can mediate uptake at neuronal synapses. They can also exacerbate tau pathology and secrete deleterious inflammatory factors that can directly or indirectly damage neurons. Thus, depending on the stage of the disease, microglia can act both protectively and detrimentally. Therefore, it is still necessary to continue with studies to better understand the role of microglia in the pathology of dementia. Currently available drugs can only improve cognitive symptoms, have no impact on progression and are not curative, so identifying and studying new therapeutic approaches is important. Considering the role played by microglia in this pathology, it has been pointed out as a possible therapeutic approach. This manuscript aims to address the relationship between microglia and dementia and how this relationship could be used for therapeutic purposes.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"43-56"},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qin Li, Jiehong Zhan, Yu-Ping Feng, Zixuan Liao, Xiaofeng Li
Background: The association of body mass index (BMI) with cognition and Alzheimer’s disease (AD) biomarkers of the elderly remains inconclusive. Objective: To investigate the relationship between BMI and cognition as well as AD biomarkers in the elderly with different cognitive status. Methods: Participants with cognitively normal (CN) were included as the CN group. Participants with mild cognitive impairment and mild dementia were included as the cognitive impairment (CI) group. The relationship between BMI and AD biomarkers (cerebrospinal fluid Aβ42 and p-tau181, hippocampal volume [HV]), global cognition (Mini-Mental State Examination [MMSE]), memory, and executive function were explored. Results: In the CI group, BMI was associated with MMSE (β= 0.03, p = 0.009), Aβ42 (β= 0.006, p = 0.029), p-tau181/Aβ42 ratio (β= -0.001, p = 0.011), and HV (β= 0.05, p < 0.001). However in the CN group, BMI exhibited associations with p-tau181 (β= 0.012, p = 0.014) and memory composite score (β= -0.04, p = 0.038), but not with p-tau181/Aβ42 ratio and HV. Moreover, mediation analysis showed that in the CI group, the positive effect of BMI on HV and MMSE score was partially mediated by diastolic blood pressure. Conclusion: The association of BMI with cognition and AD biomarkers varies across different cognitive status. In particular, a lower BMI was associated with worse cognition, higher Aβ burden, and lower HV in individuals with CI. Clinical practice should strengthen the monitoring and management of BMI in patients with AD.
{"title":"The Association of Body Mass Index with Cognition and Alzheimer’s Disease Biomarkers in the Elderly with Different Cognitive Status: A Study from the Alzheimer’s Disease Neuroimaging Initiative Database","authors":"Qin Li, Jiehong Zhan, Yu-Ping Feng, Zixuan Liao, Xiaofeng Li","doi":"10.3233/adr-230163","DOIUrl":"https://doi.org/10.3233/adr-230163","url":null,"abstract":"Background: The association of body mass index (BMI) with cognition and Alzheimer’s disease (AD) biomarkers of the elderly remains inconclusive. Objective: To investigate the relationship between BMI and cognition as well as AD biomarkers in the elderly with different cognitive status. Methods: Participants with cognitively normal (CN) were included as the CN group. Participants with mild cognitive impairment and mild dementia were included as the cognitive impairment (CI) group. The relationship between BMI and AD biomarkers (cerebrospinal fluid Aβ42 and p-tau181, hippocampal volume [HV]), global cognition (Mini-Mental State Examination [MMSE]), memory, and executive function were explored. Results: In the CI group, BMI was associated with MMSE (β= 0.03, p = 0.009), Aβ42 (β= 0.006, p = 0.029), p-tau181/Aβ42 ratio (β= -0.001, p = 0.011), and HV (β= 0.05, p < 0.001). However in the CN group, BMI exhibited associations with p-tau181 (β= 0.012, p = 0.014) and memory composite score (β= -0.04, p = 0.038), but not with p-tau181/Aβ42 ratio and HV. Moreover, mediation analysis showed that in the CI group, the positive effect of BMI on HV and MMSE score was partially mediated by diastolic blood pressure. Conclusion: The association of BMI with cognition and AD biomarkers varies across different cognitive status. In particular, a lower BMI was associated with worse cognition, higher Aβ burden, and lower HV in individuals with CI. Clinical practice should strengthen the monitoring and management of BMI in patients with AD.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"114 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139444418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Krishna, Palanimuthu Thangaraju Sivakumar, Ajit B. Dahale, S. Subramanian
Blood tests are in need, in the clinical diagnosis of Alzheimer’s disease (AD) as minimally invasive and less expensive alternatives to cerebrospinal fluid and neuroimaging methods. On these lines, single molecule array (Simoa) analysis of amyloid-β (Aβ42), total tau (t-tau), phospho-tau (p-tau 181), and neurofilament L (NfL) in the plasma samples of AD subjects, healthy controls (HC), and non-AD subjects was conducted. Findings from this study suggest that a panel of multiple plasma biomarkers (NfL, Aβ42, t-tau, and p-tau 181) combined with the clinical assessments could support differential diagnosis of AD and other dementias from healthy controls.
{"title":"Potential Utility of Plasma Biomarker Panels in Differential Diagnosis of Alzheimer’s Disease","authors":"G. Krishna, Palanimuthu Thangaraju Sivakumar, Ajit B. Dahale, S. Subramanian","doi":"10.3233/adr-230156","DOIUrl":"https://doi.org/10.3233/adr-230156","url":null,"abstract":"Blood tests are in need, in the clinical diagnosis of Alzheimer’s disease (AD) as minimally invasive and less expensive alternatives to cerebrospinal fluid and neuroimaging methods. On these lines, single molecule array (Simoa) analysis of amyloid-β (Aβ42), total tau (t-tau), phospho-tau (p-tau 181), and neurofilament L (NfL) in the plasma samples of AD subjects, healthy controls (HC), and non-AD subjects was conducted. Findings from this study suggest that a panel of multiple plasma biomarkers (NfL, Aβ42, t-tau, and p-tau 181) combined with the clinical assessments could support differential diagnosis of AD and other dementias from healthy controls.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"30 34","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139443002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleni N. Baldimtsi, C. Mouzakidis, Eleni Maria Karathanasi, Eleni Verykouki, Mary Hassandra, E. Galanis, A. Hatzigeorgiadis, M. Goudas, Paul Zikas, Giannis Evangelou, G. Papagiannakis, George Bellis, Christos Kokkotis, Themistoklis Tsatalas, Giannis Giakas, Y. Theodorakis, Magda Tsolaki
Background: Virtual reality (VR) technology has become increasingly used for assessment and intervention in the neuroscience field. Objective: We aimed to investigate the effects of a VR Training System, named VRADA (VR Exercise App for Dementia and Alzheimer’s Patients), on the cognitive functioning of older people with mild cognitive impairment (MCI). Methods: In this intervention study, 122 older adults with MCI were randomly assigned to five groups (the VRADA group (n = 28), a bike group (n = 11), a physical exercise group (n = 24), a mixed group (physical and cognitive exercise) (n = 31), and a non-contact control group (n = 28). The VRADA group underwent 32 physical and cognitive training sessions, performed 2 or 3 times weekly for 12 weeks in the VR environment. All participants had detailed neuropsychological assessments before and after intervention. Results: A series of linear regression models revealed that the VRADA group showed improvement or no deterioration in cognitive decline in global cognitive function (MMSE), verbal memory (Rey Auditory Verbal Learning Test and WAIS forward test), and executive functions, mental flexibility (Trail Making Test B). Conclusions: This interventionstudy indicates that the VRADA system improves the cognitive function of elders with MCI.
{"title":"Effects of Virtual Reality Physical and Cognitive Training Intervention On Cognitive Abilities of Elders with Mild Cognitive Impairment","authors":"Eleni N. Baldimtsi, C. Mouzakidis, Eleni Maria Karathanasi, Eleni Verykouki, Mary Hassandra, E. Galanis, A. Hatzigeorgiadis, M. Goudas, Paul Zikas, Giannis Evangelou, G. Papagiannakis, George Bellis, Christos Kokkotis, Themistoklis Tsatalas, Giannis Giakas, Y. Theodorakis, Magda Tsolaki","doi":"10.3233/adr-230099","DOIUrl":"https://doi.org/10.3233/adr-230099","url":null,"abstract":"Background: Virtual reality (VR) technology has become increasingly used for assessment and intervention in the neuroscience field. Objective: We aimed to investigate the effects of a VR Training System, named VRADA (VR Exercise App for Dementia and Alzheimer’s Patients), on the cognitive functioning of older people with mild cognitive impairment (MCI). Methods: In this intervention study, 122 older adults with MCI were randomly assigned to five groups (the VRADA group (n = 28), a bike group (n = 11), a physical exercise group (n = 24), a mixed group (physical and cognitive exercise) (n = 31), and a non-contact control group (n = 28). The VRADA group underwent 32 physical and cognitive training sessions, performed 2 or 3 times weekly for 12 weeks in the VR environment. All participants had detailed neuropsychological assessments before and after intervention. Results: A series of linear regression models revealed that the VRADA group showed improvement or no deterioration in cognitive decline in global cognitive function (MMSE), verbal memory (Rey Auditory Verbal Learning Test and WAIS forward test), and executive functions, mental flexibility (Trail Making Test B). Conclusions: This interventionstudy indicates that the VRADA system improves the cognitive function of elders with MCI.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"30 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139147610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Balietti, R. Galeazzi, R. Giacconi, E. Santillo, C. Giuli
Background: Elevated cortisol levels represent a risk factor for Alzheimer’s disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes. Objective: To assess the efficacy of a comprehensive intervention (CI) in modulating serum cortisol levels in patients with AD. Methods: CI consisted in a 2-month protocol involving cognitive stimulation, psychological support, lifestyle guidance, leisure activities, and socialization. AD subjects were randomly assigned to experimental (EG, n = 45) and control (CG, n = 45) groups. A wide range of sociodemographic, cognitive, psychosocial, and functional conditions were evaluated before, at the conclusion, and 24 months after CI. Data about lifestyle and drug prescription were also recorded. Results: Baseline evaluations revealed that higher cortisol levels correlated with worse cognitive status (higher CDR and ADAS-Cog values and lower MMSE scores), increased depressive symptoms, and reduced physical and social engagement. Following CI, EG exhibited reduced cortisol levels, improved overall cognitive status, and enhanced verbal working memory and executive functions compared to CG. However, at the 24-month follow-up, EG displayed a rebound effect, characterized by elevated cortisol levels and cognitive decline compared to CG. Conclusions: These findings strengthen the adverse relationship between excessive cortisol and deficits in cognition/behavior in AD, demonstrate the short-term benefits of CI, and emphasize the potential long-term risks, which may be attributed to the fragile nature of the AD brain. Comprehensive interventions can yield positive results, but careful calibration of type and duration is necessary, considering disease progression and the potential need for re-administration.
背景：皮质醇水平升高是阿尔茨海默病（AD）的一个危险因素，促使人们为预防或治疗目的降低激素浓度。研究目的评估综合干预（CI）在调节阿尔茨海默病患者血清皮质醇水平方面的疗效。方法综合干预包括为期 2 个月的方案，涉及认知刺激、心理支持、生活方式指导、休闲活动和社交。AD 受试者被随机分配到实验组（EG，n = 45）和对照组（CG，n = 45）。在 CI 之前、结束时和结束后 24 个月，对各种社会人口、认知、社会心理和功能状况进行了评估。此外，还记录了有关生活方式和药物处方的数据。结果显示基线评估显示，皮质醇水平越高，认知状况越差（CDR 和 ADAS-Cog 值越高，MMSE 分数越低），抑郁症状越严重，身体和社会参与度越低。在进行 CI 后，与 CG 相比，EG 的皮质醇水平降低，整体认知状况改善，言语工作记忆和执行功能增强。然而，在 24 个月的随访中，EG 显示出反弹效应，与 CG 相比，其特点是皮质醇水平升高和认知能力下降。结论：这些研究结果加强了皮质醇过多与 AD 认知/行为缺陷之间的不良关系，证明了 CI 的短期益处，并强调了潜在的长期风险，这可能是由于 AD 大脑的脆弱性质造成的。综合干预可以产生积极的效果，但考虑到疾病的进展和重新给药的潜在需求，有必要对类型和持续时间进行仔细校准。
{"title":"Early Benefits with Potential Long-Term Risks of a Comprehensive Intervention on Serum Cortisol Levels and Cognitive Performance in Patients with Alzheimer’s Disease","authors":"M. Balietti, R. Galeazzi, R. Giacconi, E. Santillo, C. Giuli","doi":"10.3233/adr-230125","DOIUrl":"https://doi.org/10.3233/adr-230125","url":null,"abstract":"Background: Elevated cortisol levels represent a risk factor for Alzheimer’s disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes. Objective: To assess the efficacy of a comprehensive intervention (CI) in modulating serum cortisol levels in patients with AD. Methods: CI consisted in a 2-month protocol involving cognitive stimulation, psychological support, lifestyle guidance, leisure activities, and socialization. AD subjects were randomly assigned to experimental (EG, n = 45) and control (CG, n = 45) groups. A wide range of sociodemographic, cognitive, psychosocial, and functional conditions were evaluated before, at the conclusion, and 24 months after CI. Data about lifestyle and drug prescription were also recorded. Results: Baseline evaluations revealed that higher cortisol levels correlated with worse cognitive status (higher CDR and ADAS-Cog values and lower MMSE scores), increased depressive symptoms, and reduced physical and social engagement. Following CI, EG exhibited reduced cortisol levels, improved overall cognitive status, and enhanced verbal working memory and executive functions compared to CG. However, at the 24-month follow-up, EG displayed a rebound effect, characterized by elevated cortisol levels and cognitive decline compared to CG. Conclusions: These findings strengthen the adverse relationship between excessive cortisol and deficits in cognition/behavior in AD, demonstrate the short-term benefits of CI, and emphasize the potential long-term risks, which may be attributed to the fragile nature of the AD brain. Comprehensive interventions can yield positive results, but careful calibration of type and duration is necessary, considering disease progression and the potential need for re-administration.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"216 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139145380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Tsatali, I. A. Angelidou, Magda Tsolaki, Birgit Teichmann
Background: Measuring dementia knowledge can be a valuable tool for assessing the effectiveness of dementia awareness activities, identifying the potential benefits of dementia training programs, and breaking down common myths and stereotypes about dementia. Objective: To compare the psychometric properties of three widely used dementia knowledge tools, the Dementia Knowledge Assessment Tool 2 (DKAT2-G), the Dementia Knowledge Assessment Scale (DKAS-G), and the Knowledge in Dementia Scale (KIDE-G) in the Greek adult population. Methods: A convenience sample of 252 participants from the general population completed the survey online. Statistical analyses included Cronbach’s internal reliability, retest reliability, factor analysis, concurrent and construct validity, and floor and ceiling effects. Results: The DKAS-G had the most appropriate reliability levels (Cronbach’s alpha = 0.845; retest reliability = 0.921), whereas the DKAT2-G had satisfactory indexes (Cronbach’s α= 0.760; retest reliability = 0.630). The KIDE-G showed unsatisfactory reliability (Cronbach’s α= 0.419; retest reliability = 0.619). Construct validity was confirmed for all questionnaires, showing that all of them detected participants with pre-existing knowledge of dementia. Confirmatory factor analysis revealed a four-factor model for the DKAS-G and proposed the removal of 5 items. Floor and ceiling effects were found for the DKAT2-G and the KIDE-G, mainly among those who had previously participated in dementia training. Conclusions: The DKAS-G was found to have the highest levels of reliability and validity. The results prove that the DKAS-G meets the requirements for measuring dementia knowledge and evaluating dementia training programs in health professionals, caregivers, and the general population.
{"title":"The Dementia Knowledge Assessment Scale, the Knowledge in Dementia Scale, and the Dementia Knowledge Assessment Tool 2: Which Is the Best Tool to Measure Dementia Knowledge in Greece?","authors":"M. Tsatali, I. A. Angelidou, Magda Tsolaki, Birgit Teichmann","doi":"10.3233/adr-230161","DOIUrl":"https://doi.org/10.3233/adr-230161","url":null,"abstract":"Background: Measuring dementia knowledge can be a valuable tool for assessing the effectiveness of dementia awareness activities, identifying the potential benefits of dementia training programs, and breaking down common myths and stereotypes about dementia. Objective: To compare the psychometric properties of three widely used dementia knowledge tools, the Dementia Knowledge Assessment Tool 2 (DKAT2-G), the Dementia Knowledge Assessment Scale (DKAS-G), and the Knowledge in Dementia Scale (KIDE-G) in the Greek adult population. Methods: A convenience sample of 252 participants from the general population completed the survey online. Statistical analyses included Cronbach’s internal reliability, retest reliability, factor analysis, concurrent and construct validity, and floor and ceiling effects. Results: The DKAS-G had the most appropriate reliability levels (Cronbach’s alpha = 0.845; retest reliability = 0.921), whereas the DKAT2-G had satisfactory indexes (Cronbach’s α= 0.760; retest reliability = 0.630). The KIDE-G showed unsatisfactory reliability (Cronbach’s α= 0.419; retest reliability = 0.619). Construct validity was confirmed for all questionnaires, showing that all of them detected participants with pre-existing knowledge of dementia. Confirmatory factor analysis revealed a four-factor model for the DKAS-G and proposed the removal of 5 items. Floor and ceiling effects were found for the DKAT2-G and the KIDE-G, mainly among those who had previously participated in dementia training. Conclusions: The DKAS-G was found to have the highest levels of reliability and validity. The results prove that the DKAS-G meets the requirements for measuring dementia knowledge and evaluating dementia training programs in health professionals, caregivers, and the general population.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"117 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139145868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. André, Sébastien Verteneuil, Laurence Ris, Zehra-Cagla Kahvecioglu, Denis Nonclercq, Julien De Winter, L. Vander Elst, Sophie Laurent, Robert N. Muller, C. Burtea
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder lacking any curative treatment up to now. Indeed, actual medication given to the patients alleviates only symptoms. The cytosolic phospholipase A2 (cPLA2-IVA) appears as a pivotal player situated at the center of pathological pathways leading to AD and its inhibition could be a promising therapeutic approach. Objective: A cPLA2-IVA inhibiting peptide was identified in the present work, aiming to develop an original therapeutic strategy. Methods: We targeted the cPLA2-IVA using the phage display technology. The hit peptide PLP25 was first validated in vitro (arachidonic acid dosage [AA], cPLA2-IVA cellular translocation) before being tested in vivo. We evaluated spatial memory using the Barnes maze, amyloid deposits by MRI and immunohistochemistry (IHC), and other important biomarkers such as the cPLA2-IVA itself, the NMDA receptor, AβPP and tau by IHC after i.v. injection in APP/PS1 mice. Results: Showing a high affinity for the C2 domain of this enzyme, the peptide PLP25 exhibited an inhibitory effect on cPLA2-IVA activity by blocking its binding to its substrate, resulting in a decreased release of AA. Coupled to a vector peptide (LRPep2) in order to optimize brain access, we showed an improvement of cognitive abilities of APP/PS1 mice, which also exhibited a decreased number of amyloid plaques, a restored expression of cPLA2-IVA, and a favorable effect on NMDA receptor expression and tau protein phosphorylation. Conclusions: cPLA2-IVA inhibition through PLP25 peptide could be a promising therapeutic strategy for AD.
{"title":"Modulation of Cytosolic Phospholipase A2 as a Potential Therapeutic Strategy for Alzheimer’s Disease","authors":"S. André, Sébastien Verteneuil, Laurence Ris, Zehra-Cagla Kahvecioglu, Denis Nonclercq, Julien De Winter, L. Vander Elst, Sophie Laurent, Robert N. Muller, C. Burtea","doi":"10.3233/adr-230075","DOIUrl":"https://doi.org/10.3233/adr-230075","url":null,"abstract":"Background: Alzheimer’s disease (AD) is a neurodegenerative disorder lacking any curative treatment up to now. Indeed, actual medication given to the patients alleviates only symptoms. The cytosolic phospholipase A2 (cPLA2-IVA) appears as a pivotal player situated at the center of pathological pathways leading to AD and its inhibition could be a promising therapeutic approach. Objective: A cPLA2-IVA inhibiting peptide was identified in the present work, aiming to develop an original therapeutic strategy. Methods: We targeted the cPLA2-IVA using the phage display technology. The hit peptide PLP25 was first validated in vitro (arachidonic acid dosage [AA], cPLA2-IVA cellular translocation) before being tested in vivo. We evaluated spatial memory using the Barnes maze, amyloid deposits by MRI and immunohistochemistry (IHC), and other important biomarkers such as the cPLA2-IVA itself, the NMDA receptor, AβPP and tau by IHC after i.v. injection in APP/PS1 mice. Results: Showing a high affinity for the C2 domain of this enzyme, the peptide PLP25 exhibited an inhibitory effect on cPLA2-IVA activity by blocking its binding to its substrate, resulting in a decreased release of AA. Coupled to a vector peptide (LRPep2) in order to optimize brain access, we showed an improvement of cognitive abilities of APP/PS1 mice, which also exhibited a decreased number of amyloid plaques, a restored expression of cPLA2-IVA, and a favorable effect on NMDA receptor expression and tau protein phosphorylation. Conclusions: cPLA2-IVA inhibition through PLP25 peptide could be a promising therapeutic strategy for AD.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":" 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139143652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jasmín Bonilla-Santos, A. González-Hernández, D. Cala-Martínez, Duván Fernando Gómez-Morales, L. N. Calceto-Garavito, Arnulfo Eduardo Forero-Aldana, R. A. González-Montealegre, Yeing Alexandra Cardona Cumaco, Luz Ángela Rojas-Bernal, Mario Alberto Zabaleta-Orozco, Mario A. Parra
Background: Recent reports suggest that by 2050 there will be an increase of around 310% of cases affected by dementia in Latin American countries. A previous study in a Southern region reported one of the highest prevalences of dementia in Latin America. Objective: To investigate the prevalence of mild cognitive impairment associated with low education, rurality, and demographic characteristics. Methods: A cross-sectional study recruited a community-dwelling sample of 823 adults from rural and urban areas of two Southern provinces of Colombia from 2020–2022. Participants were assessed with a neuropsychological protocol validated in Colombia. To obtain general and region-specific prevalence rates, age, sex, schooling, and socioeconomic level were considered and controlled for. Results: Most of the participants reported low education and socioeconomic level, the participation of women was higher. It was determined that the prevalence of mild cognitive impairment (MCI) was 53.6%, with 56.6% in the province of Caquetá followed by 51.9% in the province of Huila. The amnestic MCI represented 42.6%, the amnestic multi-domain was 39%, the non-amnestic 16.55%, and the non-amnestic multi-domain 1.81%. Our participants reported comorbidities such as diabetes and hypertension. We also observed a relationship between exposure to pesticides and MCI. Conclusions: We observed one of the highest prevalences of MCI in Latin America reported to date. Variables such as age, gender, and education proved risk factors for MCI in the explored regions. Our findings are very much in line with recent studies that highlight the influence of non-canonical risk factors of dementia in underrepresented countries from Latin America.
{"title":"Prevalence of Mild Cognitive Impairment in Southern Regions of Colombia","authors":"Jasmín Bonilla-Santos, A. González-Hernández, D. Cala-Martínez, Duván Fernando Gómez-Morales, L. N. Calceto-Garavito, Arnulfo Eduardo Forero-Aldana, R. A. González-Montealegre, Yeing Alexandra Cardona Cumaco, Luz Ángela Rojas-Bernal, Mario Alberto Zabaleta-Orozco, Mario A. Parra","doi":"10.3233/adr-230041","DOIUrl":"https://doi.org/10.3233/adr-230041","url":null,"abstract":"Background: Recent reports suggest that by 2050 there will be an increase of around 310% of cases affected by dementia in Latin American countries. A previous study in a Southern region reported one of the highest prevalences of dementia in Latin America. Objective: To investigate the prevalence of mild cognitive impairment associated with low education, rurality, and demographic characteristics. Methods: A cross-sectional study recruited a community-dwelling sample of 823 adults from rural and urban areas of two Southern provinces of Colombia from 2020–2022. Participants were assessed with a neuropsychological protocol validated in Colombia. To obtain general and region-specific prevalence rates, age, sex, schooling, and socioeconomic level were considered and controlled for. Results: Most of the participants reported low education and socioeconomic level, the participation of women was higher. It was determined that the prevalence of mild cognitive impairment (MCI) was 53.6%, with 56.6% in the province of Caquetá followed by 51.9% in the province of Huila. The amnestic MCI represented 42.6%, the amnestic multi-domain was 39%, the non-amnestic 16.55%, and the non-amnestic multi-domain 1.81%. Our participants reported comorbidities such as diabetes and hypertension. We also observed a relationship between exposure to pesticides and MCI. Conclusions: We observed one of the highest prevalences of MCI in Latin America reported to date. Variables such as age, gender, and education proved risk factors for MCI in the explored regions. Our findings are very much in line with recent studies that highlight the influence of non-canonical risk factors of dementia in underrepresented countries from Latin America.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":" 110","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139144947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sang-Won Han, Sang-Hwa Lee, Jong Ho Kim, Jae-Jun Lee, Young Ho Park, SangYun Kim, K. Nho, Jong-Hee Sohn
Background: Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and periphery, particularly the liver, in regulating Aβ homeostasis. Objective: This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance in patients with complaints of cognitive decline. Methods: A total of 1,036 patients (mean age 74 years, 66.2% female) with subjective cognitive decline, mild cognitive impairment, AD dementia, and other neurodegenerative diseases were included using the Smart Clinical Data Warehouse. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, and albumin, were assessed. After propensity score matching, logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid PET positivity. Results: Lower ALT levels and higher AST-to-ALT ratios were significantly associated with amyloid PET positivity and AD diagnosis. The AST-to-ALT ratio was also significantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (AUC = 0.642) for age, sex, and apolipoprotein E ɛ4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio. Conclusions: These findings highlight the potential association of liver function on AD and its potential as a diagnostic and therapeutic implications.
背景：阿尔茨海默病（AD）的特征是大脑中淀粉样蛋白-β（Aβ）斑块堆积和神经纤维缠结。新的证据表明，大脑和外周（尤其是肝脏）在调节 Aβ 平衡方面存在潜在的相互作用。研究目的本研究旨在调查血清肝酶与脑淀粉样变性和认知能力下降患者认知能力的关系。研究方法利用智能临床数据仓库纳入了1036名主观认知能力下降、轻度认知障碍、AD痴呆和其他神经退行性疾病患者（平均年龄74岁，66.2%为女性）。对淀粉样蛋白正电子发射断层扫描（PET）成像、综合神经心理学评估以及肝酶（包括天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶、总胆红素和白蛋白）的测量进行了评估。经过倾向得分匹配后，采用逻辑和线性回归分析来研究肝酶、淀粉样蛋白状态和认知能力之间的关联。此外，还使用机器学习方法评估了肝酶在预测淀粉样蛋白 PET 阳性方面的分类性能。结果显示较低的ALT水平和较高的AST-ALT比值与淀粉样蛋白PET阳性和AD诊断显著相关。谷草转氨酶与谷丙转氨酶的比值也与记忆功能差明显相关。机器学习分析显示，通过整合谷草转氨酶与谷丙转氨酶的比值，淀粉样蛋白状态（AUC = 0.642）对年龄、性别和载脂蛋白Eɛ4携带者状态的分类性能明显提高了6.2%。结论这些研究结果突显了肝功能与注意力缺失症的潜在联系及其作为诊断和治疗手段的潜力。
{"title":"Association of Serum Liver Enzymes with Brain Amyloidopathy and Cognitive Performance","authors":"Sang-Won Han, Sang-Hwa Lee, Jong Ho Kim, Jae-Jun Lee, Young Ho Park, SangYun Kim, K. Nho, Jong-Hee Sohn","doi":"10.3233/adr-230148","DOIUrl":"https://doi.org/10.3233/adr-230148","url":null,"abstract":"Background: Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and periphery, particularly the liver, in regulating Aβ homeostasis. Objective: This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance in patients with complaints of cognitive decline. Methods: A total of 1,036 patients (mean age 74 years, 66.2% female) with subjective cognitive decline, mild cognitive impairment, AD dementia, and other neurodegenerative diseases were included using the Smart Clinical Data Warehouse. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, and albumin, were assessed. After propensity score matching, logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid PET positivity. Results: Lower ALT levels and higher AST-to-ALT ratios were significantly associated with amyloid PET positivity and AD diagnosis. The AST-to-ALT ratio was also significantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (AUC = 0.642) for age, sex, and apolipoprotein E ɛ4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio. Conclusions: These findings highlight the potential association of liver function on AD and its potential as a diagnostic and therapeutic implications.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139147366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Max J. Goodman, Xin Ran Li, Jennifer Livschitz, Chiang-Ching Huang, B.B. Bendlin, Elias D. Granadillo
Background: Physicians may soon be able to diagnose Alzheimer’s disease (AD) in its early stages using fluid biomarkers like amyloid. However, it is acknowledged that additional biomarkers need to be characterized which would facilitate earlier monitoring of AD pathogenesis. Objective: To determine if a potential novel inflammation biomarker for AD, symmetric dimethylarginine, has utility as a baseline serum biomarker for discriminating prodromal AD from cognitively unimpaired controls in comparison to cerebrospinal fluid amyloid-β42 (Aβ42). Methods: Data including demographics, magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography scans, Mini-Mental State Examination and Functional Activities Questionnaire scores, and biomarker concentrations were obtained from the Alzheimer’s Disease Neuroimaging Initiative for a total of 146 prodromal AD participants and 108 cognitively unimpaired controls. Results: Aβ42 (p = 0.65) and symmetric dimethylarginine (p = 0.45) were unable to predict age-matched cognitively unimpaired controls and prodromal AD participants. Aβ42 was negatively associated with regional brain atrophy and hypometabolism as well as cognitive and functional decline in cognitively unimpaired control participants (p < 0.05) that generally decreased in time. There were no significant associations between Aβ42 and symmetric dimethylarginine with imaging or neurocognitive biomarkers in prodromal AD patients. Conclusions: Correlations were smaller between Aβ42 and neuropathological biomarkers over time and were absent in prodromal AD participants, suggesting a plateau effect dependent on age and disease stage. Evidence supporting symmetric dimethylarginine as a novel biomarker for AD as a single measurement was not found.
背景：医生可能很快就能利用淀粉样蛋白等体液生物标志物诊断阿尔茨海默病（AD）的早期阶段。然而，人们认识到还需要确定更多生物标志物的特征，以便更早地监测阿尔茨海默病的发病机制。研究目的与脑脊液中的淀粉样蛋白-β42（Aβ42）相比，确定一种潜在的新型 AD 炎症生物标记物--对称二甲基精氨酸--是否可作为基线血清生物标记物，用于区分前驱 AD 和认知功能未受损的对照组。研究方法从 "阿尔茨海默病神经影像学倡议"（Alzheimer's Disease Neuroimaging Initiative）中获得数据，包括人口统计学、磁共振成像和氟脱氧葡萄糖正电子发射断层扫描、迷你精神状态检查和功能活动问卷评分，以及生物标记物浓度，共收集了146名AD前驱期患者和108名认知功能未受损的对照组患者的数据。研究结果Aβ42（p = 0.65）和对称二甲基精氨酸（p = 0.45）无法预测年龄匹配的认知功能未受损的对照组和AD前驱期参与者。在认知功能未受损的对照组参与者中，Aβ42与区域性脑萎缩和低代谢以及认知和功能衰退呈负相关（p < 0.05），且随着时间的推移普遍下降。在AD前驱期患者中，Aβ42和对称二甲基精氨酸与影像学或神经认知生物标志物之间没有明显的关联。结论随着时间的推移，Aβ42与神经病理学生物标志物之间的相关性越来越小，而在前驱期AD患者中则没有相关性，这表明高原效应取决于年龄和疾病阶段。没有发现支持对称二甲基精氨酸作为AD新型生物标志物的证据。
{"title":"Comparing Symmetric Dimethylarginine and Amyloid-β42 as Predictors of Alzheimer’s Disease Development","authors":"Max J. Goodman, Xin Ran Li, Jennifer Livschitz, Chiang-Ching Huang, B.B. Bendlin, Elias D. Granadillo","doi":"10.3233/adr-230054","DOIUrl":"https://doi.org/10.3233/adr-230054","url":null,"abstract":"Background: Physicians may soon be able to diagnose Alzheimer’s disease (AD) in its early stages using fluid biomarkers like amyloid. However, it is acknowledged that additional biomarkers need to be characterized which would facilitate earlier monitoring of AD pathogenesis. Objective: To determine if a potential novel inflammation biomarker for AD, symmetric dimethylarginine, has utility as a baseline serum biomarker for discriminating prodromal AD from cognitively unimpaired controls in comparison to cerebrospinal fluid amyloid-β42 (Aβ42). Methods: Data including demographics, magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography scans, Mini-Mental State Examination and Functional Activities Questionnaire scores, and biomarker concentrations were obtained from the Alzheimer’s Disease Neuroimaging Initiative for a total of 146 prodromal AD participants and 108 cognitively unimpaired controls. Results: Aβ42 (p = 0.65) and symmetric dimethylarginine (p = 0.45) were unable to predict age-matched cognitively unimpaired controls and prodromal AD participants. Aβ42 was negatively associated with regional brain atrophy and hypometabolism as well as cognitive and functional decline in cognitively unimpaired control participants (p < 0.05) that generally decreased in time. There were no significant associations between Aβ42 and symmetric dimethylarginine with imaging or neurocognitive biomarkers in prodromal AD patients. Conclusions: Correlations were smaller between Aβ42 and neuropathological biomarkers over time and were absent in prodromal AD participants, suggesting a plateau effect dependent on age and disease stage. Evidence supporting symmetric dimethylarginine as a novel biomarker for AD as a single measurement was not found.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":" 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139143729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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