{"title":"Erratum to: Self-Reported Late-Life Hypertension Is Associated with a Healthy Cognitive Status and Reduced Alzheimer’s Disease Pathology Burden","authors":"","doi":"10.3233/jad-249010","DOIUrl":"https://doi.org/10.3233/jad-249010","url":null,"abstract":"","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141270908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benjam Kemiläinen, Sonja Tiainen, T. Rauramaa, A. Luikku, S. Herukka, A. Koivisto, Mikko Hiltunen, Steven Verdooner, Ken Johnson, Mieko Chambers, Kai Kaarniranta, V. Leinonen
Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis. Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function. Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were divided into two groups: unreliable (n = 19) and reliable (n = 43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables. Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-β (Aβ) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aβ42 and age between the groups. Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment?
{"title":"Exploring the Association Between Visual Field Testing and CERAD Neuropsychological Battery in Idiopathic Normal Pressure Hydrocephalus Patients","authors":"Benjam Kemiläinen, Sonja Tiainen, T. Rauramaa, A. Luikku, S. Herukka, A. Koivisto, Mikko Hiltunen, Steven Verdooner, Ken Johnson, Mieko Chambers, Kai Kaarniranta, V. Leinonen","doi":"10.3233/jad-231414","DOIUrl":"https://doi.org/10.3233/jad-231414","url":null,"abstract":"Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis. Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function. Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were divided into two groups: unreliable (n = 19) and reliable (n = 43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables. Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-β (Aβ) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aβ42 and age between the groups. Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment?","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141279324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Fukui, Koh Tadokoro, Minaki Hamada, Kyoichi Asada, Lyang-Ja Lee, Hidehisa Tachiki, R. Morihara, Koji Abe, Toru Yamashita
Background: With the aging of populations worldwide, Alzheimer’s disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease’s progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates. Objective: The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. Methods: We enrolled 195 subjects with normal cognitive function (NC; n = 70), MCI (n = 55), and AD (n = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen α chain (FAC), Fibrinogen β chain (FBC), Plasma protease C1 inhibitor (PPC1I), α2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. Results: The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. Conclusions: In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes.
背景：随着全球人口老龄化的加剧，阿尔茨海默病（AD）因其高发病率和持续缺乏成熟的治疗方法而备受关注。作为一种预防性干预措施，需要早期诊断以改变疾病的进展。在之前的研究中，我们利用 BLOTCHIP-MS 分析方法对 AD 患者和年龄匹配的健康受试者的血清样本进行了肽组学分析，以寻找 AD 的候选肽生物标记物，并确定了四种肽作为 AD 候选生物标记物。研究目的目的：利用一种新的肽组技术--痴呆风险测试（Dementia Risk Test），验证血清生物标志物肽与认知健康对照组相比，能区分轻度认知障碍（MCI）和AD。研究方法采用基于液相色谱-质谱联用技术的选择反应监测测定法，定量检测认知障碍标志肽（纤维蛋白原α链（FAC）、纤维蛋白原β链（FBC）、血浆蛋白酶C1抑制剂（PPC1I）、α2-HS-糖蛋白（AHSG））的浓度。结果本研究证实，FAC、FBC 和 PPC1I 这三种肽在 AD 发病期间显著上调。这三组肽在确定 AD 方面具有高度灵敏性（灵敏度：85.7%，特异性：95.7%，AUC：0.900），在区分 MCI（灵敏度：61.8%，特异性：98.6%，AUC：0.824）和 NC 方面也很有用。结论在这项验证研究中，我们证实了之前研究中发现的三种肽具有很高的诊断潜力，可作为 AD 的候选血清生物标记物。痴呆风险测试可能是检测痴呆症相关病理变化的有力工具。
{"title":"A Novel Peptidome Technology for the Diagnosis of Mild Cognitive Impairment and Alzheimer’s Disease by Selected Reaction Monitoring","authors":"Y. Fukui, Koh Tadokoro, Minaki Hamada, Kyoichi Asada, Lyang-Ja Lee, Hidehisa Tachiki, R. Morihara, Koji Abe, Toru Yamashita","doi":"10.3233/jad-230915","DOIUrl":"https://doi.org/10.3233/jad-230915","url":null,"abstract":"Background: With the aging of populations worldwide, Alzheimer’s disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease’s progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates. Objective: The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. Methods: We enrolled 195 subjects with normal cognitive function (NC; n = 70), MCI (n = 55), and AD (n = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen α chain (FAC), Fibrinogen β chain (FBC), Plasma protease C1 inhibitor (PPC1I), α2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. Results: The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. Conclusions: In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cheng-Kun Sun, Fan Guo, Ya‐nan Ou, Ming-Zhan Zhang, Lan Tan, Meng-Shan Tan
Background: The association between carotid plaque and cognitive decline has recently been reported. However, the current research evidence is insufficient, and the possible causes of cognitive changes are unknown. Objective: This study aims to explore the relationships between carotid plaque and cognition functions, cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers in cognitively intact adults, and try to study the underlying mechanisms. Methods: We enrolled 165 cognitively normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study, who had CSF AD biomarker measurements and carotid ultrasound. Linear modeling was used to assess the association of carotid plaque with CSF biomarkers and cognition. Additionally, mediation analysis was conducted through 10,000 bootstrapped iterations to explore potential links between carotid plaque, AD pathology, and cognition. Results: We found that carotid plaque exhibited significant correlations with Aβ42 (β = –1.173, p = 0.022), Aβ42/Aβ40 (β = –0.092, p < 0.001), P-tau/Aβ42 (β = 0.110, p = 0.045), and T-tau/Aβ42 (β = 0.451, p = 0.010). A significant correlation between carotid plaque and cognition decline was also found in men (β = –0.129, p = 0.021), and mediation analyses revealed that the effect of carotid plaque on cognitive function could be mediated by Aβ42/Aβ40 (proportion of mediation = 55.8%), P-tau/Aβ42 (proportion of mediation = 51.6%, p = 0.015) and T-tau/Aβ42 (proportion of mediation = 43.8%, p = 0.015) mediated. Conclusions: This study demonstrated the link between carotid plaque and CSF AD biomarkers in cognitively intact adults, and the important role that AD pathology may play in the correlation between carotid plaque and cognitive changes.
背景：最近有报道称，颈动脉斑块与认知能力下降之间存在关联。然而，目前的研究证据不足，认知能力变化的可能原因尚不清楚。研究目的本研究旨在探讨认知功能正常的成年人颈动脉斑块与认知功能、脑脊液（CSF）阿尔茨海默病（AD）生物标志物之间的关系，并尝试研究其潜在机制。研究方法我们从中国阿尔茨海默病生物标志物与生活（CABLE）研究中招募了165名认知正常的参与者，对他们进行了脑脊液AD生物标志物测量和颈动脉超声检查。研究采用线性模型评估颈动脉斑块与脑脊液生物标志物和认知能力之间的关系。此外，还通过10,000次引导迭代进行了中介分析，以探索颈动脉斑块、AD病理和认知之间的潜在联系。结果：我们发现颈动脉斑块与 Aβ42 (β = -1.173, p = 0.022)、Aβ42/Aβ40 (β = -0.092, p < 0.001)、P-tau/Aβ42 (β = 0.110, p = 0.045)和 T-tau/Aβ42 (β = 0.451, p = 0.010)呈显著相关。通过中介分析发现，颈动脉斑块对认知功能的影响可由Aβ42/Aβ40（中介比例=55.8%）、P-tau/Aβ42（中介比例=51.6%，p=0.015）和T-tau/Aβ42（中介比例=43.8%，p=0.015）中介。结论这项研究表明，在认知功能完好的成年人中，颈动脉斑块与脑脊液中的注意力缺失症生物标志物之间存在联系，而且注意力缺失症病理学可能在颈动脉斑块与认知变化之间的相关性中扮演重要角色。
{"title":"Association Between Carotid Plaque and Alzheimer’s Disease Cerebrospinal Fluid Biomarkers and Cognitive Function in Cognitively Intact Adults: The CABLE Study","authors":"Cheng-Kun Sun, Fan Guo, Ya‐nan Ou, Ming-Zhan Zhang, Lan Tan, Meng-Shan Tan","doi":"10.3233/jad-240131","DOIUrl":"https://doi.org/10.3233/jad-240131","url":null,"abstract":"Background: The association between carotid plaque and cognitive decline has recently been reported. However, the current research evidence is insufficient, and the possible causes of cognitive changes are unknown. Objective: This study aims to explore the relationships between carotid plaque and cognition functions, cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers in cognitively intact adults, and try to study the underlying mechanisms. Methods: We enrolled 165 cognitively normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study, who had CSF AD biomarker measurements and carotid ultrasound. Linear modeling was used to assess the association of carotid plaque with CSF biomarkers and cognition. Additionally, mediation analysis was conducted through 10,000 bootstrapped iterations to explore potential links between carotid plaque, AD pathology, and cognition. Results: We found that carotid plaque exhibited significant correlations with Aβ42 (β = –1.173, p = 0.022), Aβ42/Aβ40 (β = –0.092, p < 0.001), P-tau/Aβ42 (β = 0.110, p = 0.045), and T-tau/Aβ42 (β = 0.451, p = 0.010). A significant correlation between carotid plaque and cognition decline was also found in men (β = –0.129, p = 0.021), and mediation analyses revealed that the effect of carotid plaque on cognitive function could be mediated by Aβ42/Aβ40 (proportion of mediation = 55.8%), P-tau/Aβ42 (proportion of mediation = 51.6%, p = 0.015) and T-tau/Aβ42 (proportion of mediation = 43.8%, p = 0.015) mediated. Conclusions: This study demonstrated the link between carotid plaque and CSF AD biomarkers in cognitively intact adults, and the important role that AD pathology may play in the correlation between carotid plaque and cognitive changes.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141281058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Huang, Jingxuan Ma, Fugui Jiang, Shushan Zhang, Y. Lan, Yang Zhang
Background: Noise exposure and the risk of cognitive impairment are currently major public health issues. Objective: This study aimed to analyze the relationship between noise exposure and early impairment of cognitive function from the perspective of occupational epidemiology and to provide evidence for the long-term prevention and treatment of dementia in the context of aging. Methods: This study was conducted in China between May and August 2021. The independent variables were the type of hazardous factors, duration of noise exposure, perceived noise intensity, and cumulative noise exposure (CNE). The dependent variable was cognitive function, which was measured using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Multiple linear and logistic regression were used to analyze the relationship between noise exposure and cognitive function and to establish an effect curve. Results: The detection rates of cognitive dysfunction using the MMSE and MoCA were 1.1% and 36.2%, respectively. The predicted MMSE and MoCA scores showed a downward trend within the CNE value ranging from 90–140 dB.time. Each unit increase in CNE decreased cognitive function scores by 0.025 (0.037, 0.013) and 0.020 (0.037, 0.003) points,respectively. Conclusions: From the perspective of occupational epidemiology, these findings reveal a potential link between long-term noise exposure and early cognitive impairment.
{"title":"Relationship Between Work-Related Noise Exposure and Cognitive Impairment: A Cross-Sectional Study in China","authors":"Lei Huang, Jingxuan Ma, Fugui Jiang, Shushan Zhang, Y. Lan, Yang Zhang","doi":"10.3233/jad-240061","DOIUrl":"https://doi.org/10.3233/jad-240061","url":null,"abstract":"Background: Noise exposure and the risk of cognitive impairment are currently major public health issues. Objective: This study aimed to analyze the relationship between noise exposure and early impairment of cognitive function from the perspective of occupational epidemiology and to provide evidence for the long-term prevention and treatment of dementia in the context of aging. Methods: This study was conducted in China between May and August 2021. The independent variables were the type of hazardous factors, duration of noise exposure, perceived noise intensity, and cumulative noise exposure (CNE). The dependent variable was cognitive function, which was measured using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Multiple linear and logistic regression were used to analyze the relationship between noise exposure and cognitive function and to establish an effect curve. Results: The detection rates of cognitive dysfunction using the MMSE and MoCA were 1.1% and 36.2%, respectively. The predicted MMSE and MoCA scores showed a downward trend within the CNE value ranging from 90–140 dB.time. Each unit increase in CNE decreased cognitive function scores by 0.025 (0.037, 0.013) and 0.020 (0.037, 0.003) points,respectively. Conclusions: From the perspective of occupational epidemiology, these findings reveal a potential link between long-term noise exposure and early cognitive impairment.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141277251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Mitochondrial dysfunction exists in Alzheimer’s disease (AD) brain, and damaged mitochondria need to be removed by mitophagy. Small GTPase Rab7 regulates the fusion of mitochondria and lysosome, while TBC1D5 inhibits Rab7 activation. However, it is not clear whether the regulation of Rab7 activity by TBC1D5 can improve mitophagy and inhibit AD progression. Objective: To investigate the role of TBC1D5 in mitophagy and its regulatory mechanism for Rab7, and whether activation of mitophagy can inhibit the progression of AD. Methods: Mitophagy was determined by western blot and immunofluorescence. The morphology and quantity of mitochondria were tracked by TEM. pCMV-Mito-AT1.03 was employed to detect the cellular ATP. Amyloid-β secreted by AD cells was detected by ELISA. Co-immunoprecipitation was used to investigate the binding partner of the target protein. Golgi-cox staining was applied to observe neuronal morphology of mice. The Morris water maze test and Y-maze were performed to assess spatial learning and memory, and the open field test was measured to evaluate motor function and anxiety-like phenotype of experimental animals. Results: Mitochondrial morphology was impaired in AD models, and TBC1D5 was highly expressed. Knocking down TBC1D5 increased the expression of active Rab7, promoted the fusion of lysosome and autophagosome, thus improving mitophagy, and improved the morphology of hippocampal neurons and the impaired behavior in AD mice. Conclusions: Knocking down TBC1D5 increased Rab7 activity and promoted the fusion of autophagosome and lysosome. Our study provided insights into the mechanisms that bring new possibilities for AD therapy targeting mitophagy.
{"title":"Enhancing Rab7 Activity by Inhibiting TBC1D5 Expression Improves Mitophagy in Alzheimer’s Disease Models","authors":"Xiao Liang, Yangyang Wang, Siyu Li, Jianing Fan, Fanlin Zhou, Xiaoju Li, Shijie Li, Yu Li","doi":"10.3233/jad-231300","DOIUrl":"https://doi.org/10.3233/jad-231300","url":null,"abstract":"Background: Mitochondrial dysfunction exists in Alzheimer’s disease (AD) brain, and damaged mitochondria need to be removed by mitophagy. Small GTPase Rab7 regulates the fusion of mitochondria and lysosome, while TBC1D5 inhibits Rab7 activation. However, it is not clear whether the regulation of Rab7 activity by TBC1D5 can improve mitophagy and inhibit AD progression. Objective: To investigate the role of TBC1D5 in mitophagy and its regulatory mechanism for Rab7, and whether activation of mitophagy can inhibit the progression of AD. Methods: Mitophagy was determined by western blot and immunofluorescence. The morphology and quantity of mitochondria were tracked by TEM. pCMV-Mito-AT1.03 was employed to detect the cellular ATP. Amyloid-β secreted by AD cells was detected by ELISA. Co-immunoprecipitation was used to investigate the binding partner of the target protein. Golgi-cox staining was applied to observe neuronal morphology of mice. The Morris water maze test and Y-maze were performed to assess spatial learning and memory, and the open field test was measured to evaluate motor function and anxiety-like phenotype of experimental animals. Results: Mitochondrial morphology was impaired in AD models, and TBC1D5 was highly expressed. Knocking down TBC1D5 increased the expression of active Rab7, promoted the fusion of lysosome and autophagosome, thus improving mitophagy, and improved the morphology of hippocampal neurons and the impaired behavior in AD mice. Conclusions: Knocking down TBC1D5 increased Rab7 activity and promoted the fusion of autophagosome and lysosome. Our study provided insights into the mechanisms that bring new possibilities for AD therapy targeting mitophagy.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141276020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0–37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition.
卒中后认知障碍和痴呆（PSCID）是影响卒中后长期功能预后的一种并发症。有关脑卒中长期随访后痴呆的研究主要集中在缺血性脑卒中，这可能与自发性脑内出血（ICH）后痴呆的发生有所不同。在本综述中，我们总结了有关自发性 ICH 后痴呆发展的现有数据和假设，回顾了 ICH 后痴呆的处理方法，并提出了未来的研究领域。自发性 ICH 后痴呆症在 ICH 后 5 年的累积发病率高达 32.0-37.4%。虽然 ICH 后痴呆症的病理生理学尚未完全清楚，但有两个主要的理论框架可供选择：1）ICH（原发性和继发性脑损伤）在诱发认知功能下降和痴呆症方面的触发作用；2）先前存在的脑部病变（包括小血管疾病和神经退行性病变）、认知储备减少以及易导致认知功能障碍的遗传因素的促成作用。这些病理生理途径可能会产生协同效应，导致神经血管单元功能障碍和功能连接中断，从而导致重度脑缺血后痴呆症。ICH 后痴呆症的治疗可包括筛查和监测、认知疗法和药物疗法。非侵入性脑刺激是一种新兴的治疗方式，其安全性和有效性正在研究之中。我们的综述强调，关于自发性 ICH 后发生痴呆的数据和标准化报告仍然很少。进一步的研究对于确定 ICH 后痴呆症的发病率、风险因素和病理生理学至关重要，以便确定治疗这种衰弱病症的新疗法。
{"title":"Incident Dementia After Spontaneous Intracerebral Hemorrhage","authors":"Zheting Zhang, Mervyn Jun Rui Lim","doi":"10.3233/jad-240111","DOIUrl":"https://doi.org/10.3233/jad-240111","url":null,"abstract":"Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0–37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background:Psychosis, characterized by delusions and/or hallucinations, is frequently observed during the progression of Alzheimer’s disease (AD) and other neurodegenerative dementias (ND) (i.e., dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)) and cause diagnostic and managementdifficulties. Objective:This review aims at presenting a concise and up-to-date overview of psychotic symptoms that occur in patients with ND with a comparative approach. Methods:A systematic review was conducted following the PRISMA guidelines. 98 original studies investigating psychosis phenotypes in neurodegenerative dementias were identified (40 cohort studies, 57 case reports). Results:Psychosis is a frequently observed phenomenon during the course of ND, with reported prevalence ranging from 22.5% to 54.1% in AD, 55.9% to 73.9% in DLB, and 18% to 42% in FTD. Throughout all stages of these diseases, noticeable patterns emerge depending on their underlying causes. Misidentification delusions (16.6–78.3%) and visual hallucinations (50–69.6%) are frequently observed in DLB, while paranoid ideas and somatic preoccupations seem to be particularly common in AD and FTD, (respectively 9.1–60.3% and 3.10–41.5%). Limited data were found regarding psychosis in the early stages of these disorders. Conclusions:Literature data suggest that different ND are associated with noticeable variations in psychotic phenotypes, reflecting disease-specific tendencies. Further studies focusing on the early stages of these disorders are necessary to enhance our understanding of early psychotic manifestations associated with ND and help in differential diagnosis issues.
{"title":"Psychosis in Neurodegenerative Dementias: A Systematic Comparative Review","authors":"Coralie Cressot, Agathe Vrillon, Matthieu Lilamand, Hélène Francisque, Aurélie Méauzoone, Claire Hourregue, Julien Dumurgier, Emeline Marlinge, Claire Paquet, Emmanuel Cognat","doi":"10.3233/jad-231363","DOIUrl":"https://doi.org/10.3233/jad-231363","url":null,"abstract":"Background:Psychosis, characterized by delusions and/or hallucinations, is frequently observed during the progression of Alzheimer’s disease (AD) and other neurodegenerative dementias (ND) (i.e., dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)) and cause diagnostic and managementdifficulties. Objective:This review aims at presenting a concise and up-to-date overview of psychotic symptoms that occur in patients with ND with a comparative approach. Methods:A systematic review was conducted following the PRISMA guidelines. 98 original studies investigating psychosis phenotypes in neurodegenerative dementias were identified (40 cohort studies, 57 case reports). Results:Psychosis is a frequently observed phenomenon during the course of ND, with reported prevalence ranging from 22.5% to 54.1% in AD, 55.9% to 73.9% in DLB, and 18% to 42% in FTD. Throughout all stages of these diseases, noticeable patterns emerge depending on their underlying causes. Misidentification delusions (16.6–78.3%) and visual hallucinations (50–69.6%) are frequently observed in DLB, while paranoid ideas and somatic preoccupations seem to be particularly common in AD and FTD, (respectively 9.1–60.3% and 3.10–41.5%). Limited data were found regarding psychosis in the early stages of these disorders. Conclusions:Literature data suggest that different ND are associated with noticeable variations in psychotic phenotypes, reflecting disease-specific tendencies. Further studies focusing on the early stages of these disorders are necessary to enhance our understanding of early psychotic manifestations associated with ND and help in differential diagnosis issues.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kevin Duff, D. Hammers, Vincent Koppelmans, J. King, John M. Hoffman
Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.
背景：实践对轻度认知障碍（MCI）和阿尔茨海默病（AD）认知测试的影响仍未得到充分研究，尤其是这些影响与阿尔茨海默病生物标志物的比较。研究目的目前的研究旨在为这一不断增长的文献添砖加瓦。研究方法认知功能完好的老年人（68 人）、有记忆障碍的 MCI 患者（52 人）和轻度 AD 患者（45 人）分别在基线时和一周后完成了一系列简短的认知测试，他们还完成了基线淀粉样蛋白 PET 扫描、基线核磁共振成像和基线抽血以获得 APOE ɛ4 状态。结果显示与其他两组相比，完整参与者的基线认知分数和练习效果在整体综合测量中明显更高。在综合指标上，MCI 患者的基线得分和练习效果明显高于 AD 患者。在淀粉样蛋白沉积方面，完整参与者的示踪剂摄取量明显较少，而MCI和AD参与者的示踪剂摄取量相当。在海马总体积方面，所有三个组别都在预期方向上存在显著差异（完好> MCI > AD）。至于 APOE ɛ4，完好者的ɛ4拷贝数明显少于 MCI 和 AD。基线认知评分的效应大小与实践效应相当，在 9 项比较中，有 7 项的效应大小明显大于生物标志物的效应大小。结论基线认知评分和短期练习效果似乎是晚年认知障碍的敏感标志物，因为它们比常见的注意力缺失症生物标志物更能区分组别。看来有必要进一步开发基线认知和短期实践效应，将其作为临床诊断、预后指示和丰富临床试验的工具。
{"title":"Short-Term Practice Effects on Cognitive Tests Across the Late Life Cognitive Spectrum and How They Compare to Biomarkers of Alzheimer’s Disease","authors":"Kevin Duff, D. Hammers, Vincent Koppelmans, J. King, John M. Hoffman","doi":"10.3233/jad-231392","DOIUrl":"https://doi.org/10.3233/jad-231392","url":null,"abstract":"Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mounting evidence indicates that a physiological function of amyloid-β (Aβ) is to mediate neural activity-dependent homeostatic and competitive synaptic plasticity in the brain. I have previously summarized the lines of evidence supporting this hypothesis and highlighted the similarities between Aβ and anti-microbial peptides in mediating cell/synapse competition. In cell competition, anti-microbial peptides deploy a multitude of mechanisms to ensure both self-protection and competitor elimination. Here I review recent studies showing that similar mechanisms are at play in Aβ-mediated synapse competition and perturbations in these mechanisms underpin Alzheimer’s disease (AD). Specifically, I discuss evidence that Aβ and ApoE, two crucial players in AD, co-operate in the regulation of synapse competition. Glial ApoE promotes self-protection by increasing the production of trophic monomeric Aβ and inhibiting its assembly into toxic oligomers. Conversely, Aβ oligomers, once assembled, promote the elimination of competitor synapses via direct toxic activity and amplification of “eat-me” signals promoting the elimination of weak synapses. I further summarize evidence that neuronal ApoE may be part of a gene regulatory network that normally promotes competitive plasticity, explaining the selective vulnerability of ApoE expressing neurons in AD brains. Lastly, I discuss evidence that sleep may be key to Aβ-orchestrated plasticity, in which sleep is not only induced by Aβ but is also required for Aβ-mediated plasticity, underlining the link between sleep and AD. Together, these results strongly argue that AD is a disease of competitive synaptic plasticity gone awry, a novel perspective that may promote AD research.
{"title":"Evidence that Alzheimer’s Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry","authors":"Zhen Huang","doi":"10.3233/jad-240042","DOIUrl":"https://doi.org/10.3233/jad-240042","url":null,"abstract":" Mounting evidence indicates that a physiological function of amyloid-β (Aβ) is to mediate neural activity-dependent homeostatic and competitive synaptic plasticity in the brain. I have previously summarized the lines of evidence supporting this hypothesis and highlighted the similarities between Aβ and anti-microbial peptides in mediating cell/synapse competition. In cell competition, anti-microbial peptides deploy a multitude of mechanisms to ensure both self-protection and competitor elimination. Here I review recent studies showing that similar mechanisms are at play in Aβ-mediated synapse competition and perturbations in these mechanisms underpin Alzheimer’s disease (AD). Specifically, I discuss evidence that Aβ and ApoE, two crucial players in AD, co-operate in the regulation of synapse competition. Glial ApoE promotes self-protection by increasing the production of trophic monomeric Aβ and inhibiting its assembly into toxic oligomers. Conversely, Aβ oligomers, once assembled, promote the elimination of competitor synapses via direct toxic activity and amplification of “eat-me” signals promoting the elimination of weak synapses. I further summarize evidence that neuronal ApoE may be part of a gene regulatory network that normally promotes competitive plasticity, explaining the selective vulnerability of ApoE expressing neurons in AD brains. Lastly, I discuss evidence that sleep may be key to Aβ-orchestrated plasticity, in which sleep is not only induced by Aβ but is also required for Aβ-mediated plasticity, underlining the link between sleep and AD. Together, these results strongly argue that AD is a disease of competitive synaptic plasticity gone awry, a novel perspective that may promote AD research.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140679446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：