Pub Date : 2022-04-14DOI: 10.2174/1567205019666220414101251
Mustafa Doğan, R. Eröz, M. Tecellioğlu, A. Gezdirici, B. Çevik, I. Baris
BACKGROUND Early-onset Alzheimer's disease (EOAD) is commonly diagnosed with an onset age of earlier than 65 years and accounts for 5-10% of all Alzheimer's disease (AD) cases. To date, although only 10-15% of familial EOAD cases have been explained, the genetic cause of the vast proportion of cases has not been explained. The variant Alzheimer's disease with spastic paraparesis (varAD) is defined as a rare clinical entity characterized by early-onset dementia, spasticity of the lower extremities and gait disturbance. Although the disease was first associated with variants in exon 9 of the PSEN1 gene, it was later shown that variations in other exons were also responsible for the disease. OBJECTIVE The current study aims to raise awareness of varAD which occurs as a rare phenotype due to pathogenic variants in PSEN1. In addition, we aimed to evaluate the spectrum of mutations in varAD patients identified to date. METHODS Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family was done by Sanger sequencing. Also, review of the molecularly confirmed patients with (varAD) from the literature was evaluated. RESULTS We identified a heterozygous splicing variant (c.869-1G>A) in the PSEN1 gene, in a family with two affected individuals who present with varAD. We reported the clinical and genetic findings from the affected individuals. CONCLUSION We present the detailed clinical and genetic profiles of a Turkish patient with diagnosis of varAD together with subjects from the literature. Together, we think that the clinical characteristics and the effect of the (c.869-1G>A) variant will facilitate our understanding of the PSEN1 gene in AD pathogenesis.
{"title":"Clinical and Molecular Findings in a Turkish Family Who Had a (c.879-1G>A) Splicing Variant in PSEN1 Gene with A Rare Condition: The Variant Alzheimer's Disease with Spastic Paraparesis.","authors":"Mustafa Doğan, R. Eröz, M. Tecellioğlu, A. Gezdirici, B. Çevik, I. Baris","doi":"10.2174/1567205019666220414101251","DOIUrl":"https://doi.org/10.2174/1567205019666220414101251","url":null,"abstract":"BACKGROUND\u0000Early-onset Alzheimer's disease (EOAD) is commonly diagnosed with an onset age of earlier than 65 years and accounts for 5-10% of all Alzheimer's disease (AD) cases. To date, although only 10-15% of familial EOAD cases have been explained, the genetic cause of the vast proportion of cases has not been explained. The variant Alzheimer's disease with spastic paraparesis (varAD) is defined as a rare clinical entity characterized by early-onset dementia, spasticity of the lower extremities and gait disturbance. Although the disease was first associated with variants in exon 9 of the PSEN1 gene, it was later shown that variations in other exons were also responsible for the disease.\u0000\u0000\u0000OBJECTIVE\u0000The current study aims to raise awareness of varAD which occurs as a rare phenotype due to pathogenic variants in PSEN1. In addition, we aimed to evaluate the spectrum of mutations in varAD patients identified to date.\u0000\u0000\u0000METHODS\u0000Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family was done by Sanger sequencing. Also, review of the molecularly confirmed patients with (varAD) from the literature was evaluated.\u0000\u0000\u0000RESULTS\u0000We identified a heterozygous splicing variant (c.869-1G>A) in the PSEN1 gene, in a family with two affected individuals who present with varAD. We reported the clinical and genetic findings from the affected individuals.\u0000\u0000\u0000CONCLUSION\u0000We present the detailed clinical and genetic profiles of a Turkish patient with diagnosis of varAD together with subjects from the literature. Together, we think that the clinical characteristics and the effect of the (c.869-1G>A) variant will facilitate our understanding of the PSEN1 gene in AD pathogenesis.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42723886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.2174/1567205019666220413075840
G. Fernández, Ana Paula González, C. Abulafia, L. Fiorentini, Osvaldo Agamennoni, S. Guinjoan
INTRODUCTION Eye movement patterns during reading are well defined and documented. Each eye movement ends up in a fixation point, which allows the brain to process the incoming information and to program the following saccade. In this work, we investigated whether eye movement alterations during a reading task might be already present in middle-aged, cognitively normal offspring of late-onset Alzheimer's disease (O-LOAD). METHODS 18 O-LOAD and 18age-matched healthy individuals with no family history of LOAD participated in the study. Participants were seated in front of a 20-inch LCD monitor and single sentences were presented on it. Eye movements were recorded with an eye tracker, with a sampling rate of 1000 Hz. RESULTS Analysis of eye movements during reading revealed that O-LOAD displayed more fixations, shorter saccades and shorter fixation durations than controls. CONCLUSION The present study shows that O-LOAD evidenced alterations in their eye movements during reading. O-LOAD eye movement behavior could be considered an initial sign of oculomotor impairment. Hence, evaluation of eye movement during reading might provide a useful tool for monitoring well-defined cognitive resources.
{"title":"Oculomotor abnormalities during reading in offspring of late-onset Alzheimer's disease.","authors":"G. Fernández, Ana Paula González, C. Abulafia, L. Fiorentini, Osvaldo Agamennoni, S. Guinjoan","doi":"10.2174/1567205019666220413075840","DOIUrl":"https://doi.org/10.2174/1567205019666220413075840","url":null,"abstract":"INTRODUCTION\u0000Eye movement patterns during reading are well defined and documented. Each eye movement ends up in a fixation point, which allows the brain to process the incoming information and to program the following saccade. In this work, we investigated whether eye movement alterations during a reading task might be already present in middle-aged, cognitively normal offspring of late-onset Alzheimer's disease (O-LOAD).\u0000\u0000\u0000METHODS\u000018 O-LOAD and 18age-matched healthy individuals with no family history of LOAD participated in the study. Participants were seated in front of a 20-inch LCD monitor and single sentences were presented on it. Eye movements were recorded with an eye tracker, with a sampling rate of 1000 Hz.\u0000\u0000\u0000RESULTS\u0000Analysis of eye movements during reading revealed that O-LOAD displayed more fixations, shorter saccades and shorter fixation durations than controls.\u0000\u0000\u0000CONCLUSION\u0000The present study shows that O-LOAD evidenced alterations in their eye movements during reading. O-LOAD eye movement behavior could be considered an initial sign of oculomotor impairment. Hence, evaluation of eye movement during reading might provide a useful tool for monitoring well-defined cognitive resources.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43433937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-04DOI: 10.2174/1567205019666220404104854
Seong-Hi Park, Kuem-Sun Han
BACKGROUND Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are screened to distinguish whether cognitive decline in older adults is attributed to pathological causes rather than normal aging. OBJECTIVE The purpose of this review was to analyze the diagnostic performance of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in screening for MCI and AD. METHODS Electronic searches were performed on MEDLINE, EMBASE, CINAHL, and PsycArticles databases using the following keywords: dementia and ADAS-Cog. The Quality Assessment of Diagnostic Accuracy Studies-2 was used to checked the risk of bias in the diagnostic studies. RESULTS We reviewed 14 studies, including 3,875 patients who met the selection criteria. In 2,624 MCI patients from nine studies, the pooled sensitivity of ADAS-Cog was 0.80 (95% confidence interval [CI], 0.68-0.88), the pooled specificity was 0.84 (95% CI, 0.75-0.90), and the area under the curve of summary receiver-operating characteristic curves (SROC AUC) was 0.89 (SE = 0.03). In 2,517 AD patients from 10 studies, the pooled sensitivity and pooled specificity were 0.91 (95% CI, 0.86-0.95) and 0.93 (95% CI, 0.88-0.95) respectively, and the sROC AUC was 0.97 (SE = 0.01). Although sub-analyzed according to age and years of education, there was no significant difference in the predictive validity of the ADAS-Cog. CONCLUSION The ADAS-Cog has high predictive validity as a screening tool in both MCI and AD, but has better diagnostic performance in patients with AD. When early screening for AD is desired, ADAS-Cog is a first-stage screener that can be initially employed.
{"title":"Is the Alzheimer's Disease Assessment Scale-Cognitive Subscale useful in screening for mild cognitive impairment and Alzheimer's disease? A systematic review.","authors":"Seong-Hi Park, Kuem-Sun Han","doi":"10.2174/1567205019666220404104854","DOIUrl":"https://doi.org/10.2174/1567205019666220404104854","url":null,"abstract":"BACKGROUND\u0000Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are screened to distinguish whether cognitive decline in older adults is attributed to pathological causes rather than normal aging.\u0000\u0000\u0000OBJECTIVE\u0000The purpose of this review was to analyze the diagnostic performance of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in screening for MCI and AD.\u0000\u0000\u0000METHODS\u0000Electronic searches were performed on MEDLINE, EMBASE, CINAHL, and PsycArticles databases using the following keywords: dementia and ADAS-Cog. The Quality Assessment of Diagnostic Accuracy Studies-2 was used to checked the risk of bias in the diagnostic studies.\u0000\u0000\u0000RESULTS\u0000We reviewed 14 studies, including 3,875 patients who met the selection criteria. In 2,624 MCI patients from nine studies, the pooled sensitivity of ADAS-Cog was 0.80 (95% confidence interval [CI], 0.68-0.88), the pooled specificity was 0.84 (95% CI, 0.75-0.90), and the area under the curve of summary receiver-operating characteristic curves (SROC AUC) was 0.89 (SE = 0.03). In 2,517 AD patients from 10 studies, the pooled sensitivity and pooled specificity were 0.91 (95% CI, 0.86-0.95) and 0.93 (95% CI, 0.88-0.95) respectively, and the sROC AUC was 0.97 (SE = 0.01). Although sub-analyzed according to age and years of education, there was no significant difference in the predictive validity of the ADAS-Cog.\u0000\u0000\u0000CONCLUSION\u0000The ADAS-Cog has high predictive validity as a screening tool in both MCI and AD, but has better diagnostic performance in patients with AD. When early screening for AD is desired, ADAS-Cog is a first-stage screener that can be initially employed.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41956630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-30DOI: 10.2174/1567205019666220330144432
S. Lippa, J. Gill, T. Brickell, Vivian A. Guedes, L. French, R. Lange
BACKGROUND Traumatic brain injury (TBI) has been associated with increased likelihood of late-life dementia; however, the mechanisms driving this relationship are elusive. Blood-based biomarkers may provide insight into these mechanisms and serve as useful prognostic indicators of cognitive recovery or decline following a TBI. OBJECTIVE The aim of this study was to examine blood biomarkers within one year of TBI and explore their relationship with cognitive decline. METHODS Service members and veterans (n=224) without injury (n=77), or with history of bodily injury (n=37), uncomplicated mild TBI (n=55), or more severe TBI (n=55), underwent a blood draw and neuropsychological assessment within one year of their injury as part of a case-control study. A subsample (n=87) completed follow-up cognitive assessment. RESULTS In the more severe TBI group, baseline glial fibrillary acidic protein (p=.008) and ubiquitin C-terminal hydrolase-L1 (p=.026) were associated with processing speed at baseline, and baseline ubiquitin C-terminal hydrolase-L1 predicted change in immediate (R2Δ=.244, p=.005) and delayed memory (R2Δ=.390, p=.003) over time. In the mild TBI group, higher baseline tau predicted greater negative change in perceptual reasoning (R2Δ=.188, p=.033) and executive functioning (R2Δ=.298, p=.007); higher baseline neurofilament light predicted greater negative change in perceptual reasoning (R2Δ=.211, p=.012). CONCLUSION Baseline ubiquitin C-terminal hydrolase-L1 strongly predicted memory decline in the more severe TBI group, while tau and neurofilament light strongly predicted decline in the mild TBI group. A panel including these biomarkers could be particularly helpful in identifying those at risk for future cognitive decline following TBI.
{"title":"Blood Biomarkers Predict Future Cognitive Decline after Military-Related Traumatic Brain Injury.","authors":"S. Lippa, J. Gill, T. Brickell, Vivian A. Guedes, L. French, R. Lange","doi":"10.2174/1567205019666220330144432","DOIUrl":"https://doi.org/10.2174/1567205019666220330144432","url":null,"abstract":"BACKGROUND\u0000Traumatic brain injury (TBI) has been associated with increased likelihood of late-life dementia; however, the mechanisms driving this relationship are elusive. Blood-based biomarkers may provide insight into these mechanisms and serve as useful prognostic indicators of cognitive recovery or decline following a TBI.\u0000\u0000\u0000OBJECTIVE\u0000The aim of this study was to examine blood biomarkers within one year of TBI and explore their relationship with cognitive decline.\u0000\u0000\u0000METHODS\u0000Service members and veterans (n=224) without injury (n=77), or with history of bodily injury (n=37), uncomplicated mild TBI (n=55), or more severe TBI (n=55), underwent a blood draw and neuropsychological assessment within one year of their injury as part of a case-control study. A subsample (n=87) completed follow-up cognitive assessment.\u0000\u0000\u0000RESULTS\u0000In the more severe TBI group, baseline glial fibrillary acidic protein (p=.008) and ubiquitin C-terminal hydrolase-L1 (p=.026) were associated with processing speed at baseline, and baseline ubiquitin C-terminal hydrolase-L1 predicted change in immediate (R2Δ=.244, p=.005) and delayed memory (R2Δ=.390, p=.003) over time. In the mild TBI group, higher baseline tau predicted greater negative change in perceptual reasoning (R2Δ=.188, p=.033) and executive functioning (R2Δ=.298, p=.007); higher baseline neurofilament light predicted greater negative change in perceptual reasoning (R2Δ=.211, p=.012).\u0000\u0000\u0000CONCLUSION\u0000Baseline ubiquitin C-terminal hydrolase-L1 strongly predicted memory decline in the more severe TBI group, while tau and neurofilament light strongly predicted decline in the mild TBI group. A panel including these biomarkers could be particularly helpful in identifying those at risk for future cognitive decline following TBI.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44681215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-18DOI: 10.2174/1567205019666220318092003
F. Neta, Francisco Emílio Simplício de Souza, André Lima Batista, Francisco Irochima Pinheiro, R. Cobucci, F. Guzen
BACKGROUND Conditions along the brain-gut-microbiota (BGM) axis can significantly contribute to the pathogenesis of Alzheimer's disease (AD). Evidence from animal studies indicates a role for probiotics in regulating mood, cognition, and stress response via the BGM axis. However, the effect of probiotics on AD needs to be better clarified in preclinical and clinical studies. METHOD We prepared this systematic review according to PRISMA. PubMed, Web of Science, Embase, and Virtual Health Library (VHL) were searched for original articles concerning the effects of probiotics in experimental AD. RESULTS Results were presented as a narrative synthesis according to the Synthesis Without Meta-analysis (SWiM) Guideline.Seventeen studies met the inclusion criteria. The results showed significant effects in the experimental models of AD treated with probiotics alone or in mixture form due to expressive improvements in cognitive tests. CONCLUSION Furthermore, in most of the included studies, it was possible to observe a reduction in inflammatory processes, an increase in the concentration of peptide hormones, insulin homeostasis in the brain, increased antioxidant enzymes, and a decrease in beta-amyloid deposition and tau hyperphosphorylation. Supplementation of probiotics seems to improve performance in cognitive tests and increase the concentration of substances capable of delaying the neurodegenerative process of AD in experimental models.
背景脑肠微生物群（BGM）轴上的条件可显著促进阿尔茨海默病（AD）的发病机制。来自动物研究的证据表明，益生菌通过BGM轴在调节情绪、认知和应激反应中发挥作用。然而，益生菌对AD的影响需要在临床前和临床研究中更好地阐明。方法根据PRISMA编制本系统综述。检索PubMed、Web of Science、Embase和虚拟健康图书馆（VHL）中关于益生菌在实验性AD中的作用的原创文章。结果根据无荟萃分析综合（SWiM）指南作为叙述性综合呈现。17项研究符合纳入标准。结果显示，由于认知测试中的表达改善，单独或混合使用益生菌治疗的AD实验模型具有显著效果。结论此外，在大多数纳入的研究中，可以观察到炎症过程减少，肽激素浓度增加，大脑中胰岛素稳态，抗氧化酶增加，β淀粉样蛋白沉积和tau过度磷酸化减少。在实验模型中，补充益生菌似乎可以提高认知测试的表现，并增加能够延缓AD神经退行性过程的物质的浓度。
{"title":"Effects of supplementation with probiotics in experimental models of Alzheimer's Disease: a systematic review of animal experiments.","authors":"F. Neta, Francisco Emílio Simplício de Souza, André Lima Batista, Francisco Irochima Pinheiro, R. Cobucci, F. Guzen","doi":"10.2174/1567205019666220318092003","DOIUrl":"https://doi.org/10.2174/1567205019666220318092003","url":null,"abstract":"BACKGROUND\u0000Conditions along the brain-gut-microbiota (BGM) axis can significantly contribute to the pathogenesis of Alzheimer's disease (AD). Evidence from animal studies indicates a role for probiotics in regulating mood, cognition, and stress response via the BGM axis. However, the effect of probiotics on AD needs to be better clarified in preclinical and clinical studies.\u0000\u0000\u0000METHOD\u0000We prepared this systematic review according to PRISMA. PubMed, Web of Science, Embase, and Virtual Health Library (VHL) were searched for original articles concerning the effects of probiotics in experimental AD.\u0000\u0000\u0000RESULTS\u0000Results were presented as a narrative synthesis according to the Synthesis Without Meta-analysis (SWiM) Guideline.Seventeen studies met the inclusion criteria. The results showed significant effects in the experimental models of AD treated with probiotics alone or in mixture form due to expressive improvements in cognitive tests.\u0000\u0000\u0000CONCLUSION\u0000Furthermore, in most of the included studies, it was possible to observe a reduction in inflammatory processes, an increase in the concentration of peptide hormones, insulin homeostasis in the brain, increased antioxidant enzymes, and a decrease in beta-amyloid deposition and tau hyperphosphorylation. Supplementation of probiotics seems to improve performance in cognitive tests and increase the concentration of substances capable of delaying the neurodegenerative process of AD in experimental models.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46606531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-15DOI: 10.2174/1567205019666220315092008
E. Mukaetova-Ladinska, C. De Lillo, Qadeer Arshad, H. Subramaniam, John J Maltby
{"title":"DEMENTIA COGNITIVE ASSESSMENT: NEED FOR AN INCLUSIVE TOOL DESIGN.","authors":"E. Mukaetova-Ladinska, C. De Lillo, Qadeer Arshad, H. Subramaniam, John J Maltby","doi":"10.2174/1567205019666220315092008","DOIUrl":"https://doi.org/10.2174/1567205019666220315092008","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42839911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-08DOI: 10.2174/1567205019666220308152219
Ryan P. Coburn, H. Botha, J. Graff‐Radford, R. Reichard, David T. Jones, V. Ramanan
BACKGROUND Alzheimer's disease can present atypically as a progressive dysexecutive syndrome (dAD), an entity which preferentially affects younger individuals and is frequently misdiagnosed, highlighting the imperative for additional research. OBJECTIVE To characterize the clinical, antemortem neuroimaging, and postmortem neuropathologic features of two cases of young-onset dAD who displayed evidence of Lewy body disease (LBD) co-pathology at autopsy. METHODS Clinical histories, antemortem MRI and PET imaging, and postmortem neuropathologic data were reviewed for each patient. Case Descriptions/Results: Canonical features of dAD were observed in both cases, including progressive and predominant impairment in tasks related to working memory and cognitive flexibility, a lack of major behavioral/personality changes, and evidence of abnormal amyloid and tau deposition by antemortem amyloid and tau PET and postmortem neuropathology. Relative sparing of hippocampal involvement was observed in both individuals, in keeping with many cases of clinically atypical AD. One of the patients developed subtle parkinsonian signs as well as paranoia and irritability in the years prior to passing. In both cases, transitional (brainstem and limbic) LBD co-pathology was observed at autopsy. DISCUSSION Although LBD co-pathology is not uncommon in AD overall, the presence of LBD pathology in these young-onset cases of dAD (including a case with apparent symptomatic correlate) warrants further investigation for broader frequency and underlying pathophysiology. CONCLUSION A better understanding of which specific young-onset AD phenotypes are associated with LBD co-pathology would have important implications for counseling, treatment, clinical trial enrollment, and knowledge on disease mechanisms.
{"title":"Dysexecutive Alzheimer's Disease with Lewy Body Disease Co-Pathology.","authors":"Ryan P. Coburn, H. Botha, J. Graff‐Radford, R. Reichard, David T. Jones, V. Ramanan","doi":"10.2174/1567205019666220308152219","DOIUrl":"https://doi.org/10.2174/1567205019666220308152219","url":null,"abstract":"BACKGROUND\u0000Alzheimer's disease can present atypically as a progressive dysexecutive syndrome (dAD), an entity which preferentially affects younger individuals and is frequently misdiagnosed, highlighting the imperative for additional research.\u0000\u0000\u0000OBJECTIVE\u0000To characterize the clinical, antemortem neuroimaging, and postmortem neuropathologic features of two cases of young-onset dAD who displayed evidence of Lewy body disease (LBD) co-pathology at autopsy.\u0000\u0000\u0000METHODS\u0000Clinical histories, antemortem MRI and PET imaging, and postmortem neuropathologic data were reviewed for each patient. Case Descriptions/Results: Canonical features of dAD were observed in both cases, including progressive and predominant impairment in tasks related to working memory and cognitive flexibility, a lack of major behavioral/personality changes, and evidence of abnormal amyloid and tau deposition by antemortem amyloid and tau PET and postmortem neuropathology. Relative sparing of hippocampal involvement was observed in both individuals, in keeping with many cases of clinically atypical AD. One of the patients developed subtle parkinsonian signs as well as paranoia and irritability in the years prior to passing. In both cases, transitional (brainstem and limbic) LBD co-pathology was observed at autopsy.\u0000\u0000\u0000DISCUSSION\u0000Although LBD co-pathology is not uncommon in AD overall, the presence of LBD pathology in these young-onset cases of dAD (including a case with apparent symptomatic correlate) warrants further investigation for broader frequency and underlying pathophysiology.\u0000\u0000\u0000CONCLUSION\u0000A better understanding of which specific young-onset AD phenotypes are associated with LBD co-pathology would have important implications for counseling, treatment, clinical trial enrollment, and knowledge on disease mechanisms.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44779385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-04DOI: 10.2174/1567205019666220304091241
C. Musaeus, L. B. Johansen, S. Hasselbalch, N. Beyer, P. Høgh, H. Siebner, K. Frederiksen
INTRODUCTION In healthy elderly persons and patients with mild cognitive impairment, physical exercise can increase functional brain connectivity in the default mode network (DMN) measured by restingstate functional magnetic resonance imaging (rs-fMRI). However, no studies have so far investigated the effect of physical exercise on functional resting-state connectivity in the DMN in patients with Alzheimer's disease (AD). OBJECTIVE In a single-blinded randomized controlled trial, we assessed the effects of an aerobic exercise intervention of 16 weeks of physical exercise on DMN connectivity using rs-fMRI in patients with AD. METHODS Forty-five patients were randomly assigned to either a control or exercise group. The exercise group performed 60-min of aerobic exercise three times per week for 16 weeks. All the patients underwent whole-brain rs-fMRI at 3 T, at baseline, and after 16 weeks. Since the posterior cingulate cortex (PCC) and adjacent precuneus constitute a central hub of the DMN, this parietal region was defined as region-ofinterest and used as the seed region for functional connectivity analysis of the rs-fMRI data treating age and gender as covariates. RESULTS Neither seed-based analysis, seeded in the PCC/precuneus region nor ICA-based analyses, focusing on components of the DMN network, showed any exercise-induced changes in functional resting-state connectivity from baseline to follow-up. CONCLUSION 16 weeks of aerobic exercise does not modify functional connectivity of the PCC/precuneus region in patients with AD. A longer intervention may be needed to show the effect of exercise on brain connectivity.
{"title":"Sixteen weeks of aerobic exercise does not alter resting-state connectivity of the precuneus in patients with Alzheimer's disease.","authors":"C. Musaeus, L. B. Johansen, S. Hasselbalch, N. Beyer, P. Høgh, H. Siebner, K. Frederiksen","doi":"10.2174/1567205019666220304091241","DOIUrl":"https://doi.org/10.2174/1567205019666220304091241","url":null,"abstract":"INTRODUCTION\u0000In healthy elderly persons and patients with mild cognitive impairment, physical exercise can increase functional brain connectivity in the default mode network (DMN) measured by restingstate functional magnetic resonance imaging (rs-fMRI). However, no studies have so far investigated the effect of physical exercise on functional resting-state connectivity in the DMN in patients with Alzheimer's disease (AD).\u0000\u0000\u0000OBJECTIVE\u0000In a single-blinded randomized controlled trial, we assessed the effects of an aerobic exercise intervention of 16 weeks of physical exercise on DMN connectivity using rs-fMRI in patients with AD.\u0000\u0000\u0000METHODS\u0000Forty-five patients were randomly assigned to either a control or exercise group. The exercise group performed 60-min of aerobic exercise three times per week for 16 weeks. All the patients underwent whole-brain rs-fMRI at 3 T, at baseline, and after 16 weeks. Since the posterior cingulate cortex (PCC) and adjacent precuneus constitute a central hub of the DMN, this parietal region was defined as region-ofinterest and used as the seed region for functional connectivity analysis of the rs-fMRI data treating age and gender as covariates.\u0000\u0000\u0000RESULTS\u0000Neither seed-based analysis, seeded in the PCC/precuneus region nor ICA-based analyses, focusing on components of the DMN network, showed any exercise-induced changes in functional resting-state connectivity from baseline to follow-up.\u0000\u0000\u0000CONCLUSION\u000016 weeks of aerobic exercise does not modify functional connectivity of the PCC/precuneus region in patients with AD. A longer intervention may be needed to show the effect of exercise on brain connectivity.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47139651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-02DOI: 10.2174/1567205019666220302120950
O. Šerý, T. Zeman, Alice Hálová, V. Janout, J. Janoutová, J. Lochman, V. Balcar
BACKGROUND Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form β-structures. These include insulin and amyloid-β peptides. Accumulation and fibrillation of amyloid-β peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology. OBJECTIVE The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (Mild cognitive impairment) and AD. METHODS Two independent groups of 1670 patients and controls were included. The AD group consisted of 595 patients and 400 controls; the MCI group involved 135 patients and 540 matched controls. PCR and restriction fragment length analysis was used for analysis of the rs2421943 polymorphism. Using the miRBase and RNA22 prediction tools in silico indicated that the rs2421943 polymorphism is a potential target for a specific miRNA (hsa-miR-7110-5p). RESULTS AG and GG genotypes of rs2421943 significantly increased the risk of AD and the AG genotype increased the risk of MCI. It seems G allele both increases the risk of AD and accelerates the transition through the MCI phase. In silico study revealed that rs2421943 is inside the sequence binding miRNA hsa-miR-7110-5p. The polymorphism could affect the rate of IDE pre-RNA (heterogeneous nuclear RNA, hnRNA) processing, resulting in slower translation, lower levels of IDE, deficient removal of amyloid-β fragments and greater risk of and/or accelerated progression of AD. CONCLUSIONS GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulin degrading enzyme gene increase the risk of AD and MCI.
{"title":"Polymorphism Rs2421943 of the insulin-Degrading Enzyme Gene and the Risk of Late-Onset Alzheimer's Disease.","authors":"O. Šerý, T. Zeman, Alice Hálová, V. Janout, J. Janoutová, J. Lochman, V. Balcar","doi":"10.2174/1567205019666220302120950","DOIUrl":"https://doi.org/10.2174/1567205019666220302120950","url":null,"abstract":"BACKGROUND\u0000Insulin-degrading enzyme (IDE) is a widely distributed Zn2+-binding metalloprotease that cleaves multiple short and medium-sized peptides prone to form β-structures. These include insulin and amyloid-β peptides. Accumulation and fibrillation of amyloid-β peptides leading to the formation of amyloid plaques is a characteristic sign of Alzheimer's disease (AD) pathology.\u0000\u0000\u0000OBJECTIVE\u0000The study investigated the rs2421943 single nucleotide polymorphism (SNP) of the IDE gene as a risk factor for MCI (Mild cognitive impairment) and AD.\u0000\u0000\u0000METHODS\u0000Two independent groups of 1670 patients and controls were included. The AD group consisted of 595 patients and 400 controls; the MCI group involved 135 patients and 540 matched controls. PCR and restriction fragment length analysis was used for analysis of the rs2421943 polymorphism. Using the miRBase and RNA22 prediction tools in silico indicated that the rs2421943 polymorphism is a potential target for a specific miRNA (hsa-miR-7110-5p).\u0000\u0000\u0000RESULTS\u0000AG and GG genotypes of rs2421943 significantly increased the risk of AD and the AG genotype increased the risk of MCI. It seems G allele both increases the risk of AD and accelerates the transition through the MCI phase. In silico study revealed that rs2421943 is inside the sequence binding miRNA hsa-miR-7110-5p. The polymorphism could affect the rate of IDE pre-RNA (heterogeneous nuclear RNA, hnRNA) processing, resulting in slower translation, lower levels of IDE, deficient removal of amyloid-β fragments and greater risk of and/or accelerated progression of AD.\u0000\u0000\u0000CONCLUSIONS\u0000GG and AG genotypes of the single nucleotide polymorphism rs2421943 of insulin degrading enzyme gene increase the risk of AD and MCI.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45103436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 10.2174/1567205019666220228152655
H. Hanyu, Yumi Koyama, Haruka Horita, Toshinori Aoki, Tomohiko Sato, H. Kanetaka, S. Shimizu, K. Hirao
BACKGROUND/OBJECTIVE Although a large number of studies have been performed on the association between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM), the underlying pathophysiology of AD associated with DM has not been fully elucidated to date. We compared cognitive functions and brain imaging findings between AD patients with and without DM to characterize the association between cognition and imaging findings in AD patients with DM. METHODS Cognitive functions and brain imaging findings, including medial temporal lobe atrophy analyzed by magnetic resonance imaging, and hypoperfusion in the parietal, posterior cingulate, and frontal regions analyzed by single-photon emission computed tomography were compared between 126 AD patients without DM ([AD-DM]) and 51 AD patients with DM ([AD+DM]). Factors associated with cognitive-imaging associations, including education, occupation, leisure activity, comorbidity, frailty, and other demographics, were analyzed. RESULTS The [AD+DM] group showed significantly more severe cognitive dysfunction than the [AD- DM] group, despite a similar degree of brain imaging abnormalities. Among the factors associated with cognitive-imaging associations, the level of leisure activity was significantly lower in the [AD+DM] group than in the [AD-DM] group, but no significant differences in other factors were observed between the 2 groups. CONCLUSION The cognitive-imaging discrepancy observed in AD patients with DM may be associated with their low cognitive reserve, possibly caused by their low amount of leisure activities. Our findings suggest that lifestyle interventions, including physical, cognitive, and social activities, may reduce cognitive decline in AD patients with DM.
{"title":"Discrepancy between cognitive test and brain imaging results in Alzheimer's disease associated with diabetes.","authors":"H. Hanyu, Yumi Koyama, Haruka Horita, Toshinori Aoki, Tomohiko Sato, H. Kanetaka, S. Shimizu, K. Hirao","doi":"10.2174/1567205019666220228152655","DOIUrl":"https://doi.org/10.2174/1567205019666220228152655","url":null,"abstract":"BACKGROUND/OBJECTIVE\u0000Although a large number of studies have been performed on the association between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM), the underlying pathophysiology of AD associated with DM has not been fully elucidated to date. We compared cognitive functions and brain imaging findings between AD patients with and without DM to characterize the association between cognition and imaging findings in AD patients with DM.\u0000\u0000\u0000METHODS\u0000Cognitive functions and brain imaging findings, including medial temporal lobe atrophy analyzed by magnetic resonance imaging, and hypoperfusion in the parietal, posterior cingulate, and frontal regions analyzed by single-photon emission computed tomography were compared between 126 AD patients without DM ([AD-DM]) and 51 AD patients with DM ([AD+DM]). Factors associated with cognitive-imaging associations, including education, occupation, leisure activity, comorbidity, frailty, and other demographics, were analyzed.\u0000\u0000\u0000RESULTS\u0000The [AD+DM] group showed significantly more severe cognitive dysfunction than the [AD- DM] group, despite a similar degree of brain imaging abnormalities. Among the factors associated with cognitive-imaging associations, the level of leisure activity was significantly lower in the [AD+DM] group than in the [AD-DM] group, but no significant differences in other factors were observed between the 2 groups.\u0000\u0000\u0000CONCLUSION\u0000The cognitive-imaging discrepancy observed in AD patients with DM may be associated with their low cognitive reserve, possibly caused by their low amount of leisure activities. Our findings suggest that lifestyle interventions, including physical, cognitive, and social activities, may reduce cognitive decline in AD patients with DM.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46494825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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