Pub Date : 2024-04-08eCollection Date: 2024-01-01DOI: 10.3233/ADR-230120
Congcong Zhu, Tong Tong, John J Farrell, Eden R Martin, William S Bush, Margaret A Pericak-Vance, Li-San Wang, Gerard D Schellenberg, Jonathan L Haines, Kathryn L Lunetta, Lindsay A Farrer, Xiaoling Zhang
Background: Mitochondrial DNA (mtDNA) is a double-stranded circular DNA and has multiple copies in each cell. Excess heteroplasmy, the coexistence of distinct variants in copies of mtDNA within a cell, may lead to mitochondrial impairments. Accurate determination of heteroplasmy in whole-genome sequencing (WGS) data has posed a significant challenge because mitochondria carrying heteroplasmic variants cannot be distinguished during library preparation. Moreover, sequencing errors, contamination, and nuclear mtDNA segments can reduce the accuracy of heteroplasmic variant calling.
Objective: To efficiently and accurately call mtDNA homoplasmic and heteroplasmic variants from the large-scale WGS data generated from the Alzheimer's Disease Sequencing Project (ADSP), and test their association with Alzheimer's disease (AD).
Methods: In this study, we present MitoH3-a comprehensive computational pipeline for calling mtDNA homoplasmic and heteroplasmic variants and inferring haplogroups in the ADSP WGS data. We first applied MitoH3 to 45 technical replicates from 6 subjects to define a threshold for detecting heteroplasmic variants. Then using the threshold of 5% ≤variant allele fraction≤95%, we further applied MitoH3 to call heteroplasmic variants from a total of 16,113 DNA samples with 6,742 samples from cognitively normal controls and 6,183 from AD cases.
Results: This pipeline is available through the Singularity container engine. For 4,311 heteroplasmic variants identified from 16,113 samples, no significant variant count difference was observed between AD cases and controls.
Conclusions: Our streamlined pipeline, MitoH3, enables computationally efficient and accurate analysis of a large number of samples.
{"title":"MitoH3: Mitochondrial Haplogroup and Homoplasmic/Heteroplasmic Variant Calling Pipeline for Alzheimer's Disease Sequencing Project.","authors":"Congcong Zhu, Tong Tong, John J Farrell, Eden R Martin, William S Bush, Margaret A Pericak-Vance, Li-San Wang, Gerard D Schellenberg, Jonathan L Haines, Kathryn L Lunetta, Lindsay A Farrer, Xiaoling Zhang","doi":"10.3233/ADR-230120","DOIUrl":"10.3233/ADR-230120","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial DNA (mtDNA) is a double-stranded circular DNA and has multiple copies in each cell. Excess heteroplasmy, the coexistence of distinct variants in copies of mtDNA within a cell, may lead to mitochondrial impairments. Accurate determination of heteroplasmy in whole-genome sequencing (WGS) data has posed a significant challenge because mitochondria carrying heteroplasmic variants cannot be distinguished during library preparation. Moreover, sequencing errors, contamination, and nuclear mtDNA segments can reduce the accuracy of heteroplasmic variant calling.</p><p><strong>Objective: </strong>To efficiently and accurately call mtDNA homoplasmic and heteroplasmic variants from the large-scale WGS data generated from the Alzheimer's Disease Sequencing Project (ADSP), and test their association with Alzheimer's disease (AD).</p><p><strong>Methods: </strong>In this study, we present MitoH3-a comprehensive computational pipeline for calling mtDNA homoplasmic and heteroplasmic variants and inferring haplogroups in the ADSP WGS data. We first applied MitoH3 to 45 technical replicates from 6 subjects to define a threshold for detecting heteroplasmic variants. Then using the threshold of 5% ≤variant allele fraction≤95%, we further applied MitoH3 to call heteroplasmic variants from a total of 16,113 DNA samples with 6,742 samples from cognitively normal controls and 6,183 from AD cases.</p><p><strong>Results: </strong>This pipeline is available through the Singularity container engine. For 4,311 heteroplasmic variants identified from 16,113 samples, no significant variant count difference was observed between AD cases and controls.</p><p><strong>Conclusions: </strong>Our streamlined pipeline, MitoH3, enables computationally efficient and accurate analysis of a large number of samples.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923993","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}
Joshua Batesole, Grant R Tomkinson, Kirk I. Erickson, Donald Jurivich, Justin J Lang, Brenda M. McGrath, Sheria G. Robinson-Lane, Ashleigh E. Smith, Ryan McGrath
Background: Weakness can be operationalized with several thresholds, which in turn, could impact associations with cognitive impairment when considering obesity status. Objective: We examined the associations of absolute, normalized, and collective weakness thresholds on future cognitive impairment by obesity status in older adults. Methods: We performed a secondary data analysis on the 2006–2018 waves of the Health and Retirement Study. A spring-type dynamometer collected handgrip strength (HGS). Males were categorized weak if their HGS was <35.5-kg (absolute), <0.45-kg/kg (body mass normalized), or <1.05-kg/kg/m2 (body mass index (BMI) normalized), while females were defined as weak if their HGS was <20.0-kg, <0.337-kg/kg, or <0.79-kg/kg/m2. The modified Telephone Interview of Cognitive Status examined cognitive function. Persons scoring ≤10 had a cognitive impairment. Obesity was categorized as BMI ≥30 kg/m2. Results: We included 7,532 and 3,584 persons aged ≥65-years living without and with obesity, respectively. Those without obesity but beneath the absolute weakness threshold had 1.54 (95% confidence interval (CI): 1.24–1.91) greater odds for future cognitive impairment. Persons with obesity and beneath each threshold also had greater odds for future cognitive impairment: 1.89 (95% CI: 1.28–2.78) for absolute, 2.17 (95% CI: 1.02–4.62) for body mass normalized, and 1.75 (95% CI: 1.10–2.80) for BMI normalized. Older Americans without obesity but underneath all the weakness thresholds had 1.32 (95% CI: 1.00–1.74) greater odds for impairment in cognitive function, while persons with obesity had 2.76 (95% CI: 1.29–5.93) greater odds. Conclusions: There should be consideration for how body size and different weakness thresholds may influence future cognitive outcomes.
{"title":"Weakness Thresholds Are Differentially Linked to Cognitive Function by Obesity Status in Older Americans","authors":"Joshua Batesole, Grant R Tomkinson, Kirk I. Erickson, Donald Jurivich, Justin J Lang, Brenda M. McGrath, Sheria G. Robinson-Lane, Ashleigh E. Smith, Ryan McGrath","doi":"10.3233/adr-230190","DOIUrl":"https://doi.org/10.3233/adr-230190","url":null,"abstract":"Background: Weakness can be operationalized with several thresholds, which in turn, could impact associations with cognitive impairment when considering obesity status. Objective: We examined the associations of absolute, normalized, and collective weakness thresholds on future cognitive impairment by obesity status in older adults. Methods: We performed a secondary data analysis on the 2006–2018 waves of the Health and Retirement Study. A spring-type dynamometer collected handgrip strength (HGS). Males were categorized weak if their HGS was <35.5-kg (absolute), <0.45-kg/kg (body mass normalized), or <1.05-kg/kg/m2 (body mass index (BMI) normalized), while females were defined as weak if their HGS was <20.0-kg, <0.337-kg/kg, or <0.79-kg/kg/m2. The modified Telephone Interview of Cognitive Status examined cognitive function. Persons scoring ≤10 had a cognitive impairment. Obesity was categorized as BMI ≥30 kg/m2. Results: We included 7,532 and 3,584 persons aged ≥65-years living without and with obesity, respectively. Those without obesity but beneath the absolute weakness threshold had 1.54 (95% confidence interval (CI): 1.24–1.91) greater odds for future cognitive impairment. Persons with obesity and beneath each threshold also had greater odds for future cognitive impairment: 1.89 (95% CI: 1.28–2.78) for absolute, 2.17 (95% CI: 1.02–4.62) for body mass normalized, and 1.75 (95% CI: 1.10–2.80) for BMI normalized. Older Americans without obesity but underneath all the weakness thresholds had 1.32 (95% CI: 1.00–1.74) greater odds for impairment in cognitive function, while persons with obesity had 2.76 (95% CI: 1.29–5.93) greater odds. Conclusions: There should be consideration for how body size and different weakness thresholds may influence future cognitive outcomes.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140731029","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}
Weiye Wang, Ruxin Cui, Luming Leng, Gang Wang, Guoping Peng
Cognitive impairment is a primary manifestation of neurological symptoms associated with COVID-19 and may occur after disease resolution. Although cognitive impairment has been extensively reported in the literature, its duration and rate of remission remain controversial. This study discusses the various factors that influence cognitive impairment, including demographic characteristics, genetics, as well as disease course and severity. Furthermore, imaging and laboratory data have suggested various associations with cognitive impairment, most notably changes in EEG patterns, PET imaging, and serum markers. Some findings suggest similarities and potential links between COVID-related cognitive impairment and Alzheimer’s disease. Moreover, this study reviews the various mechanisms proposed to explain the development of cognitive impairment in COVID-19, including cytokine storm, damage to the blood-brain barrier, compromise of small vessel integrity, hypoxic conditions, and immune dysregulation.
{"title":"Cognitive Impairment in the Post-Acute Phases of COVID-19 and Mechanisms: An Introduction and Narrative Review","authors":"Weiye Wang, Ruxin Cui, Luming Leng, Gang Wang, Guoping Peng","doi":"10.3233/adr-230172","DOIUrl":"https://doi.org/10.3233/adr-230172","url":null,"abstract":"Cognitive impairment is a primary manifestation of neurological symptoms associated with COVID-19 and may occur after disease resolution. Although cognitive impairment has been extensively reported in the literature, its duration and rate of remission remain controversial. This study discusses the various factors that influence cognitive impairment, including demographic characteristics, genetics, as well as disease course and severity. Furthermore, imaging and laboratory data have suggested various associations with cognitive impairment, most notably changes in EEG patterns, PET imaging, and serum markers. Some findings suggest similarities and potential links between COVID-related cognitive impairment and Alzheimer’s disease. Moreover, this study reviews the various mechanisms proposed to explain the development of cognitive impairment in COVID-19, including cytokine storm, damage to the blood-brain barrier, compromise of small vessel integrity, hypoxic conditions, and immune dysregulation.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140728611","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}
Michelle Nguyen, Colby Wood, Andres Rios, Zach Salter, P. H. Reddy
Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-β protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies.
{"title":"Circulating Cell Free DNA and DNA Double-Strand Breakage in Alzheimer’s Disease","authors":"Michelle Nguyen, Colby Wood, Andres Rios, Zach Salter, P. H. Reddy","doi":"10.3233/adr-240012","DOIUrl":"https://doi.org/10.3233/adr-240012","url":null,"abstract":"Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-β protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140728932","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}
Michael Turner, Antonio Belli, Rudolph J. Castellani
Background: Cumulative effects of traumatic brain injury is of increasing concern, especially with respect to its role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Objective: Compare regional brain volume and connectivity between athletes with a history of concussion and controls. Methods: We evaluated whole-brain volumetric effects with Bayesian regression models and functional connectivity with network-based statistics, in 125 retired athletes (a mean of 11 reported concussions) and 36 matched controls. Results: Brain regions significantly lower in volume in the concussed group included the middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger included the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial postcentral gyrus. Functional connectivity analyses revealed increased edge strength, most marked in motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with concussion. Aligned to meta-analytic neuroimaging data, the observed changes suggest functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language. Conclusions: These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury. Future studies with longitudinal cohorts including autopsy examination are needed to determine whether the latter reflects tissue loss from brain shearing, or the onset of a progressive Alzheimer’s disease like proteinopathy.
{"title":"Changes in Brain Structure and Function in a Multisport Cohort of Retired Female and Male Athletes, Many Years after Suffering a Concussion: Implications for Neuroplasticity and Neurodegenerative Disease Pathogenesis","authors":"Michael Turner, Antonio Belli, Rudolph J. Castellani","doi":"10.3233/adr-240021","DOIUrl":"https://doi.org/10.3233/adr-240021","url":null,"abstract":"Background: Cumulative effects of traumatic brain injury is of increasing concern, especially with respect to its role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Objective: Compare regional brain volume and connectivity between athletes with a history of concussion and controls. Methods: We evaluated whole-brain volumetric effects with Bayesian regression models and functional connectivity with network-based statistics, in 125 retired athletes (a mean of 11 reported concussions) and 36 matched controls. Results: Brain regions significantly lower in volume in the concussed group included the middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger included the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial postcentral gyrus. Functional connectivity analyses revealed increased edge strength, most marked in motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with concussion. Aligned to meta-analytic neuroimaging data, the observed changes suggest functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language. Conclusions: These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury. Future studies with longitudinal cohorts including autopsy examination are needed to determine whether the latter reflects tissue loss from brain shearing, or the onset of a progressive Alzheimer’s disease like proteinopathy.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140228773","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. El Haj, C. Boutoleau-Bretonnière, K. Gallouj, Nathalie Wagemann, Pascal Antoine, Dimitrios Kapogiannis, G. Chapelet
Background: The potential of ChatGPT in medical diagnosis has been explored in various medical conditions. Objective: We assessed whether ChatGPT can contribute to the diagnosis of Alzheimer’s disease (AD). Methods: We provided ChatGPT with four generated cases (mild, moderate, or advanced stage AD dementia, or mild cognitive impairment), including descriptions of their complaints, physical examinations, as well as biomarker, neuroimaging, and neuropsychological data. Results: ChatGPT accurately diagnosed the test cases similarly to two blinded specialists. Conclusions: While the use of generated cases can be a limitation to our study, our findings demonstrate that ChatGPT can be a useful tool for symptom assessment and the diagnosis of AD. However, while the use of ChatGPT in AD diagnosis is promising, it should be seen as an adjunct to clinical judgment rather than a replacement.
背景：ChatGPT 在各种疾病诊断中的潜力已得到探索。目的：我们评估了 ChatGPT 是否有助于阿尔茨海默病（AD）的诊断：我们评估了 ChatGPT 是否有助于阿尔茨海默病（AD）的诊断。方法我们向 ChatGPT 提供了四个生成病例（轻度、中度或晚期 AD 痴呆或轻度认知障碍），包括他们的主诉描述、体格检查以及生物标记物、神经影像学和神经心理学数据。结果ChatGPT 对测试病例的诊断准确度与两位盲人专家相似。结论：虽然使用生成的病例可能会限制我们的研究，但我们的研究结果表明，ChatGPT 可以作为症状评估和诊断 AD 的有用工具。不过，虽然 ChatGPT 在诊断注意力缺失症方面的应用前景广阔，但它应被视为临床判断的辅助工具而非替代品。
{"title":"ChatGPT as a Diagnostic Aid in Alzheimer’s Disease: An Exploratory Study","authors":"M. El Haj, C. Boutoleau-Bretonnière, K. Gallouj, Nathalie Wagemann, Pascal Antoine, Dimitrios Kapogiannis, G. Chapelet","doi":"10.3233/adr-230191","DOIUrl":"https://doi.org/10.3233/adr-230191","url":null,"abstract":"Background: The potential of ChatGPT in medical diagnosis has been explored in various medical conditions. Objective: We assessed whether ChatGPT can contribute to the diagnosis of Alzheimer’s disease (AD). Methods: We provided ChatGPT with four generated cases (mild, moderate, or advanced stage AD dementia, or mild cognitive impairment), including descriptions of their complaints, physical examinations, as well as biomarker, neuroimaging, and neuropsychological data. Results: ChatGPT accurately diagnosed the test cases similarly to two blinded specialists. Conclusions: While the use of generated cases can be a limitation to our study, our findings demonstrate that ChatGPT can be a useful tool for symptom assessment and the diagnosis of AD. However, while the use of ChatGPT in AD diagnosis is promising, it should be seen as an adjunct to clinical judgment rather than a replacement.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140229068","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, D. Moraitou, Moses Gialaouzidis, Evaggelia Bakoglidou, Vasilis Psaltis, Natalia Bertzes, Hany Ibrahim Hassanin, Eudokia Emmanouilidou, Michael Totonidis, Nikoleta Frantzi, K. Avdikou, Andromachi Gavra, A. Diamantidou, Nikolina Kapsali, Eleni Kouroundi, Magda Tsolaki
Background: Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is a widely used screening tool for detecting older adults with Alzheimer’s disease among their cognitively healthy peers. A previous study in Greek population showed that ADAS-Cog-Greek (G) is a valid tool and can identify people with Alzheimer’s disease from older adult control group; however, there is no current data about whether ADAS-Cog can differentiate older adults with mild cognitive impairment (MCI) from those who have subjective cognitive decline (SCD). Objective: The current study aimed to examine the discriminant potential of ADAS-Cog-G in Greek older adults who meet the criteria for SCD or MCI. Methods: Four hundred eighty-two community-dwelling older adults, visitors of the Greek Alzheimer Association and Related Disorders, were enrolled in the current study. One hundred seventy-six of them met the criteria for SCD and three hundred six had MCI. Results: Path analysis applied to the data showed that age, as well as educational level affected ADAS-Cog-G performance. Results showed that the cut-off scores, which better discriminate people with SCD from MCI as well as their sensitivity and specificity values, were extracted in participants with high educational level (13 educational years<) and mainly under the age of 75 years. Conclusions: The current study provided evidence concerning the discriminant potential of ADAS-Cog-G to differentiate older adults with SCD from those with MCI in the Greek population, and therefore contributes to the relevant literature on the field.
{"title":"Discriminant Potential of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) in Greek Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment","authors":"M. Tsatali, D. Moraitou, Moses Gialaouzidis, Evaggelia Bakoglidou, Vasilis Psaltis, Natalia Bertzes, Hany Ibrahim Hassanin, Eudokia Emmanouilidou, Michael Totonidis, Nikoleta Frantzi, K. Avdikou, Andromachi Gavra, A. Diamantidou, Nikolina Kapsali, Eleni Kouroundi, Magda Tsolaki","doi":"10.3233/adr-230151","DOIUrl":"https://doi.org/10.3233/adr-230151","url":null,"abstract":"Background: Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is a widely used screening tool for detecting older adults with Alzheimer’s disease among their cognitively healthy peers. A previous study in Greek population showed that ADAS-Cog-Greek (G) is a valid tool and can identify people with Alzheimer’s disease from older adult control group; however, there is no current data about whether ADAS-Cog can differentiate older adults with mild cognitive impairment (MCI) from those who have subjective cognitive decline (SCD). Objective: The current study aimed to examine the discriminant potential of ADAS-Cog-G in Greek older adults who meet the criteria for SCD or MCI. Methods: Four hundred eighty-two community-dwelling older adults, visitors of the Greek Alzheimer Association and Related Disorders, were enrolled in the current study. One hundred seventy-six of them met the criteria for SCD and three hundred six had MCI. Results: Path analysis applied to the data showed that age, as well as educational level affected ADAS-Cog-G performance. Results showed that the cut-off scores, which better discriminate people with SCD from MCI as well as their sensitivity and specificity values, were extracted in participants with high educational level (13 educational years<) and mainly under the age of 75 years. Conclusions: The current study provided evidence concerning the discriminant potential of ADAS-Cog-G to differentiate older adults with SCD from those with MCI in the Greek population, and therefore contributes to the relevant literature on the field.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140229916","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}
Tanmoy Mondal, Zarish Noreen, Christopher A. Loffredo, Jheannelle Johnson, Attya Bhatti, Gail Nunlee-Bland, Ruth Quartey, Charles D. Howell, Gemeyel Moses, Thomas Nnanabu, Sharleine T. Cotin, Marika Clark, Vijay Chandra, S. Jana, Bernard Kwabi-Addo, Brent E. Korba, Sharoon Shahzad, Muhammad Farrukh Bhatti, Somiranjan Ghosh
Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan. Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population. Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; n = 33 subjects) coupled with Affymetrix Arrays (n = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways. Results: We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in CAPNS2 and CAPN1. The global gene expression study observed that 61% and 39% of genes were significantly (p-value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., Amyloid Processing, Neuroinflammation Signaling, and ErbB4 Signaling. The top-scoring networks in Diseases and Disorders Development were Neurological Disease, Organismal Injury and Abnormalities, and Psychological Disorders. Conclusions: Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to Amyloid Processing, which could play potential role in future studies to identify sensitive, early biomarkers of AD in general.
背景：阿尔茨海默病（AD）是一种多因素神经退行性疾病，多发于老年人，尤其是在发达国家，目前在巴基斯坦等发展中国家的发病率也在上升。研究目的我们的目标是在巴基斯坦人群中开展一项试点病例对照研究，分析与阿兹海默症发病机制相关的关键基因及其表达水平和相关分子转录组网络。研究方法为了获得与巴基斯坦AD患者发病机制相关的分子网络谱（比较病例和对照），我们使用了高通量qRT-PCR（TaqMan低密度阵列；n = 33名受试者）和Affymetrix阵列（n = 8）以及Ingenuity Pathway Analysis（IPA）来识别与淀粉样蛋白加工和疾病通路相关的特征基因。结果：我们确认了 16 个差异表达的 AD 相关基因，包括在 CAPNS2 和 CAPN1 中观察到的最大倍数变化。全球基因表达研究发现，与健康对照组相比，AD 患者中分别有 61% 和 39% 的基因被显著上调和下调（P 值为 0.05）。关键通路包括淀粉样蛋白加工、神经炎症信号转导和 ErbB4 信号转导等。疾病和失调发展中得分最高的网络是神经系统疾病、机体损伤和异常以及心理障碍。结论我们的试验性研究提供了一种非侵入性的高效方法，通过利用全血将 TLDA 和全局基因表达法相结合，研究 AD 患者的基因表达模式。这为了解淀粉样蛋白加工相关基因的表达状况提供了宝贵的信息，可在未来研究中发挥潜在作用，以确定敏感的早期 AD 生物标志物。
{"title":"Transcriptomic Analysis of Alzheimer’s Disease Pathways in a Pakistani Population1","authors":"Tanmoy Mondal, Zarish Noreen, Christopher A. Loffredo, Jheannelle Johnson, Attya Bhatti, Gail Nunlee-Bland, Ruth Quartey, Charles D. Howell, Gemeyel Moses, Thomas Nnanabu, Sharleine T. Cotin, Marika Clark, Vijay Chandra, S. Jana, Bernard Kwabi-Addo, Brent E. Korba, Sharoon Shahzad, Muhammad Farrukh Bhatti, Somiranjan Ghosh","doi":"10.3233/adr-230146","DOIUrl":"https://doi.org/10.3233/adr-230146","url":null,"abstract":"Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan. Objective: Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population. Methods: To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; n = 33 subjects) coupled with Affymetrix Arrays (n = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways. Results: We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in CAPNS2 and CAPN1. The global gene expression study observed that 61% and 39% of genes were significantly (p-value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., Amyloid Processing, Neuroinflammation Signaling, and ErbB4 Signaling. The top-scoring networks in Diseases and Disorders Development were Neurological Disease, Organismal Injury and Abnormalities, and Psychological Disorders. Conclusions: Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to Amyloid Processing, which could play potential role in future studies to identify sensitive, early biomarkers of AD in general.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140230391","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}
Background: Alzheimer’s disease (AD) poses a growing public health challenge, particularly with an aging population. While extensive research has explored the relationships between AD, socio-demographic factors, and cardiovascular risk factors, a notable gap exists in understanding these connections within the Asian American elderly population. Objective: This study aims to address this gap by employing the Classification and Regression Tree (CART) approach to investigate the intricate interplay of socio-demographic variables, cardiovascular risk factors, sleep patterns, prior antidepressant use, and AD among Asian American elders. Methods: Data from the 2017 Uniform Data Set, provided by the National Alzheimer’s Coordinating Center, were analyzed, focusing on a sample of Asian American elders (n = 4,343). The analysis utilized the Classification and Regression Tree (CART) approach. Results: CART analysis identified critical factors, including levels of independence, specific age thresholds (73.5 and 84.5 years), apnea, antidepressant use, and body mass index, as significantly associated with AD risk. Conclusions: These findings have far-reaching implications for future research, particularly in examining the roles of gender, cultural nuances, socio-demographic factors, and cardiovascular risk elements in AD within the Asian American elderly population. Such insights can inform tailored interventions, improved healthcare access, and culturally sensitive policies to address the complex challenges posed by AD in this community.
{"title":"Dissecting Alzheimer’s Disease Risk in Asian American Elders: A Classification and Regression Tree Approach","authors":"Sung Seek Moon, Lindsey Anderson, Jinyu Liu, Jinwon Lee, Youngkwang Moon","doi":"10.3233/adr-230162","DOIUrl":"https://doi.org/10.3233/adr-230162","url":null,"abstract":"Background: Alzheimer’s disease (AD) poses a growing public health challenge, particularly with an aging population. While extensive research has explored the relationships between AD, socio-demographic factors, and cardiovascular risk factors, a notable gap exists in understanding these connections within the Asian American elderly population. Objective: This study aims to address this gap by employing the Classification and Regression Tree (CART) approach to investigate the intricate interplay of socio-demographic variables, cardiovascular risk factors, sleep patterns, prior antidepressant use, and AD among Asian American elders. Methods: Data from the 2017 Uniform Data Set, provided by the National Alzheimer’s Coordinating Center, were analyzed, focusing on a sample of Asian American elders (n = 4,343). The analysis utilized the Classification and Regression Tree (CART) approach. Results: CART analysis identified critical factors, including levels of independence, specific age thresholds (73.5 and 84.5 years), apnea, antidepressant use, and body mass index, as significantly associated with AD risk. Conclusions: These findings have far-reaching implications for future research, particularly in examining the roles of gender, cultural nuances, socio-demographic factors, and cardiovascular risk elements in AD within the Asian American elderly population. Such insights can inform tailored interventions, improved healthcare access, and culturally sensitive policies to address the complex challenges posed by AD in this community.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140228372","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}
Patrick J. Pruitt, J. Damoiseaux, B. Hampstead, Scott J. Peltier, A. Bhaumik, Roger L. Albin, Hiroko H. Dodge
Background: Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition. Objective: We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance. Methods: 112 older adults (70.7±7.3 years, range 54.6–89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer’s Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models. Results: Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition. Conclusions: Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults.
{"title":"Salience Network Functional Connectivity Mediates Association Between Social Engagement and Cognition in Non-Demented Older Adults: Exploratory Investigation","authors":"Patrick J. Pruitt, J. Damoiseaux, B. Hampstead, Scott J. Peltier, A. Bhaumik, Roger L. Albin, Hiroko H. Dodge","doi":"10.3233/adr-220082","DOIUrl":"https://doi.org/10.3233/adr-220082","url":null,"abstract":"Background: Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition. Objective: We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance. Methods: 112 older adults (70.7±7.3 years, range 54.6–89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer’s Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models. Results: Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition. Conclusions: Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140229790","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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