sang Geun Kim, Yunyeong Jeong, chae Yeon Hwang, Kang‐Hyun Park
BackgroundParticipation in various social activities of elderly has a significant impact on overall health and quality of life, including physical and metal health. Therefore, in this study, we aim to analyze the types of social activity participation among community‐dwelling elderly and examine differences in characteristics, health status, and quality of life according to these types of participation of social activities. Thus, we purpose to utilize the findings of this study as a foundation basis for research aimed at promoting services and intervention related to social activities of elderly in community.MethodThis study utilized the 9th wave (2022) panel data from the Korean Longitudinal Study of Elderly Employment(KLoSA). Latent class analysis was utilized to explore types of social activities. To assess the goodness of fit of the latent model, χ² (Chi‐square) test, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), Sample‐Size Adjusted Bayesian Information Criteria (SABIC) indices, and Lo‐Mendell‐Rubin adjusted Likelihood Ratio Test (LMR‐LRT) were employed. One‐way ANOVA was conducted to examine characteristics across different types.ResultThe study included a total of 6,057 elderly individuals aged 60 and above residing in the local community for analysis. The results demonstrate four distinct types of social activity participation among the elderly. These four groups were named based on the types of social activities they engaged in: “Religious and Social Activity Centered,” “Social and Leisure Activity Centered,” “Social Activity Centered,” and “Inactive.” The analysis of characteristics across these types showed statistically significant differences in demographic factors such as age, marital status, and religion. In terms of health‐related aspects, subjective health and overall quality of life indices exhibited statistically significant differences among the types.ConclusionSocial activities among the elderly were analyzed into four distinct types based on the activities they engaged in. The participation of elderly individuals in various social activities is considered a crucial indicator for improving health and quality of life. It is hoped that this study will serve as a foundational basis for developing services and intervention programs for elderly individuals in the community, aimed at facilitating their participation in diverse social activities.
{"title":"Analysis of the types of social activity participation of older adults living in the community and the health level and quality of life by types: Applying Latent Class Analysis","authors":"sang Geun Kim, Yunyeong Jeong, chae Yeon Hwang, Kang‐Hyun Park","doi":"10.1002/alz.094765","DOIUrl":"https://doi.org/10.1002/alz.094765","url":null,"abstract":"BackgroundParticipation in various social activities of elderly has a significant impact on overall health and quality of life, including physical and metal health. Therefore, in this study, we aim to analyze the types of social activity participation among community‐dwelling elderly and examine differences in characteristics, health status, and quality of life according to these types of participation of social activities. Thus, we purpose to utilize the findings of this study as a foundation basis for research aimed at promoting services and intervention related to social activities of elderly in community.MethodThis study utilized the 9th wave (2022) panel data from the Korean Longitudinal Study of Elderly Employment(KLoSA). Latent class analysis was utilized to explore types of social activities. To assess the goodness of fit of the latent model, χ² (Chi‐square) test, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), Sample‐Size Adjusted Bayesian Information Criteria (SABIC) indices, and Lo‐Mendell‐Rubin adjusted Likelihood Ratio Test (LMR‐LRT) were employed. One‐way ANOVA was conducted to examine characteristics across different types.ResultThe study included a total of 6,057 elderly individuals aged 60 and above residing in the local community for analysis. The results demonstrate four distinct types of social activity participation among the elderly. These four groups were named based on the types of social activities they engaged in: “Religious and Social Activity Centered,” “Social and Leisure Activity Centered,” “Social Activity Centered,” and “Inactive.” The analysis of characteristics across these types showed statistically significant differences in demographic factors such as age, marital status, and religion. In terms of health‐related aspects, subjective health and overall quality of life indices exhibited statistically significant differences among the types.ConclusionSocial activities among the elderly were analyzed into four distinct types based on the activities they engaged in. The participation of elderly individuals in various social activities is considered a crucial indicator for improving health and quality of life. It is hoped that this study will serve as a foundational basis for developing services and intervention programs for elderly individuals in the community, aimed at facilitating their participation in diverse social activities.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"28 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shivangi Jain, Alina Lesnovskaya, Lu Wan, Cristina Molina‐Hidalgo, Haiqing Huang, Anna Marsland, George Grove, Lauren Oberlin, Chaeryon Kang, Arthur Kramer, Charles Hillman, Edward McAuley, Jeffrey M Burns, Eric D Vidoni, Brad Sutton, Kirk I. Erickson
BackgroundAging is associated with heightened systemic inflammation, decline in selective aspects of cognition, and an increase in white matter lesions (WMLs). Both WMLs and systemic inflammation have been related to cognition. However, it is not clear how they interdependently relate to cognitive aging. In this study we examined whether WMLs mediate the relation between markers of systemic inflammation and cognition in late adulthood.MethodBaseline data from the randomized clinical trial “Investigating Gains in Neurocognition in an Intervention Trial of Exercise” (IGNITE) were used, which included 598 healthy older adults (mean age=69.9±3.75 years). Interleukin 6 (IL‐6) and Tumor Necrosis Factor Alpha (TNF‐α) were included as markers of systemic inflammation. A confirmatory factor analysis of cognitive performance resulted in factors measuring episodic memory (EM), processing speed (PS), working memory (WM), attentional control (AC), and visuospatial function (VF). WML volumes were computed from FLAIR and T1 scans using UBO detector. Mediation models were run with age, sex, years of education, and study site included as covariates.ResultHigher levels of IL‐6 were associated with more WMLs (b = 0.12, p < 0.001) as well as lower scores on all cognitive factors (all p < 0.03). In contrast, higher levels of TNF‐ α were associated with more WMLs (b = 0.10, p < 0.05) but not with any of the cognitive measures (all p > 0.3). More WMLs were associated with poorer PS, WM, AC, and VF (all p < 0.03), but not EM (all p > 0.05). Further, associations between IL‐6 and measures of PS, WM, AC, and VF were statistically mediated by WMLs (all b = ‐0.01, all p < 0.05).ConclusionThese findings suggest that markers of systemic inflammation might lead to poorer cognitive performance by impacting WMLs. The differences between IL‐6 and TNF‐α with cognition highlight the need for more research to understand how different cytokine pathways relate to cognition. Our results are important for building a mechanistic framework to understand the interplay between inflammation, WMLs, and cognition and could inform the development of targeted interventions focusing on regulating cytokines to support brain health and cognitive aging.
{"title":"Relation Between Markers of Systemic Inflammation, White Matter Lesions, and Cognitive Performance in Late Adulthood","authors":"Shivangi Jain, Alina Lesnovskaya, Lu Wan, Cristina Molina‐Hidalgo, Haiqing Huang, Anna Marsland, George Grove, Lauren Oberlin, Chaeryon Kang, Arthur Kramer, Charles Hillman, Edward McAuley, Jeffrey M Burns, Eric D Vidoni, Brad Sutton, Kirk I. Erickson","doi":"10.1002/alz.087429","DOIUrl":"https://doi.org/10.1002/alz.087429","url":null,"abstract":"BackgroundAging is associated with heightened systemic inflammation, decline in selective aspects of cognition, and an increase in white matter lesions (WMLs). Both WMLs and systemic inflammation have been related to cognition. However, it is not clear how they interdependently relate to cognitive aging. In this study we examined whether WMLs mediate the relation between markers of systemic inflammation and cognition in late adulthood.MethodBaseline data from the randomized clinical trial “Investigating Gains in Neurocognition in an Intervention Trial of Exercise” (IGNITE) were used, which included 598 healthy older adults (mean age=69.9±3.75 years). Interleukin 6 (IL‐6) and Tumor Necrosis Factor Alpha (TNF‐α) were included as markers of systemic inflammation. A confirmatory factor analysis of cognitive performance resulted in factors measuring episodic memory (EM), processing speed (PS), working memory (WM), attentional control (AC), and visuospatial function (VF). WML volumes were computed from FLAIR and T1 scans using UBO detector. Mediation models were run with age, sex, years of education, and study site included as covariates.ResultHigher levels of IL‐6 were associated with more WMLs (b = 0.12, p < 0.001) as well as lower scores on all cognitive factors (all p < 0.03). In contrast, higher levels of TNF‐ α were associated with more WMLs (b = 0.10, p < 0.05) but not with any of the cognitive measures (all p > 0.3). More WMLs were associated with poorer PS, WM, AC, and VF (all p < 0.03), but not EM (all p > 0.05). Further, associations between IL‐6 and measures of PS, WM, AC, and VF were statistically mediated by WMLs (all b = ‐0.01, all p < 0.05).ConclusionThese findings suggest that markers of systemic inflammation might lead to poorer cognitive performance by impacting WMLs. The differences between IL‐6 and TNF‐α with cognition highlight the need for more research to understand how different cytokine pathways relate to cognition. Our results are important for building a mechanistic framework to understand the interplay between inflammation, WMLs, and cognition and could inform the development of targeted interventions focusing on regulating cytokines to support brain health and cognitive aging.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"14 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subhashini K Rangarajan, Sonika Nichenametla, Vanteemar S Sreeraj, Vijaykumar Harbishettar, Preeti Sinha, Palanimuthu Thangaraju Sivakumar, Ganesan Venkatasubramanian
BackgroundMild cognitive impairment(MCI) is characterized by an impairment in one or more cognitive domains greater than expected for a person’s age and educational background with preserved functional independence. Functional Near Infra‐Red Spectroscopy (fNIRS) is a modality of non‐invasive neuroimaging that utilizes the optical properties of oxygenated and deoxygenated hemoglobin in the tissue to measure their absolute or relative concentrations following neuronal activity. fNIRS has been used to evaluate neurohemodynamics in MCI. Lower tissue oxygenation in bilateral frontal and parietal regions was found at resting state, which correlated with cognitive functioning in MCI. The objective of this study was to evaluate the correlation between cognitive functioning and resting state functional connectivity on fNIRS in MCI.MethodsThe study was conducted at the Geriatric Clinic and Services, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India (Institutional Ethics Committee approval no.: NIMHANS/34th IEC (BEH.SC.DIV.)/2022) on consenting participants with MCI (N = 38). Detailed cognitive assessment was performed using a validated comprehensive computerised cognitive battery. fNIRS data acquisition was done using the NIRScout device, NIRx medical technologies LLC, CA, USA, operating on continuous wave domain, with two wavelengths of 760nm and 850 nm. 8 sources and 8 detectors were placed in a bilateral prefrontal montage placement resulting in 18 channels (9 on each side). Nodal metrics such as clustering coefficient, degree centrality, shortest path length, local efficiency and a Global metric‐ small worldness was evaluated. Correlation coefficients were computed for the nodal and global metrics with cognitive domains such as reaction time, complex attention, memory, language functioning and perceptuomotor functioning.ResultsMean age of participants was 66.18 ± 6.18 years. The mean duration of illness was 2.63 ± 2.5 years. The results of the resting state nodal and global metrics and their correlation with cognitive functioning will be presented during the conference.ConclusionfNIRS is reported to have a temporal resolution that is comparable to fMRI, at the same time being less expensive, portable and having less interference because of motion artifacts. Findings from this study will provide insights on the functional connectivity correlates of cognitive functioning in MCI.
{"title":"Resting‐state functional connectivity correlates of cognitive function in Mild Cognitive Impairment on functional Near Infrared Spectroscopy","authors":"Subhashini K Rangarajan, Sonika Nichenametla, Vanteemar S Sreeraj, Vijaykumar Harbishettar, Preeti Sinha, Palanimuthu Thangaraju Sivakumar, Ganesan Venkatasubramanian","doi":"10.1002/alz.093543","DOIUrl":"https://doi.org/10.1002/alz.093543","url":null,"abstract":"BackgroundMild cognitive impairment(MCI) is characterized by an impairment in one or more cognitive domains greater than expected for a person’s age and educational background with preserved functional independence. Functional Near Infra‐Red Spectroscopy (fNIRS) is a modality of non‐invasive neuroimaging that utilizes the optical properties of oxygenated and deoxygenated hemoglobin in the tissue to measure their absolute or relative concentrations following neuronal activity. fNIRS has been used to evaluate neurohemodynamics in MCI. Lower tissue oxygenation in bilateral frontal and parietal regions was found at resting state, which correlated with cognitive functioning in MCI. The objective of this study was to evaluate the correlation between cognitive functioning and resting state functional connectivity on fNIRS in MCI.MethodsThe study was conducted at the Geriatric Clinic and Services, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India (Institutional Ethics Committee approval no.: NIMHANS/34th IEC (BEH.SC.DIV.)/2022) on consenting participants with MCI (N = 38). Detailed cognitive assessment was performed using a validated comprehensive computerised cognitive battery. fNIRS data acquisition was done using the NIRScout device, NIRx medical technologies LLC, CA, USA, operating on continuous wave domain, with two wavelengths of 760nm and 850 nm. 8 sources and 8 detectors were placed in a bilateral prefrontal montage placement resulting in 18 channels (9 on each side). Nodal metrics such as clustering coefficient, degree centrality, shortest path length, local efficiency and a Global metric‐ small worldness was evaluated. Correlation coefficients were computed for the nodal and global metrics with cognitive domains such as reaction time, complex attention, memory, language functioning and perceptuomotor functioning.ResultsMean age of participants was 66.18 ± 6.18 years. The mean duration of illness was 2.63 ± 2.5 years. The results of the resting state nodal and global metrics and their correlation with cognitive functioning will be presented during the conference.ConclusionfNIRS is reported to have a temporal resolution that is comparable to fMRI, at the same time being less expensive, portable and having less interference because of motion artifacts. Findings from this study will provide insights on the functional connectivity correlates of cognitive functioning in MCI.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"6 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yatian Li, Jingnan Wu, Zhixing Zhou, Nan Chen, Huanhuan Xia
BackgroundOlder adults with cognitive impairments will benefit from multicomponent interventions include cognitive training, exercise, and lifestyle modifications. However, many existing digital therapeutic products predominantly focus on computerized cognitive training, lacking effective approaches to other crucial interventions. We proposed a multidimensional comprehensive cognitive intervention training program – Brain and Body Rehab Training (BBRT), which integrates multidomain cognitive training with physical‐cognitive training and multidimensional lifestyle interventions and developed the digital therapeutic product – BBRT‐online based on WeChat mini‐program. The present study was to assess the effectiveness of BBRT in older adults with subjective memory impairments.MethodUsing the WeChat mini‐program platform, we developed the BBRT‐online digital therapeutics product. Prior to the intervention, users undergo Game‐based Cognitive Assessment – Three‐Minute Version (G3). Subsequently, an individualized training program is assigned consisting of completing four to five daily tasks, including cognitive training, physical‐cognitive training, lifestyle interventions, chronic disease/diet/sleep/emotion management, and traditional Chinese medicine non‐pharmacological interventions among others (Figure 1). The intervention duration ranges 15‐25 minutes per day, and task difficulty is dynamically adjusted based on individual task performance and periodic cognitive assessments. Additionally, remote online administration services and internet communities are strongly recommended to offer emotional support and enhance intervention effectiveness. Sixty older adults reporting subjective memory complaints were recruited, with 30 assigned to receive BBRT‐online training and the remainder serving as the control group. Cognitive function was evaluated using the G3 at baseline and three months later. T‐tests were conducted to assess the impact of BBRT‐online on cognitive function.ResultAt baseline, there was no significant difference in G3 scores between the BBRT group (53.5±10.87) and the control group (55.1±11.77, p = 0.583). Following three months of intervention, the BBRT group demonstrated a significantly higher G3 score (61.5±6.85) compared to baseline (p<0.001, Figure 2). Conversely, no such difference was observed in the control group (55.5 ± 9.34, p = 0.911).ConclusionThe BBRT digital therapeutics enabled cognitive assessment and individualized cognitive interventions and significantly improved cognitive function in older adults. Further studies are required to evaluate its effectiveness.
{"title":"A Multidimensional Comprehensive Cognitive Intervention Training Program: Introduction of a Non‐Pharmacological Digital Therapeutic and Preliminary Results of Effectiveness on Cognitive Function","authors":"Yatian Li, Jingnan Wu, Zhixing Zhou, Nan Chen, Huanhuan Xia","doi":"10.1002/alz.089572","DOIUrl":"https://doi.org/10.1002/alz.089572","url":null,"abstract":"BackgroundOlder adults with cognitive impairments will benefit from multicomponent interventions include cognitive training, exercise, and lifestyle modifications. However, many existing digital therapeutic products predominantly focus on computerized cognitive training, lacking effective approaches to other crucial interventions. We proposed a multidimensional comprehensive cognitive intervention training program – Brain and Body Rehab Training (BBRT), which integrates multidomain cognitive training with physical‐cognitive training and multidimensional lifestyle interventions and developed the digital therapeutic product – BBRT‐online based on WeChat mini‐program. The present study was to assess the effectiveness of BBRT in older adults with subjective memory impairments.MethodUsing the WeChat mini‐program platform, we developed the BBRT‐online digital therapeutics product. Prior to the intervention, users undergo Game‐based Cognitive Assessment – Three‐Minute Version (G3). Subsequently, an individualized training program is assigned consisting of completing four to five daily tasks, including cognitive training, physical‐cognitive training, lifestyle interventions, chronic disease/diet/sleep/emotion management, and traditional Chinese medicine non‐pharmacological interventions among others (Figure 1). The intervention duration ranges 15‐25 minutes per day, and task difficulty is dynamically adjusted based on individual task performance and periodic cognitive assessments. Additionally, remote online administration services and internet communities are strongly recommended to offer emotional support and enhance intervention effectiveness. Sixty older adults reporting subjective memory complaints were recruited, with 30 assigned to receive BBRT‐online training and the remainder serving as the control group. Cognitive function was evaluated using the G3 at baseline and three months later. T‐tests were conducted to assess the impact of BBRT‐online on cognitive function.ResultAt baseline, there was no significant difference in G3 scores between the BBRT group (53.5±10.87) and the control group (55.1±11.77, p = 0.583). Following three months of intervention, the BBRT group demonstrated a significantly higher G3 score (61.5±6.85) compared to baseline (p<0.001, Figure 2). Conversely, no such difference was observed in the control group (55.5 ± 9.34, p = 0.911).ConclusionThe BBRT digital therapeutics enabled cognitive assessment and individualized cognitive interventions and significantly improved cognitive function in older adults. Further studies are required to evaluate its effectiveness.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"45 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hash Brown Taha, Allison Birnbaum, Ian Matthews, Karel Aceituno, Jocelyne Leon, Max A Thorwald, Jose A Godoy‐Lugo, Constanza J Cortes
BackgroundAlzheimer’s disease (AD) is associated with complex pathophysiology including synaptic dysregulation, compromised neurotrophic signaling, deficits in autophagic flux and neuroinflammation). Skeletal muscle regulates many brain functions relevant to aging, by activating the muscle‐to‐brain axis through the secretion of skeletal muscle originating factors (myokines) with cellular‐modifying, neuro and geroprotective properties. Our group developed transgenic mice that overexpress the skeletal muscle human Transcription Factor EB (TFEB), a master regulator of lysosomal‐to‐nucleus signaling, resulting in enhanced proteostasis and neuroprotection in a Tau mouse model. However, the precise mechanisms remain unknown. Therefore, we further validated these effects in an AD amyloid β (Aβ) mouse model and investigated the underlying mechanism.MethodWe crossbred female 5xFAD mice, carrying 5 AD familial mutations, with transgenic mice that overexpress human TFEB to create 5xFAD;cTFEB;HSA‐Cre (3FA) mice. At 4 and 8 months of age, we analyzed Aβ plaque accumulation through immunohistochemistry and conducted western blot analysis for multiple synaptic markers, growth factors, autophagic/lysosomal regulators, and myokines across the muscle‐to‐brain axis. We also performed a battery of neurocognitive tests (open field, the Barnes maze, and fear conditioning) at 8 months of age, when this model has previously been reported to demonstrate robust cognitive impairment.ResultSkeletal muscle‐targeted TFEB expression reduced Aβ plaque accumulation in cortices of 4‐month‐old female mice. Furthermore, muscle‐TFEB expression altered synaptic‐associated gene transcriptional signatures in hippocampi, and rescued behavioral deficits in 8‐month‐old female 5xFAD mice. Western blots of cortex from 8‐month‐old female 3FA mice confirmed a rescue of several synaptic markers including SNAP25, synaptophysin I, synaptotagmin I and PSD95, neurotrophic factors such as BDNF and autophagic/lysosomal regulators such as Cathepsin D and B, prosaposin (PSAP) and saposin C. Levels of PSAP (a recently identified exercise‐responsive myokine) were also increased in skeletal muscle, plasma and cortices, suggesting that PSAP may act as a novel myokine involved in muscle‐to‐brain rescue mechanisms. scle, plasma and cortices of 8‐month‐old female mice, suggesting that PSAP may act as a novel myokine involved in muscle‐to‐brain rescue mechanisms.ConclusionSkeletal muscle directly regulates CNS function and health in the 5xFAD model regulating synaptic integrity, neurotrophic signaling and autophagic flux, potentially through release of CNS‐targeting myokines.
{"title":"Activation of the muscle‐to‐brain‐axis reduces amyloid plaque accumulation and rescues behavioral deficits by enhancing synaptic integrity and neurotrophic signaling in a mouse model of Alzheimer’s disease","authors":"Hash Brown Taha, Allison Birnbaum, Ian Matthews, Karel Aceituno, Jocelyne Leon, Max A Thorwald, Jose A Godoy‐Lugo, Constanza J Cortes","doi":"10.1002/alz.094857","DOIUrl":"https://doi.org/10.1002/alz.094857","url":null,"abstract":"BackgroundAlzheimer’s disease (AD) is associated with complex pathophysiology including synaptic dysregulation, compromised neurotrophic signaling, deficits in autophagic flux and neuroinflammation). Skeletal muscle regulates many brain functions relevant to aging, by activating the muscle‐to‐brain axis through the secretion of skeletal muscle originating factors (myokines) with cellular‐modifying, neuro and geroprotective properties. Our group developed transgenic mice that overexpress the skeletal muscle human Transcription Factor EB (TFEB), a master regulator of lysosomal‐to‐nucleus signaling, resulting in enhanced proteostasis and neuroprotection in a Tau mouse model. However, the precise mechanisms remain unknown. Therefore, we further validated these effects in an AD amyloid β (Aβ) mouse model and investigated the underlying mechanism.MethodWe crossbred female 5xFAD mice, carrying 5 AD familial mutations, with transgenic mice that overexpress human TFEB to create 5xFAD;cTFEB;HSA‐Cre (3FA) mice. At 4 and 8 months of age, we analyzed Aβ plaque accumulation through immunohistochemistry and conducted western blot analysis for multiple synaptic markers, growth factors, autophagic/lysosomal regulators, and myokines across the muscle‐to‐brain axis. We also performed a battery of neurocognitive tests (open field, the Barnes maze, and fear conditioning) at 8 months of age, when this model has previously been reported to demonstrate robust cognitive impairment.ResultSkeletal muscle‐targeted TFEB expression reduced Aβ plaque accumulation in cortices of 4‐month‐old female mice. Furthermore, muscle‐TFEB expression altered synaptic‐associated gene transcriptional signatures in hippocampi, and rescued behavioral deficits in 8‐month‐old female 5xFAD mice. Western blots of cortex from 8‐month‐old female 3FA mice confirmed a rescue of several synaptic markers including SNAP25, synaptophysin I, synaptotagmin I and PSD95, neurotrophic factors such as BDNF and autophagic/lysosomal regulators such as Cathepsin D and B, prosaposin (PSAP) and saposin C. Levels of PSAP (a recently identified exercise‐responsive myokine) were also increased in skeletal muscle, plasma and cortices, suggesting that PSAP may act as a novel myokine involved in muscle‐to‐brain rescue mechanisms. scle, plasma and cortices of 8‐month‐old female mice, suggesting that PSAP may act as a novel myokine involved in muscle‐to‐brain rescue mechanisms.ConclusionSkeletal muscle directly regulates CNS function and health in the 5xFAD model regulating synaptic integrity, neurotrophic signaling and autophagic flux, potentially through release of CNS‐targeting myokines.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"23 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeewon Suh, Mi Kyoung Kang, Kyung‐hae Lee, Myoung Hwa Park, Im‐Seok Koh
ObjectiveThis study aims to validate the effectiveness of the education program for dementia family caregivers (so‐called Value Care program), and to assess the applicability of the program at local dementia centers in the community.MethodThe Value Care program is an educational program designed for family caregivers of dementia, conducted once a week for 90 minutes over a total duration of 8 weeks. This program aims to enhance understanding of the characteristics and symptoms of dementia at various stages and to provide specific response strategies for caregivers.In this case‐control study, family caregivers of dementia patients were recruited from 38 local dementia centers in Korea. Each participants were randomly assigned to either the experimental group or the control group in a 1:1 ratio. After 8 weeks, assessment was conducted on measure such as depression, care‐burden scales, caregiver self‐efficacy and satisfaction surveys.ResultsA total of 226 family caregivers were recruited in the experimental group, and 210 participants in the control group. The experimental group showed significant reductions in depression (P<0.001) and care‐burden scores (P<0.001) and significant increases in caregiver self‐efficacy scores (P<0.001) after participating in the Value Care program. The overall satisfaction score averaged 4.47 over 5.ConclusionThe “Value Care Program” demonstrated effectiveness in reducing depression, care burden, and enhancing the efficacy of care for family caregivers of dementia patients. Participants expressed a high likelihood of rejoining the program and recommending it to others. Therefore, the Value Care Program could be a crucial initiative for alleviating caregiver burden, stress, and feelings of depression among dementia family caregivers.
{"title":"Validation study of the effectiveness of a stepwise care program for dementia family caregivers","authors":"Jeewon Suh, Mi Kyoung Kang, Kyung‐hae Lee, Myoung Hwa Park, Im‐Seok Koh","doi":"10.1002/alz.092289","DOIUrl":"https://doi.org/10.1002/alz.092289","url":null,"abstract":"ObjectiveThis study aims to validate the effectiveness of the education program for dementia family caregivers (so‐called Value Care program), and to assess the applicability of the program at local dementia centers in the community.MethodThe Value Care program is an educational program designed for family caregivers of dementia, conducted once a week for 90 minutes over a total duration of 8 weeks. This program aims to enhance understanding of the characteristics and symptoms of dementia at various stages and to provide specific response strategies for caregivers.In this case‐control study, family caregivers of dementia patients were recruited from 38 local dementia centers in Korea. Each participants were randomly assigned to either the experimental group or the control group in a 1:1 ratio. After 8 weeks, assessment was conducted on measure such as depression, care‐burden scales, caregiver self‐efficacy and satisfaction surveys.ResultsA total of 226 family caregivers were recruited in the experimental group, and 210 participants in the control group. The experimental group showed significant reductions in depression (P<0.001) and care‐burden scores (P<0.001) and significant increases in caregiver self‐efficacy scores (P<0.001) after participating in the Value Care program. The overall satisfaction score averaged 4.47 over 5.ConclusionThe “Value Care Program” demonstrated effectiveness in reducing depression, care burden, and enhancing the efficacy of care for family caregivers of dementia patients. Participants expressed a high likelihood of rejoining the program and recommending it to others. Therefore, the Value Care Program could be a crucial initiative for alleviating caregiver burden, stress, and feelings of depression among dementia family caregivers.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"20 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The population of older adults in India is projected to increase from the current estimate of 150 million to 350 million by the year 2050. The prevalence of older adults with mental health problems including dementia is also increasing rapidly. The socio‐cultural changes in the joint family system have necessitated the increasing requirement of formal caregivers for supporting the care of older adults in home as well as residential care institutions. Home care services providing caregiver assistance, day care, old age homes, residential care institutions for persons with mental illness or dementia are available predominantly in major cities. However, there is a huge variability in the profile of formal caregivers ranging from those with no training to qualified nurses as caregivers depending on the affordability. The need for training of formal caregivers in geriatric mental health and dementia care is acknowledged by most of the the stakeholders in the care of older adults. However, there are no minimum standards of training for the formal caregivers. The lack of trained caregivers has contributed to the increase of elder abuse, higher stress, and burnout for the caregivers with adverse impact on the quality of care of older adults. This presentation will summarize the experience and challenges related to the implementation of the training of formal caregivers in geriatric mental health and dementia care. The training initiatives for the formal caregivers conducted by the Government and Non‐Governmental organizations ranges from brief sensitization program for half a day to formal certificate course for 3 months. Most of the training programs are focused on the basic aspects of geriatric care with inadequate component of practical training. High rates of discontinuation and change of jobs, poor working conditions, lack of motivation among the caregivers and employers, lack of mandatory requirement of training are some of the important challenges limiting the progress in ensuring trained formal caregivers.
{"title":"Training of formal caregivers in geriatric mental health and dementia care: Experiences and challenges from the Indian context","authors":"Palanimuthu Thangaraju Sivakumar","doi":"10.1002/alz.087183","DOIUrl":"https://doi.org/10.1002/alz.087183","url":null,"abstract":"The population of older adults in India is projected to increase from the current estimate of 150 million to 350 million by the year 2050. The prevalence of older adults with mental health problems including dementia is also increasing rapidly. The socio‐cultural changes in the joint family system have necessitated the increasing requirement of formal caregivers for supporting the care of older adults in home as well as residential care institutions. Home care services providing caregiver assistance, day care, old age homes, residential care institutions for persons with mental illness or dementia are available predominantly in major cities. However, there is a huge variability in the profile of formal caregivers ranging from those with no training to qualified nurses as caregivers depending on the affordability. The need for training of formal caregivers in geriatric mental health and dementia care is acknowledged by most of the the stakeholders in the care of older adults. However, there are no minimum standards of training for the formal caregivers. The lack of trained caregivers has contributed to the increase of elder abuse, higher stress, and burnout for the caregivers with adverse impact on the quality of care of older adults. This presentation will summarize the experience and challenges related to the implementation of the training of formal caregivers in geriatric mental health and dementia care. The training initiatives for the formal caregivers conducted by the Government and Non‐Governmental organizations ranges from brief sensitization program for half a day to formal certificate course for 3 months. Most of the training programs are focused on the basic aspects of geriatric care with inadequate component of practical training. High rates of discontinuation and change of jobs, poor working conditions, lack of motivation among the caregivers and employers, lack of mandatory requirement of training are some of the important challenges limiting the progress in ensuring trained formal caregivers.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"24 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Bethell, Karen Myers, Myrna Norman, Ellen Snowball, Katherine S McGilton
Engagement of People with Lived Experience of Dementia (EPLED) was a new cross‐cutting program introduced as part of the Canadian Consortium on Neurodegeneration in Aging (CCNA) for their second 5‐year phase (from 2019 to 2024). The initiative was supported by the Alzheimer Society of Canada as part of their commitment to the CCNA. EPLED had three objectives: (1) support persons with dementia and care partners to be actively involved in the CCNA research process; (2) work with CCNA research Teams, Cross‐cutting Programs and Partners to develop novel mechanisms and formats to further this collaboration; and, (3) advance the methods of patient engagement in research by embedding evaluation. One of the main activities of EPLED was to recruit and support an Advisory Group of people from across Canada with diverse lived experiences of dementia. Since 2020, EPLED Advisory Group members became involved in various CCNA central and research team activities as well as contributing as co‐presenters and co‐authors in academic and non‐academic venues and as co‐applicants and co‐investigators on research grants. Advisory Group members also took on roles advocating for more people living with dementia in research roles. Key factors described for the success of the Advisory Group were developing trusting relationships, providing education, offering support, being flexible and acknowledging tensions between research, practice and lived experience. Ongoing challenges often related to the gap between research and practice and balancing EPLED’s research objectives with aspirations for advocacy and system‐level change. Looking forward to the third phase of the CCNA, key challenges will include: developing capacity to meet increasing research funding expectations of engagement while also ensuring meaningful engagement, engaging new perspectives by recruiting new Advisory Group members while also retaining expertise from existing members, evaluating the impact of engagement and initiating EPLED‐driven research initiatives.
{"title":"Engaging people with lived experience in a national research network: Experience from the Canadian Consortium on Neurodegeneration in Aging","authors":"Jennifer Bethell, Karen Myers, Myrna Norman, Ellen Snowball, Katherine S McGilton","doi":"10.1002/alz.085965","DOIUrl":"https://doi.org/10.1002/alz.085965","url":null,"abstract":"Engagement of People with Lived Experience of Dementia (EPLED) was a new cross‐cutting program introduced as part of the Canadian Consortium on Neurodegeneration in Aging (CCNA) for their second 5‐year phase (from 2019 to 2024). The initiative was supported by the Alzheimer Society of Canada as part of their commitment to the CCNA. EPLED had three objectives: (1) support persons with dementia and care partners to be actively involved in the CCNA research process; (2) work with CCNA research Teams, Cross‐cutting Programs and Partners to develop novel mechanisms and formats to further this collaboration; and, (3) advance the methods of patient engagement in research by embedding evaluation. One of the main activities of EPLED was to recruit and support an Advisory Group of people from across Canada with diverse lived experiences of dementia. Since 2020, EPLED Advisory Group members became involved in various CCNA central and research team activities as well as contributing as co‐presenters and co‐authors in academic and non‐academic venues and as co‐applicants and co‐investigators on research grants. Advisory Group members also took on roles advocating for more people living with dementia in research roles. Key factors described for the success of the Advisory Group were developing trusting relationships, providing education, offering support, being flexible and acknowledging tensions between research, practice and lived experience. Ongoing challenges often related to the gap between research and practice and balancing EPLED’s research objectives with aspirations for advocacy and system‐level change. Looking forward to the third phase of the CCNA, key challenges will include: developing capacity to meet increasing research funding expectations of engagement while also ensuring meaningful engagement, engaging new perspectives by recruiting new Advisory Group members while also retaining expertise from existing members, evaluating the impact of engagement and initiating EPLED‐driven research initiatives.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"24 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arthur C. Macedo, Joseph Therriault, Nesrine Rahmouni, Stijn Servaes, Yi‐Ting Wang, Cécile Tissot, Firoza Z Lussier, Jaime Fernandez Arias, Kely Monica Quispialaya Socualaya, Seyyed Ali Hosseini, Pamela C.L. Ferreira, Bruna Bellaver, João Pedro Ferrari‐Souza, Cristiano Schaffer Aguzzoli, Guilherme Povala, Belen Pascual, Brian A. Gordon, Val J. Lowe, Hwamee Oh, David N. soleimani‐meigooni, Suzanne L. Baker, Tharick Ali Pascoal, Pedro Rosa‐Neto
BackgroundTau‐PET tracers allow for in vivo Braak staging of individuals in the Alzheimer’s disease (AD) continuum. The impact of tracers’ characteristics for Braak staging using tau‐PET remains unclear. Therefore, we performed a head‐to‐head comparison of Braak staging using first‐ and second‐generation tau‐PET tracers.MethodWe assessed 51 cognitively unimpaired (CU) and 49 cognitively impaired participants (mean [SD] age 69.4 [7.5] years) with at least two tau‐PET ligands ([18F]MK6240, [18F]AV1451, and/or [18F]RO948) at McGill University, as part of the HEAD study. We calculated standardized uptake value ratios (SUVR) in Braak‐like regions of interest (ROI) for each ligand and investigated their association using Spearman’s correlation. Thresholds defined the presence of tauopathy in each Braak ROI, which was used to assign a Braak stage to each participant. Finally, we assessed the agreement between the Braak staging provided by each tracer, both for the traditional (using separate Braak stages – 0, I, II, III, IV, V, and VI) and simplified (using joint Braak stages – 0, I‐II, III‐IV, and V‐VI) frameworks.ResultIn all Braak ROIs, we found positive correlations between the SUVR values of the three tracers (Figure 1). The strongest correlation was between [18F]MK6240 and [18F]RO948 in Braak II (r=0.94), and the weakest between [18F]AV1451 and [18F]RO948 in VI (r=0.51). Inter‐tracer agreement regarding the latest stage of abnormality was substantial or nearly perfect between pairs of tracers but moderate between the three tracers (Figure 2A). The simplified framework presented greater agreement compared to traditional Braak staging, except between [18F]MK6240 and [18F]RO948. At the ROI level, the lowest agreements were observed for Braak II and I‐II, when [18F]MK6240 and [18F]RO948 were compared to [18F]AV1451 (Figure 2B‐C). [18F]AV1451 had the highest probability of overestimating the Braak stage assigned by [18F]MK6240 and by [18F]RO948, especially at earlier stages (Figure 3).ConclusionThe ligands presented moderate to nearly perfect agreement for in vivo staging of AD severity. Off‐target binding of [18F]AV1451 to the choroid plexus might explain disagreements at early stages. Overall, slight improvements in agreements were achieved with the simplified framework, as observed in histopathological staging.
{"title":"Comparison of tau‐PET tracers for in vivo Braak staging: the HEAD Study","authors":"Arthur C. Macedo, Joseph Therriault, Nesrine Rahmouni, Stijn Servaes, Yi‐Ting Wang, Cécile Tissot, Firoza Z Lussier, Jaime Fernandez Arias, Kely Monica Quispialaya Socualaya, Seyyed Ali Hosseini, Pamela C.L. Ferreira, Bruna Bellaver, João Pedro Ferrari‐Souza, Cristiano Schaffer Aguzzoli, Guilherme Povala, Belen Pascual, Brian A. Gordon, Val J. Lowe, Hwamee Oh, David N. soleimani‐meigooni, Suzanne L. Baker, Tharick Ali Pascoal, Pedro Rosa‐Neto","doi":"10.1002/alz.087615","DOIUrl":"https://doi.org/10.1002/alz.087615","url":null,"abstract":"BackgroundTau‐PET tracers allow for in vivo Braak staging of individuals in the Alzheimer’s disease (AD) continuum. The impact of tracers’ characteristics for Braak staging using tau‐PET remains unclear. Therefore, we performed a head‐to‐head comparison of Braak staging using first‐ and second‐generation tau‐PET tracers.MethodWe assessed 51 cognitively unimpaired (CU) and 49 cognitively impaired participants (mean [SD] age 69.4 [7.5] years) with at least two tau‐PET ligands ([<jats:sup>18</jats:sup>F]MK6240, [<jats:sup>18</jats:sup>F]AV1451, and/or [<jats:sup>18</jats:sup>F]RO948) at McGill University, as part of the HEAD study. We calculated standardized uptake value ratios (SUVR) in Braak‐like regions of interest (ROI) for each ligand and investigated their association using Spearman’s correlation. Thresholds defined the presence of tauopathy in each Braak ROI, which was used to assign a Braak stage to each participant. Finally, we assessed the agreement between the Braak staging provided by each tracer, both for the traditional (using separate Braak stages – 0, I, II, III, IV, V, and VI) and simplified (using joint Braak stages – 0, I‐II, III‐IV, and V‐VI) frameworks.ResultIn all Braak ROIs, we found positive correlations between the SUVR values of the three tracers (Figure 1). The strongest correlation was between [<jats:sup>18</jats:sup>F]MK6240 and [<jats:sup>18</jats:sup>F]RO948 in Braak II (r=0.94), and the weakest between [<jats:sup>18</jats:sup>F]AV1451 and [<jats:sup>18</jats:sup>F]RO948 in VI (r=0.51). Inter‐tracer agreement regarding the latest stage of abnormality was substantial or nearly perfect between pairs of tracers but moderate between the three tracers (Figure 2A). The simplified framework presented greater agreement compared to traditional Braak staging, except between [<jats:sup>18</jats:sup>F]MK6240 and [<jats:sup>18</jats:sup>F]RO948. At the ROI level, the lowest agreements were observed for Braak II and I‐II, when [<jats:sup>18</jats:sup>F]MK6240 and [<jats:sup>18</jats:sup>F]RO948 were compared to [<jats:sup>18</jats:sup>F]AV1451 (Figure 2B‐C). [<jats:sup>18</jats:sup>F]AV1451 had the highest probability of overestimating the Braak stage assigned by [<jats:sup>18</jats:sup>F]MK6240 and by [<jats:sup>18</jats:sup>F]RO948, especially at earlier stages (Figure 3).ConclusionThe ligands presented moderate to nearly perfect agreement for in vivo staging of AD severity. Off‐target binding of [<jats:sup>18</jats:sup>F]AV1451 to the choroid plexus might explain disagreements at early stages. Overall, slight improvements in agreements were achieved with the simplified framework, as observed in histopathological staging.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"38 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tobey J. Betthauser, Eric E Abrahamson, Elena Ruiz De Chavez, Jordan P Teague, Andrew K McVea, Yuetiva Deming, Brooke E Schroeder, Madeleine R Barger, Sterling C. Johnson, Sanjay Asthana, Victor L Villemagne, Bradley T. Christian, Shahriar Salamat, Milos D Ikonomovic
Background[18F]MK‐6240 was developed for PET imaging of AD tau pathology, but the exact molecular signature of specific binding remains unclear. This study quantified levels of four phospho‐tau forms and total tau in postmortem brain tissues from [18F]MK‐6240 imaged cases to investigate associations with antemortem [18F]MK‐6240 PET.MethodsThis study included four participants from the Wisconsin ADRC or WRAP with antemortem [18F]MK‐6240 and [11C]PiB PET imaging and postmortem brain tissue obtained on average 32‐months after imaging (Table 1). Parametric SUVR were generated using T1‐w MRI to delineate regions matched to equivalent ROIs on fresh frozen brain tissue slabs. Tissue ROI dissected from ten brain regions per case were homogenized and ELISA was used to quantify concentrations of guanidine‐extracted total tau and tau phosphorylated at epitopes pThr181, pSer199, pThr231, and pSer396.ResultsMatched PET‐autopsy ROI analysis showed significant correlations of higher [18F]MK‐6240 SUVR with higher levels of all measured p‐tau forms or their ratios to total tau across all regions and cases. Analyses of two A+T+ cases with clinical AD dementia and postmortem Thal Phase 5/Braak NFT Stage VI showed higher [18F]MK‐6240 SUVR correlated significantly with higher levels of pThr181, pSer199, pThr231, and pSer396 tau or their ratios to total tau in a 79‐yo APOE‐ε4ε4 case, and with higher levels of pThr231 and pSer396 tau in a 78‐yo APOE‐ε3ε3 case. In two T‐ cases, we observed weak correlations of [18F]MK‐6240 SUVR with pThr181 and pSer396 tau in an A‐T‐ cognitively unimpaired case (Thal Phase 2/Braak NFT Stage II; 70‐yo; APOE‐ε3ε3), but no correlations in A+T‐ early‐onset AD dementia case with Thal Phase 4/Braak NFT Stage V (63‐yo; APOE‐ε4ε4). This latter case also had high [18F]MK‐6240 uptake outside the brain and a low tangle density outside the MTL.ConclusionsHigher [18F]MK‐6240 PET binding reflects high brain concentrations of pThr181, pSer199, pThr231, and pSer396 tau in AD dementia cases with high AD neuropathological change. Lack of associations between PET and p‐tau biochemistry in the T‐, Braak V early‐onset dementia case suggests that the T‐ PET status is more closely associated with p‐tau biochemistry than postmortem neuropathological staging, likely due to low tangle density.
{"title":"Correlations of antemortem [18F]MK‐6240 PET with ROI‐matched postmortem biochemical assessment of total tau and tau phospho‐epitopes pThr181, pSer199, pThr231, and pSer396","authors":"Tobey J. Betthauser, Eric E Abrahamson, Elena Ruiz De Chavez, Jordan P Teague, Andrew K McVea, Yuetiva Deming, Brooke E Schroeder, Madeleine R Barger, Sterling C. Johnson, Sanjay Asthana, Victor L Villemagne, Bradley T. Christian, Shahriar Salamat, Milos D Ikonomovic","doi":"10.1002/alz.089407","DOIUrl":"https://doi.org/10.1002/alz.089407","url":null,"abstract":"Background[<jats:sup>18</jats:sup>F]MK‐6240 was developed for PET imaging of AD tau pathology, but the exact molecular signature of specific binding remains unclear. This study quantified levels of four phospho‐tau forms and total tau in postmortem brain tissues from [<jats:sup>18</jats:sup>F]MK‐6240 imaged cases to investigate associations with antemortem [<jats:sup>18</jats:sup>F]MK‐6240 PET.MethodsThis study included four participants from the Wisconsin ADRC or WRAP with antemortem [<jats:sup>18</jats:sup>F]MK‐6240 and [<jats:sup>11</jats:sup>C]PiB PET imaging and postmortem brain tissue obtained on average 32‐months after imaging (Table 1). Parametric SUVR were generated using T1‐w MRI to delineate regions matched to equivalent ROIs on fresh frozen brain tissue slabs. Tissue ROI dissected from ten brain regions per case were homogenized and ELISA was used to quantify concentrations of guanidine‐extracted total tau and tau phosphorylated at epitopes pThr181, pSer199, pThr231, and pSer396.ResultsMatched PET‐autopsy ROI analysis showed significant correlations of higher [<jats:sup>18</jats:sup>F]MK‐6240 SUVR with higher levels of all measured p‐tau forms or their ratios to total tau across all regions and cases. Analyses of two A+T+ cases with clinical AD dementia and postmortem Thal Phase 5/Braak NFT Stage VI showed higher [<jats:sup>18</jats:sup>F]MK‐6240 SUVR correlated significantly with higher levels of pThr181, pSer199, pThr231, and pSer396 tau or their ratios to total tau in a 79‐yo APOE‐ε4ε4 case, and with higher levels of pThr231 and pSer396 tau in a 78‐yo APOE‐ε3ε3 case. In two T‐ cases, we observed weak correlations of [<jats:sup>18</jats:sup>F]MK‐6240 SUVR with pThr181 and pSer396 tau in an A‐T‐ cognitively unimpaired case (Thal Phase 2/Braak NFT Stage II; 70‐yo; APOE‐ε3ε3), but no correlations in A+T‐ early‐onset AD dementia case with Thal Phase 4/Braak NFT Stage V (63‐yo; APOE‐ε4ε4). This latter case also had high [<jats:sup>18</jats:sup>F]MK‐6240 uptake outside the brain and a low tangle density outside the MTL.ConclusionsHigher [<jats:sup>18</jats:sup>F]MK‐6240 PET binding reflects high brain concentrations of pThr181, pSer199, pThr231, and pSer396 tau in AD dementia cases with high AD neuropathological change. Lack of associations between PET and p‐tau biochemistry in the T‐, Braak V early‐onset dementia case suggests that the T‐ PET status is more closely associated with p‐tau biochemistry than postmortem neuropathological staging, likely due to low tangle density.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"15 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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