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Aron S Buchman - One of the best experts on this subject based on the ideXlab platform.

  • Spinal Arteriolosclerosis Is Common in Older Adults and Associated With Parkinsonism
    Stroke, 2017
    Co-Authors: Aron S Buchman, Sukriti Nag, Sue Leurgans, Veronique G.j.m. Vanderhorst, Alifiya Kapasi
    Abstract:

    Background and Purpose— There are few studies of spinal microvascular pathologies in older adults. We characterized spinal cord microvascular pathologies and examined their associations with other spinal and brain postmortem indices and parkinsonism in older adults. Methods— We documented 3 features of microvascular pathologies in spinal cord and brain specimens from 165 deceased older participants. We also measured spinal white matter pallor. Parkinsonian signs were assessed with a modified version of the motor section of the Unified Parkinson’s Disease Rating Scale. We examined the associations of spinal Arteriolosclerosis with other spinal and brain postmortem indices and parkinsonism proximate to death using regression models which controlled for age and sex. Results— Microinfarcts and cerebral amyloid angiopathy were not observed within the spinal cord parenchyma. Spinal Arteriolosclerosis was observed at all spinal levels (C7, T7, L4, S4) examined and was more severe posteriorly than anteriorly (posterior: 4.3, SD=0.72 versus anterior: 3.9, SD=0.74; t =14.58; P t =10.39; P r =0.47; P Conclusions— Although the regional distribution of microvascular pathologies varies within the central nervous system, spinal Arteriolosclerosis is common and may contribute to the severity of spinal white matter pallor and parkinsonism in older adults.

  • response to letter regarding article sleep fragmentation cerebral Arteriolosclerosis and brain infarct pathology in community dwelling older people
    Stroke, 2016
    Co-Authors: Andrew S P Lim, David A Bennett, Aron S Buchman
    Abstract:

    We thank Dr Kawada1 for his interest in our study, which showed that sleep fragmentation is associated with postmortem evidence of areteriolosclerosis and subcortical infarcts. We collected objective measures of sleep fragmentation in the community-setting from more than a 1000 older participants in the Rush Memory and Aging Project—a volunteer cohort in which all participants agree to brain donation on death and in which the autopsy rate is ≈ 90%.2 Because this was a selected cohort, we …

  • sleep fragmentation cerebral Arteriolosclerosis and brain infarct pathology in community dwelling older people
    Stroke, 2016
    Co-Authors: Andrew S P Lim, David A Bennett, Julie A Schneider, Aron S Buchman
    Abstract:

    Background and Purpose— Although several forms of sleep disruption are associated with stroke, few studies have examined the relationship between sleep and histopathologic measures of cerebrovascular disease. We tested the hypothesis that greater sleep fragmentation is associated with a higher burden of cerebral vessel and infarct pathology at autopsy. Methods— We used ordinal logistic regression models to relate sleep fragmentation measured by actigraphy to the severity of Arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy, and the number of macroscopic and microscopic infarcts assessed by structured brain autopsy in 315 participants from the Rush Memory and Aging Project. Results— Greater sleep fragmentation was associated with more severe Arteriolosclerosis (odds ratio, 1.27; 95% confidence interval, 1.02–1.59; P =0.03 per 1 SD greater sleep fragmentation) and more subcortical macroscopic infarcts (odds ratio, 1.31; 95% confidence interval, 1.01–1.68; P =0.04). These associations were independent of established cardiovascular risk factors and diseases, and several medical comorbidities. Conclusions— Sleep fragmentation is associated with Arteriolosclerosis and subcortical infarcts in older adults.

  • microvascular brain pathology and late life motor impairment
    Neurology, 2013
    Co-Authors: Aron S Buchman, Patricia A Boyle, Steven R Levine, Sukriti Nag, Julie A Schneider, David A Bennett
    Abstract:

    Objective: To test the hypothesis that microvascular brain pathology is associated with late-life motor impairment. Methods: More than 2,500 persons participating in the Religious Orders Study or the Memory and Aging Project agreed to annual motor assessment and autopsy. Brains from 850 deceased participants were assessed for microvascular pathology including microinfarcts, cerebral amyloid angiopathy, and Arteriolosclerosis, and we examined their association with global motor scores proximate to death. Results: Mean age at death was 88.5 years. More than 60% of cases had evidence of 1 or more microvascular pathologies and of these more than half did not have observed macroinfarcts. In separate regression models adjusted for age, sex, and education, microinfarcts and Arteriolosclerosis were associated with level of motor function proximate to death (Arteriolosclerosis, estimate, −0.027, SE 0.005, p p = 0.026). These associations were not attenuated when controlling for vascular risk factors and diseases, postmortem interval, or interval from last clinical examination, and did not vary with level of cognition or presence of dementia proximate to death. When the 3 microvascular pathologies, macroinfarcts, and atherosclerosis were considered together in a single model, more severe Arteriolosclerosis (estimate, −0.021, SE 0.005, p p Conclusions: Microvascular brain pathology is common in older adults and may represent an under-recognized, independent cause of late-life motor impairment.

  • genetic susceptibility for ischemic infarction and Arteriolosclerosis based on neuropathologic evaluations
    Cerebrovascular Diseases, 2013
    Co-Authors: Sherry H Y Chou, Aron S Buchman, David A Bennett, Joshua M Shulman, Brendan T Keenan, Elizabeth Secor, J A Schneider, P L De Jager
    Abstract:

    Background: Recent genetic studies of stroke and related risk factors have identified a growing number of susceptibility loci; however, the relationship of these

David A Bennett - One of the best experts on this subject based on the ideXlab platform.

  • brain insulin signaling and cerebrovascular disease in human postmortem brain
    Acta neuropathologica communications, 2021
    Co-Authors: Zoe Arvanitakis, Julie A Schneider, David A Bennett, Alifiya Kapasi, Ana W Capuano, Hoau Yan Wang, Rexford S Ahima, Steven E Arnold
    Abstract:

    Insulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, Arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T308 following ex vivo stimulation with insulin (OR = 1.916; estimate = 0.650; p = 0.007) and greater pS616IRS1 immunolabeling in neuronal cytoplasm (OR = 1.610; estimate = 0.476; p = 0.013), were each associated with a higher number of brain infarcts. Secondary analyses showed consistent results for gross infarcts and microinfarcts separately, but no other association including by infarct location (cortical or subcortical). AKT S473 phosphorylation following insulin stimulation was associated with less amyloid angiopathy severity, but not with other vessel pathology including atherosclerosis and Arteriolosclerosis. In summary, insulin resistance in the human brain, even among persons without diabetes, is associated with cerebrovascular disease and especially infarcts. The underlying pathophysiologic mechanisms need further elucidation. Because brain infarcts are known to be associated with lower cognitive function and dementia, these data are relevant to better understanding the link between brain metabolism and brain function.

  • arts a novel in vivo classifier of Arteriolosclerosis for the older adult brain
    NeuroImage: Clinical, 2021
    Co-Authors: Nazanin Makkinejad, David A Bennett, Sue Leurgans, Arnold M Evia, Ashish A Tamhane, Carles Javierrepetit, Melissa Lamar, Lisa L Barnes, Alzheimers Disease Neuroimaging Initiative, Julie A Schneider
    Abstract:

    Abstract Brain Arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, Arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of Arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of Arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of Arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for Arteriolosclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from Arteriolosclerosis. The performance of ARTS in predicting the presence of Arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that Arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to Arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of Arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/ .

  • response to letter regarding article sleep fragmentation cerebral Arteriolosclerosis and brain infarct pathology in community dwelling older people
    Stroke, 2016
    Co-Authors: Andrew S P Lim, David A Bennett, Aron S Buchman
    Abstract:

    We thank Dr Kawada1 for his interest in our study, which showed that sleep fragmentation is associated with postmortem evidence of areteriolosclerosis and subcortical infarcts. We collected objective measures of sleep fragmentation in the community-setting from more than a 1000 older participants in the Rush Memory and Aging Project—a volunteer cohort in which all participants agree to brain donation on death and in which the autopsy rate is ≈ 90%.2 Because this was a selected cohort, we …

  • sleep fragmentation cerebral Arteriolosclerosis and brain infarct pathology in community dwelling older people
    Stroke, 2016
    Co-Authors: Andrew S P Lim, David A Bennett, Julie A Schneider, Aron S Buchman
    Abstract:

    Background and Purpose— Although several forms of sleep disruption are associated with stroke, few studies have examined the relationship between sleep and histopathologic measures of cerebrovascular disease. We tested the hypothesis that greater sleep fragmentation is associated with a higher burden of cerebral vessel and infarct pathology at autopsy. Methods— We used ordinal logistic regression models to relate sleep fragmentation measured by actigraphy to the severity of Arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy, and the number of macroscopic and microscopic infarcts assessed by structured brain autopsy in 315 participants from the Rush Memory and Aging Project. Results— Greater sleep fragmentation was associated with more severe Arteriolosclerosis (odds ratio, 1.27; 95% confidence interval, 1.02–1.59; P =0.03 per 1 SD greater sleep fragmentation) and more subcortical macroscopic infarcts (odds ratio, 1.31; 95% confidence interval, 1.01–1.68; P =0.04). These associations were independent of established cardiovascular risk factors and diseases, and several medical comorbidities. Conclusions— Sleep fragmentation is associated with Arteriolosclerosis and subcortical infarcts in older adults.

  • microvascular brain pathology and late life motor impairment
    Neurology, 2013
    Co-Authors: Aron S Buchman, Patricia A Boyle, Steven R Levine, Sukriti Nag, Julie A Schneider, David A Bennett
    Abstract:

    Objective: To test the hypothesis that microvascular brain pathology is associated with late-life motor impairment. Methods: More than 2,500 persons participating in the Religious Orders Study or the Memory and Aging Project agreed to annual motor assessment and autopsy. Brains from 850 deceased participants were assessed for microvascular pathology including microinfarcts, cerebral amyloid angiopathy, and Arteriolosclerosis, and we examined their association with global motor scores proximate to death. Results: Mean age at death was 88.5 years. More than 60% of cases had evidence of 1 or more microvascular pathologies and of these more than half did not have observed macroinfarcts. In separate regression models adjusted for age, sex, and education, microinfarcts and Arteriolosclerosis were associated with level of motor function proximate to death (Arteriolosclerosis, estimate, −0.027, SE 0.005, p p = 0.026). These associations were not attenuated when controlling for vascular risk factors and diseases, postmortem interval, or interval from last clinical examination, and did not vary with level of cognition or presence of dementia proximate to death. When the 3 microvascular pathologies, macroinfarcts, and atherosclerosis were considered together in a single model, more severe Arteriolosclerosis (estimate, −0.021, SE 0.005, p p Conclusions: Microvascular brain pathology is common in older adults and may represent an under-recognized, independent cause of late-life motor impairment.

Julie A Schneider - One of the best experts on this subject based on the ideXlab platform.

  • brain insulin signaling and cerebrovascular disease in human postmortem brain
    Acta neuropathologica communications, 2021
    Co-Authors: Zoe Arvanitakis, Julie A Schneider, David A Bennett, Alifiya Kapasi, Ana W Capuano, Hoau Yan Wang, Rexford S Ahima, Steven E Arnold
    Abstract:

    Insulin is an important hormone for brain function, and alterations in insulin metabolism may be associated with neuropathology. We examined associations of molecular markers of brain insulin signaling with cerebrovascular disease. Participants were enrolled in the Religious Orders Study (ROS), an ongoing epidemiologic community-based, clinical-pathologic study of aging from across the United States. Using cross-sectional analyses, we studied a subset of ROS: 150 persons with or without diabetes, matched 1:1 by sex on age-at-death and education. We used ELISA, immunohistochemistry, and ex vivo stimulation with insulin, to document insulin signaling in postmortem midfrontal gyrus cortex tissue. Postmortem neuropathologic data identified cerebrovascular disease including brain infarcts, classified by number (as none for the reference; one; and more than one), size (gross and microscopic infarcts), and brain region/location (cortical and subcortical). Cerebral vessel pathologies were assessed, including severity of atherosclerosis, Arteriolosclerosis, and amyloid angiopathy. In separate regression analyses, greater AKT1 phosphorylation at T308 following ex vivo stimulation with insulin (OR = 1.916; estimate = 0.650; p = 0.007) and greater pS616IRS1 immunolabeling in neuronal cytoplasm (OR = 1.610; estimate = 0.476; p = 0.013), were each associated with a higher number of brain infarcts. Secondary analyses showed consistent results for gross infarcts and microinfarcts separately, but no other association including by infarct location (cortical or subcortical). AKT S473 phosphorylation following insulin stimulation was associated with less amyloid angiopathy severity, but not with other vessel pathology including atherosclerosis and Arteriolosclerosis. In summary, insulin resistance in the human brain, even among persons without diabetes, is associated with cerebrovascular disease and especially infarcts. The underlying pathophysiologic mechanisms need further elucidation. Because brain infarcts are known to be associated with lower cognitive function and dementia, these data are relevant to better understanding the link between brain metabolism and brain function.

  • arts a novel in vivo classifier of Arteriolosclerosis for the older adult brain
    NeuroImage: Clinical, 2021
    Co-Authors: Nazanin Makkinejad, David A Bennett, Sue Leurgans, Arnold M Evia, Ashish A Tamhane, Carles Javierrepetit, Melissa Lamar, Lisa L Barnes, Alzheimers Disease Neuroimaging Initiative, Julie A Schneider
    Abstract:

    Abstract Brain Arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, Arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of Arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of Arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of Arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for Arteriolosclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from Arteriolosclerosis. The performance of ARTS in predicting the presence of Arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that Arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to Arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of Arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/ .

  • sleep fragmentation cerebral Arteriolosclerosis and brain infarct pathology in community dwelling older people
    Stroke, 2016
    Co-Authors: Andrew S P Lim, David A Bennett, Julie A Schneider, Aron S Buchman
    Abstract:

    Background and Purpose— Although several forms of sleep disruption are associated with stroke, few studies have examined the relationship between sleep and histopathologic measures of cerebrovascular disease. We tested the hypothesis that greater sleep fragmentation is associated with a higher burden of cerebral vessel and infarct pathology at autopsy. Methods— We used ordinal logistic regression models to relate sleep fragmentation measured by actigraphy to the severity of Arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy, and the number of macroscopic and microscopic infarcts assessed by structured brain autopsy in 315 participants from the Rush Memory and Aging Project. Results— Greater sleep fragmentation was associated with more severe Arteriolosclerosis (odds ratio, 1.27; 95% confidence interval, 1.02–1.59; P =0.03 per 1 SD greater sleep fragmentation) and more subcortical macroscopic infarcts (odds ratio, 1.31; 95% confidence interval, 1.01–1.68; P =0.04). These associations were independent of established cardiovascular risk factors and diseases, and several medical comorbidities. Conclusions— Sleep fragmentation is associated with Arteriolosclerosis and subcortical infarcts in older adults.

  • microvascular brain pathology and late life motor impairment
    Neurology, 2013
    Co-Authors: Aron S Buchman, Patricia A Boyle, Steven R Levine, Sukriti Nag, Julie A Schneider, David A Bennett
    Abstract:

    Objective: To test the hypothesis that microvascular brain pathology is associated with late-life motor impairment. Methods: More than 2,500 persons participating in the Religious Orders Study or the Memory and Aging Project agreed to annual motor assessment and autopsy. Brains from 850 deceased participants were assessed for microvascular pathology including microinfarcts, cerebral amyloid angiopathy, and Arteriolosclerosis, and we examined their association with global motor scores proximate to death. Results: Mean age at death was 88.5 years. More than 60% of cases had evidence of 1 or more microvascular pathologies and of these more than half did not have observed macroinfarcts. In separate regression models adjusted for age, sex, and education, microinfarcts and Arteriolosclerosis were associated with level of motor function proximate to death (Arteriolosclerosis, estimate, −0.027, SE 0.005, p p = 0.026). These associations were not attenuated when controlling for vascular risk factors and diseases, postmortem interval, or interval from last clinical examination, and did not vary with level of cognition or presence of dementia proximate to death. When the 3 microvascular pathologies, macroinfarcts, and atherosclerosis were considered together in a single model, more severe Arteriolosclerosis (estimate, −0.021, SE 0.005, p p Conclusions: Microvascular brain pathology is common in older adults and may represent an under-recognized, independent cause of late-life motor impairment.

  • Cerebrovascular Disease Pathology and Parkinsonian Signs in Old Age
    Stroke, 2011
    Co-Authors: Aron S Buchman, Sukriti Nag, David A Bennett, Sue Leurgans, Julie A Schneider
    Abstract:

    Background and Purpose—Mild motor symptoms including parkinsonian signs are common in old age, but their underlying neuropathology is unclear. We tested the hypothesis that cerebrovascular pathologies are related to parkinsonian signs. Methods—We studied brain autopsies from 418 deceased participants from the Religious Order Study, who underwent evaluation of parkinsonian signs with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. Brains were evaluated for macroscopic and microinfarcts and the severity of Arteriolosclerosis. Regression analyses were used to examine the association of cerebrovascular pathologies with parkinsonian signs. Results—More than 35% of cases (N=149) showed macroscopic infarcts. Almost 30% of cases without macroscopic infarcts showed pathologies not detected by conventional brain imaging: microinfarcts (N=33 [7.9%]), Arteriolosclerosis (N=62 [14.8%]), or both (N=24 [5.7%]). Macroscopic infarcts, specifically multiple cortical and ≥1 subcortic...

Andrew S P Lim - One of the best experts on this subject based on the ideXlab platform.

  • response to letter regarding article sleep fragmentation cerebral Arteriolosclerosis and brain infarct pathology in community dwelling older people
    Stroke, 2016
    Co-Authors: Andrew S P Lim, David A Bennett, Aron S Buchman
    Abstract:

    We thank Dr Kawada1 for his interest in our study, which showed that sleep fragmentation is associated with postmortem evidence of areteriolosclerosis and subcortical infarcts. We collected objective measures of sleep fragmentation in the community-setting from more than a 1000 older participants in the Rush Memory and Aging Project—a volunteer cohort in which all participants agree to brain donation on death and in which the autopsy rate is ≈ 90%.2 Because this was a selected cohort, we …

  • sleep fragmentation cerebral Arteriolosclerosis and brain infarct pathology in community dwelling older people
    Stroke, 2016
    Co-Authors: Andrew S P Lim, David A Bennett, Julie A Schneider, Aron S Buchman
    Abstract:

    Background and Purpose— Although several forms of sleep disruption are associated with stroke, few studies have examined the relationship between sleep and histopathologic measures of cerebrovascular disease. We tested the hypothesis that greater sleep fragmentation is associated with a higher burden of cerebral vessel and infarct pathology at autopsy. Methods— We used ordinal logistic regression models to relate sleep fragmentation measured by actigraphy to the severity of Arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy, and the number of macroscopic and microscopic infarcts assessed by structured brain autopsy in 315 participants from the Rush Memory and Aging Project. Results— Greater sleep fragmentation was associated with more severe Arteriolosclerosis (odds ratio, 1.27; 95% confidence interval, 1.02–1.59; P =0.03 per 1 SD greater sleep fragmentation) and more subcortical macroscopic infarcts (odds ratio, 1.31; 95% confidence interval, 1.01–1.68; P =0.04). These associations were independent of established cardiovascular risk factors and diseases, and several medical comorbidities. Conclusions— Sleep fragmentation is associated with Arteriolosclerosis and subcortical infarcts in older adults.

Tomoyuki Kawada - One of the best experts on this subject based on the ideXlab platform.