Jose M Farfel, Ana W Capuano, Aron S Buchman, Julie A Schneider, David A Bennett
Background Dementia results from multiple neuropathologies causing cognitive impairment sufficiently severe to impact functional status. However, these pathologies and functional impairment are common in persons without dementia. We examined the association of AD and multiple other neuropathologies with instrumental and basic activities of daily living in persons with and without dementia. Methods Participants were 1,509 deceased from the Religious Orders Study or Rush Memory and Aging Project. Pathologic AD and three other AD indices were examined, in addition to four non-AD neurodegenerative pathologies: cerebral amyloid angiopathy (CAA), hippocampal sclerosis, TDP-43 and Lewy bodies, and four cerebrovascular pathologies: gross- and microinfarctions, athero- and arteriolosclerosis. Functional assessment included Lawton and Katz Index Instrumental and Basic Activities of Daily Living (IADL and BADL). Ordinal regression models adjusted for age, sex, and education were used to examine the association of neuropathologies with IADL and BADL. Results AD and the other neuropathologies were associated with impaired IADL (all Ps<0.001) and with impaired BADL (Ps<0.01), except for atherosclerosis and CAA which were not associated with BADL. The effects of most neuropathologies were largely affected by dementia. However, small effects on IADL remained for PHFtau tangles after adjusting models for dementia. Direct effects of gross infarcts on IADL and BADL, and of microinfarcts on BADL remained unchanged after adjusting the models for dementia. Conclusion AD and all other neuropathologies are strongly associated with functional disability. The association of most neuropathologies with disability was eliminated or attenuated by dementia, except for gross infarcts and microinfarcts.
{"title":"Association of Alzheimer’s Disease and Other Neuropathologies with Functional Disability in Persons With and Without Dementia","authors":"Jose M Farfel, Ana W Capuano, Aron S Buchman, Julie A Schneider, David A Bennett","doi":"10.1093/gerona/glae118","DOIUrl":"https://doi.org/10.1093/gerona/glae118","url":null,"abstract":"Background Dementia results from multiple neuropathologies causing cognitive impairment sufficiently severe to impact functional status. However, these pathologies and functional impairment are common in persons without dementia. We examined the association of AD and multiple other neuropathologies with instrumental and basic activities of daily living in persons with and without dementia. Methods Participants were 1,509 deceased from the Religious Orders Study or Rush Memory and Aging Project. Pathologic AD and three other AD indices were examined, in addition to four non-AD neurodegenerative pathologies: cerebral amyloid angiopathy (CAA), hippocampal sclerosis, TDP-43 and Lewy bodies, and four cerebrovascular pathologies: gross- and microinfarctions, athero- and arteriolosclerosis. Functional assessment included Lawton and Katz Index Instrumental and Basic Activities of Daily Living (IADL and BADL). Ordinal regression models adjusted for age, sex, and education were used to examine the association of neuropathologies with IADL and BADL. Results AD and the other neuropathologies were associated with impaired IADL (all Ps&lt;0.001) and with impaired BADL (Ps&lt;0.01), except for atherosclerosis and CAA which were not associated with BADL. The effects of most neuropathologies were largely affected by dementia. However, small effects on IADL remained for PHFtau tangles after adjusting models for dementia. Direct effects of gross infarcts on IADL and BADL, and of microinfarcts on BADL remained unchanged after adjusting the models for dementia. Conclusion AD and all other neuropathologies are strongly associated with functional disability. The association of most neuropathologies with disability was eliminated or attenuated by dementia, except for gross infarcts and microinfarcts.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"159 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953874","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}
Shu Chen, Shanquan Chen, Katja Hanewald, Yafei Si, Hazel Bateman, Bingqin Lin, Xiaolin Xu, Suraj Samtani, Chenkai Wu, Henry Brodaty
Background The role of social environment, i.e., the aggregate effect of social determinants of health (SDOHs), in determining dementia is unclear. Methods We developed a novel polysocial risk score for dementia based on 19 SDOH among 5,199 participants in the Health and Retirement Study, US, to measure the social environmental risk. We used a survival analysis approach to assess the association between social environment and dementia risk in 2006-2020. We further studied the interaction between social environment and lifestyles, and explored racial disparities. Results The study participants (mean age=73.4 years, SD=8.3; 58.0% female; 11.6% African American) were followed up for an average of 6.2 years, and 1,089 participants developed dementia. Every one-point increase in the polysocial risk score (ranging from 0-10) was associated with a 21.6% higher risk (aHR=1.21, 95% CI=1.15-1.26) of developing dementia, other things being equal. Among participants with high social environmental risk, regular exercise and moderate drinking were associated with a 43-60% lower risk of developing dementia (p<0.001). In addition, African Americans were 1.3 times (aHR=2.28, 95% CI=1.96-2.66) more likely to develop dementia than European Americans, other things being equal. Discussion An adverse social environment is linked to higher dementia risk, but healthy lifestyles can partially offset the increased social environmental risk. The polysocial risk score can complement the existing risk tools to identify high-risk older populations, and guide the design of targeted social environmental interventions, particularly focusing on improving the companionship of the older people, to prevent dementia.
{"title":"Social environment, lifestyle, and genetic predisposition with dementia risk: A long-term longitudinal study among older adults","authors":"Shu Chen, Shanquan Chen, Katja Hanewald, Yafei Si, Hazel Bateman, Bingqin Lin, Xiaolin Xu, Suraj Samtani, Chenkai Wu, Henry Brodaty","doi":"10.1093/gerona/glae128","DOIUrl":"https://doi.org/10.1093/gerona/glae128","url":null,"abstract":"Background The role of social environment, i.e., the aggregate effect of social determinants of health (SDOHs), in determining dementia is unclear. Methods We developed a novel polysocial risk score for dementia based on 19 SDOH among 5,199 participants in the Health and Retirement Study, US, to measure the social environmental risk. We used a survival analysis approach to assess the association between social environment and dementia risk in 2006-2020. We further studied the interaction between social environment and lifestyles, and explored racial disparities. Results The study participants (mean age=73.4 years, SD=8.3; 58.0% female; 11.6% African American) were followed up for an average of 6.2 years, and 1,089 participants developed dementia. Every one-point increase in the polysocial risk score (ranging from 0-10) was associated with a 21.6% higher risk (aHR=1.21, 95% CI=1.15-1.26) of developing dementia, other things being equal. Among participants with high social environmental risk, regular exercise and moderate drinking were associated with a 43-60% lower risk of developing dementia (p&lt;0.001). In addition, African Americans were 1.3 times (aHR=2.28, 95% CI=1.96-2.66) more likely to develop dementia than European Americans, other things being equal. Discussion An adverse social environment is linked to higher dementia risk, but healthy lifestyles can partially offset the increased social environmental risk. The polysocial risk score can complement the existing risk tools to identify high-risk older populations, and guide the design of targeted social environmental interventions, particularly focusing on improving the companionship of the older people, to prevent dementia.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907210","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}
Robert T Olender, Sandipan Roy, Hamish A Jamieson, Sarah N Hilmer, Prasad S Nishtala
Background Older adults (≥ 65 years) account for a disproportionately high proportion of hospitalization and in-hospital mortality, some of which may be avoidable. Although machine learning (ML) models have already been built and validated for predicting hospitalization and mortality, there remains a significant need to optimise ML models further. Accurately predicting hospitalization may tremendously impact the clinical care of older adults as preventative measures can be implemented to improve clinical outcomes for the patient. Methods In this retrospective cohort study, a dataset of 14,198 community-dwelling older adults (≥ 65 years) with complex care needs from the Inter-Resident Assessment Instrument database was used to develop and optimise three ML models to predict 30-day-hospitalization. The models developed and optimized were Random Forest (RF), XGBoost (XGB), and Logistic Regression (LR). Variable importance plots were generated for all three models to identify key predictors of 30-day-hospitalization. Results The area under the receiver operating characteristics curve for the RF, XGB and LR models were 0.97, 0.90 and 0.72, respectively. Variable importance plots identified the Drug Burden Index and alcohol consumption as important, immediately potentially modifiable variables in predicting 30-day-hospitalization. Conclusions Identifying immediately potentially modifiable risk factors such as the Drug Burden Index and alcohol consumption is of high clinical relevance. If clinicians can influence these variables, they could proactively lower the risk of 30-day-hospitalization. ML holds promise to improve the clinical care of older adults. It is crucial that these models undergo extensive validation through large-scale clinical studies before being utilized in the clinical setting.
背景 老年人（≥ 65 岁）在住院和院内死亡率中所占比例过高，其中有些可能是可以避免的。虽然已经建立并验证了用于预测住院和死亡率的机器学习（ML）模型，但仍亟需进一步优化 ML 模型。准确预测住院治疗可能会对老年人的临床护理产生巨大影响，因为可以采取预防措施来改善患者的临床预后。方法 在这项回顾性队列研究中，研究人员利用居民间评估工具数据库中 14198 名社区居住的、有复杂护理需求的老年人（≥ 65 岁）的数据集，开发并优化了三种预测 30 天住院情况的 ML 模型。开发和优化的模型包括随机森林（RF）、XGBoost（XGB）和逻辑回归（LR）。所有三个模型都生成了变量重要性图，以确定 30 天住院的关键预测因素。结果 RF、XGB 和 LR 模型的接收器操作特征曲线下面积分别为 0.97、0.90 和 0.72。变量重要性图显示，药物负担指数和饮酒量是预测 30 天住院率的重要且立即可能改变的变量。结论 识别药物负担指数和饮酒量等可立即改变的风险因素具有很高的临床意义。如果临床医生能够影响这些变量，就能主动降低 30 天住院的风险。ML 有望改善老年人的临床护理。至关重要的是，这些模型在应用于临床之前，必须经过大规模临床研究的广泛验证。
{"title":"Drug Burden Index is a Modifiable Predictor of 30-Day-Hospitalization in Community-Dwelling Older Adults with Complex Care Needs: Machine Learning Analysis of InterRAI Data","authors":"Robert T Olender, Sandipan Roy, Hamish A Jamieson, Sarah N Hilmer, Prasad S Nishtala","doi":"10.1093/gerona/glae130","DOIUrl":"https://doi.org/10.1093/gerona/glae130","url":null,"abstract":"Background Older adults (≥ 65 years) account for a disproportionately high proportion of hospitalization and in-hospital mortality, some of which may be avoidable. Although machine learning (ML) models have already been built and validated for predicting hospitalization and mortality, there remains a significant need to optimise ML models further. Accurately predicting hospitalization may tremendously impact the clinical care of older adults as preventative measures can be implemented to improve clinical outcomes for the patient. Methods In this retrospective cohort study, a dataset of 14,198 community-dwelling older adults (≥ 65 years) with complex care needs from the Inter-Resident Assessment Instrument database was used to develop and optimise three ML models to predict 30-day-hospitalization. The models developed and optimized were Random Forest (RF), XGBoost (XGB), and Logistic Regression (LR). Variable importance plots were generated for all three models to identify key predictors of 30-day-hospitalization. Results The area under the receiver operating characteristics curve for the RF, XGB and LR models were 0.97, 0.90 and 0.72, respectively. Variable importance plots identified the Drug Burden Index and alcohol consumption as important, immediately potentially modifiable variables in predicting 30-day-hospitalization. Conclusions Identifying immediately potentially modifiable risk factors such as the Drug Burden Index and alcohol consumption is of high clinical relevance. If clinicians can influence these variables, they could proactively lower the risk of 30-day-hospitalization. ML holds promise to improve the clinical care of older adults. It is crucial that these models undergo extensive validation through large-scale clinical studies before being utilized in the clinical setting.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907258","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}
Braden K Popelsky, Kelley Pettee Gabriel, Erin E Dooley, Kelly R Ylitalo
Background Physical activity (PA) may be an important fall prevention strategy. Current PA guidelines emphasize total PA dose, but daily patterning of PA is underappreciated. With aging, PA bouts become less frequent and shorter in duration (i.e.: more fragmented). PA fragmentation may be an indicator of fall risk, but the relationship is not well understood. This study examined daily PA accumulation and patterns with fall risk in older adults. Methods Participants (n=685, 54.3% female, 61.5% aged 70-79 years) from the National Health and Aging Trends Study (NHATS) with wrist-worn accelerometry PA data from Round 11 (baseline) and sample person interviews with fall data from Round 12 (follow-up) were included. PA variables were categorized into tertiles and incident falls were defined as ≥1 self-reported fall in the year following the PA assessment between baseline and follow-up. A modified Poisson approach was used to estimate the relative risk of both PA accumulation and fragmentation with falls. Results Overall, 40.0% reported an incident fall. After adjustment for sociodemographic and health characteristics, those in the highest tertile of total PA accumulation had lower fall risk (aRR=0.74, 95% CI: 0.57, 0.95) and those in the highest tertile of PA fragmentation had increased fall risk (aRR=1.33, 95% CI: 1.03, 1.73). Models were attenuated after adjustment for physical functioning. Conclusions PA fragmentation may identify fall risk in older adults. Longitudinal studies are needed to disentangle the temporal sequencing of the complex relationship between PA and physical functioning across the life-course.
{"title":"Physical Activity Fragmentation and Falls in Older Adults: Findings from the National Health and Aging Trends Study","authors":"Braden K Popelsky, Kelley Pettee Gabriel, Erin E Dooley, Kelly R Ylitalo","doi":"10.1093/gerona/glae129","DOIUrl":"https://doi.org/10.1093/gerona/glae129","url":null,"abstract":"Background Physical activity (PA) may be an important fall prevention strategy. Current PA guidelines emphasize total PA dose, but daily patterning of PA is underappreciated. With aging, PA bouts become less frequent and shorter in duration (i.e.: more fragmented). PA fragmentation may be an indicator of fall risk, but the relationship is not well understood. This study examined daily PA accumulation and patterns with fall risk in older adults. Methods Participants (n=685, 54.3% female, 61.5% aged 70-79 years) from the National Health and Aging Trends Study (NHATS) with wrist-worn accelerometry PA data from Round 11 (baseline) and sample person interviews with fall data from Round 12 (follow-up) were included. PA variables were categorized into tertiles and incident falls were defined as ≥1 self-reported fall in the year following the PA assessment between baseline and follow-up. A modified Poisson approach was used to estimate the relative risk of both PA accumulation and fragmentation with falls. Results Overall, 40.0% reported an incident fall. After adjustment for sociodemographic and health characteristics, those in the highest tertile of total PA accumulation had lower fall risk (aRR=0.74, 95% CI: 0.57, 0.95) and those in the highest tertile of PA fragmentation had increased fall risk (aRR=1.33, 95% CI: 1.03, 1.73). Models were attenuated after adjustment for physical functioning. Conclusions PA fragmentation may identify fall risk in older adults. Longitudinal studies are needed to disentangle the temporal sequencing of the complex relationship between PA and physical functioning across the life-course.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907218","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}
Mathias Skjødt, Mark A Tully, Li-Tang Tsai, Kasper Degn Gejl, Niels Ørtenblad, Kurt Jensen, Annemarie Koster, Marjolein Visser, Marianne Skovsager Andersen, Paolo Caserotti
Background Multiples of resting metabolic rate (RMR) are often used to classify physical activity intensity, a concept known as the Metabolic Equivalent of Task (MET). However, the METs metrics may misclassify physical activity intensity in older adults because of age related changes in RMR and maximal aerobic capacity (V̇O2max). This study aimed to 1) compare classifications of activity intensity by estimated (METsestimated) and measured (METsmeasured) METs and 2) compare physical activity classified by absolute (METsmeasured) versus relative intensity (%V̇O2Reserve) in older adults. Methods Ninety-eight adults aged 75-90 years participated in the study. RMR and V̇O2 during sitting, standing, daily activities and 6-minute-walking-test were measured. V̇O2Reserve was defined as the difference between V̇O2max and RMR. Moderate and vigorous intensity was classified as 3 and 6 METs and 40% and 60% of V̇O2Reserve, respectively. Paired t-tests and a confusion matrix were used to investigate aim 1 and 2, respectively. Results METsmeasured was 24% lower than the standard 1 MET of 3.5 ml O2·min-1·kg-1. METsestimated underestimated the intensity during daily and walking activities when compared to METsmeasured. Nevertheless, when comparing METsmeasured to percentages of V̇O2Reserve, a mismatch was shown for moderate intensity in 47-67% of the participants during daily activities, and 21% of the participants during self-selected gait speed. Conclusion Applying METsestimated for older adults leads to potential underestimation of physical activity intensity, suggesting that current classification metrics should be revised for older adults. V̇O2Reserve is a candidate metric for establishing precise physical activity intensity cut-points for older adults.
{"title":"Need to revise classification of physical activity intensity in older adults? The use of estimated METs, measured METs and V̇O2Reserve","authors":"Mathias Skjødt, Mark A Tully, Li-Tang Tsai, Kasper Degn Gejl, Niels Ørtenblad, Kurt Jensen, Annemarie Koster, Marjolein Visser, Marianne Skovsager Andersen, Paolo Caserotti","doi":"10.1093/gerona/glae120","DOIUrl":"https://doi.org/10.1093/gerona/glae120","url":null,"abstract":"Background Multiples of resting metabolic rate (RMR) are often used to classify physical activity intensity, a concept known as the Metabolic Equivalent of Task (MET). However, the METs metrics may misclassify physical activity intensity in older adults because of age related changes in RMR and maximal aerobic capacity (V̇O2max). This study aimed to 1) compare classifications of activity intensity by estimated (METsestimated) and measured (METsmeasured) METs and 2) compare physical activity classified by absolute (METsmeasured) versus relative intensity (%V̇O2Reserve) in older adults. Methods Ninety-eight adults aged 75-90 years participated in the study. RMR and V̇O2 during sitting, standing, daily activities and 6-minute-walking-test were measured. V̇O2Reserve was defined as the difference between V̇O2max and RMR. Moderate and vigorous intensity was classified as 3 and 6 METs and 40% and 60% of V̇O2Reserve, respectively. Paired t-tests and a confusion matrix were used to investigate aim 1 and 2, respectively. Results METsmeasured was 24% lower than the standard 1 MET of 3.5 ml O2·min-1·kg-1. METsestimated underestimated the intensity during daily and walking activities when compared to METsmeasured. Nevertheless, when comparing METsmeasured to percentages of V̇O2Reserve, a mismatch was shown for moderate intensity in 47-67% of the participants during daily activities, and 21% of the participants during self-selected gait speed. Conclusion Applying METsestimated for older adults leads to potential underestimation of physical activity intensity, suggesting that current classification metrics should be revised for older adults. V̇O2Reserve is a candidate metric for establishing precise physical activity intensity cut-points for older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821716","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}
The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid β (Aβ) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting and ELISA were used to detect Aβ deposition, tau phosphorylation and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aβ pathology, tau phosphorylation and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.
{"title":"Selective orexin 2 receptor blockade alleviates cognitive impairments and the pathological progression of Alzheimer’s disease in 3xTg-AD mice","authors":"Xiao-Hong Hu, Kai-Yue Yu, Xin-Xin Li, Jin-Nan Zhang, Juan-Juan Jiao, Zhao-Jun Wang, Hong-Yan Cai, Lei Wang, Ye-Xin He, Mei-Na Wu","doi":"10.1093/gerona/glae115","DOIUrl":"https://doi.org/10.1093/gerona/glae115","url":null,"abstract":"The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid β (Aβ) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting and ELISA were used to detect Aβ deposition, tau phosphorylation and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aβ pathology, tau phosphorylation and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814850","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}
Kelly Cotton, Emmeline Ayers, Ying Jin, Olivier Beauchet, Carol A Derby, Richard B Lipton, Mindy Katz, Kevin Galery, Pierrette Gaudreau, Joe Verghese
Background Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. Methods We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1,826 community-dwelling older adults (55% female) from two cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. Results Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (> 14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI = 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. Conclusions Higher blood homocysteine levels are associated with increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.
{"title":"Elevated blood homocysteine increases the risk of incident Motoric Cognitive Risk syndrome: A two cohort study","authors":"Kelly Cotton, Emmeline Ayers, Ying Jin, Olivier Beauchet, Carol A Derby, Richard B Lipton, Mindy Katz, Kevin Galery, Pierrette Gaudreau, Joe Verghese","doi":"10.1093/gerona/glae114","DOIUrl":"https://doi.org/10.1093/gerona/glae114","url":null,"abstract":"Background Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. Methods We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1,826 community-dwelling older adults (55% female) from two cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. Results Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (&gt; 14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI = 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. Conclusions Higher blood homocysteine levels are associated with increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140807345","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}
Aurélio Faria, Tiago Sousa, João R Vaz, Ronaldo Gabriel, Jorge Gama, Nick Stergiou
Background Physical decline due to aging has been associated with the risk of falls. Minimum toe clearance (MTC) is a gait parameter that might play a role in the mechanism of tripping and falling. However, it is unclear if there are any sex-related effects regarding MTC as people age. The present study investigated if there are sex-related differences in MTC in older active adults. Methods Twenty-three females and 23 males (F: 65.5 ± 4.8 yrs; M: 61.9 ± 5.2 yrs) walked on a treadmill at a preferred walking speed, while kinematic data were obtained at a sampling frequency of 100 Hz and up-sampled to 120 and 240Hz. MTC was calculated from the kinematics data and evaluated concerning its magnitude (i.e., MTC and MTC/leg length), the time between left/right MTC (i.e., T-MTC), amount of variability (i.e., CV and CVm), and temporal structure of variability i.e., the complexity of the time series (i.e., MTC α, T-MTC α). Results No sex effects were found for MTC/leg length, for the amount of variability (i.e., CV and CVm), and for the complexity of the time series (MTC α, T-MTC α). However, females exhibited significantly lower MTC and T-MTC after adjusting for walking speed, mass, and age as covariates. Conclusions The reduced MTC in females suggests a potential sex-related disparity in the risk of tripping and falling among active older adults.
{"title":"Females present reduced minimum toe clearance during walking as compared to males in active older adults","authors":"Aurélio Faria, Tiago Sousa, João R Vaz, Ronaldo Gabriel, Jorge Gama, Nick Stergiou","doi":"10.1093/gerona/glae109","DOIUrl":"https://doi.org/10.1093/gerona/glae109","url":null,"abstract":"Background Physical decline due to aging has been associated with the risk of falls. Minimum toe clearance (MTC) is a gait parameter that might play a role in the mechanism of tripping and falling. However, it is unclear if there are any sex-related effects regarding MTC as people age. The present study investigated if there are sex-related differences in MTC in older active adults. Methods Twenty-three females and 23 males (F: 65.5 ± 4.8 yrs; M: 61.9 ± 5.2 yrs) walked on a treadmill at a preferred walking speed, while kinematic data were obtained at a sampling frequency of 100 Hz and up-sampled to 120 and 240Hz. MTC was calculated from the kinematics data and evaluated concerning its magnitude (i.e., MTC and MTC/leg length), the time between left/right MTC (i.e., T-MTC), amount of variability (i.e., CV and CVm), and temporal structure of variability i.e., the complexity of the time series (i.e., MTC α, T-MTC α). Results No sex effects were found for MTC/leg length, for the amount of variability (i.e., CV and CVm), and for the complexity of the time series (MTC α, T-MTC α). However, females exhibited significantly lower MTC and T-MTC after adjusting for walking speed, mass, and age as covariates. Conclusions The reduced MTC in females suggests a potential sex-related disparity in the risk of tripping and falling among active older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651359","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}
Shaoxi Pan, Shanshan Li, Shaoxiang Jiang, Jung-Im Shin, Gordon G Liu, Hongyan Wu, Beini Lyu
Background Contemporary data on the quantity and quality of medication use among older adults are lacking. This study examined recent trends in number and appropriateness of prescription medication use among older adults in the US. Method Data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and March 2020 were used and 6336 adult participants aged 65 and older were included. We examined the number of prescription medication, prevalence of polypharmacy (≥5 prescription drugs), use of potentially inappropriate medication (PIM), and use of recommended medications (ACEI/ARBs plus beta-blockers among patients with heart failure and ACEI/ARBs among patients with albuminuria). Results There has been a slight increase in the prevalence of polypharmacy (39.3% in 2011-2012 to 43.8% in 2017-2020, p for trend= 0.32). Antihypertensive, antihyperlipidemic, antidiabetic medications, and antidepressants are the most commonly used medications. There was no substantial change in the use of PIM (17.0% to 14.7%). Less than 50% of older adults with heart failure received ACEI/ARBs plus beta-blockers (44.3% in 2017-2020) and approximately 50% patients with albuminuria received ACEI/ARBs (54.0 in 2017-2020), with no improvement over the study period. Polypharmacy, older age, female, and lower socioeconomic status generally were associated with greater use of PIM but lower use of recommended medications. Conclusions The medication burden remained high among older adults in the US and the appropriate utilization of medications did not improve in the recent decade. Our results underscore the need for greater attentions and interventions to the quality of medication use among older adults.
{"title":"Trends in Number and Appropriateness of Prescription Medication Utilization among Community-Dwelling Older Adults in the US: 2011-2020","authors":"Shaoxi Pan, Shanshan Li, Shaoxiang Jiang, Jung-Im Shin, Gordon G Liu, Hongyan Wu, Beini Lyu","doi":"10.1093/gerona/glae108","DOIUrl":"https://doi.org/10.1093/gerona/glae108","url":null,"abstract":"Background Contemporary data on the quantity and quality of medication use among older adults are lacking. This study examined recent trends in number and appropriateness of prescription medication use among older adults in the US. Method Data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and March 2020 were used and 6336 adult participants aged 65 and older were included. We examined the number of prescription medication, prevalence of polypharmacy (≥5 prescription drugs), use of potentially inappropriate medication (PIM), and use of recommended medications (ACEI/ARBs plus beta-blockers among patients with heart failure and ACEI/ARBs among patients with albuminuria). Results There has been a slight increase in the prevalence of polypharmacy (39.3% in 2011-2012 to 43.8% in 2017-2020, p for trend= 0.32). Antihypertensive, antihyperlipidemic, antidiabetic medications, and antidepressants are the most commonly used medications. There was no substantial change in the use of PIM (17.0% to 14.7%). Less than 50% of older adults with heart failure received ACEI/ARBs plus beta-blockers (44.3% in 2017-2020) and approximately 50% patients with albuminuria received ACEI/ARBs (54.0 in 2017-2020), with no improvement over the study period. Polypharmacy, older age, female, and lower socioeconomic status generally were associated with greater use of PIM but lower use of recommended medications. Conclusions The medication burden remained high among older adults in the US and the appropriate utilization of medications did not improve in the recent decade. Our results underscore the need for greater attentions and interventions to the quality of medication use among older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637628","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}
Inhaled air pollutants (AirP) comprise extraordinarily diverse particles, volatiles, and gases from traffic, wildfire, cigarette smoke, dust, and various other sources. These pollutants contain numerous toxic components which collectively differ in relative levels of components, but broadly share chemical classes. Exposure and health outcomes from AirP are complex, depending on pollutant source, duration of exposure, and socioeconomic status. We discuss examples in the current literature on organ responses to AirP, with a focus on lung, arteries, and brain. Some transcriptional responses are shared. It is well accepted that AirP contributes to Alzheimer’s disease and other neurodegenerative conditions in the Gero-Exposome. However, we do not know which chemical compounds initiate these changes and how activation of these transcriptional pathways is further modified by genetics and prenatal development.
{"title":"Inhaled pollutants of the Gero-Exposome and later life health","authors":"Caleb E Finch, Max A Thorwald","doi":"10.1093/gerona/glae107","DOIUrl":"https://doi.org/10.1093/gerona/glae107","url":null,"abstract":"Inhaled air pollutants (AirP) comprise extraordinarily diverse particles, volatiles, and gases from traffic, wildfire, cigarette smoke, dust, and various other sources. These pollutants contain numerous toxic components which collectively differ in relative levels of components, but broadly share chemical classes. Exposure and health outcomes from AirP are complex, depending on pollutant source, duration of exposure, and socioeconomic status. We discuss examples in the current literature on organ responses to AirP, with a focus on lung, arteries, and brain. Some transcriptional responses are shared. It is well accepted that AirP contributes to Alzheimer’s disease and other neurodegenerative conditions in the Gero-Exposome. However, we do not know which chemical compounds initiate these changes and how activation of these transcriptional pathways is further modified by genetics and prenatal development.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637619","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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