The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

Background: Mechanistic factors on the pathway to improving independent ambulatory ability among hip fracture patients by a multicomponent home-based physical therapy intervention that emphasized aerobic, strength, balance, and functional training are unknown. The aim of this study was to determine the effects of 2 different home-based physical therapy programs on muscle area and attenuation (reflects muscle density) of the lower extremities, bone mineral density (BMD), and aerobic capacity.

Methods: Randomized controlled trial of home-based 16 weeks of strength, endurance, balance, and function exercises (PUSH, n = 19) compared to seated active range-of-motion exercises and transcutaneous electrical neurostimulation (PULSE, n = 18) in community-dwelling adults >60 years of age within 26 weeks of hip fracture.

Results: In PUSH and PULSE groups combined, the fractured leg had lower muscle area and muscle attenuation and higher subcutaneous fat than the nonfractured leg (p < .001) at baseline. At 16 weeks, mean muscle area of the fractured leg was higher in the PUSH than PULSE group (p = .04). Changes in muscle area were not significantly different when compared to the comparative PULSE group. There was a clinically relevant difference in change in femoral neck BMD between groups (p = .05) that showed an increase after PULSE and decrease after PUSH. There were generally no between-group differences in mean VO2peak tests at 16-week follow-up, except the PUSH group reached a higher max incline (p = .04).

Conclusions: The treatment effects of a multicomponent home-based physical therapy intervention on muscle composition, BMD, and aerobic capacity were not significantly different than an active control intervention in older adults recovering from hip fracture.

Trial registration: ClinicalTrials.gov Identifier: NCT01783704.

There is consistent evidence that immune response declines with aging, with wide interindividual variability and a still unclear relationship with the development of frailty. To address this question, we assessed the role of immune resilience (capacity to restore immune functions), operationalized as the neutrophil-to-lymphocytes ratio (NL-ratio) and monocytes-to-lymphocytes ratio (ML-ratio), in the pathway that from robust status shifts to pre-frailty and frailty, and finally to death. The InCHIANTI study enrolled representative samples from the registry lists of 2 towns in Tuscany, Italy. Baseline data were collected in 1998, with follow-up visits every 3 years. The 1 453 participants enrolled were assessed and followed for lifestyle, clinical condition, physical performance, clinical, and physiological measures. For the purpose of this analysis, we used only 1 022 subjects aged 65 or older at baseline. Participants in the 3 highest deciles of distribution for NL-ratio (>2.44) were more likely to experience a transition from robust to pre-frail, and to overt frailty status. Moreover, NL-ratio (tenth decile > 3.53) and ML-ratio (tenth decile > 2.02) were both predictors of mortality. These results were independent of chronological age, sex, comorbidities, and chronic low-grade inflammation assessed by high sensitivity C-reactive protein measurement. The 2 leucocytes-derived ratios, NL-ratio and ML-ratio, represent markers of immune resilience and predict changes in physical resilience and mortality. These biomarkers are inexpensive because they are based on data routinely collected in clinical practice and can be used to assess the risk of frailty progression and mortality. Clinical Trials Registration Number: NCT01331512.

Background: Low socioeconomic position (SEP) has been linked to an increased risk of dementia. However, little is known about the association between SEP trajectory and regional brain volumes related to dementia.

Methods: A random sample of community-dwelling older adults (n = 428, age = 73.1 ± 5.5) living in Tokamachi City (Niigata Prefecture, Japan) without medical histories of dementia, Parkinson's disease, and depression who underwent automated assessment of brain volumes on magnetic resonance imaging and responded to a self-administered questionnaire survey in 2017. We measured SEP in childhood (household SEP at age 15), young adulthood (education), mid-adulthood (the longest occupation), and late adulthood (current wealth), and further performed group-based trajectory analysis to identify lifetime trajectory patterns on SEP. Multivariate regression models were employed to investigate the association between SEP trajectories and 4 regional brain volumes related to the development of Alzheimer's disease (ie, entorhinal cortex, hippocampus, amygdala, and the parahippocampus), the most common type of dementia.

Results: We found 3 distinct SEP trajectories (stable middle class [68%], downward [23%], and upward [9%]). Compared to those who experienced stable middle class, older adults who experienced the upward SEP mobility had significantly larger hippocampus (β: 213.2, 95% confidence interval: 14.7, 411.8). On the other hand, older adults who experienced downward SEP mobility showed no significant differences in any of the 4 brain structural volumes.

Conclusions: Our findings indicate that upward life-course SEP mobility is associated with larger volumes of hippocampus in old age. SEP trajectory may offer us a useful lens to enhance our understanding of the etiology of dementia.

Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.

Background: Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM.

Methods: A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA).

Results: Of 2 984 older adults (aged 64.3 ± 8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; p = .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81-0.99]; p = .047).

Conclusions: T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.

Background: Chewing disability is associated with impaired quality of life, potentially leading to depression, and cognitive impairment. Although the chewing-ability-cognition relationship has been explored, examining whether depression mediates this relationship remains unclear. We investigated the association between chewing disability and cognitive impairment development and a potential mediation via depression among older persons.

Methods: Older persons without cognitive impairment at baseline (n = 973) from the 3 waves of the Panel on Health and Ageing of Singaporean Elderly were investigated. The outcome was incident cognitive impairment by the end of the study, while the exposure was chewing disability over the study period. Time-varying depression was the mediator. Time-fixed confounders included sex, ethnicity, education, marital status, living arrangement, and housing type, and time-varying confounders included age, smoking, cardiovascular diseases, diabetes, number of teeth, and denture wearing. We used marginal structural modeling to evaluate the effect of chewing disability on cognitive impairment development.

Results: After 6 years, 11% developed cognitive impairment, and chewing disability was reported by 33%. Chewing disability was associated with higher odds of developing cognitive impairment (OR 1.43, 95% CI: 1.09, 1.87), of which 85.3% was explained by the controlled direct effect of chewing disability, whereas the remaining 14.7% could be eliminated if there was no depression.

Conclusions: Our findings indicate an association between chewing disability and cognitive impairment, while the role of depression could not be fully elucidated. Oral health should be incorporated as part of older persons' care for its potential to assess the risk for other systemic conditions.

Background: Prognostic indices can enhance personalized predictions of health burdens. However, a simple, practical, and reproducible tool is lacking for clinical use. This study aimed to develop a machine learning-based prognostic index for predicting all-cause mortality in community-dwelling older individuals.

Methods: We utilized the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort, encompassing data from 5 663 participants. Over the 5-year follow-up, 447 deaths were confirmed. A machine learning-based routine blood examination prognostic index (MARBE-PI) was developed using common laboratory tests based on machine learning techniques. Participants were grouped into multiple risk categories by stratum-specific likelihood ratio analysis based on their MARBE-PI scores. The MARBE-PI was subsequently externally validated with an independent population-based cohort from Japan.

Results: Beyond age, sex, education level, and BMI, 6 laboratory tests (low-density lipoprotein, albumin, aspartate aminotransferase, lymphocyte count, high-sensitivity C-reactive protein, and creatinine) emerged as pivotal predictors via stepwise logistic regression (LR) for 5-year mortality. The area under curves of MARBE-PI constructed by LR were 0.799 (95% confidence interval [95% CI]: 0.778-0.819) and 0.756 (95% CI: 0.694-0.814) for the internal and external validation data sets, and were 0.801 (95% CI: 0.790-0.811) and 0.809 (95% CI: 0.774-0.845) for the extended 10-year mortality in both data sets, respectively. Risk categories stratified by MARBE-PI showed a consistent dose-response association with mortality. The MARBE-PI also performed comparably with indices constructed with clinical health deficits and/or laboratory results.

Conclusions: The MARBE-PI is considered the most applicable measure for risk stratification in busy clinical settings. It holds potential to pinpoint older individuals at elevated mortality risk, thereby aiding clinical decision-making.

Background: Everyday discrimination-experiences of being treated unfairly based on background characteristics like race-is linked to poor physical and mental health throughout the lifespan. Whether more experiences of discrimination are associated with higher odds of being hospitalized in older African Americans has not been explored.

Methods: Community-dwelling participants from 3 longitudinal cohort studies (N = 446, age 65+ years) with discrimination scores and ≥12 months of linked Medicare claims were included. Hospitalizations were identified using Medicare fee-for-service claims, available for an average of 6.2 (SD: 3.7) years of follow-up after baseline.

Results: In mixed-effects ordinal logistic regression models (outcomes of 0, 1, or 2+ hospitalizations per year) adjusted for age, sex, education, and income, higher discrimination was associated with higher odds of total annual hospitalizations (odds ratio [OR] per point higher = 1.09, 95% confidence intervals [95% CI]: 1.02-1.17). Results were similar when accounting for depressive symptoms.

Conclusions: Higher exposure to everyday discrimination is associated with higher odds of hospitalization among older African Americans. Mechanisms underlying associations should be explored further to understand how hospitalizations may be reduced in older African Americans.

Poor oral health is associated with cardiovascular disease and dementia. Potential pathways include sepsis from oral bacteria, systemic inflammation, and nutritional deficiencies. However, in post-industrialized populations, links between oral health and chronic disease may be confounded because the lower socioeconomic exposome (poor diet, pollution, and low physical activity) often entails insufficient dental care. We assessed tooth loss, caries, and damaged teeth, in relation to cardiovascular and brain aging among the Tsimane, a subsistence population living a relatively traditional forager-horticulturalist lifestyle with poor dental health, but minimal cardiovascular disease and dementia. Dental health was assessed by a physician in 739 participants aged 40-92 years with cardiac and brain health measured by chest computed tomography (CT; n = 728) and brain CT (n = 605). A subset of 356 individuals aged 60+ were also assessed for dementia and mild cognitive impairment (n = 33 impaired). Tooth loss was highly prevalent, with 2.2 teeth lost per decade and a 2-fold greater loss in women. The number of teeth with exposed pulp was associated with higher inflammation, as measured by cytokine levels and white blood cell counts, and lower body mass index. Coronary artery calcium and thoracic aortic calcium were not associated with tooth loss or damaged teeth. However, aortic valve calcification and brain tissue loss were higher in those who had more teeth with exposed pulp. Overall, these results suggest that dental health is associated with indicators of chronic diseases in the absence of typical confounds, even in a population with low cardiovascular and dementia risk factors.

Several population-based studies have reported that higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with brain morphological changes. However, no population-based studies have examined the relationship between serum NT-proBNP and various regional brain volumes in detail. We here analyzed the brain MRI data of 1 201 community-dwelling Japanese aged ≥65 years. Regional gray matter volumes (GMV) and intracranial volume (ICV) were estimated by applying voxel-based morphometry (VBM) methods. The associations of serum NT-proBNP with regional GMV/ICV were examined by analysis of covariance. The regional gray matter atrophy patterns associated with elevated serum NT-proBNP levels were investigated using VBM without a priori regions of interest. The multivariable-adjusted means of the frontal, temporal, hippocampal, parahippocampal, and entorhinal GMV/ICV decreased significantly with elevated serum NT-proBNP levels (all p for trend and q values of false discovery rate correction < .05). In VBM, elevated serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral entorhinal areas, bilateral fusiform gyri, left middle temporal gyrus, left inferior temporal gyrus, right central operculum, right posterior orbital gyrus, bilateral middle frontal gyri, anterior cingulate gyrus and bilateral medial frontal cortices. In a sensitivity analysis excluding 254 participants with mild cognitive impairment or dementia, serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral fusiform gyri, and left middle frontal gyrus. Our data suggest that elevated serum NT-proBNP levels are associated with gray matter atrophy in brain regions that play an important role in cognitive function.