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Abstract

Background
Loneliness precedes the onset of cognitive impairment (CI) in older adults. Although the mechanisms through which loneliness "gets under the skin" to influence the risk of developing CI have been conceptually proposed, they are rarely empirically examined. The Evolutionary Theory of Loneliness posits that loneliness as a stressor could cause dysregulations in multiple physiological systems. The current study investigated whether inflammatory, cardiovascular, and kidney biomarkers mediate the longitudinal association between loneliness and CI.


Methods
Cross-lagged panel models were used to examine the hypothesized relationships, using 2006, 2010, and 2014 waves of data from the Health and Retirement Study (N = 7,037). Loneliness was measured with the 3-item UCLA loneliness scale. CI was assessed with the modified telephone interview for cognitive status. Biomarkers included HbA1C, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, and Cystatin C. Using a stepwise model-building approach, first, the model included only loneliness, CI, and biomarker variables; then, sociodemographic covariates were added; lastly, health status were controlled for.


Results
In unadjusted and partially adjusted models, loneliness was associated with higher odds of worse cognitive status in an 8-year follow-up. Only HbA1C mediated the longitudinal association between loneliness and CI. However, after further controlling for health status, all associations became nonsignificant.


Conclusions
Examining a large number of participants and linking a limited number of biological markers with cognition and loneliness longitudinally, our empirical data did not support theoretical propositions, highlighting the critical importance of controlling for confounders in future studies examining longitudinal mediational relationships underlying loneliness and CI.

Abstract

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.

Abstract

Background
The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia.


Methods
Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006–2010) and follow-ups (median = 13 years). The propensity score matching method and the Cox proportional hazard models were employed.


Results
A total of 448 374 adults (mean age: 56.8 ± 8.1 years), of whom 3 795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR = 3.15, 95% CI: 2.54–3.90, p < .001), stroke (HR = 1.72, 95% CI: 1.33–2.23, p < .001), and dementia (HR = 1.26, 95% CI: 1.02–1.57, p = .034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age.


Conclusions
Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia.

Abstract

Background
Contemporary data on the quantity and quality of medication use among older adults are lacking. This study examined recent trends in the number and appropriateness of prescription medication use among older adults in the United States.


Methods
Data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and March 2020 were used, and 6 336 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 (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin receptor blockers [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 = .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% of 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 were generally associated with greater use of PIM but lower use of recommended medications.


Conclusions
The medication burden remained high among older adults in the United States 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.

Abstract

Background
We aimed to analyze the trajectories of cognitive decline as a function of the presence of type 2 diabetes and glycemic control in analyzes stratified by sex in an 8-year follow-up period.


Methods
A total of 1 752 men and 2 232 women aged ≥50 years who participated in the English Longitudinal Study of Ageing (ELSA), conducted from 2004 to 2012, were analyzed. The outcomes of interest were performance on the cognitive domains of memory, executive function, and temporal orientation as well as the global cognition score. Cognitive performance was standardized in z-scores in strata based on schooling and age. The participants were classified as without diabetes, with controlled glycemia, and with uncontrolled glycemia, according to medical diagnosis, glucose-lowering medications use and HbA1c levels. Generalized linear mixed models controlled by sociodemographic, behavioral, and health-related characteristics were used for the trajectory analyses.


Results
No differences in z-scores were found for global cognition or cognitive domains based on diabetes classification in men and women at baseline. More than 8 years of follow up, women with uncontrolled glycemia had a greater decline in z-scores for global cognition (−0.037 SD/year [95% CI: −0.073; −0.001]) and executive function (−0.049 SD/year [95% CI: −0.092; −0.007]) compared with those without diabetes. No significant difference in trajectories of global cognition or any cognitive domain was found in men as a function of diabetes classification.


Conclusions
Women with uncontrolled glycemia are at greater risk of a decline in global cognition and executive function than those without diabetes.

Abstract

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