Search

Introduction: Neighborhood environments may promote neurocognitive health in part by providing amenities that encourage physical activity. We examined associations between quantity of walkable facilities, including specifically physical activity facilities (e.g., gyms, recreation centers), with risk of incident dementia., Methods: Participants included 2923 adults ≥ 65 years old from the Cardiovascular Health Cognition Study (1992-1999), with clinically adjudicated dementia classified over a median 6.0 years of follow-up. Walkable facilities were measured within 1 km (Euclidean) of home. Self-reported baseline physical activity was considered a moderator., Results: In adjusted Cox models, participants with ≥ 2 (vs. 0) physical activity facilities had reduced risk of mixed/vascular dementia, but not Alzheimer's disease, particularly after excluding individuals in the bottom 20th percentile of physical activity (hazard ratio = 0.56, 95% confidence interval: 0.35-0.89)., Discussion: Neighborhood amenities that encourage physical activity may mitigate dementia risk via improved vascular health, especially for individuals with sufficient baseline mobility to use these resources., Highlights: We examined associations between nearby walkable facilities and incident dementia. Facilities within 1 km were counted via the National Establishment Time Series Database. More physical activity facilities predicted lower risk of mixed/vascular dementia. No associations were found between walkable facilities and incident Alzheimer's disease., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Air pollution is a modifiable risk factor for dementia. Yet, studies on specific sources of air pollution (i.e., toxic chemical emissions from industrial facilities) and dementia risk are scarce. We examined associations between toxicity-weighted concentrations of industrial pollution and dementia outcomes among a large, multi-site cohort of older adults., Methods: Participants (n = 2770) were ≥ 65 years old (Mean = 75.3, SD = 5.1 years) from the Cardiovascular Health Cognition Study (1992-1999). Toxicity-weighted concentrations were estimated using the Risk Screening Environmental Indicator (RSEI) model which incorporates total reported chemical emissions with toxicity, fate, and transport models. Estimates were aggregated to participants' baseline census tract, averaged across 1988-1992, and log2-transformed. Dementia status was clinically adjudicated in 1998-1999 and categorized by subtype (Alzheimer's, vascular, mixed). We assessed whether RSEI-estimated toxicity-weighted concentrations were associated with 1) odds of prevalent dementia and 2) incident dementia risk by subtype., Results: After adjusting for individual and census-tract level covariates, a doubling in toxicity-weighted concentrations was associated with 9 % higher odds of prevalent dementia (OR = 1.09, 95 % CI: 1.00, 1.19). In discrete-time survival models, each doubling in toxicity-weighted concentrations was associated with a 16 % greater hazard of vascular dementia (HR = 1.16, 95 % CI: 1.01, 1.34) but was not significantly associated with all-cause, Alzheimer's disease, or mixed dementia (p's > 0.05)., Discussion: Living in regions with higher toxicity-weighted concentrations was associated with higher odds of prevalent dementia and a higher risk of incident vascular dementia in this large, community-based cohort of older adults. These findings support the need for additional studies to examine whether toxic chemical emissions from industrial and federal facilities may be a modifiable target for dementia prevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Neighborhood walkability may encourage greater out-of-home travel (ie, community mobility) to support independent functioning in later life. We examined associations between a novel walkability audit index and Global Positioning System (GPS)-derived community mobility in community-dwelling older adults. We compared associations with the validated Environmental Protection Agency (EPA) National Walkability Index and further examined moderation by clinical walking speed., Methods: Participants were 146 older adults (Mean = 77.0 ± 6.5 years, 68% women) at baseline of a randomized trial to improve walking speed. A walkability index (range: 0-5; eg, land-use mix, crosswalks, and so on) was created using Google Street View audits within 1/8-mile of the home. Participants carried a GPS device for 5-7 days to derive objective measures of community mobility (eg, time spent out of home, accumulated distance from home)., Results: Each 1 SD (~1.3-point) greater walkability audit score was associated with a median 2.16% more time spent out of home (95% confidence interval [95% CI]: 0.30-4.03, p = .023), adjusting for individual demographics/health and neighborhood socioeconomic status. For slower walkers (4-m walking speed <1 m/s), each 1 SD greater audit score was also associated with a median 4.54 km greater accumulated distance from home (95% CI: 0.01-9.07, p (interaction) = .034). No significant associations were found for the EPA walkability index., Conclusions: Walkability immediately outside the home was related to greater community mobility, especially for older adults with slower walking speeds. Results emphasize the need to consider the joint influence of local environment and individual functioning when addressing community mobility in older populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: We examined the relationship between global positioning system (GPS) indicators of community mobility and incident hospitalizations, emergency department (ED) visits, and falls over 1-year in community-dwelling older adults., Methods: We performed a secondary analysis of a randomized trial investigating a physical therapy intervention to improve mobility in older adults. One hundred and forty-eight participants (mean age: 76.9 ± 6.2 years; 65% female) carried a GPS device following the postintervention visit. Over 1-year, new hospitalizations, falls, and ED visits were reported. GPS indicators of community mobility included the median area and compactness of the standard deviation ellipse (SDE), the median percentage of time spent outside of home (TOH), and median maximum distance from home. Generalized linear models assessed the association between 1-year risk of outcomes and GPS measures adjusted for age, race, gender, body mass index, comorbidity burden, and fall history., Results: The mean ± standard deviation of the median SDE area was 4.4 ± 8.5 km2, median SDE compactness 0.7 ± 0.2, median percentage TOH 14.4 ± 12.0%, and median maximum distance from home was 38 ± 253 km. Each 5% increase in median percentage TOH was associated with a 24% lower risk of hospitalization (incident rate ratio = IRR = 0.76, 95%CI: 0.61-0.95; p = .01). The association persisted after covariate adjustment (IRR = 0.78, 95%CI: 0.63-0.98; p = .03). No significant associations appeared for any GPS indicators with incident falls or ED visits., Conclusions: Increased TOH was associated with a lower risk of incident hospitalization over 1 year among community-dwelling older adults. Restricted community mobility may be an indicator of activity limitations related to future health outcomes, but further study is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Walking is a key component of daily-life mobility. We examined associations between laboratory-measured gait quality and daily-life mobility through Actigraphy and Global Positioning System (GPS). We also assessed the relationship between two modalities of daily-life mobility i.e., Actigraphy and GPS., Methods: In community-dwelling older adults (N = 121, age = 77±5 years, 70% female, 90% white), we obtained gait quality from a 4-m instrumented walkway (gait speed, walk-ratio, variability) and accelerometry during 6-Minute Walk (adaptability, similarity, smoothness, power, and regularity). Physical activity measures of step-count and intensity were captured from an Actigraph. Time out-of-home, vehicular time, activity-space, and circularity were quantified using GPS. Partial Spearman correlations between laboratory gait quality and daily-life mobility were calculated. Linear regression was used to model step-count as a function of gait quality. ANCOVA and Tukey analysis compared GPS measures across activity groups [high, medium, low] based on step-count. Age, BMI, and sex were used as covariates., Results: Greater gait speed, adaptability, smoothness, power, and lower regularity were associated with higher step-counts (0.20<|ρ p | < 0.26, p < .05). Age(β = -0.37), BMI(β = -0.30), speed(β = 0.14), adaptability(β = 0.20), and power(β = 0.18), explained 41.2% variance in step-count. Gait characteristics were not related to GPS measures. Participants with high (>4800 steps) compared to low activity (steps<3100) spent more time out-of-home (23 vs 15%), more vehicular travel (66 vs 38 minutes), and larger activity-space (5.18 vs 1.88 km 2 ), all p < .05., Conclusions: Gait quality beyond speed contributes to physical activity. Physical activity and GPS-derived measures capture distinct aspects of daily-life mobility. Wearable-derived measures should be considered in gait and mobility-related interventions.

The objective of this study was to understand older adults' perceptions of the connections between an exergame intervention, "I Am Dolphin," and their subjective well-being. Researchers conducted three focus groups with 14 older adults who participated in the exergame feasibility study. The semi-structured focus groups were transcribed, coded, and analysed using deductive and inductive techniques. Three themes were constructed related to playing the exergame and participants' subjective well-being: 1) elevated mood (through scheduled activity, immersion, and socialization), 2) feelings of achievement (especially following frustration and competition), and 3) perceived cognitive or physical changes. These findings will help researchers better understand how exergames may relate to the well-being of older adults. Future investigators could use these findings to create and implement new exergame interventions.

Objective: The authors compared the effects of a standard strength and endurance intervention with a standard plus timing and coordination training intervention on community mobility measured using global positioning systems (GPS) among community-dwelling older adults in this secondary analysis of a randomized controlled trial., Methods: Participants were randomized to a standard or a standard plus timing and coordination training program. Community mobility was measured using the Life Space Assessment (LSA) and GPS indicators of community mobility at baseline, as well as at 12 (immediately after the intervention), 24, and 36 weeks. Linear mixed models were used for analysis., Results: There were 166 participants with GPS data at baseline, including 81 in the standard plus group and 85 in the standard group. The groups did not differ in participant characteristics or GPS measures at baseline. There were no significant within-group changes in GPS indicators of community mobility or LSA score over time, nor between-group differences of the same., Conclusion: There were no significant changes in community mobility with either intervention or between-intervention differences. These findings suggest that interventions targeting physical function alone may not be sufficient to improve community mobility or participation in older adults. Future research should focus on the development of multifaceted interventions targeted to improve real-world participation., Impact: The studied interventions did not significantly change community mobility measured using GPS-derived community mobility measures or self-report measures in older adults, suggesting that more comprehensive interventions may be needed to target improvements in community mobility., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Higher mid-life body mass index (BMI) is associated with lower late-life cognition. Associations between later-life BMI and cognition are less consistent; evidence suggests reverse causation may play a role. We aimed to characterize associations between BMI and cognition across a wide age range during mid- to late life (55-85 years) and examine whether associations vary by gender., Methods: We used data from the Health and Retirement Study (HRS) (N = 39,153) to examine the association between BMI and 3 cognitive outcomes: cognitive level, cognitive decline, and cognitive impairment. We used a series of linear regression, mixed effects regression, and logistic regression models, adjusting for potential confounders., Results: Higher BMI before age 65 (midlife) was associated with lower cognitive performance, faster rates of cognitive decline, and higher odds of cognitive impairment in late life. Averaging across analyses assessing associations between BMI measured before age 60 and late-life cognition, a 5-unit higher level of BMI was associated with a 0.26 point lower cognitive score. Beyond age 65, associations flipped, and higher BMI was associated with better late-life cognitive outcomes. Associations in both directions were stronger in women. Excluding those with BMI loss attenuated findings among women in older ages, supporting the reverse causation hypothesis., Conclusions: In this sample, age 65 represented a critical turning point between mid- and late life for the association between BMI and cognition, which has important implications for recruitment strategies for studies focused on risk factors for late-life cognitive outcomes. Evidence of gender differences raises the need to further investigate plausible mechanisms., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Objective measures of community mobility are advantageous for capturing movement outside the home. Compared with subjective, self-reported techniques, global positioning system (GPS) technologies leverage passive, real-time location data to reduce recall bias and increase measurement precision. We developed methods to quantify community mobility among community-dwelling older adults and assessed how GPS-derived indicators relate to clinical measures of physical and cognitive performance., Methods: Participants (n = 149; M ± standard deviation [SD] = 77.1 ± 6.5 years) from the program to improve mobility in aging (PRIMA) study, a physical therapy intervention to improve walking ability, carried a GPS device for 7 days. Community mobility was characterized by assessing activity space, shape, duration, and distance. Associations between GPS-derived indicators and cognition and physical function were evaluated using Spearman correlations., Results: In adjusted models, a larger activity space, greater duration (eg, time out-of-home), and greater distance traveled from home were correlated with better 6-Minute Walk Test performance (ρ = 0.17-0.23, p's < .05). A more circular activity shape was related to poorer performance on the Trail Making Test, Part A (ρ = 0.18, p < .05). More time out-of-home and a larger activity space were correlated with faster times on the Trail Making Test, Part B (ρ = -0.18 to -0.24, p's < .05). Community mobility measures were not associated with global cognition, skilled walking, or usual gait speed., Conclusion: GPS-derived community mobility indicators capture real-world activity among older adults and were correlated with clinical measures of executive function and walking endurance. These findings will guide the design of future interventions to promote community mobility., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cognitive and physical activity are important for daily functioning. However, limited research exists on the motivators and barriers associated with older adults participating and adhering to exergame studies that promote physical and cognitive activity. Our objective was to examine older adults' motivators and barriers to joining and completing a three-dimensional exergame study. Methods: Fourteen older adults who participated in the exergame study contributed to one of three focus group discussions. Inductive and deductive methods were used to analyze the qualitative data. Results: Motivators for joining were generativity, peer referrals, self-improvement, and curiosity. Accomplishment, immersion, and exercise were motivators for retention. Participants also cited the structured schedule and adaptive difficulty features as motivators for retention. Barriers to participation included frustration due to lack of level advancement and fatigue/pain during gameplay. Some ( n  = 3) reported camera tracking issues as a barrier. Unanticipated gender-based trends arose when examining perceptions of the study team's role and motivators for retention. Conclusion: These findings will inform future research strategies for participant recruitment, enrollment, and retention, in addition to providing insights into the design of motivating, enjoyable, and sustainable exergames for older adults.

The cognitive benefits associated with mid- to late-life engagement have been demonstrated in several studies. However, the link between engagement in enriching early-life activities (EELAs) during adolescence and later-life cognition has been relatively unexplored in major epidemiological studies. We examined the EELA-cognition relationship in a nationally representative sample of adults aged 50+. A subset of Health and Retirement Study respondents ( n =3482) completed cognitive tests and returned a retrospective early-life activity inventory. Linear regression models analyzed the EELA-cognition relationship, and multiple imputation addressed missingness. Each additional EELA was associated with a 0.36 point higher cognitive score (95% CI: 0.24, 0.47). This relationship remained significant after adjusting for potential confounders (B=0.16; 95% CI: [0.06, 0.26]). EELA engagement was associated with better later-life cognitive performance. This study is understood to be the first to examine the EELA-cognition relationship using a large, nationally representative dataset. The findings highlight the importance of early-life engagement during an important developmental period (e.g., adolescence).

To synthesize and critique studies that examined the impact of exergames on depressive symptoms in older adults. Articles were retrieved from the databases CINAHL, Embase, PsychINFO, and Medline. Studies were included in the review if they involved a physical activity/videogame intervention and measured outcomes of depressive symptoms in older adults. The search generated 957 articles for consideration, which were narrowed to 17 articles after applying exclusion criteria. In studies that required depressive symptoms as an inclusion criterion, there was an improvement in depressive symptoms in older adults following the exergame intervention. In studies that did not require depressive symptoms as an inclusion criterion, researchers found mixed results. Future older adult exergame research should measure depression as a primary outcome, utilize control groups with random sampling, consist of larger sample sizes, and include people with disabilities.

When normal cells come under stress, the wild-type (WT) p53 level increases resulting in the regulation of gene expression responsible for growth arrest or apoptosis. Here we show that elevated levels of WT p53 or its homologue, p73, inhibit expression of a number of cell cycle regulatory and growth promoting genes. Our analysis also identified a group of genes whose expression is differentially regulated by WT p53 and p73. We have infected p53-null H1299 human lung carcinoma cells with recombinant adenoviruses expressing WT p53, p73 or beta-galactosidase, and have undertaken microarray hybridization analyses to identify genes whose expression profile is altered by p53 or p73. Quantitative real-time PCR verified the repression of E2F-5, centromere protein A and E, minichromosome maintenance proteins (MCM)-2, -3, -5, -6 and -7 and human CDC25B after p53 expression. 5-Fluorouracil treatment of colon carcinoma HCT116 cells expressing WT p53 results in a reduction of the cyclin B2 protein level suggesting that DNA damage may indeed cause repression of these genes. Transient transcriptional assays verified that WT p53 repressed promoters of a number of these genes. Interestingly, a gain-of-function p53 mutant instead upregulated a number of these promoters in transient transfection. Using promoter deletion mutants of MCM-7 we have found that WT p53-mediated repression needs a minimal promoter that contains a single E2F site and surrounding sequences. However, a single E2F site cannot be significantly repressed by WT p53. Many of the genes identified are also repressed by p21. Thus, our work shows that WT p53 and p73 repress a number of growth-related genes and that in many instances this repression may be through the induction of p21.

RCK (regulator of conductance of potassium) domains form a family of ligand-binding domains found in many prokaryotic K+ channels and transport proteins. Although many RCK domains contain an apparent nucleotide binding motif, some are known instead to bind Ca2+, which can then facilitate channel opening. Here we report on the molecular architecture and ligand activation properties of an RCK-containing potassium channel cloned from the prokaryote Thermoplasma volcanium. This channel, called TvoK, is of an apparent molecular mass and subunit composition that is consistent with the hetero-octameric configuration hypothesized for the related MthK (Methanobacterium thermoautotrophicum potassium) channel, in which four channel-tethered RCK domains coassemble with four soluble (untethered) RCK domains. The expression of soluble TvoK RCK subunits arises from an unconventional UUG start codon within the TvoK gene; silent mutagenesis of this alternative start codon abolishes expression of the soluble form of the TvoK RCK domain. Using single channel recording of purified, reconstituted TvoK, we found that the channel is activated by Ca2+ as well as Mg2+, Mn2+, and Ni2+. This non-selective divalent activation is in contrast with the activation properties of MthK, which is selectively activated by Ca2+. Transplantation of the TvoK RCK domain into MthK generates a channel that can be activated by Mg2+, illustrating that the Mg2+ binding site is likely contained within the RCK domain. We present a working hypothesis for TvoK gating in which the binding of either Ca2+ or Mg2+ can contribute approximately 5 kcal/mol toward stabilization of the open conformation of the channel.

We used a bacterial complementation screen with the LB2003 K(+) uptake-deficient strain of Escherichia coli to analyze residues that are critical to Methanobacterium thermoautotrophicum potassium channel (MthK) function. Channel expression and relative structural integrity of mutants were analyzed by SDS-PAGE and Western blot, and mechanisms underlying altered mutant channel function were analyzed using single-channel recording. We observed that wild-type MthK expression complements K(+) uptake deficiency. Although MthK function was previously thought to require Ca(2+) in the millimolar range, we demonstrate that at elevated temperatures the requirement for Ca(2+) becomes much lower. Mutations at the cytoplasmic mouth of the MthK pore can blunt complementation, indicating that those mutant channels cannot support K(+) uptake. In contrast, substitutions at the Ca(2+)-binding site in the MthK RCK domain did not decrease complementation compared with wild-type MthK. We focused on mutations to residues Glu-92 and Glu-96, which may form the narrowest part of the pore in the channel's closed state. Mutations at these residues can yield slight changes in single-channel conductance that do not necessarily correlate with effects on bacterial complementation. However, mutations at Glu-92 could also change channel open probability, and these changes correlated with complementation effects. The most striking of these mutations was E92A, which nearly eliminated bacterial complementation by decreasing the open probability of MthK. Our results suggest that the small, hydrophobic alanine side chain at the K(+) channel bundle crossing may generate an intrinsically stable structure, which in turn shifts the closed-to-open-state equilibrium toward the closed state.