Thomas G. Travison

Purpose: (1) To describe cognitive trajectory patterns over 6 years after major surgery in older adults, and (2) To identify patient characteristics associated with severe cognitive decline. Methods: Group‐based semiparametric trajectory modeling was performed on longitudinal cognitive data from the SAGES study, which enrolled patients aged ≥ 70 years undergoing major elective noncardiac surgery. Participants received comprehensive neuropsychological testing prior to surgery and postoperatively every 6–12 months up to 72 months. The primary outcome was change in general cognitive performance score, a composite of neuropsychological tests, at each of 11 follow‐up timepoints relative to baseline. Generalized linear models were used to assess the associations of pre‐surgical patient characteristics and incidence of postoperative delirium with cognitive trajectory. Results: Of 560 participants, 326 were women (58%) and the average age was 76.7 (standard deviation 5.2) years. They underwent orthopedic (81%), gastrointestinal (13%), and vascular surgeries (6%), and 24% experienced postoperative delirium. We found the 3‐group cognitive trajectory model to be optimal, with the groups characterized as severe decline trajectory (SDT) (15% of the cohort), slight decline (59%), or stable (26%). Of pre‐surgical factors, age (relative risk [RR]: 1.06, 95% confidence interval [CI] 1.03–1.10 per 1 year increase) and 3MS (Modified‐Mini‐Mental) score (RR 0.95, 95% CI 0.92–0.99 per one point increase) were significantly associated with SDT. Participants who developed delirium had over two‐fold higher risk of SDT compared to those who did not (RR: 2.15, 95% CI: 1.35–3.42). Conclusions: Among older adults undergoing major surgery, 15% experienced severe cognitive decline over the ensuing 6 years, 59% experienced slight decline, and 26% remained stable. Older age, baseline cognitive impairment, and delirium were associated with severe decline, with delirium having the strongest association. Our findings provide valuable information for older patients considering major surgery and may help clinicians target interventions.

Background: Insufficient physical activity in older adults remains a global health issue. Several interrelated factors contributing to inactivity are linked to the prefrontal cortex. We conducted a pilot study to assess the feasibility, acceptability, and effects of combining transcranial direct current stimulation (tDCS) and behavior counseling to improve physical activity in older adults. Methods: Inactive older adults living in subsidized housing participated in this randomized controlled trial. Baseline physical activity (daily steps) was measured with a Fitbit for 2 weeks. Participants then received an 8-week intervention, including 10 daily sessions of tDCS or Sham stimulation during the first 2 weeks, along with 4 biweekly behavior sessions. Functional outcomes were assessed at baseline, poststimulation, and after the entire intervention. Step counts were measured throughout the intervention and a 12-week retention period. Results: Twenty-eight participants completed the study. Compliance was 97%, 93%, and 92% for brain stimulation, behavior sessions, and follow-up assessments, respectively. Fitbit adherence was 96% and 71% during the intervention and retention periods. The tDCS arm, compared to Sham, exhibited greater increase in average daily steps (p .001). Participants increased 1 179 (+ 22%) and 550 (+ 15%) steps/day from baseline in the tDCS and Sham arms, respectively. Motivation (p .03) and self-reported walking performance (p .02) were also improved in the tDCS arm compared to Sham. Conclusions: Combining tDCS and personalized behavior counseling to improve physical activity was feasible, acceptable, and appeared to be effective in a cohort of inactive older adults living within subsidized housing. Larger and more definitive studies are warranted.

Background: Climate change is expected to disrupt weather patterns across the world, exposing older adults to more intense and frequent periods of hot weather. Meanwhile, lab-based studies have established a causal relationship between ambient temperature and cognitive abilities, suggesting the expected rise in temperature may influence older adults’ cognitive functioning. Nevertheless, it is not clear whether, and to what extent, the temperature variations in older adults’ own homes—which unlike lab settings are under their control—influence their cognitive functioning. Our objective was to provide proof of concept that home ambient temperature influences self-reported ability to maintain attention in older adults. Methods: We conducted a longitudinal observational study, continuously monitoring the home ambient temperature and self-reported difficulty keeping attention for 12 months in 47 of community-dwelling older adults living in Boston, Massachusetts. Results: We observed a U-shaped relationship between home ambient temperature at the time of assessment and the odds ratio (OR) of reporting difficulty keeping attention such that the OR was lowest between 20°C and 24°C and doubled when moving away from this range by 4°C in either direction. Discussion: Our results suggest that even under the current climate, a considerable portion of older adults encounter indoor temperatures detrimental to their cognitive abilities. Climate change may exacerbate this problem, particularly among low-income and underserved older adults. Addressing this issue in public health and housing policy is essential to building climate resiliency in this vulnerable population.

Background: Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (eg, mortality); however, inflammatory indices have not yet been examined in delirium. Methods: Four inflammatory markers, C-reactive protein, interleukin-6, soluble tumor necrosis factor alpha receptor-1, and chitinase-3 like protein-1, were measured preoperatively and on postoperative day 2 in 548 adults aged 70+ undergoing major noncardiac surgery (mean age 76.7 [standard deviation 5.2], 58% female, 24% delirium). From these markers, 4 inflammatory indices were considered: (i) quartile summary score, (ii) weighted summary score, (iii) principal component score, and (iv) a well-established inflammatory (least absolute shrinkage and selection operator-derived) index associated with mortality. Delirium was assessed using the Confusion Assessment Method, supplemented by chart review. Generalized linear models with a log-link term were used to determine the association between each inflammatory index and delirium incidence. Results: Among the inflammatory indices, the weighted summary score demonstrated the strongest association with delirium: participants in the weighted summary score quartile (Q)4 had a higher risk of delirium versus participants in Q1, after clinical variable adjustment (relative risk, 95% confidence interval for preoperatively: 3.07, 1.80–5.22; and postoperative day 2: 2.65, 1.63–4.30). The weighted summary score was more strongly associated with delirium than the strongest associated individual inflammatory marker (preoperatively chitinase-3 like protein-1 [relative risk 2.45, 95% confidence interval 1.53–3.92]; postoperative day 2 interleukin-6 [relative risk 2.39, 95% confidence interval 1.50–3.82]). Conclusions: A multi-protein inflammatory index using a weighted summary score provides a slight advantage over individual inflammatory markers in their association with delirium.

Introduced in 2010, the subdiscipline of gerontologic biostatistics was conceptualized to address the specific challenges of analyzing data from clinical research studies involving older adults. Since then, the evolving technological landscape has led to a proliferation of advancements in biostatistics and other data sciences that have significantly influenced the practice of gerontologic research, including studies beyond the clinic. Data science is the field at the intersection of statistics and computer science, and although the term “data science” was not widely used in 2010, the field has quickly made palpable effects on gerontologic research. In this Review in Depth, we describe multiple advancements of biostatistics and data science that have been particularly impactful. Moreover, we propose the subdiscipline of “gerontologic biostatistics and data science,” which subsumes gerontologic biostatistics into a more encompassing practice. Prominent gerontologic biostatistics and data science advancements that we discuss herein include cutting-edge methods in experimental design and causal inference, adaptations of machine learning, the rigorous quantification of deep phenotypic measurement, and analysis of high-dimensional -omics data. We additionally describe the need for integration of information from multiple studies and propose strategies to foster reproducibility, replicability, and open science. Lastly, we provide information on software resources for gerontologic biostatistics and data science practitioners to apply these approaches to their own work and propose areas where further advancement is needed. The methodological topics reviewed here aim to enhance data-rich research on aging and foster the next generation of gerontologic researchers.

Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and “free” T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages. This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study. Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses. Cohort median ages ranged from 40 to 76 years and median cFT concentrations from 174.3 to 422.8 pmol/L. In men aged 17-99 years, there was a linear inverse association of cFT with age (−57.2 pmol/L [95% confidence interval, −69.4, −44.9] per 1 SD increase in age). Calculated free T increased with increasing baseline body mass index (BMI) among men with BMI < 23.6 kg/m², but decreased among men with BMI > 23.6 kg/m² (−24.7 pmol/L [−29.1, −20.3] per 1 SD increase in the 25.4-29.6 kg/m² BMI range). Calculated free T was lower in younger men, who were married or in a de facto relationship (−18.4 pmol/L [−27.6, −9.3]) and in men who formerly smoked (−5.7 pmol/L [−8.9, −2.6]), were in poor general health (−14.0 pmol/L [−20.1, −7.8]), and had diabetes (−19.6 pmol/L [−23.0, −16.3]), cardiovascular disease (−5.8 pmol/L [−8.3, −3.2]), or cancer (−19.2 pmol/L [−24.4, −14.1]). Calculated free T was most prominently associated with age and BMI. The linear, inverse association with age, nonlinear association with BMI, and presence of diabetes, cancer, and sociodemographic factors should be considered when interpreting cFT values.

Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. To clarify associations of sex hormones with these outcomes. Systematic literature review to July 2019, with bridge searches to March 2024. Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. Observational study design, heterogeneity among studies, and imputation of missing data. Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

The four-meter gait speed (4MGS) is a recommended physical performance test in older adults but is challenging to implement clinically. We developed a smartphone application (App) with a four-meter ribbon for remote 4MGS testing at home. This study aimed to assess the validity and reliability of this smartphone App-based assessment of the home 4MGS. We assessed the validity of the smartphone App by comparing it against a gold standard video assessment of the 4MGS conducted by study staff visiting community-dwelling older adults and against the stopwatch-based measurement. Moreover, we assessed the test–retest reliability in two supervised sessions and three additional sessions performed by the participants independently, without staff supervision. The 4MGS measured by the smartphone App was highly correlated with video-based 4MGS (r = 0.94), with minimal differences (mean = 0.07 m/s, ± 1.96 SD = 0.12) across a range of gait speeds. The test–retest reliability for the smartphone App 4MGS was high (ICC values: 0.75 to 0.93). The home 4MGS in older adults can be measured accurately and reliably using a smartphone in the pants pocket and a four-meter strip of ribbon. Leveraging existing technology carried by a significant portion of the older adult population could overcome barriers in busy clinical settings for this well-established objective mobility test.

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Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. To clarify factors associated with variations in sex hormone concentrations. Systematic literature searches (to July 2019). Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).