Stephanie A Studenski’s research while affiliated with University of Pittsburgh and other places

Background Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions. Methods In 125 older adults participating in the Study of Muscle, Mobility and Aging, performance fatigability was measured as performance deterioration during a fast 400 meter walk (% slowing down from the 2nd to the 9th lap). Nigrostriatal DA integrity was measured using (+)-[11C] dihydrotetrabenazine (DTBZ) PET imaging. The binding signal was obtained separately for the subregions regulating sensorimotor (posterior putamen), reward (ventral striatum) and executive control processes (dorsal striatum). Multivariable linear regression models of performance fatigability (dependent variable) estimated the coefficients of dopamine integrity in striatal subregions, adjusted for demographics, comorbidities, and cognition. Models were further adjusted for skeletal muscle energetics (via biopsy) and cardiopulmonary fitness (via cardiopulmonary exercise testing). Results Higher [11C]-DTBZ binding in the posterior putamen was significantly associated with lower performance fatigability (demographic-adjusted standardized Beta = -1.08, 95% CI: -1.96, -0.20); results remained independent of adjustment for other covariates, including cardiopulmonary and musculoskeletal energetics. Associations with other striatal subregions were not significant. Discussion Dopaminergic integrity in the sensorimotor striatum may influence performance fatigability in older adults without clinically overt diseases, independent of other aging systems.

Background and objectives Olfactory function declines with aging and olfactory deficits are one of the earliest features of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Previous studies have shown that olfaction is associated with brain volumes and cognitive function, but data are exclusively cross-sectional. We aimed to examine longitudinal associations of olfaction with changes in brain volumes and neuropsychological function. Methods In the Baltimore Longitudinal Study of Aging, we chose the first assessment of olfaction to examine the associations with retrospective and prospective changes in neuropsychological performance and brain volumes in participants aged 50 or older using linear mixed-effects models, adjusted for demographic variables and cardiovascular disease. Olfaction was measured as odor identification scores via the 16-item Sniffin’ sticks. Results We analyzed data from 567 (58% women, 42% men, 27% Black, 66% White, 7% Others) participants who had data on odor identification scores and brain volumetric MRI (n=420 with retrospective repeats over a mean of 3.7 years, n=280 with prospective repeats over a mean of 1.2 years). We also analyzed data from 754 participants (56% women, 44% men, 29% Black, 65% White, 6% Others) with neuropsychological assessments (n=630 with retrospective repeats over a mean of 6.6 years, n=280 with prospective repeats over a mean of 1.5 years). After adjustment, higher odor identification scores were associated with prior and subsequent slower brain atrophy in entorhinal cortex (β±SE=0.0093±0.0031,p=0.0028 and β±SE=0.0176±0.0073,p=0.0169,respectively), hippocampus (β±SE=0.0070±0.0030,p=0.0192 and β±SE=0.0173±0.0066,p=0.0089,respectively), and additional frontal and temporal areas (all p<0.05). Higher odor identification scores were also associated with prior slower decline in memory, attention, processing speed, and manual dexterity, and subsequent slower decline in attention (all p<0.05). Some associations were attenuated after exclusion of data points at and after symptom onset of cognitive impairment or dementia. Discussion In older adults, olfaction is related to brain atrophy of specific brain regions and neuropsychological changes in specific domains over time. The observed associations are driven, in part, by those who developed cognitive impairment or dementia. Future longitudinal studies with longer follow-ups are needed to understand whether olfactory decline precedes cognitive decline and whether it is mediated through regionally-specific brain atrophy.

Objective: To develop and validate a high-risk predictive model that identifies, at least, one common adverse event in older population: early readmission (up to 30 days after discharge), long hospital stays (10 days or more) or in-hospital deaths. Methods: This was a retrospective cohort study including patients aged 60 years or older (n=340) admitted at a 630-beds tertiary hospital, located in the city of São Paulo, Brazil. A predictive model of high-risk indication was developed by analyzing logistical regression models. This model prognostic capacity was assessed by measuring accuracy, sensitivity, specificity, and positive and negative predictive values. Areas under the receiver operating characteristic curve with 95% confidence intervals were also obtained to assess the discriminatory power of the model. Internal validation of the prognostic model was performed in a separate sample (n=168). Results: Statistically significant predictors were identified, such as current Barthel Index, number of medications in use, presence of diabetes mellitus, difficulty chewing or swallowing, extensive surgery, and dementia. The study observed discrimination model acceptance in the construction sample 0.77 (95% confidence interval: 0.71-0.83) and good calibration. The characteristics of the validation samples were similar, and the receiver operating characteristic curve area was 0.687 (95% confidence interval: 0.598-0.776). We could assess an older patient's adverse health events during hospitalization after admission. Conclusion: A predictive model with acceptable discrimination was obtained, with satisfactory results for early readmission (30 days), long hospital stays (10 days), or in-hospital death.

Importance: Observational evidence suggests that higher physical activity is associated with slower kidney function decline; however, to our knowledge, no large trial has evaluated whether activity and exercise can ameliorate kidney function decline in older adults. Objective: To evaluate whether a moderate-intensity exercise intervention can affect the rate of estimated glomerular filtration rate per cystatin C (eGFRCysC) change in older adults. Design, setting, and participants: This ancillary analysis of the Lifestyle Interventions and Independence For Elders randomized clinical trial enrolled 1199 community-dwelling, sedentary adults aged 70 to 89 years with mobility limitations and available blood specimens. The original trial was conducted across 8 academic centers in the US from February 2010 through December 2013. Data for this study were analyzed from March 29, 2021, to February 28, 2022. Interventions: Structured, 2-year, partially supervised, moderate-intensity physical activity and exercise (strength, flexibility) intervention compared with a health education control intervention with 2-year follow-up. Physical activity was measured by step count and minutes of moderate-intensity activity using accelerometers. Main outcomes and measures: The primary outcome was change in eGFRCysC. Rapid eGFRCysC decline was defined by the high tertile threshold of 6.7%/y. Results: Among the 1199 participants in the analysis, the mean (SD) age was 78.9 (5.2) years, and 800 (66.7%) were women. At baseline, the 2 groups were well balanced by age, comorbidity, and baseline eGFRCysC. The physical activity and exercise intervention resulted in statistically significantly lower decline in eGFRCysC over 2 years compared with the health education arm (mean difference, 0.96 mL/min/1.73 m2; 95% CI, 0.02-1.91 mL/min/1.73 m2) and lower odds of rapid eGFRCysC decline (odds ratio, 0.79; 95% CI, 0.65-0.97). Conclusions and relevance: Results of this ancillary analysis of a randomized clinical trial showed that when compared with health education, a physical activity and exercise intervention slowed the rate of decline in eGFRCysC among community-dwelling sedentary older adults. Clinicians should consider targeted recommendation of physical activity and moderate-intensity exercise for older adults as a treatment to slow decline in eGFRCysC. Trial registration: ClinicalTrials.gov Identifier: NCT01072500.

Importance Among older people, slow walking is an early indicator of risk for Alzheimer disease (AD). However, studies that have assessed this association have not considered that slow walking may have different causes, some of which are not necessarily associated with higher AD risk. Objective To evaluate whether low activity fragmentation among older adults with slow gait speed indicates neurological causes of slow walking that put these individuals at higher risk of AD. Design, Setting, and Participants This prospective cohort study performed survival analyses using data from the Baltimore Longitudinal Study of Aging. Participants included 520 initially cognitively normal persons aged 60 years or older. New diagnoses of mild cognitive impairment (MCI) or AD were adjudicated during a mean (SD) follow-up of 7.3 (2.7) years. Initial assessment of gait speed and activity fragmentation occurred from January 3, 2007, to May 11, 2015, with follow-up completed on December 31, 2020. Data were analyzed from February 1 to May 15, 2021. Exposures Gait speed for 6 m and activity fragmentation assessed by accelerometry. Main Outcomes and Measures Associations of gait speed, activity fragmentation, and their interaction with incident MCI/AD were evaluated using Cox proportional hazards models, adjusted for covariates. Results Among the 520 participants (265 women [51.0%]; 125 Black participants [24.0%]; 367 White participants [70.6%]; mean [SD] age, 73 [8] years), MCI/AD developed in 64 participants. Each 0.05-m/s slower gait was associated with a 7% increase in risk of developing MCI/AD (hazard ratio [HR], 1.07 [95% CI, 1.00-1.15]; P = .04). Activity fragmentation alone was not associated with MCI/AD risk (HR, 0.83 [95% CI, 0.56-1.23]; P = .35), but there was a significant interaction between gait speed and activity fragmentation (HR, 0.92 [95% CI, 0.87-0.98]; P = .01). At low activity fragmentation (−1 SD), each 0.05-m/s slower gait speed was associated with a 19% increase in hazard of developing MCI/AD (HR, 1.19 [95% CI, 1.07-1.32]), whereas at higher activity fragmentation (+1 SD), gait speed was not associated with MCI/AD (HR, 1.01 [95% CI, 0.93-1.10]). Among participants with slow gait, higher activity fragmentation was associated with higher odds of having lower extremity osteoarthritis (odds ratio, 1.31 [95% CI, 1.01-1.69]) and less decline in pegboard dominant hand performance (β = 0.026 [SE, 0.009]; P > .05). Conclusions and Relevance These findings suggest that frequent rests among older adults with slow gait speed are associated with lower risk of future MCI/AD and that this behavioral strategy is associated with a lower likelihood of subclinical neurological impairment.

Aging is associated with distinct phenotypical, physiological, and functional changes, leading to disease and death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, and genetics. In this study, we conducted physiologic and functional tests cross-sectionally throughout the entire lifespan of male C57BL/6N mice. In parallel, metabolomics analyses in serum, brain, liver, heart, and skeletal muscle were also performed to identify signatures associated with frailty and age-dependent functional decline. Our findings indicate that declines in gait speed as a function of age and frailty are associated with a dramatic increase in the energetic cost of physical activity and decreases in working capacity. Aging and functional decline prompt organs to rewire their metabolism and substrate selection and towards redox-related pathways, mainly in liver and heart. Collectively, the data provide a framework to further understand and characterize processes of aging at the individual organism and organ levels.

Background and objectives: Lawton's Ecological Model of Aging suggests that associations between environment and mobility differ based on individual factors such as cognitive decline. Research design and methods: Virtual walkability audits were conducted within 1/8 mile of residences of older adults (n=545; average age=82; 57% female; 33% Black) who had been enrolled in the Health ABC cohort for 10 years. The primary outcome was self-reported walking in past week and secondary was mobility disability, self-reported difficulty to walk ¼ mile. Linear mixed models of general cognitive function over the prior 10 years calculated participant-specific slopes; those below 0 were cognitive decliners. Logistic regression models, adjusted for demographics and neighborhood socioeconomic status, tested associations between each walkability variable and each mobility outcome. Interaction terms between walkability and cognitive status were tested and walkability analyses stratified on cognitive status where p for interaction <0.2. Results: In the sample, 57.4% reported walking, 24.2% reported mobility disability, and 51% were cognitive decliners. Sidewalk quality was related to walking in cognitive maintainers; slope was related in decliners. Mixed land use (odds ratio=1.61; 95% confidence interval: 1.12, 2.30) and senior residence (odds ratio=2.14; 95% confidence interval: 1.27, 3.60) were related to greater walking, regardless of cognitive status. Mixed land use was related to less mobility disability in decliners and abandoned properties were related to greater mobility disability in maintainers. Discussion and implications: Policy-level interventions targeted at walkability, including improved sidewalk quality and increasing mixed land use could support walking in older adults, regardless of cognitive status.

We previously showed that dual decline in memory and gait speed was associated with an increased risk of dementia compared to memory or gait decline only or no decline. We now characterized cognitive and neuroimaging profiles of dual decliners by comparing longitudinal rates of change in various cognitive domains (n = 664) and brain volumes (n = 391; selected frontal, temporal, parietal, subcortical, and cerebellar areas) in Baltimore Longitudinal Study of Aging participants who experienced age-related dual decline to others. Compared to others, dual decliners had steeper declines in verbal fluency, attention, and sensorimotor function by Pegboard nondominant hand performance. Dual decliners had greater brain volume loss in superior frontal gyrus, superior parietal gyrus, precuneus, thalamus, and cerebellum (all p ≤ 0.01). Participants with age-related dual decline experienced steeper declines in multiple cognitive domains and greater brain volume loss in cognitive, sensorimotor, and locomotion areas. Impaired sensorimotor integration and locomotion are underlying features of dual decline. Whether these features contribute to the increased risk of dementia should be investigated.

Impaired mobility occurs in up to half of community-dwelling older adults and is associated with poor health outcomes and high health care costs. Although the built environment impacts mobility, most studies of older adults lack information about environmental-level factors. In-person observational audits can be utilized but cannot assess the historical environment. We applied a 78-item checklist to archived Google Street View imagery to assess historical residence access and neighborhood characteristics. Interrater reliability between two raters was tested on 50 addresses using prevalence-adjusted and bias-adjusted kappa (PABAK). The mean PABAK for all items was .75, with 81% of the items having substantial (PABAK ≥ .61) or almost perfect (PABAK ≥ .81) agreement. Environmental assessment using archived virtual imagery has excellent reliability for factors related to residence access and many neighborhood characteristics. Archived imagery can assess past neighborhood characteristics, facilitating the use of historical environment data within existing cohorts.