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1.  Physical Activity and Change in Long Distance Corridor Walk Performance in the Health, Aging and Body Composition Study 
OBJECTIVES
To examine the prospective relationship between self-reported physical activity and aerobic fitness in the Health, Aging and Body Composition (Health ABC) study using the Long Distance Corridor Walk (LDCW).
DESIGN
Cohort study with 7 years follow-up.
SETTING
Two U.S. clinical sites.
PARTICIPANTS
Community dwelling older adults enrolled in Health ABC (n=3075, age 70–79, 52% women, 42% black) with no self-reported difficulty walking one-quarter mile or climbing 10 steps.
MEASURES
Participants were classified based on a physical activity questionnaire as being inactive (≤1,000 kcal/week exercise activity and ≤2,719 kcal/week total physical activity), lifestyle active (≤1,000 kcal/week exercise activity and >2,719 kcal/week total physical activity), or exercisers (reporting ≥ 1,000 kcal/week exercise activity). The Long Distance Corridor Walk,an endurance walking test (400m), was administered at Year 1 (baseline), 2, 4, 6, and 8 to assess aerobic fitness.
RESULTS
At baseline, LDCW completion times (adjusted for age and sex) were 351.8 (95% Confidence Interval= 346.9–356.8), 335.9 (95% CI= 332.7–339.1), and 307.7 (95% CI= 303.2–312.3) seconds for the inactive, lifestyle active, and exerciser groups, respectively (P<0.001). Slowing from baseline to Year 8 was 36.1 (95% CI= 28.4–43.8), 38.1 (95% CI= 33.6–42.4), and 40.8 (95% CI= 35.2–46.5) seconds for the inactive, lifestyle active, and exerciser groups, respectively and did not differ significantly between groups. In linear mixed-effects models, the rate of change in LDCW time did not differ across groups, although exercisers consistently had the fastest completion times (P<0.001 for all pair wise comparisons).
CONCLUSIONS
Decline in the LDCW time occurred regardless of baseline activity. However, exercisers maintained higher aerobic fitness, which may delay reaching critically low threshold of aerobic fitness where independence is impaired.
doi:10.1111/jgs.13487
PMCID: PMC4770787  PMID: 26096803
aerobic fitness; physical activity; 400m walk
2.  Antihypertensive Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study 
Background.
Despite wide-spread use of antihypertensives in older adults, the literature is unclear about their association with incident recurrent falls over time.
Methods.
Health, Aging and Body Composition study participants (n = 2,948) who were well functioning at baseline (1997) were followed to Year 7 (2004). The main outcome was recurrent falls (≥2) in the ensuing 12 months. Antihypertensive use was examined as: (a) any versus none, (b) long- versus short-term (≥2 vs <2 years), and by (c) summated standardized daily dose (SDD; 1 = maximum recommended daily dose for one antihypertensive), and (d) subclass.
Results.
Controlling for potential demographic, health status/behavior and access to care confounders, we found no increase in risk of recurrent falls in antihypertensive users compared to nonusers (adjusted odds ratio [AOR] = 1.13; 95% CI = 0.88–1.46), or those taking higher SDDs or for longer durations. Only those using a loop diuretic were found to have a modest increased risk of recurrent falls (AOR = 1.50; 95% CI = 1.11–2.03).
Conclusions.
Antihypertensive use overall was not statistically significantly associated with recurrent falls after adjusting for important confounders. Loop diuretic use may be associated with recurrent falls and needs further study.
doi:10.1093/gerona/glv095
PMCID: PMC4643613  PMID: 26265732
Falls; Medication; Epidemiology; Drug related
3.  Chronic Low-Calorie Sweetener Use and Risk of Abdominal Obesity among Older Adults: A Cohort Study 
PLoS ONE  2016;11(11):e0167241.
Introduction
Low-calorie sweetener use for weight control has come under increasing scrutiny as obesity, especially abdominal obesity, remain entrenched despite substantial low-calorie sweetener use. We evaluated whether chronic low-calorie sweetener use is a risk factor for abdominal obesity.
Participants and Methods
We used 8268 anthropometric measurements and 3096 food diary records with detailed information on low-calorie sweetener consumption in all food products, from 1454 participants (741 men, 713 women) in the Baltimore Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of 10 years (range: 0–28 years). At baseline, 785 were low-calorie sweetener non-users (51.7% men) and 669 participants were low-calorie sweetener users (50.1% men). Time-varying low-calorie sweetener use was operationalized as the proportion of visits since baseline at which low-calorie sweetener use was reported. We used marginal structural models to determine the association between baseline and time-varying low-calorie sweetener use with longitudinal outcomes—body mass index, waist circumference, obesity and abdominal obesity—with outcome status assessed at the visit following low-calorie sweetener ascertainment to minimize the potential for reverse causality. All models were adjusted for year of visit, age, sex, age by sex interaction, race, current smoking status, dietary intake (caffeine, fructose, protein, carbohydrate, and fat), physical activity, diabetes status, and Dietary Approaches to Stop Hypertension score as confounders.
Results
With median follow-up of 10 years, low-calorie sweetener users had 0.80 kg/m2 higher body mass index (95% confidence interval [CI], 0.17–1.44), 2.6 cm larger waist circumference (95% CI, 0.71–4.39), 36.7% higher prevalence (prevalence ratio = 1.37; 95% CI, 1.10–1.69) and 53% higher incidence (hazard ratio = 1.53; 95% CI 1.10–2.12) of abdominal obesity than low-calorie sweetener non-users.
Conclusions
Low-calorie sweetener use is independently associated with heavier relative weight, a larger waist, and a higher prevalence and incidence of abdominal obesity suggesting that low-calorie sweetener use may not be an effective means of weight control.
doi:10.1371/journal.pone.0167241
PMCID: PMC5120853  PMID: 27880832
4.  Skeletal Muscle Mitochondrial Function and Fatigability in Older Adults 
Background.
Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults.
Methods.
The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 ± 5.0 years (47% female, 93% white), with a body mass index of 25.9 ± 2.7 kg/m2 and usual gait-speed of 1.2 ± 0.2 m/s. Fatigability was defined using rating of perceived exertion (6–20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using 31P magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax (mM ATP/s) and oxidative capacity of the quadriceps (ATPmax·Quadriceps volume) were calculated. Peak aerobic capacity (VO2peak) was measured using a modified Balke protocol.
Results.
ATPmax·Quadriceps volume was associated with VO2peak and was 162.61mM ATP·mL/s lower (p = .03) in those with high (rating of perceived exertion ≥10) versus low (rating of perceived exertion ≤9) fatigability. Participants with high fatigability required a significantly higher proportion of VO2peak to walk at 0.72 m/s compared with those with low fatigability (58.7 ± 19.4% vs 44.9 ± 13.2%, p < .05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability (odds ratio: 0.34, 95% CI: 0.11–1.01, p = .05).
Conclusions.
Lower capacity for oxidative phosphorylation in the quadriceps, perhaps by contributing to lower VO2peak, is associated with higher fatigability in older adults.
doi:10.1093/gerona/glu134
PMCID: PMC4612379  PMID: 25167867
Mitochondrial function; Fatigability; Aerobic capacity; Skeletal muscle.
5.  Energy Metabolism and the Burden of Multimorbidity in Older Adults: Results From the Baltimore Longitudinal Study of Aging 
Excessively elevated resting metabolic rate (RMR) for persons of a certain age, sex, and body composition is a mortality risk factor. Whether elevated RMR constitutes an early marker of health deterioration in older adult has not been fully investigated. Using data from the Baltimore Longitudinal Study of Aging, we hypothesized that higher RMR (i) was cross-sectionally associated with higher multimorbidity and (ii) predicted higher multimorbidity in subsequent follow-ups. The analysis included 695 Baltimore Longitudinal Study of Aging participants, aged 60 or older at baseline, of whom 248 had follow-up data available 2 years later and 109 four years later. Multimorbidity was assessed as number of chronic diseases. RMR was measured by indirect calorimetry and was tested in regression analyses adjusted for covariates age, sex, and dual-energy x-ray absorptiometry–measured total body fat mass and lean mass. Baseline RMR and multimorbidity were positively associated, independent of covariates (p = .002). Moreover, in a three-wave bivariate autoregressive cross-lagged model adjusted for covariates, higher prior RMR predicted greater future multimorbidity above and beyond the cross-sectional and autoregressive associations (p = .034). RMR higher than expected, given age, sex, and body composition, predicts future higher multimorbidity in older adults and may be used as early biomarker of impending health deterioration. Replication and the development of normative data are required for clinical translation.
doi:10.1093/gerona/glu209
PMCID: PMC4612383  PMID: 25409892
Multimorbidity; Resting metabolic rate; Aging; Health status; Metabolism.
6.  Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54–96 years from the Baltimore Longitudinal Study of Aging 
Aging Cell  2016;15(5):825-831.
Summary
Cardiorespiratory fitness (VO 2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO 2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA). Individual species of ceramide were quantified by HPLC–tandem mass spectrometry. VO 2 peak was measured by a graded treadmill test. We applied multiple regression models to test the associations between ceramide species and VO 2 peak, while adjusting for age, sex, blood pressure, serum LDL, HDL, triglycerides, and other covariates. We found that higher levels of circulating C18:0, C20:0, C24:1 ceramides and C20:0 dihydroceramides were strongly associated with lower aerobic capacity (P < 0.001, P < 0.001, P = 0.018, and P < 0.001, respectively). The associations held true for both sexes (with men having a stronger association than women, P value for sex interaction <0.05) and were unchanged after adjusting for confounders and multiple comparison correction. Interestingly, no significant association was found for C16:0, C22:0, C24:0, C26:0, and C22:1 ceramide species, C24:0 dihydroceramide, or total ceramides. Our analysis reveals that specific long‐chain ceramides strongly associate with low cardiovascular fitness in older adults and may be implicated in the pathogenesis of low fitness with aging. Longitudinal studies are needed to further validate these associations and investigate the relationship between ceramides and health outcomes.
doi:10.1111/acel.12491
PMCID: PMC5013023  PMID: 27135629
aging; cardiovascular fitness; ceramide; morbidity; plasma sphingolipids
7.  Does Sensory Function Decline Independently or Concomitantly with Age? Data from the Baltimore Longitudinal Study of Aging 
Journal of Aging Research  2016;2016:1865038.
Objectives. To investigate whether sensory function declines independently or in parallel with age within a single individual. Methods. Cross-sectional analysis of Baltimore Longitudinal Study of Aging (BLSA) participants who underwent vision (visual acuity threshold), proprioception (ankle joint proprioceptive threshold), vestibular function (cervical vestibular-evoked myogenic potential), hearing (pure-tone average audiometric threshold), and Health ABC physical performance battery testing. Results. A total of 276 participants (mean age 70 years, range 26–93) underwent all four sensory tests. The function of all four systems declined with age. After age adjustment, there were no significant associations between sensory systems. Among 70–79-year-olds, dual or triple sensory impairment was associated with poorer physical performance. Discussion. Our findings suggest that beyond the common mechanism of aging, other distinct (nonshared) etiologic mechanisms may contribute to decline in each sensory system. Multiple sensory impairments influence physical performance among individuals in middle old-age (age 70–79).
doi:10.1155/2016/1865038
PMCID: PMC5059583  PMID: 27774319
8.  Lap time variation and executive function in older adults: the Baltimore Longitudinal Study of Aging 
Age and Ageing  2015;44(5):796-800.
Background: poor cognitive and motor performance predicts neurological dysfunction. Variable performance may be a subclinical indicator of emerging neurological problems.
Objective: examine the cross-sectional association between a clinically accessible measure of variable walking and executive function.
Methods: older adults aged 60 or older from the Baltimore Longitudinal Study of Aging (n = 811) with data on the 400-m walk test and cognition. Based on ten 40-m laps, we calculated mean lap time (MLT) and variation in time across ten 40-m laps (lap time variation, LTV). Executive function tests assessed attention and short-term memory (digit span forward and backward), psychomotor speed [Trail Making Test (TMT) part A] and multicomponent tasks requiring cognitive flexibility [TMT part B, part B-A (Delta TMT) and digit symbol substitution test (DSST)]. Multivariate linear regression analysis examined the cross-sectional association between LTV and executive function, adjusted for MLT, age, sex and education, as well as the LTV × MLT interaction.
Results: the LTV was univariately associated with all executive function tests except digit span (P < 0.001); after adjustment, the association with TMT part A remained (standardised β = 0.142, P = 0.002). There was an interaction between MLT and LTV; among fast walkers, greater LTV was associated with a greater Delta TMT (β for LTV × MLT = −1.121, P = 0.016) after adjustment.
Conclusion: at any walking speed, greater LTV is associated with psychomotor slowing. Among persons with faster walking speed, variation is associated with worse performance on a complex measure of cognitive flexibility. A simple measure of variability in walking time is independently associated with psychomotor slowing.
doi:10.1093/ageing/afv076
PMCID: PMC4547927  PMID: 26082177
lap time variation; psychomotor speed; cognitive flexibility; older people
9.  Thyroid Hormone Therapy and Risk of Thyrotoxicosis in Community-Resident Older Adults: Findings from the Baltimore Longitudinal Study of Aging 
Thyroid  2015;25(9):979-986.
Background: Both endogenous and exogenous thyrotoxicosis has been associated with atrial fibrillation and low bone mineral density. Therefore, this study investigated the risk factors associated with prevalent and incident thyrotoxicosis and the initiation of thyroid hormone therapy in a healthy, aging cohort.
Methods: A total of 1450 ambulatory community volunteer participants in the Baltimore Longitudinal Study of Aging examined at the NIA Clinical Research Unit in Baltimore, MD, have undergone longitudinal monitoring of serum thyrotropin (TSH) and thyroid hormone (free thyroxine and free triiodothryonine) levels as well as medication use every one to four years, depending on age, between 2003 and 2014.
Results: The prevalence of low TSH was 9.6% for participants on thyroid hormone and 0.8% for nontreated individuals (p < 0.001). New cases occurred at a rate of 17.7/1000 person-years of exposure to thyroid hormone therapy [CI 9–32/1000] and 1.5/1000 person-years in the unexposed population [CI 0.7–2.9/1000]. Women were more likely to be treated and more often overtreated than men were. The adjusted hazard ratio (HR) for thyrotoxicosis between treated and untreated women was 27.5 ([CI 7.2–105.4]; p < 0.001) and 3.8 for men ([CI 1.2–6.3]; p < 0.01). White race/ethnicity and older age were risk factors for thyroid hormone therapy but not overtreatment. Body mass index was not associated with starting therapy (HR = 1.0). Thyroid hormone initiation was highest among women older than 80 years of age (3/100 person-years). For one-third of treated participants with follow-up data, overtreatment persisted at least two years.
Conclusions: Iatrogenic thyrotoxicosis accounts for approximately half of both prevalent and incident low TSH events in this community-based cohort, with the highest rates among older women, who are vulnerable to atrial fibrillation and osteoporosis. Physicians should be particularly cautious in treating subclinical hypothyroidism in elderly women in light of recent studies demonstrating no increased risk of cardiovascular morbidity or death for individuals with elevated TSH levels <10 mIU/L.
doi:10.1089/thy.2015.0180
PMCID: PMC4560848  PMID: 26177259
10.  The Pittsburgh Fatigability Scale for Older Adults: Development and Validation 
OBJECTIVES
To describe the development of the Pittsburgh Fatigability Scale (PFS) and establish its reliability and concurrent and convergent validity against performance measures.
DESIGN
Cross-sectional.
SETTING
University of Pittsburgh, Pittsburgh, Pennsylvania.
PARTICIPANTS
Scale development sample: 1,013 individuals aged 60 and older from two registries; validation sample: 483 adults aged 60 and older from the Baltimore Longitudinal Study of Aging (BLSA).
MEASUREMENTS
The scale development sample and BLSA participants self-administered an initial 26-item perceived fatigability scale. BLSA participants also completed measures of performance fatigability (perceived exertion from a standard treadmill task and performance deterioration from a fast-paced long-distance corridor walk), a 6-m usual-paced corridor walk, and five timed chair stands.
RESULTS
Principal components analysis with varimax rotation reduced the 26-item scale to the 10-item PFS. The PFS showed strong internal consistency (Cronbach’s alpha 0.88) and excellent test–retest reliability (intraclass correlation 0.86). In the validation sample, PFS scores, adjusted for age, sex, and race, were greater for those with high performance fatigability, slow gait speed, worse physical function, and lower fitness, with differences between high and low fatigability ranging from 3.2 to 5.1 points (P < .001).
CONCLUSION
The 10-item PFS physical fatigability score is a valid and reliable measure of perceived fatigability in older adults and can serve as an adjunct to performance- based fatigability measures for identifying older adults at risk of mobility limitation in clinical and research settings.
doi:10.1111/jgs.13191
PMCID: PMC4971882  PMID: 25556993
fatigue; fatigability; performance measures; validation; mobility
11.  Antidepressant Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study 
The Annals of pharmacotherapy  2016;50(7):525-533.
Background
Few studies have compared the risk of recurrent falls across various antidepressant agents—using detailed dosage and duration data—among community-dwelling older adults, including those who have a history of a fall/fracture.
Objective
To examine the association of antidepressant use with recurrent falls, including among those with a history of falls/fractures, in community-dwelling elders.
Methods
This was a longitudinal analysis of 2948 participants with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Any antidepressant medication use was self-reported at years 1, 2, 3, 5, and 6 and further categorized as (1) selective serotonin reuptake inhibitors (SSRIs), (2) tricyclic antidepressants, and (3) others. Dosage and duration were examined. The outcome was recurrent falls (≥2) in the ensuing 12-month period following each medication data collection.
Results
Using multivariable generalized estimating equations models, we observed a 48% greater likelihood of recurrent falls in antidepressant users compared with nonusers (adjusted odds ratio [AOR] = 1.48; 95% CI = 1.12-1.96). Increased likelihood was also found among those taking SSRIs (AOR = 1.62; 95% CI = 1.15-2.28), with short duration of use (AOR = 1.47; 95% CI = 1.04-2.00), and taking moderate dosages (AOR = 1.59; 95% CI = 1.15-2.18), all compared with no antidepressant use. Stratified analysis revealed an increased likelihood among users with a baseline history of falls/fractures compared with nonusers (AOR = 1.83; 95% CI = 1.28-2.63).
Conclusion
Antidepressant use overall, SSRI use, short duration of use, and moderate dosage were associated with recurrent falls. Those with a history of falls/fractures also had an increased likelihood of recurrent falls.
doi:10.1177/1060028016644466
PMCID: PMC4892949  PMID: 27066988
antidepressants; aging; drug-related problems; epidemiology; geriatrics; outcomes research/analysis; pharmacoepidemiology
12.  Association of Hearing Impairment with Risk of Hospitalization in Older Adults 
OBJECTIVES
To determine the association of hearing impairment (HI) with risk and duration of hospitalization in community-dwelling older adults in the United States.
DESIGN
Prospective observational study.
SETTING
Health, Aging and Body Composition study.
PARTICIPANTS
Well-functioning community-dwelling White and Black Medicare beneficiaries aged 70–79 years at study enrollment in 1997–1998 were followed for a median of 12 years.
MEASUREMENTS
Incidence, annual rate, and duration of hospitalization were the primary outcomes. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: Hearing Level (dB HL) at octave frequencies from 0.5–4 kHz. Mild HI was defined as PTA >25–40 dB HL, and moderate-or-greater HI was defined as PTA >40 dB HL.
RESULTS
Of the 2,148 participants included in the analysis, 1,801 (83.5%) experienced one or more hospitalizations, with 7,007 adjudicated hospitalization events occurring during the study period. A total of 882 (41.1%) participants had normal hearing, 818 (38.1%) had mild HI, and 448 (20.9%) had moderate-or-greater HI. After adjusting for demographics and cardiovascular comorbidities, persons with mild and moderate-or-greater HI, respectively, experienced a 16% (Hazard Ratio [HR]: 1.16, 95% CI: 1.04–1.29) and 21% (HR: 1.21, 95% CI: 1.06–1.38) greater risk of incident hospitalization and a 17% (Incidence Rate Ratio [IRR]: 1.17, 95% CI: 1.04–1.32) and 19% (IRR: 1.19, 95% CI: 1.04–1.38) greater annual rate of hospitalization compared to persons with normal hearing. There was no significant association of HI with mean duration of hospitalization.
CONCLUSION
Hearing-impaired older adults experience a greater incidence and annual rate of hospitalization than those with normal hearing. Investigating whether hearing rehabilitative therapies could affect the risk of hospitalization in older adults requires further study.
doi:10.1111/jgs.13456
PMCID: PMC4477278  PMID: 26096388
hearing impairment; hospitalization; older adults; epidemiology
13.  Low 25-Hydroxyvitamin D Concentrations Predict Incident Depression in Well-Functioning Older Adults: The Health, Aging, and Body Composition Study 
Background.
Cross-sectional studies suggest that low 25-hydroxyvitamin D (25[OH]D) may be a risk factor for depression; however, there are few prospective studies. We examined the association between 25(OH)D and depressive symptoms in community-dwelling persons aged 70–79 years in the Health, Aging, and Body Composition (Health ABC) Study (n = 2598).
Methods.
Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D) at baseline and 2-, 3- and 4-year follow-up. Serum 25(OH)D was measured at 1-year follow-up and categorized as <20, 20–<30, and ≥30 ng/mL. Mixed models were used to examine change in CES-D scores according to 25(OH)D categories. The association between 25(OH)D categories and incident depression (CES-D short score ≥10 or antidepressant medication use) were assessed using Cox proportional hazards models. Analyses were adjusted for socio-demographic and behavioral characteristics, season, and chronic conditions.
Results.
Thirty-three percent of participants had 25(OH)D <20ng/mL. Serum 25(OH)D was not associated with CES-D scores at baseline (p = .51); however, CES-D scores increased over time and were significantly associated with 25(OH)D at 2-year (p = .003) and 4-year follow-up (p < .001). Among 2,156 participants free of depression at the 1-year follow-up, the cumulative incidence of depression was 26.9%. Participants with 25(OH)D <20ng/mL were at greater risk of developing depression (HR [95% CI]: 1.65 [1.23–2.22]) over 4 years of follow-up compared with those with 25(OH)D ≥30ng/mL.
Conclusion.
Low 25(OH)D was independently associated with a greater increase in depressive symptom scores and incident depression in community-dwelling older adults.
doi:10.1093/gerona/glu184
PMCID: PMC4447802  PMID: 25326643
Depression; Epidemiology; Risk factors; Nutrition.
14.  Impact of drug-drug and drug-disease interactions on gait speed in community-dwelling older adults 
Drugs & aging  2016;33(6):411-418.
Background
Gait speed decline, an early marker of functional impairment, is a sensitive predictor of adverse health outcomes in older adults. The effect of potentially inappropriate prescribing on gait speed decline is not well known.
Objective
To determine if potentially inappropriate drug interactions impair functional status as measured by gait speed.
Methods
The sample included 2,402 older adults with medication and gait speed data from the Health, Aging and Body Composition study. The independent variable was the frequency of drug-disease and/or drug-drug interactions at baseline and three additional years. The main outcome was a clinically meaningful gait speed decline ≥ 0.1 m/s the year following drug interaction assessment. Adjusted odds ratios and 95% confidence intervals were calculated using multivariate generalized estimating equations for both the overall sample and a sample stratified by gait speed at time of drug interaction assessment.
Results
The prevalence of drug-disease and drug-drug interactions ranged from 7.6–9.3% and 10.5–12.3%, respectively, with few participants (3.8–5.7%) having multiple drug interactions. At least 22% of participants had a gait speed decline of ≥ 0.1 m/s annually. Drug interactions were not significantly associated with gait speed decline overall or in the stratified sample of fast walkers. There was some evidence, however, that drug interactions increased the risk of gait speed decline among those participants with slower gait speeds, though p values did not reach statistical significance (adjusted odds ratio 1.22, 95% confidence intervals 0.96–1.56, p=0.11). Moreover, a marginally significant dose-response relationship was seen with multiple drug interactions and gait speed decline (adjusted odds ratio 1.40; 95% confidence intervals 0.95–2.04, p=0.08).
Conclusions
Drug interactions may increase the likelihood of gait speed decline among older adults with evidence of preexisting debility. Future studies should focus on frail elders with less physiological reserve who may be more susceptible to the harms associated with potentially inappropriate medications.
doi:10.1007/s40266-016-0373-2
PMCID: PMC4873384  PMID: 27138955
15.  Association Between Visuospatial Ability and Vestibular Function in the Baltimore Longitudinal Study of Aging 
OBJECTIVES
To investigate the relationship between vestibular loss associated with aging and age-related decline in visuospatial function.
DESIGN
Cross-sectional analysis within a prospective cohort study.
SETTING
Baltimore Longitudinal Study of Aging (BLSA).
PARTICIPANTS
Community-dwelling BLSA participants with a mean age of 72 (range 26–91) (N = 183).
MEASUREMENTS
Vestibular function was measured using vestibular-evoked myogenic potentials. Visuospatial cognitive tests included Card Rotations, Purdue Pegboard, Benton Visual Retention Test, and Trail-Making Test Parts A and B. Tests of executive function, memory, and attention were also considered.
RESULTS
Participants underwent vestibular and cognitive function testing. In multiple linear regression analyses, poorer vestibular function was associated with poorer performance on Card Rotations (P = .001), Purdue Pegboard (P = .005), Benton Visual Retention Test (P = 0.008), and Trail-Making Test Part B (P = .04). Performance on tests of executive function and verbal memory were not significantly associated with vestibular function. Exploratory factor analyses in a subgroup of participants who underwent all cognitive tests identified three latent cognitive abilities: visuospatial ability, verbal memory, and working memory and attention. Vestibular loss was significantly associated with lower visuospatial and working memory and attention factor scores.
CONCLUSION
Significant consistent associations between vestibular function and tests of visuospatial ability were observed in a sample of community-dwelling adults. Impairment in visuospatial skills is often one of the first signs of dementia and Alzheimer’s disease. Further longitudinal studies are needed to evaluate whether the relationship between vestibular function and visuospatial ability is causal.
doi:10.1111/jgs.13609
PMCID: PMC4883683  PMID: 26311169
vestibular function; cognition; aging; visuospatial ability
16.  Objective Measures of Physical Activity, White Matter Integrity and Cognitive Status in Adults Over Age 80 
Behavioural brain research  2015;284:51-57.
The neuroprotective effects of physical activity (PA) are consistently shown in older adults, but the neural substrates, particularly in white matter (WM), are understudied, especially in very old adults with the fastest growth rate and the highest risk of dementia. This study quantified the association between PA and WM integrity in adults over 80. The moderating effects of cardiometabolic conditions, physical functional limitations and WM hyperintensities were also examined, as they can affect PA and brain integrity. Fractional anisotropy (FA) from normal-appearing WM via diffusion tensor imaging and WM hyperintensities were obtained in 90 participants (mean age=87.4, 51.1% female, 55.6% white) with concurrent objective measures of steps, active energy expenditure (AEE in kcal), duration (minutes), and intensity (Metabolic equivalents, METs) via SenseWear Armband. Clinical adjudication of cognitive status, prevalence of stroke and diabetes, systolic blood pressure, and gait speed were assessed at time of neuroimaging. Participants were on average sedentary (mean±SD/day: 1766±1345 steps, 202±311 kcal, 211±39 minutes, 1.8±1.1 METs). Higher steps, AEE and duration, but not intensity, were significantly associated with higher FA. Associations were localized in frontal and temporal areas. Moderating effects of cardiometabolic conditions, physical functional limitations, and WM hyperintensities were not significant. Neither FA nor PA was related to cognitive status. Older adults with a sedentary lifestyle and a wide range of cardiometabolic conditions and physical functional limitations, displayed higher WM integrity in relation to higher PA. Studies of very old adults to quantify the role of PA in reducing dementia burden via WM integrity are warranted.
doi:10.1016/j.bbr.2015.01.045
PMCID: PMC4369426  PMID: 25655514
White matter integrity; diffusion tensor imaging; SenseWear Armband; very old adults
17.  Association of Hearing Impairment with Declines in Physical Functioning and the Risk of Disability in Older Adults 
Background:
Identifying factors associated with functional declines in older adults is important given the aging of the population. We investigated if hearing impairment is independently associated with objectively measured declines in physical functioning in a community-based sample of older adults.
Methods:
Prospective observational study of 2,190 individuals from the Health, Aging, and Body Composition study. Participants were followed annually for up to 11 visits. Hearing was measured with pure-tone audiometry. Physical functioning and gait speed were measured with the Short Physical Performance Battery (SPPB). Incident disability and requirement for nursing care were assessed semiannually through self-report.
Results:
In a mixed-effects model, greater hearing impairment was associated with poorer physical functioning. At both Visit 1 and Visit 11, SPPB scores were lower in individuals with mild (10.14 [95% CI 10.04–10.25], p < .01; 7.35 [95% CI 7.12–7.58], p < .05) and moderate or greater hearing impairment (10.04 [95% CI 9.90–10.19], p < .01; 7.00 [95% CI 6.69–7.32], p < .01) than scores in normal hearing individuals (10.36 [95% CI 10.26–10.46]; 7.71 [95% CI 7.49–7.92]). We observed that women with moderate or greater hearing impairment had a 31% increased risk of incident disability (Hazard ratio [HR] =1.31 [95% CI 1.08–1.60], p < .01) and a 31% increased risk of incident nursing care requirement (HR = 1.31 [95% CI 1.05–1.62], p = .02) compared to women with normal hearing.
Conclusions:
Hearing impairment is independently associated with poorer objective physical functioning in older adults, and a 31% increased risk for incident disability and need for nursing care in women.
doi:10.1093/gerona/glu207
PMCID: PMC4400396  PMID: 25477427
Physical function; Physical performance; Epidemiology.
18.  Restricted activity and persistent pain following motor vehicle collision among older adults: a multicenter prospective cohort study 
BMC Geriatrics  2016;16:86.
Background
Restricted physical activity commonly occurs following acute musculoskeletal pain in older adults and may influence long-term outcomes. We sought to examine the relationship between restricted physical activity after motor vehicle collision (MVC) and the development of persistent pain.
Methods
We examined data from a prospective study of adults ≥65 years of age presenting to the emergency department (ED) after MVC without life-threatening injuries. Restricted physical activity 6 weeks after MVC was defined in three different ways: 1) by a ≥25 point decrease in Physical Activity Scale in the Elderly (PASE) score, 2) by the answer “yes” to the question, “during the past two weeks, have you stayed in bed for at least half a day?”, and 3) by the answer “yes” to the question, “during the past two weeks, have you cut down on your usual activities as compared to before the accident?” We examined relationships between each definition of restricted activity and pain severity, pain interference, and functional capacity at 6 months with adjustment for confounders.
Results
Within the study sample (N = 164), adjusted average pain severity scores at 6 months did not differ between patients with and without restricted physical activity based on decreased PASE score (2.54 vs. 2.07, p = 0.32). In contrast, clinically and statistically important differences in adjusted average pain severity at 6 months were observed for patients who reported spending half a day in bed vs. those who did not (3.56 vs. 1.91, p < 0.01). In adjusted analyses, both decreased PASE score and cutting down on activity were associated with functional capacity at 6 months, but only decreased PASE score was associated with increased ADL difficulty at 6 months (0.70 vs. -0.01, p = 0.02).
Conclusions
Among older adults experiencing MVC, those reporting bed rest or reduced activity 6 weeks after the collision reported higher pain and pain interference scores at 6 months. More research is needed to determine if interventions to promote activity can improve outcomes after MVC in older adults.
doi:10.1186/s12877-016-0260-z
PMCID: PMC4837524  PMID: 27094038
Aged; Motor Activity; Emergency medicine; Pain; Geriatrics; Traffic accidents
19.  Gait Characteristics Associated with Walking Speed Decline in Older Adults: Results from the Baltimore Longitudinal Study of Aging 
Background
Understanding the mechanisms that contribute to walking speed decline can provide needed insight for developing targeted interventions to reduce the rate and likelihood of decline.
Objective
Examine the association between gait characteristics and walking speed decline in older adults.
Methods
Participants in the Baltimore Longitudinal Study of Aging aged 60 to 89 were evaluated in the gait laboratory which used a three dimensional motion capture system and force platforms to assess cadence, stride length, stride width, percent of gait cycle in double stance, anterior-posterior mechanical work expenditure (MWE), and medial-lateral MWE. Usual walking speed was assessed over 6 meters at baseline and follow-up. Gait characteristics associated with meaningful decline (decline ≥ 0.05 m/s/y) in walking speed were evaluated by logistic regression adjusted for age, sex, race, height, weight, initial walking speed and follow-up time.
Results
Among 362 participants, the average age was 72.4 (SD=8.1) years, 51% were female, 27% were black and 23% were identified has having meaningful decline in usual walking speed with an average follow-up time of 3.2 (1.1) years. In the fully adjusted model, faster cadence [ORadj=0.65 95% CI (0.43,0.97)] and longer strides [ORadj=0.87 95% CI (0.83,0.91)] were associated with lower odds of decline. However age [ORadj=1.04 95% CI (0.99,1.10)] was not associated with decline when controlling for gait characteristics and other demographics.
Conclusion
A sizable proportion of healthy older adults experienced walking speed decline over an average of 3 years. Longer stride and faster cadence were protective against meaningful decline in usual walking speed.
doi:10.1016/j.archger.2015.01.007
PMCID: PMC4330111  PMID: 25614178
20.  Association Between the Mediterranean Diet and Cognitive Decline in a Biracial Population 
Background.
Results from numerous studies suggest protective effects of the Mediterranean diet for cardiovascular disease, cancer, and mortality. Evidence for an association with a decreased risk of cognitive decline is less consistent and studies are limited by a lack of diversity in their populations.
Methods.
We followed 2,326 older adults (38.2% black, 51.3% female, aged 70–79 at baseline) over 8 years in a prospective cohort study in the United States (Health, Aging and Body Composition study). To measure adherence to a Mediterranean diet, we calculated race-specific tertiles of the MedDiet score (range: 0–55) using baseline food frequency questionnaires. Cognitive decline was assessed using repeated Modified Mini Mental State Examination scores over the study. We used linear mixed models to assess the association between MedDiet score and trajectory of cognitive decline.
Results.
Among blacks, participants with high MedDiet scores had a significantly lower mean rate of decline on the Modified Mini Mental State Examination score compared with participants with lower MedDiet scores (middle and bottom tertiles). The mean difference in points per year was 0.22 (95% confidence interval: 0.05–0.39; p = .01) after adjustment for age, sex, education, body mass index, current smoking, physical activity, depression, diabetes, total energy intake, and socioeconomic status. No association between MedDiet scores and change in Modified Mini Mental State Examination score was seen among white participants (p = .14).
Conclusions.
Stronger adherence to the Mediterranean diet may reduce the rate of cognitive decline among black, but not white older adults. Further studies in diverse populations are needed to confirm this association and pinpoint mechanisms that may explain these results.
doi:10.1093/gerona/glu097
PMCID: PMC4351391  PMID: 24994847
Epidemiology; Nutrition; Cognitive aging; Alzheimers; Cognition.
21.  SARC‐F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes 
Background
A brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients. To screen for persons with sarcopenia, we developed a simple five‐item questionnaire (SARC‐F) based on cardinal features or consequences of sarcopenia.
Methods
We investigated the utility of SARC‐F in the African American Health (AAH) study, Baltimore Longitudinal Study of Aging (BLSA), and National Health and Nutrition Examination Survey (NHANES). Internal consistency reliability for SARC‐F was determined using Cronbach's alpha. We evaluated SARC‐F factorial validity using principal components analysis and criterion validity by examining its association with exam‐based indicators of sarcopenia. Construct validity was examined using cross‐sectional and longitudinal differences among those with high (≥4) vs. low (<4) SARC‐F scores for mortality and health outcomes.
Results
SARC‐F exhibited good internal consistency reliability and factorial, criterion, and construct validity. AAH participants with SARC‐F scores ≥ 4 had more Instrumental Activity of Daily Living (IADL) deficits, slower chair stand times, lower grip strength, lower short physical performance battery scores, and a higher likelihood of recent hospitalization and of having a gait speed of <0.8 m/s. SARC‐F scores ≥ 4 in AAH also were associated with 6 year IADL deficits, slower chair stand times, lower short physical performance battery scores, having a gait speed of <0.8 m/s, being hospitalized recently, and mortality. SARC‐F scores ≥ 4 in the BLSA cohort were associated with having more IADL deficits and lower grip strength (both hands) in cross‐sectional comparisons and with IADL deficits, lower grip strength (both hands), and mortality at follow‐up. NHANES participants with SARC‐F scores ≥ 4 had slower 20 ft walk times, had lower peak force knee extensor strength, and were more likely to have been hospitalized recently in cross‐sectional analyses.
Conclusions
The SARC‐F proved internally consistent and valid for detecting persons at risk for adverse outcomes from sarcopenia in AAH, BLSA, and NHANES.
doi:10.1002/jcsm.12048
PMCID: PMC4799853  PMID: 27066316
Sarcopenia; Screening; Mobility; Function
22.  Apolipoprotein E Allele and Hearing Thresholds in Older Adults 
Background
Whether ApolipoproteinE (APOE) E4 allele status which is associated with an increased risk of cognitive decline is also associated with hearing impairment is unknown.
Methods
We studied 1833 men and women enrolled in the Health, Aging and Body Composition study. Regression models adjusted for demographic and cardiovascular risk factors were used to assess the cross-sectional association of APOE-E4 status with individual pure tone hearing thresholds and the 4-frequency pure tone average (0.5 kHz–4kHz) in the better hearing ear.
Results
Compared to participants with no APOE-E4 alleles, participants with one allele had better thresholds at 4.0kHz (β= −2.72dB, p = 0.013) and 8.0 kHz (β= −3.05kHz, p = 0.006), and participants with two alleles had better hearing thresholds at 1.0kHz (β= −8.56dB, p=0.021).
Conclusion
Our results suggest that APOE-E4 allele status may be marginally associated with better hearing thresholds in older adults.
doi:10.1177/1533317514537549
PMCID: PMC4258173  PMID: 24906966
Apolipoprotein E; hearing thresholds; hearing loss; cognition; aging; dementia
23.  Gait energetic efficiency in older adults with and without knee pain: results from the Baltimore Longitudinal Study of Aging 
Age  2015;37(1):15.
With aging, customary gait patterns change and energetic efficiency declines, but the relationship between these alterations is not well understood. If gait characteristics that develop with aging explain part of the decline in energetic efficiency that occur in most aging individuals, then efforts to modify these characteristics could delay or prevent mobility limitation. This study characterizes gait patterns in older persons with and without knee pain and tests the hypothesis that changes in gait characteristics due to knee pain are associated with increased energetic cost of walking in older adults. Study participants were 364 men and 170 women aged 60 to 96 years enrolled in the Baltimore Longitudinal Study of Aging (BLSA), of whom 86 had prevalent knee pain. Gait patterns were assessed at participant self-selected usual pace in the gait laboratory, and the energetic cost of walking was assessed by indirect calorimetry during self-selected usual pace walking over 2.5 min in a tiled corridor using a portable equipment. Participants with knee pain were less energetically efficient than those without pain (oxygen consumption 0.97 vs. 0.88 ml/(10 m · 100 kg); p = 0.002) and had slower gait speed and smaller range of motion (ROM) at the hip and knee joints (p < 0.05, for all). Slower gait speed and lower knee ROM in participants with knee pain and longer double support time and higher ankle ROM in participants without knee pain were associated with lower energetic efficiency (p < 0.05, for all). Slower gait speed and lower knee ROM were correlates of knee pain and were found to mediate the association between age and oxygen consumption. Although knee pain is associated with a higher energetic cost of walking, gait characteristics associated with energetic efficiency differ by pain status which suggests that compensatory strategies both in the presence and absence of pain may impact gait efficiency.
doi:10.1007/s11357-015-9754-4
PMCID: PMC4322038  PMID: 25666574
Oxygen consumption; Knee pain; Energy efficiency in gait; Compensatory effort
24.  Is Cancer Incidence Decreased in the Frail Elderly? 
Journal of geriatric oncology  2013;4(1):19-25.
OBJECTIVES
Lower rates of cancer in the oldest old and in nursing home populations may reflect the increasing prevalence of frailty and a diminished capacity to sustain cancer cell growth and proliferation. This study aimed to determine cancer incidence in the frail relative to non-frail community resident older adults.
MATERIALS AND METHODS
Data come from 3,969 participants free of diagnosed cancer at the sixth follow up from three sites of the Established Populations for Epidemiologic Studies of the Elderly (EPESE), a population-based cohort study. Frailty status was determined from physical performance testing and self reported dependency in activities of daily living. Cancer incidence over the four subsequent years was identified through linkage with Medicare claims data. Logistic regression was used to estimate the odds of cancer incidence with respect to frailty status in multiple models with progressive adjustment for covariates.
RESULTS
Of the 3,969 participants, 1,340 (33·8%) were identified as frail. Cancer incidence at 4 years was lower in frail participants overall (OR 0·64; 95% CI 0·46–0·89) and frail men in particular (OR 0·54; 95% CI 0·33–0·87). Incidence was lower in women (3.7%) than men (8.8%), but was not lower in frail women compared with non-frail women (OR 0·77; 95% CI 0·48 –1·23).
CONCLUSION
Frailty status was associated with decreased cancer incidence, particularly in men, and suggests that mechanisms related to the pathogenesis of frailty may also play a role in inhibiting tumorigenesis. Why this would be more apparent in men than women remains to be clarified.
doi:10.1016/j.jgo.2012.08.005
PMCID: PMC4704439  PMID: 24071488
frailty; cancer; incidence; cellular senescence; microenvironment; elderly
25.  Association of Hearing Impairment and Mortality in Older Adults 
Background.
Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults.
Methods.
Prospective observational data from 1,958 adults ≥70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4kHz. HI was defined as pure-tone average >25 dB HL in the better ear.
Results.
Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36–1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03–1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00–1.29 per 10 dB of threshold elevation up to 35 dB HL).
Conclusions.
HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation.
doi:10.1093/gerona/glu094
PMCID: PMC4296166  PMID: 25024235
Epidemiology; Longevity; Outcomes; Public health; Successful aging.

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