NHANES 2011-2014: Objective Physical Activity is the Strongest Predictor of All-Cause Mortality.

INTRODUCTION: Objectively measured physical activity (PA) is a modifiable risk factor for mortality. Understanding the predictive performance of PA is essential to establish potential targets for early intervention to reduce mortality among older adults. METHODS: The study used a subset of the National Health and Nutrition Examination Survey (NHANES) 2011-2014 data consisting of participants aged 50 to 80 years old (n = 3653, 24297.5 person-years of follow-up, 416 deaths). Eight accelerometry derived features and 14 traditional predictors of all-cause mortality were compared and ranked in terms of their individual and combined predictive performance using the 10-fold cross-validated Concordance (C) from Cox regression. RESULTS: The top three predictors of mortality in univariate analysis were PA related: average MIMS in the 10 most active hours (C = 0.697), total MIMS per day (C = 0.686), and average log transformed MIMS in the most 10 active hours of the day (C = 0.684), outperforming age (C = 0.676) and other traditional predictors of mortality. In multivariate regression, adding objectively measured PA to the top performing model without PA variables increased concordance from C = 0.776 to C = 0.790 (p < 0.001). CONCLUSIONS: These findings highlight the importance of PA as a risk marker of mortality and are consistent with prior studies, confirming the importance of accelerometer-derived activity measures beyond total volume.

Validation of a Zio XT Patch Accelerometer for the Objective Assessment of Physical Activity in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Combination devices to monitor heart rate/rhythms and physical activity are becoming increasingly popular in research and clinical settings. The Zio XT Patch (iRhythm Technologies, San Francisco, CA, USA) is US Food and Drug Administration (FDA)-approved for monitoring heart rhythms, but the validity of its accelerometer for assessing physical activity is unknown. OBJECTIVE: To validate the accelerometer in the Zio XT Patch for measuring physical activity against the widely-used ActiGraph GT3X. METHODS: The Zio XT and ActiGraph wGT3X-BT (Actigraph, Pensacola, FL, USA) were worn simultaneously in two separately-funded ancillary studies to Visit 6 of the Atherosclerosis Risk in Communities (ARIC) Study (2016-2017). Zio XT was worn on the chest and ActiGraph was worn on the hip. Raw accelerometer data were summarized using mean absolute deviation (MAD) for six different epoch lengths (1-min, 5-min, 10-min, 30-min, 1-h, and 2-h). Participants who had ≥3 days of at least 10 h of valid data between 7 a.m-11 p.m were included. Agreement of epoch-level MAD between the two devices was evaluated using correlation and mean squared error (MSE). RESULTS: Among 257 participants (average age: 78.5 ± 4.7 years; 59.1% female), there were strong correlations between MAD values from Zio XT and ActiGraph (average r: 1-min: 0.66, 5-min: 0.90, 10-min: 0.93, 30-min: 0.93, 1-h: 0.89, 2-h: 0.82), with relatively low error values (Average MSE × 106: 1-min: 349.37 g, 5-min: 86.25 g, 10-min: 56.80 g, 30-min: 45.46 g, 1-h: 52.56 g, 2-h: 54.58 g). CONCLUSIONS: These findings suggest that Zio XT accelerometry is valid for measuring duration, frequency, and intensity of physical activity within time epochs of 5-min to 2-h.

Mid-Life Vascular Risk and Rate of Physical Function Decline Among Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline. METHODS: This prospective cohort included 5 481 older adults aged 67-91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45-64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1-4. RESULTS: The average adjusted rate of SPPB decline (points per 5 years) for older adults was -0.79 (confidence interval [CI]: -0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of -0.47, 95% CI: -0.64, -0.30), diabetes (+73% decline vs no diabetes: additional decline of -0.67, 95% CI: -1.09, -0.24), elevated systolic blood pressure (+17% decline per SD: -0.16, 95% CI: -0.23, -0.10), and elevated fasting blood glucose (+16% decline per SD: -0.015, 95% CI: -0.24, -0.06). Each decade greater mid-life exposure to hypertension (+32% decline: -0.93, 95% CI: -1.25, -0.61) and diabetes (+35% decline: -1.03, 95% CI: -1.68, -0.38) was associated with faster SPPB decline. CONCLUSIONS: Mid-life control of blood pressure and diabetes may offset aging-related functional decline.

The association of vitamin D supplementation and serum vitamin D levels with physical activity in older adults: Results from a randomized trial.

BACKGROUND: To assess whether vitamin D3 supplementation attenuates the decline in daily physical activity in low-functioning adults at risk for falls. METHODS: Secondary data analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You), a response-adaptive randomized clinical trial. Participants included 571 adults aged 70 years and older with baseline serum 25(OH)D levels of 10-29 ng/mL and elevated fall risk, who wore a wrist accelerometer at baseline and at least one follow-up visit and were randomized to receive: 200 IU/day (control), 1000, 2000, or 4000 IU/day of vitamin D3 . Objective physical activity quantities and patterns (total daily activity counts, active minutes/day, and activity fragmentation) were measured for 7-days, 24-h/day, in the free-living environment using the Actigraph GT9x over up to 24-months of follow-up. RESULTS: In adjusted models, physical activity quantities declined (p < 0.001) and became more fragmented, or "broken up", (p = 0.017) over time. Supplementation with vitamin D3 did not attenuate this decline. Changes in physical activity were more rapid among those with baseline serum 25(OH)D <20 ng/mL compared to those with baseline 25(OH)D levels of 20-29 ng/mL (time*baseline 25(OH)D, p < 0.05). CONCLUSION: In low-functioning older adults with serum 25(OH)D levels 10-29 ng/mL, vitamin D3 supplementation of 1000 IU/day or higher did not attenuate declines in physical activity compared with 200 IU/day. Those with baseline 25(OH)D <20 ng/mL showed accelerated declines in physical activity. Alternative interventions to supplementation are needed to curb declines in physical activity in older adults with low serum 25(OH)D.

Associations Between Objectively Measured Sleep and Cognition: Main Effects and Interactions With Race in Adults Aged ≥50 Years.

BACKGROUND: This study examined associations of actigraphy-estimated sleep parameters with concurrent and future cognitive performance in adults aged ≥ 50 years and explored interactions with race. METHODS: Participants were 435 cognitively normal adults in the Baltimore Longitudinal Study of Aging who completed wrist actigraphy at baseline (mean = 6.6 nights) and underwent longitudinal testing of memory, attention, executive function, language, and visuospatial ability. On average, participants with follow-up data were followed for 3.1 years. Primary predictors were baseline mean total sleep time, sleep onset latency, sleep efficiency (SE), and wake after sleep onset (WASO). Fully adjusted linear mixed-effects models included demographics, baseline health-related characteristics, smoking status, sleep medication use, APOE e4 carrier status, and interactions of each covariate with time. RESULTS: In adjusted models, higher SE (per 10%; B = 0.11, p = .012) and lower WASO (per 30 minutes; B = -0.12, p = .007) were associated with better memory cross-sectionally. In contrast, higher SE was associated with greater visuospatial ability decline longitudinally (B = -0.02, p = .004). Greater WASO was associated with poorer visuospatial ability cross-sectionally (B = -0.09, p = .019) but slower declines in visuospatial abilities longitudinally (B = 0.02, p = .002). Several sleep-cognition cross-sectional and longitudinal associations were stronger in, or limited to, Black participants (compared to White participants). CONCLUSIONS: This study suggests cross-sectional sleep-cognition associations differ across distinct objective sleep parameters and cognitive domains. This study also provides preliminary evidence for racial differences across some sleep-cognition relationships. Unexpected directions of associations between baseline sleep and cognitive performance over time may be attributable to the significant proportion of participants without follow-up data and require further investigation.

Patterns of Daily Physical Movement, Chronic Inflammation, and Frailty Incidence.

INTRODUCTION: Low physical activity is a criterion of phenotypic frailty defined as an increased state of vulnerability to adverse health outcomes. Whether disengagement from daily all-purpose physical activity is prospectively associated with frailty and possibly modified by chronic inflammation-a pathway often underlying frailty-remains unexplored. METHODS: Using the Study to Understand Fall Reduction and Vitamin D in You data from 477 robust/prefrail adults (mean age = 76 ± 5 yr; 42% women), we examined whether accelerometer patterns (activity counts per day, active minutes per day, and activity fragmentation [broken accumulation]) were associated with incident frailty using Cox proportional hazard regression. Baseline interactions between each accelerometer metric and markers of inflammation that include interleukin-6, C-reactive protein, and tumor necrosis factor-alpha receptor 1 were also examined. RESULTS: Over an average of 1.3 yr, 42 participants (9%) developed frailty. In Cox regression models adjusted for demographics, medical conditions, and device wear days, every 30 min·d -1 higher baseline active time, 100,000 more activity counts per day, and 1% lower activity fragmentation was associated with a 16% ( P = 0.003), 13% ( P = 0.001), and 8% ( P < 0.001) lower risk of frailty, respectively. No interactions between accelerometer metrics and baseline interleukin-6, C-reactive protein, or tumor necrosis factor-alpha receptor 1 were detected (interaction P > 0.06 for all). CONCLUSIONS: Among older adults who are either robust or prefrail, constricted patterns of daily physical activity (i.e., lower total activity minutes and counts, and higher activity fragmentation) were prospectively associated with higher risk of frailty but not modified by frailty-related chronic inflammation. Additional studies, particularly trials, are needed to understand if this association is causal.

Development of a Novel Accelerometry-Based Performance Fatigability Measure for Older Adults.

INTRODUCTION: Efforts to study performance fatigability have been limited because of measurement constrains. Accelerometry and advanced statistical methods may enable us to quantify performance fatigability more granularly via objective detection of performance decline. Thus, we developed the Pittsburgh Performance Fatigability Index (PPFI) using triaxial raw accelerations from wrist-worn accelerometer from two in-laboratory 400-m walks. METHODS: Sixty-three older adults from our cross-sectional study (mean age, 78 yr; 56% women; 88% White) completed fast-paced ( n = 59) and/or usual-paced 400-m walks ( n = 56) with valid accelerometer data. Participants wore ActiGraph GT3X+ accelerometers (The ActiGraph LLC, Pensacola, FL) on nondominant wrist during the walking task. Triaxial raw accelerations from accelerometers were used to compute PPFI, which quantifies percentage of area under the observed gait cadence-versus-time trajectory during a 400-m walk to a hypothetical area that would be produced if the participant sustained maximal cadence throughout the entire walk. RESULTS: Higher PPFI scores (higher score = greater fatigability) correlated with worse physical function, slower chair stands speed and gait speed, worse cardiorespiratory fitness and mobility, and lower leg peak power (| ρ | = 0.36-0.61 from fast-paced and | ρ | = 0.28-0.67 from usual-paced walks, all P < 0.05). PPFI scores from both walks remained associated with chair stands speed, gait speed, fitness, and mobility, after adjustment for sex, age, race, weight, height, and smoking status; PPFI scores from the fast-paced walk were associated with leg peak power. CONCLUSIONS: Our findings revealed that the objective PPFI is a sensitive measure of performance fatigability for older adults and can serve as a risk assessment tool or outcome measure in future studies and clinical practice.

Association of walking energetics with amyloid beta status: Findings from the Baltimore Longitudinal Study of Aging.

INTRODUCTION: Higher energetic costs for mobility predict gait speed decline. Slow gait is linked to cognitive decline and Alzheimer's disease (AD). Whether the energetic cost of walking is linked to AD pathology is unknown. We investigated the cross-sectional association between the energetic cost of walking, gait speed, and amyloid beta (Aß) status (+/-) in older adults. METHODS: One hundred forty-nine cognitively normal adults (56% women, mean age 77.5 ± 8.4 years) completed customary-paced walking assessments with indirect calorimetry and 11C-Pittsburgh compound B positron emission tomography. Logistic regression models examined associations adjusted for demographics, body composition, comorbid conditions, and apolipoprotein E ε4. RESULTS: Each 0.01 mL/kg/m greater energy cost was associated with 18% higher odds of being Aß+ (odds ratio [OR] = 1.18; 95% confidence interval [CI]: 1.04 to 1.34; P = .011). These findings were not observed when investigating gait speed (OR = 0.99; 95% CI: 0.97 to 1.01; P = .321). DISCUSSION: High energetic cost of walking is linked to AD pathology and may be a potential target for therapeutic intervention.

Strategies to Prevent or Remediate Cancer and Treatment-Related Aging.

Up to 85% of adult cancer survivors and 99% of adult survivors of childhood cancer live with an accumulation of chronic conditions, frailty, and/or cognitive impairments resulting from cancer and its treatment. Thus, survivors often show an accelerated development of multiple geriatric syndromes and need therapeutic interventions. To advance progress in this area, the National Cancer Institute convened the second of 2 think tanks under the auspices of the Cancer and Accelerated Aging: Advancing Research for Healthy Survivors initiative. Experts assembled to share evidence of promising strategies to prevent, slow, or reverse the aging consequences of cancer and its treatment. The meeting identified research and resource needs, including geroscience-guided clinical trials; comprehensive assessments of functional, cognitive, and psychosocial vulnerabilities to assess and predict age-related outcomes; preclinical and clinical research to determine the optimal dosing for behavioral (eg, diet, exercise) and pharmacologic (eg, senolytic) therapies; health-care delivery research to evaluate the efficacy of integrated cancer care delivery models; optimization of intervention implementation, delivery, and uptake; and patient and provider education on cancer and treatment-related late and long-term adverse effects. Addressing these needs will expand knowledge of aging-related consequences of cancer and cancer treatment and inform strategies to promote healthy aging of cancer survivors.

Association of Total Daily Physical Activity and Fragmented Physical Activity With Mortality in Older Adults.

Importance: Fragmented daily physical activity may be a sign of physiological decline that provides more powerful insight into impending mortality than total daily activity. Objective: To compare and contrast the association between total daily activity and activity fragmentation, which encompasses activity bouts and duration, and mortality risk. Design, Setting, and Participants: In this cohort study, accelerometer data from 2007 through 2015 and mortality data from 2007 through 2017 were collected from 548 adults aged 65 years and older participating in the Baltimore Longitudinal Study of Aging. The dates of analysis were November 2016 to June 2019, with data collected through December 31, 2017. Using Cox proportional hazards regression, the association between accelerometer-derived patterns of physical activity and mortality was estimated after adjusting for demographic characteristics, lifestyle factors, and comorbidities. Exposures: Minute-by-minute physical activity data were collected over a 24-hour, 7-day period (excluding times between 11:00 pm and 4:59 am) using an accelerometer. Each minute was labeled either active or sedentary, and 5 features of accelerometer data were extracted: total daily activity (defined as any activity performed throughout the day), activity fragmentation (defined as an active-to-sedentary transition probability), and 3 measures of activity bouts (<5, 5-10, and ≥10 active minutes). Main Outcomes and Measures: All-cause mortality. Results: Among 548 well-functioning older adults (mean [SD] age, 75.8 [7.2] years; 262 [47.8%] women), 61 participants (11.1%) died. Total daily physical activity was not associated with mortality risk (hazard ratio [HR], 0.90 [95% CI, 0.75-1.08]; P = .28). However, more fragmented physical activity patterns were associated with greater mortality risk (HR, 1.49 [95% CI, 1.02-2.19]; P = .04) after adjusting for age, sex, race/ethnicity, body mass index, smoking history, employment, self-reported health, grip strength, usual gait speed, comorbidities, and device wear time. In addition, more frequently engaging in activity bouts lasting less than 5 minutes was associated with greater mortality risk (HR, 1.28 [95% CI, 1.01-1.61]; P = .04), whereas activity bouts of 5 to 10 minutes (HR, 0.99 [95% CI, 0.58-1.69]; P = .97) and 10 minutes or longer (HR, 0.81 [95% CI, 0.65-1.01]; P = .06) were not associated with mortality risk. Conclusions and Relevance: In this cohort study of well-functioning adults aged 65 years and older, fragmented daily physical activity, particularly activity bouts lasting less than 5 minutes, was associated with greater mortality risk. These findings suggest that activity fragmentation in older adults may precede declines in functional capability and overall physical activity that typically indicate impending mortality.

Moderate-to-Vigorous Physical Activity Is Associated With Higher Muscle Oxidative Capacity in Older Adults.

BACKGROUND: Age-related decline in muscle oxidative capacity reduces muscle function and physical performance, leading to disability and frailty. Whether age-related decline in oxidative capacity is modified by exercise and other lifestyle practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity, independent of age. DESIGN: Cross-sectional study performed in the Baltimore Longitudinal Study of Aging, conducted by the Intramural Research Program (IRP) of the National Institute on Aging (NIA). SETTING: NIA IRP Clinical Research Unit, Baltimore, MD. PARTICIPANTS: Participants included 384 adults (54.7% women), aged 22 to 92 years, seen between 2013 and 2017. MEASUREMENTS: Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the postexercise time constant (τPCr ; in seconds) for phosphocreatine (PCr) recovery, with lower values of τPCr, (ie, more rapid recovery of PCr levels after exercise) reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using wearable accelerometers that participants wore 5.9 ± 0.9 consecutive days in the free-living environment. RESULTS: In linear regression models, higher τPCr was associated with older age (standardized ß = .39; P < .001) after adjusting for sex, race, height, and weight. After including MVPA as an independent variable, the standardized regression coefficient of age decreased by 40%, but remained associated with τPCr (ßage = .22; P < .001) and had a smaller standardized regression coefficient than MVPA (ßMVPA = -.33; P < .001). After adjusting for health status, education, and smoking history, the standardized regression coefficient for age decreased 12% (ßage = .20; P = .003), while the standardized coefficient for MVPA decreased only 3% (ßMVPA = -.32; P < .001). CONCLUSION: Study findings suggest that MVPA is strongly associated with muscle oxidative capacity, independent of age, providing mechanistic insights into the health benefits of exercise in older age. J Am Geriatr Soc 67:1695-1699, 2019.

Association Between Adiposity and Perceived Physical Fatigability in Mid- to Late Life.

OBJECTIVE: This study aimed to compare and contrast the associations between measures of adiposity and fat distribution and perceived fatigability among well-functioning individuals in mid- to late life. METHODS: In 1,054 adults (70.4 ± 12.4 years, 52% female), adiposity was measured as BMI, percent fat (dual-energy x-ray absorptiometry), waist and hip circumferences, and waist to height ratio. In a subset of 383 participants, visceral fat was measured. Perceived fatigability was evaluated after a 5-minute treadmill walk (1.5 mph) using the Borg rating of perceived exertion (range, 6-20). Associations between adiposity measures and perceived fatigability were assessed using regression models adjusting for age, sex, race, smoking, and comorbidities. RESULTS: All adiposity measures, except subcutaneous fat, were positively associated with perceived fatigability after adjustment (P < 0.05 for all). Standardized coefficients indicated that BMI, hip circumference, and visceral fat had the strongest associations with fatigability. Associations between BMI and fatigability were present only among those above the threshold for overweight and strongest in those aged ≥ 65 years. Moreover, BMI was associated with fatigability only among participants with higher waist circumference. CONCLUSIONS: Measures of adiposity, particularly central adiposity, are strongly associated with fatigability, suggesting that weight management may be an effective target for curbing fatigability and maintaining quality of life with aging.

Longitudinal Relationship Between Interleukin-6 and Perceived Fatigability Among Well-Functioning Adults in Mid-to-Late Life.

BACKGROUND: Chronically elevated interleukin-6 (IL-6) levels contribute to fatigue and functional decline via multiple pathways that often lead to frailty. Lesser known is the contribution of IL-6 to fatigue in relation to a standardized workload (fatigability), a precursor to functional decline. Therefore, the purpose of this study was to examine the longitudinal relationship between IL-6 and fatigability. METHODS: About 985 participants from the Baltimore Longitudinal Study of Aging (mean age: 70 ± 10 years) were evaluated every 1-4 years. IL-6 was measured in fasting serum samples at each visit and log-transformed for analyses. Perceived fatigability (PF) was defined as self-reported exertion (rate of perceived exertion; RPE) after a 5-min, 0.67 m/s, 0% grade treadmill walk. Continuous and categorical associations between IL-6 (baseline and repeated measures) and PF were assessed using generalized estimating equations, adjusting for demographics, behavioral factors, and comorbid conditions. RESULTS: In fully adjusted continuous models, twofold higher baseline IL-6 was associated with a 0.28 higher RPE (p = .03). This relationship tended to remain constant annually (baseline log IL-6 by time interaction p = .29). To provide clinical relevance, the sample median (3.7 pg/mL) was used to examine high versus low IL-6 levels. Over time, the high group reported an average 0.25 higher RPE (p = .03) than the low group. Annual change in logged IL-6 was not associated with annual change in PF (p = .48). CONCLUSION: Findings suggest that elevated IL-6 is a biomarker of physiological dysregulation associated with greater fatigability, but there is no longitudinal association between IL-6 and fatigability. Future studies should evaluate whether interventions that aim to reduce inflammation also attenuate fatigability.

Contrasting characteristics of daily physical activity in older adults by cancer history.

BACKGROUND: Using objectively collected physical activity (PA) data from the Baltimore Longitudinal Study of Aging, the authors tested whether patterns of daily activity and sedentary time differed by cancer survivorship in older adults. METHODS: In total, 659 participants (mean age ± standard deviation, 71 ± 10 years; 51% women) who had self-reported information on cancer history were instructed to wear an accelerometer for 7 consecutive days. Accelerometer data were summarized into: 1) PA volume and 2) activity fragmentation (interrupted activity), expressed as both continuous and as dichotomized (low and high) variables. Participants were categorized into 4 groups by cross-classification of dichotomous PA volume and fragmentation. Multiple regression models were used to estimate differences in PA patterns by cancer history. RESULTS: Cancer survivors averaged 0.12 fewer log-transformed activity counts per day (standard error, 0.05; P = .02) than individuals who reported no history of cancer after adjusting for demographics, behavioral factors, and comorbidities. Although fragmentation did not differ by cancer survivorship in the continuous model (P = .13), cancer survivorship was associated with 77% greater odds (odds ratio, 1.77; 95% confidence interval, 1.11-2.82) of having high (vs low) fragmentation and 94% greater odds (odds ratio, 1.94; 95% confidence interval, 1.13-3.33) of having combined low PA/high fragmentation (vs high PA/low fragmentation) relative to those with no cancer history. CONCLUSIONS: The current findings suggest that cancer survivors engage in lower total daily PA and that they perform this activity in a more fragmented manner compared with adults without a history of cancer. These results may reflect the onset and progression of a low-activity phenotype that is more vulnerable to heightened levels of fatigue and functional decline with aging.

Lumbopelvic Pain and Threats to Walking Ability in Well-Functioning Older Adults: Findings from the Baltimore Longitudinal Study of Aging.

OBJECTIVES: To examine the potential contribution of severity of lumbopelvic pain (LPP) in well-functioning older adults to poorer walking efficiency, lack of endurance, slower gait speed, and decline in these mobility parameters over 1 to 5 years. DESIGN: Longitudinal analysis of Baltimore Longitudinal Study of Aging data. SETTING: National Institute on Aging, Clinical Research Unit, Baltimore, Maryland. PARTICIPANTS: Well-functioning men and women aged 60 to 89 (N=878). MEASUREMENTS: An interviewer-administered questionnaire was used to ascertain reported presence and severity of back and hip pain in the preceding 12 months and reported walking ability, including ease of walking a mile. Certified examiners assessed usual gait speed, the energetic cost of walking (oxygen consumption, mL per kg/m), and time taken to walk 400 m as quickly as possible. Covariates included sex, age, age-squared, race, height, weight, exercise, and smoking. RESULTS: Overall, 31.4% had mild LPP, and 15.7% had moderate to severe LPP. In adjusted analyses, reported walking ability (p<.001), endurance walk performance (p=.007), and energetic cost of walking (p=.049) were worse with increasing LPP severity. Usual gait speed did not vary according to LPP (p=.31). Longitudinally, over an average 2.3 years, persons with new or sustained LPP had worse follow-up level, greater mean decline, and higher likelihood of meaningful decline in reported walking ability than persons free of LPP or whose LPP resolved. Walking performance did not differ according to LPP follow-up status. CONCLUSION: LPP was common in well-functioning older adults and was associated with greater energetic cost of walking and poorer perceived and observed walking endurance. The longitudinal effect of LPP is unclear, but worsening perception of walking ability and its contribution to future mobility loss warrants further attention.

Fatigability and endurance performance in cancer survivors: Analyses from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Fatigue is prevalent and distressing among cancer survivors, but its subjective nature makes it difficult to identify. Fatigability, defined as task-specific fatigue, and endurance performance may be useful supplemental measures of functional status in cancer survivors. METHODS: Fatigability, endurance performance, and cancer history were assessed every 2 years in Baltimore Longitudinal Study of Aging participants between 2007 and 2015. Fatigability was defined according to the Borg rating of perceived exertion scale after a 5-minute, slow treadmill walk; and endurance performance was calculated according to the ability and time to complete a fast-paced, 400-meter walk. The association between cancer history, fatigability, and endurance performance was evaluated using longitudinal analyses adjusted for age, sex, body mass index, and comorbidities. RESULTS: Of 1665 participants, 334 (20%) reported a history of cancer. A combination of older age (>65 years) and a history of cancer was associated with 3.8 and 8.6 greater odds of high perceived fatigability and poor endurance, respectively (P < .01). Older adults with and without a history of cancer walked 42 and 23 seconds slower than younger adults without a history of cancer, respectively (P < .01). The median times to the development of high fatigability and poor endurance were shorter among those who had a history of cancer compared with those who had no history of cancer (P < .01). CONCLUSIONS: The current findings suggest that a history of cancer is associated with fatigability and poor endurance and that this effect is significantly greater in older adults. Evaluating the effects of cancer and age on fatigability may illuminate potential pathways and targets for future interventions. Cancer 2018;124:1279-87. © 2018 American Cancer Society.

The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.

Background: Age-related gait speed decline is accelerated in men with human immunodeficiency virus (HIV). Mitochondrial genetic variation is associated with frailty and mortality in the general population and may provide insight into mechanisms of functional decline in people aging with HIV. Methods: Gait speed was assessed semiannually in the Multicenter AIDS Cohort Study. Mitochondrial DNA (mtDNA) haplogroups were extracted from genome-wide genotyping data, classifying men aged ≥50 years into 5 groups: mtDNA haplogroup H, J, T, Uk, and other. Differences in gait speed by haplogroups were assessed as rate of gait speed decline per year, probability of slow gait speed (<1.0 m/s), and hazard of slow gait using multivariable linear mixed-effects models, mixed-effects logistic regression models, and the Andersen-Gill model, controlling for hepatitis C virus infection, previous AIDS diagnosis, thymidine analogues exposure, education, body composition, smoking, and peripheral neuropathy. Age was further controlled for in the mixed-effects logistic regression models. Results: A total of 455 HIV-positive white men aged ≥50 years contributed 3283 person-years of follow-up. Among them, 70% had achieved HIV viral suppression. In fully adjusted models, individuals with haplogroup J had more rapid decline in gait speed (adjusted slopes, 0.018 m/s/year vs 0.011 m/s/year, pinteraction = 0.012) and increased risk of developing slow gait (adjusted odds ratio, 2.97; 95% confidence interval, 1.24-7.08) compared to those with other haplogroups. Conclusions: Among older, HIV-infected men, mtDNA haplogroup J was an independent risk factor for more rapid age-related gait speed decline.

Physical Activity in Midlife is not Associated with Cognitive Health in Later Life Among Cognitively Normal Older Adults.

BACKGROUND: Links between physical activity and dementia are based primarily on cross-sectional data or studies with unsatisfactory follow-up. OBJECTIVE: We leveraged three decades of follow-up from an established cohort to determine whether physical activity in midlife is associated with late-life cognition and dementia. METHODS: The Johns Hopkins Precursors study (n = 646) enrolled participants from 1948-1964 and administered questions about physical activity, from which we calculated metabolic equivalents (MET h/day), and exercise from 1978-present. Cognitive tests were administered in 2008. Dementia was adjudicated through 2011. To characterize associations with midlife physical activity, we used linear regression for cognitive tests and Cox proportional hazards models for dementia onset. Models adjusted for age, sex, smoking, diabetes, and hypertension. RESULTS: No physical activity measure from 1978 was associated with late-life cognition or onset of dementia. Both MET h/day (ß= 0.007, 95% CI: 0.002, 0.013) and regular exercise (ß= 0.357, 95% CI: 0.202, 0.513) in 2006, however, were associated with better cognition in 2008. CONCLUSION: Findings from this 30-year cohort study that physical activity measured recently, but not in mid-life, is associated with late-life cognition fits with null findings from randomized trials and other observational studies with extensive follow-up. Cross-sectional findings may be misleading due to reverse causation.