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ObjectiveType 2 diabetes (T2D) has heterogeneous patient clinical characteristics and outcomes. In previous work, we investigated the genetic basis of this heterogeneity by clustering 94 T2D genetic loci using their associations with 47 diabetes-related traits and identified five clusters, termed β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. The relationship between these clusters and individual-level metabolic disease outcomes has not been assessed.Research design and methodsHere we constructed individual-level partitioned polygenic scores (pPS) for these five clusters in 12 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (n = 454,193) and tested for cross-sectional association with T2D-related outcomes, including blood pressure, renal function, insulin use, age at T2D diagnosis, and coronary artery disease (CAD).ResultsDespite all clusters containing T2D risk-increasing alleles, they had differential associations with metabolic outcomes. Increased obesity and lipodystrophy cluster pPS, which had opposite directions of association with measures of adiposity, were both significantly associated with increased blood pressure and hypertension. The lipodystrophy and liver/lipid cluster pPS were each associated with CAD, with increasing and decreasing effects, respectively. An increased liver/lipid cluster pPS was also significantly associated with reduced renal function. The liver/lipid cluster includes known loci linked to liver lipid metabolism (e.g., GCKR, PNPLA3, and TM6SF2), and these findings suggest that cardiovascular disease risk and renal function may be impacted by these loci through their shared disease pathway.ConclusionsOur findings support that genetically driven pathways leading to T2D also predispose differentially to clinical outcomes.

IntroductionMultifactorial biological processes underpin dysregulation over several individual physiological systems. However, it is challenging to characterize and model this multisystemic dysregulation and its relationship with individual physiologic systems. We operationalized a theory-driven measure of multisystem dysregulation and empirically tested for measurement differences by key characteristics.MethodsWe used the Women's Health and Aging Studies (WHAS) I and II (N = 649), and the Health ABC study (N = 1515). Twelve biomarkers representing multiple systems including stress response (e.g., inflammation), endocrine system, and energy regulation were identified. A series of confirmatory factor analyses (CFA) were conducted to evaluate the interplay between physiological systems and underlying multisystem dysregulation. We evaluated convergent criterion validity of a score for multisystem dysregulation against the physical frailty phenotype, and predictive criterion validity with incidence of walking difficulty and mortality.ResultsA bifactor CFA, a model in which dysregulation of individual systems proceeds independently of generalized dysregulation, fit data well in WHAS (RMSEA: 0.019; CFI: 0.977; TLI: 0.961) and Health ABC (RMSEA: 0.047; CFI: 0.874; TLI: 0.787). The general dysregulation factor was associated with frailty (OR: 2.2, 95 % CI: 1.4, 3.5), and elevated risk of incident walking difficulty and mortality. Findings were replicated in Health ABC.DiscussionBiomarker data from two epidemiologic studies support the construct of multisystem physiological dysregulation. Results further suggest system-specific and system-wide processes have unique and non-overlapping contributions to dysregulation in biological markers.

BackgroundAn association between visual impairment and cognitive outcomes has been documented, but there is limited research examining this relationship using multiple measures of vision.MethodsParticipants included non-demented individuals in Year 3 of the Visual impairment was assessed using visual acuity, contrast sensitivity, and stereo acuity. Cognitive function was defined using the digit symbol test and the Modified Mini-Mental State Examination (3MS). Incident cognitive impairment was defined as a 3MS score 5 points following Year 3. Linear mixed effects models examined longitudinal associations adjusting for year, age, sex, race, education, smoking, depression, diabetes, study site, as well as interaction terms between the vision parameters and years in study, between baseline age and years in study, and quadratic terms of baseline age and years in study. Discrete Cox regression models examined the risk of incident cognitive impairment.ResultsAnalyses included 2,444 participants (mean age = 74). Visual acuity, contrast sensitivity, and stereo acuity impairments were not associated with statistically significant changes in annual digit symbol test scores over 7 years of follow-up, as compared to those without these impairments. However, visual acuity, contrast sensitivity, and stereo acuity impairments were associated with greater declines in annual 3MS scores over 9 years. Participants with impaired visual acuity, contrast sensitivity, and stereo acuity had a greater risk of incident cognitive impairment.ConclusionsOur results suggest that visual acuity, contrast sensitivity, and stereo acuity impairments may be risk factors for cognitive decline.

Context Body composition and glucose metabolism change with aging. Whether different levels of body-mass-index (BMI) are needed to define diabetes risk across the adult lifespan is unknown. Objective This work aimed to investigate whether BMI similarly reflects relative fat mass (FM) and diabetes risk across age groups. Methods Participants without diabetes from the Baltimore Longitudinal Study of Aging (973 men, 1073 women), stratified by age (<50, 50-59, 60-69, ≥70 years) and categorized by either World Health Organization (WHO)-defined BMI categories (for normal weight, overweight or obesity) or BMI quartiles. The primary exposure was BMI. The primary outcome was diabetes incidence. The relationship of BMI to dual-energy x-ray absorptiometry–derived FM was also investigated in older vs younger participants. Results The median (range) follow-up time was 7.1 years (range, 0-29.0 years). Within WHO-defined BMI categories, different age groups demonstrated significantly different FM percentage, FM/lean mass, and waist circumference (P <.05). WHO-defined BMI categories for overweight and obesity were generally related to higher diabetes risk compared to normal weight in all ages except 50 to 59 years. When BMI was categorized by quartiles, diabetes incidence increased dramatically beginning in quartile 2 (23-25 kg/m2) in older groups. BMI cutoffs with equivalent diabetes incidence rate as BMI 25 kg/m2 and 30.0 kg/m2 in individuals younger than 50 years were 22.7 kg/m2 and 25.2 kg/m2 for ages 50 to 59 years; 22.8 kg/m2 and 25.0 kg/m2 for ages 60 to 69 years; and 23.2 kg/m2 and 25.8 kg/m2 for ages 70 years and older, respectively. Conclusion WHO-defined BMI categories do not reflect similar diabetes risk across the lifespan. Diabetes incidence is greater at lower levels of BMI in older adults and may lead to underestimation of diabetes risk with aging, particularly among those traditionally classified as normal-weight individuals. [ABSTRACT FROM AUTHOR]

Introduction: Spatial navigation, the ability to move through one's environment, is a complex skill utilized in everyday life. The effects of specific vestibular end-organ deficits and hearing impairments on spatial navigation have received little to no attention. We hypothesized that hearing impairment adversely affects spatial navigation and that bimodal impairments (vestibular and hearing) further impair navigation ability. Methods: Data from 182 participants in the Baltimore Longitudinal Study of Aging who had interpretable results for the video head impulse test (vHIT), cervical vestibular evoked myogenic potentials (cVEMP) and ocular vestibular evoked myogenic potentials (oVEMP), audiometric testing, and the triangle completion test (TCT) were retrospectively analyzed. Multiple linear regression, controlling for age, sex, and cognition, was employed to identify predictors of TCT performance in terms of end-point error, angle deviation, and distance walked. Results: oVEMP abnormalities were associated with larger end-point error (p = 0.008) and larger angle deviation (p = 0.002) but were not associated with distance walked (p = 0.392). Abnormalities on cVEMP testing and vHIT were not associated with distance walked (p = 0.835, p = 0.300), end-point error (p = 0.256, p = 0.808), or angle deviation (p = 0.192, p = 0.966). Compared with normal-hearing adults, hearing-impaired adults walked a shorter distance during the TCT (p = 0.049) but had a similar end-point error (p = 0.302) and angle deviation (p = 0.466). There was no interaction between vestibular and hearing function for predicting spatial navigation ability. Conclusion: In this cohort analysis, utricular dysfunction and hearing impairment were associated with poorer spatial navigation performance. We postulate that hearing impairment negatively affects one's ability to use real-time, intrinsic auditory cues and/or prior experience to guide navigation. Plain Language Summary: Spatial navigation, the ability to move through one's environment, is a complex skill utilized in everyday life. The effects of specific balance and hearing deficits on spatial navigation have not been extensively studied. Thus, we analyzed data from 182 participants in the Baltimore Longitudinal Study of Aging who completed balance, hearing, and spatial navigation tests to determine if hearing impairment may adversely affect spatial navigation and if combined deficits in balance and hearing further impair navigation ability. Our analyses accounted for the confounding effects of age, sex, and cognition on aspects of spatial navigation performance. We found that deficits in hearing and in the balance organ that senses horizontal translational movements were associated with worse performance on spatial navigation. However, deficits in the balance organs that sense vertical translational movements and horizontal rotational movements were not associated with worse spatial navigation ability. Surprisingly, we found that those with combined balance and hearing deficits did not perform significantly worse on spatial navigation than those with deficits in either balance or hearing alone. We believe that the abnormal function of the horizontal translational movement sensors likely explains the gait disorientation experienced by persons with inner ear problems. Additionally, we propose that hearing deficits impede one's ability to use real-time sound cues to guide navigation. Many of our participants had mild deficits; thus, further research on the effects of more severe balance and hearing deficits on spatial navigation is needed to gain a better understanding of how different sensory inputs contribute to spatial navigation ability. [ABSTRACT FROM AUTHOR]

ObjectiveLower health literacy is associated with higher rates of mortality and chronic disease. It remains unclear whether health literacy is associated with diabetes and/or hyperglycemia in older adults, and if this relationship differs by sex.Research design and methodsWe performed a cross-sectional analysis of 2510 older adults in the Health, Aging and Body Composition (Health ABC) Study who had both a Rapid Estimate of Adult Literacy in Medicine (REALM) measurement and diabetes status available. Sex-stratified logistic regression models were used to analyze the relationship of health literacy categories (low, medium, and high) to diabetes status, adjusting for key covariates. Secondary analyses examined the relationship of health literacy to glycemic markers (A1C, fasting blood glucose).ResultsAmong participants in the Health ABC cohort, 429 had diabetes. Mean age was 76years old and 45% were female. Men with diabetes more commonly had low health literacy levels than men without diabetes (10.1% versus 9.3%, p=0.02). Similar results were seen among women (14.7% versus 6.1%, p

Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as 1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were

Mobility declines in older adults can be determined through monitoring longitudinal changes in gait speed. We examined longitudinal changes [in] ankle proprioception among those with and without baseline lower extremity numbness to develop a better understanding of mobility declines in healthy older adults. Participants included 568 adults (52.8% women) aged 60–98 years from the Baltimore Longitudinal Study of Aging. Larger ankle proprioception decreases during plantar flexion were found in the participants with lower extremity numbness compared with those without numbness (p =.034). Among participants with lower extremity numbness, slower baseline speeds from both usual and fast pace gait were associated with performance decline in ankle proprioception measured during ankle dorsiflexion (p =.039 and p =.004, respectively). Assisting older adults, especially those with lower extremity numbness, to maintain and improve ankle proprioception may help prevent mobility declines that have previously been considered age related. [ABSTRACT FROM AUTHOR]

Wrist-worn accelerometry metrics are not well defined in older adults. Accelerometry data from 720 participants (mean age 70 years, 55% women) were summarized into (a) total activity counts per day, (b) active minutes per day, (c) active bouts per day, and (d) activity fragmentation (the reciprocal of the mean active bout length). Linear regression and mixed-effects models were utilized to estimate associations between age and gait speed with wrist accelerometry. Activity counts per day, daily active minutes per day, and active bouts per day were negatively associated with age among all participants, while positive associations with activity fragmentation were only observed among those ≥65 years. More activity counts, more daily active minutes, and lower activity fragmentation were associated with faster gait speed. There were baseline age interactions with annual changes in total activity counts per day, active minutes per day, and activity fragmentation (Baseline age × Time, p <.01 for all). These results help define and characterize changes in wrist-based physical activity patterns among older adults. [ABSTRACT FROM AUTHOR]

ObjectiveData on the association between subclinical thyroid dysfunction and dementia are limited and conflicting. We aimed to determine whether subclinical thyroid dysfunction was associated with dementia and cognitive decline.DesignPopulation-based prospective cohort study.PatientsAdults aged 70-79 years with measured thyroid function, but no dementia at baseline, and Modified Mini-Mental State (3MS) at baseline and follow-up.MeasurementsPrimary outcome was incident-adjudicated dementia, based on 3MS, hospital records and dementia drugs. Secondary outcome was change in 3MS. Models were adjusted for age, sex, race, education and baseline 3MS, and then further for cardiovascular risk factors.ResultsAmong 2558 adults, 85% were euthyroid (TSH 0.45-4.49mIU/L), 2% had subclinical hyperthyroidism with mildly decreased TSH (TSH 0.10-0.44 mIU/L), 1% subclinical hyperthyroidism with suppressed TSH (TSH

BackgroundPrevalence of heart failure (HF) increases significantly with age, coinciding with age-related changes in body composition that are common and consequential. Still, body composition is rarely factored in routine HF care.Methods and resultsThe Health, Aging, and Body Composition study is a prospective cohort study of nondisabled adults. Using yearly dual-energy x-ray absorptiometry, body composition was assessed in the Health, Aging, and Body Composition study over 6 years, comparing those who developed incident HF versus those who did not. Among 2815 Health, Aging, and Body Composition participants (48.5% men; 59.6% whites; mean age, 73.6±2.9 years), 111 developed incident HF over the 6-year study period. At entry into the Health, Aging, and Body Composition study, men and women who later developed HF had higher total body mass when compared with those versus those who did not develop HF (men, 80.9±10 versus 78.6±12.9 kg, P=0.05; women, 72.7±15.0 versus 68.2±14.2 kg, P=0.01, respectively). However, after developing HF, loss of total lean body mass was disproportionate; men with HF lost 654.6 versus 391.4 g/y in non-HF participants, P=0.02. Loss of appendicular lean mass was also greater with HF (-419.9 versus -318.2 g/y; P=0.02), even after accounting for total weight change. Among women with HF, loss of total and appendicular lean mass were also greater than in non-HF participants but not to the extent seen among men.ConclusionsIncident HF in older adults was associated with disproportionate loss of lean mass, particularly among men. Prognostic implications are significant, with key sex-specific inferences on physical function, frailty, disability, and pharmacodynamics that all merit further investigation.

Previous studies have shown that more active older adults have better cognition and brain health based on a variety of structural neuroimaging measures. Nevertheless, the effects of maintaining physical activity (PA) over an extended period of time on future changes in older adults' cognition and brain structure are unknown. Participants were 141 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 60% female; 42% black) studied over a 13-year period. PA (self-reported time spent walking) was assessed annually from years 1 to 10. Magnetic resonance imaging with diffusion tensor was performed at years 10 and 13. Time spent walking decreased on average by 8.4% annually from year 1 to year 10. Independent of initial time spent walking, demographics, and APOE e4 status, better maintenance of time spent walking over the decade predicted less reduction in hippocampal volume (p = 0.03), smaller increases in global gray matter mean diffusivity and white matter axial diffusivity (p < 0.01), and maintenance of general cognitive performance (p < 0.01). Maintenance of cognitive performance was associated with smaller increases in white matter axial diffusivity (p < 0.01). PA at baseline and at year 10, as well as changes in PA over a 5-year period, was less predictive of future changes in brain structure and cognition. Thus, how PA levels change over longer periods of aging may be an important contributor to cognitive and neural protection.

BackgroundAge-related peripheral hearing impairment (HI) is prevalent, treatable, and may be a risk factor for dementia in older adults. In prospective analysis, we quantified the association of HI with incident dementia and with domain-specific cognitive decline in memory, perceptual speed, and processing speed.MethodsData were from the Health, Aging and Body Composition (Health ABC) study, a biracial cohort of well-functioning adults aged 70-79 years. Dementia was defined using a prespecified algorithm incorporating medication use, hospital records, and neurocognitive test scores. A pure-tone average in decibels hearing level (dBHL) was calculated in the better hearing ear using thresholds from 0.5 to 4kHz, and HI was defined as normal hearing (≤25 dBHL), mild (26-40 dBHL), and moderate/severe (>40 dBHL). Associations between HI and incident dementia and between HI and cognitive change were modeled using Cox proportional hazards models and linear mixed models, respectively.ResultsThree-hundred eighty seven (20%) participants had moderate/severe HI, and 716 (38%) had mild HI. After adjustment for demographic and cardiovascular factors, moderate/severe audiometric HI (vs. normal hearing) was associated with increased risk of incident dementia over 9 years (hazard ratio: 1.55, 95% confidence interval [CI]: 1.10, 2.19). Other than poorer baseline memory performance (difference of -0.24 SDs, 95% CI: -0.44, -0.04), no associations were observed between HI and rates of domain-specific cognitive change during 7 years of follow-up.ConclusionsHI is associated with increased risk of developing dementia in older adults. Randomized trials are needed to determine whether treatment of hearing loss could postpone dementia onset in older adults.

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (vitamin K-1) was associated with increased CAC progression, especially in persons treated for hypertension. It is unknown whether hypertension treatment modifies this putative role of vitamin K in clinical CVD risk.Objective: We determined the association between vitamin K status and incident clinical CVD in older adults in the Health ABC (Health, Aging, and Body Composition Study) and whether the association differed by hypertension treatment status.Methods: Plasma phylloquinone was measured in 1061 participants free of CVD (70-79 y of age, 58% women, 39% black). Plasma uncarboxylated MGP [(dp)ucMGP] was measured in a subset of 635 participants. Multivariate Cox models estimated the HR for incident CVD over 12.1 follow-up years. Effect modification by hypertension was tested with the use of interaction terms.Results: Neither low plasma phylloquinone (

ObjectiveThe objective of the study is was investigate the association between hearing impairment and anxiety.MethodWe conducted a cross-sectional analysis of 1,732 community-based adults aged 76 to 85 years who participated in the Health Aging and Body Composition (ABC) study. Logistic regression models were adjusted for demographic and cardiovascular risk factors. Hearing impairment was defined by the speech-frequency pure tone average. Anxiety was defined as reporting two symptoms of at least "a little" or one symptom "quite a bit" on the three-item Hopkins Symptom Checklist.ResultsCompared with individuals with no hearing impairment, the odds of prevalent anxiety were higher among individuals with mild hearing impairment (odds ratio [OR] = 1.32, 95% confidence interval [CI] = [1.01, 1.73]) and moderate or greater hearing impairment (OR = 1.59, 95% CI = [1.14, 2.22]). Hearing aid use was not significantly associated with lower odds of anxiety.DiscussionHearing impairment is independently associated with greater odds of anxiety symptoms in older adults.

IntroductionData on the association between exercise capacity and risk for heart failure (HF) in older adults are limited.MethodsThis study examined the association of exercise capacity, and its change over time, with 10-year mortality and incident HF in 2,935 participants of the Health, Aging, and Body Composition Study without HF at baseline (age, 73.6 [SD=2.9] years; 52.1% women; 41.4% black; 58.6% white). This cohort was initiated in 1997-1998 and exercise capacity was evaluated with a long-distance corridor walk test (LDCW) at baseline and Year 4. Outcomes were collected in 2007-2008 and initial analysis performed in 2014.ResultsTen-year incident HF for completers (n=2,245); non-completers (n=331); and those excluded from LDCW for safety reasons (n=359) was 11.4%, 19.2%, and 23.0%, respectively. The corresponding 10-year mortality was 27.9%, 41.1%, and 42.4%. In models accounting for competing mortality, the adjusted subhazard ratio for HF was 1.37 (95% CI=1.00, 1.88; p=0.049) in non-completers and 1.41 (95% CI=1.06, 1.89; p=0.020) in those excluded versus completers. Non-completers (adjusted hazard ratio, 1.49; 95% CI=1.21, 1.84; p

BackgroundFew cohort studies have examined longitudinal associations between age-related changes in cognition and physical performance. Further, whether these associations differ for men versus women or can be attributed to differences in physical activity (PA) is unknown.MethodsParticipants were 2,876 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 52% female; 39% black) studied over a 9-year period. Usual gait speed, self-reported PA, and two cognitive measures-Digit Symbol Substitution Test (DSST) and Mini-Modified Mental State examination (3MS)-were assessed years 0 (ie, baseline), 4, and 9.ResultsEarly decline between years 0 and 4 in gait speed predicted later decline between years 4 and 9 in performance on the 3MS (β = 0.10, p = .004) and on the DSST (β = 0.16, p < .001). In contrast, the associations between early decline in cognition and later decline in gait speed were weaker and were non-significant after correcting for multiple comparisons (β = 0.08, p = .019 for 3MS and β = .06, p = .051 for DSST). All associations were similar for women and men and were unaltered when accounting for PA levels.ConclusionsThe results indicate declining gait speed as a precursor to declining cognitive functioning, and suggest a weaker reciprocal process among older women and men.

Background The relative intensity of physical activity (PA) can be estimated as the percent of one's maximal effort required. Methods We compared associations of relative and absolute intensity PA with incident major cardiovascular disease (CVD) and all-cause mortality in 5 633 women from the Objective Physical Activity and Cardiovascular Health Study (mean age 78.5 ± 6.7). Absolute intensity was measured by accelerometry. Relative intensity was estimated by dividing accelerometer-estimated metabolic equivalents (METs) by maximal MET capacity. Both were aggregated into mean daily hours of light intensity PA (LPA) and moderate-to-vigorous PA (MVPA). Cox proportional hazard models estimated hazard ratios (HRs) for 1-hour higher amounts of PA on outcomes. Results During follow-up (median = 7.4 years), there were 748 incident CVD events and 1 312 deaths. Greater LPA and MVPA, on either scale, were associated with reduced risk of both outcomes. HRs for a 1-hour increment of absolute LPA were 0.88 (95% CI: 0.83–0.93) and 0.88 (95% CI: 0.84–0.92) for incident CVD and mortality, respectively. HRs for a 1-hour increment of absolute MPVA were 0.73 (95% CI: 0.61–0.87) and 0.55 (95% CI: 0.48–0.64) for the same outcomes. HRs for a 1-hour increment of relative LPA were 0.70 (95% CI: 0.59–0.84) and 0.78 (95% CI: 0.68–0.89) for incident CVD and mortality, respectively. HRs for a 1-hour increment of relative MPVA were 0.89 (95% CI: 0.83–0.96) and 0.82 (95% CI: 0.77–0.87) for the same outcomes. On the relative scale, LPA was more strongly, and inversely associated with both outcomes than relative MVPA. Absolute MVPA was more strongly inversely associated with the outcomes than relative MVPA. Conclusions Findings support the continued shift in the PA intensity paradigm toward recommendation of more movement, regardless of intensity. Relative LPA––a modifiable, more easily achieved behavioral target, particularly among ambulatory older adults––was associated with reduced risk of incident major CVD and death. [ABSTRACT FROM AUTHOR]

Background Lower urinary tract symptoms (LUTS) in older men are associated with an increased risk of mobility limitations. Lower extremity muscle quality may represent a novel shared mechanism of both LUTS and mobility limitations. Methods We evaluated associations of thigh skeletal muscle measures (strength, area, and specific force) with total LUTS severity (American Urologic Association Symptom Index; AUASI) and voiding and storage subscores among 352 men aged ≥60 years enrolled in the Baltimore Longitudinal Study of Aging. Thigh muscle strength (Nm) was defined as maximum concentric 30°/s knee extensor torque, area (cm2), and specific force (Nm/cm2) defined as strength/area. Associations with AUASI score were estimated using multivariable linear regression and linear mixed models. Results Mean thigh muscle strength at baseline was 139.7Nm. In cross-sectional multivariable models, each 39Nm increment in thigh muscle strength and 0.28Nm/cm2 increment in specific force was associated with −1.17 point (95% CI: −1.93 to −.41) and −0.95 point (95% CI: −1.63 to −0.27) lower AUASI score, respectively. Similar associations were observed for voiding and storage subscores, although somewhat attenuated. In longitudinal analyses, baseline muscle measures were not associated with annual change in AUASI, and current changes in muscle measures and AUASI were unrelated. Conclusions Cross-sectionally, higher thigh muscle strength and specific force were associated with decreased LUTS severity in older men. However, we did not observe concurrent worsening LUTS severity with declining thigh muscle strength, area, or specific force in longitudinal analyses. [ABSTRACT FROM AUTHOR]

BackgroundWhile low vitamin K status has been associated with several chronic diseases that can lead to lower extremity disability, it is not known if low vitamin K status is associated with worse lower extremity function.MethodsVitamin K status was measured according to plasma phylloquinone (vitamin K1) and dephosphorylated-uncarboxylated MGP (dp-ucMGP) in 1,089 community-dwelling older adults (mean ± SD age =74±3 years; 67% female). Lower extremity function was assessed using the short physical performance battery (SPPB), gait speed, and isokinetic leg strength. Linear regression and mixed models were used to determine the cross-sectional and longitudinal associations between vitamin K status and functional outcome measures.ResultsCross-sectionally, higher plasma phylloquinone was associated with better SPPB scores and 20-m gait speed (p ≤ .05). After 4-5 years, those with ≥1.0nM plasma phylloquinone (the concentration achieved when recommended intakes are met) had better SPPB scores (p = .03) and 20-m gait speed (p < .05). Lower plasma dp-ucMGP (reflective of better vitamin K status) was associated with better SPPB scores and leg strength cross-sectionally (p ≤ .04), but not longitudinally. Neither measure of vitamin K status was associated with walking endurance or with the rate of decline in function.ConclusionOlder adults with higher vitamin K status had better physical performance scores at baseline, but data are less consistent longitudinally. Since lower extremity disability is a common consequence of multiple chronic diseases for which a role of vitamin K has been suggested, future studies are needed to determine if vitamin K supplementation could improve function in those with vitamin K insufficiency and clarify underlying mechanism(s).