Background Dementia is a major health concern for which prevention and treatment strategies remain elusive. Lowering high blood pressure with specific antihypertensive medications (AHMs) could reduce the burden of disease. We investigated whether specific AHM classes reduced the risk for dementia. Methods We did a meta-analysis of individual participant data from eligible observational studies published between Jan 1, 1980, and Jan 1, 2019. Cohorts were eligible for inclusion if they prospectively recruited community-dwelling adults; included more than 2000 participants; collected data for dementia events over at least 5 years; had measured blood pressure and verified use of AHMs; included in-person exams, supplemented with additional data, to capture dementia events; and had followed up cases for mortality. We assessed the association of incident dementia and clinical Alzheimer's disease with use of five AHM classes, within strata of baseline high (systolic blood pressure [SBP] >= 140 mm Hg or diastolic blood pressure [DBP] >= 90 mm Hg) and normal (SBP <140 mm Hg and DBP <90 mm Hg) blood pressure. We used a propensity score to control for confounding factors related to the probability of receiving AHM. Study-specific effect estimates were pooled using random-effects meta-analyses. Results Six prospective community-based studies (n=31090 well phenotyped dementia-free adults older than 55 years) with median follow-ups across cohorts of 7-22 years were eligible for analysis. There were 3728 incident cases of dementia and 1741 incident Alzheimer's disease diagnoses. In the high blood pressure stratum (n=15 537), those using any AHM had a reduced risk for developing dementia (hazard ratio [HR] 0.88, 95% CI 0.79-0.98; p=0.019) and Alzheimer's disease (HR 0.84, 0.73-0.97; p=0.021) compared with those not using AHM. We did not find any significant differences between one drug class versus all others on risk of dementia. In the normal blood pressure stratum (n=15 553), there was no association between AHM use and incident dementia or Alzheimer's disease. Interpretation Over a long period of observation, no evidence was found that a specific AHM drug class was more effective than others in lowering risk of dementia. Among people with hypertensive levels of blood pressure, use of any AHM with efficacy to lower blood pressure might reduce the risk for dementia. These findings suggest future clinical guidelines for hypertension management should also consider the beneficial effect of AHM on the risk for dementia. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

BACKGROUND:Measures of cardiac ventricular electrophysiology have been associated with cognitive performance in cross-sectional studies. We sought to evaluate the association of worsening ventricular repolarization in midlife, as measured by incident prolonged QT interval, with cognitive decline in late life.METHODS:Midlife QT interval was assessed by electrocardiography during three study visits from 1965/68 to 1971/74 in a cohort of Japanese American men aged 46-68 at Exam 1 from the Honolulu Heart Study. We defined incident prolonged QT as the QT interval in the upper quartile at Exam 2 or 3 after QT interval in lower three quartiles at Exam 1. Cognitive performance was assessed at least once using the Cognitive Abilities Screening Instrument (CASI), scored using item response theory (CASI-IRT), during four subsequent visits from 1991/93 to 1999/2000 among 2,511 of the 4,737 men in the Honolulu-Asia Aging Study otherwise eligible for inclusion in analyses. We used marginal structural modeling to determine the association of incident prolonged QT with cognitive decline, using weighting to account for confounding and attrition.RESULTS:Incident prolonged QT interval in midlife was not associated with late-life CASI-IRT at cognitive baseline (estimated difference in CASI-IRT: 0.04; 95% CI: -0.28, 0.35; p = 0.81), or change in CASI-IRT over time (estimated difference in annual change in CASI-IRT: -0.002; 95%CI: -0.013, 0.010; p = 0.79). Findings were consistent across sensitivity analyses.CONCLUSIONS:Although many midlife cardiovascular risk factors and cardiac structure and function measures are associated with late-life cognitive decline, incident prolonged QT interval in midlife was not associated with late-life cognitive performance or cognitive decline.

Importance It is uncertain whether unrecognized myocardial infarction (MI) is a risk factor for cerebral infarction. Objective To determine whether unrecognized MI detected by cardiac magnetic resonance imaging (MRI) is associated with cerebral infarction. Design, Setting, and Participants This is a cross-sectional study of ICELAND MI, a cohort substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study conducted in Iceland. Enrollment occurred from January 2004 to January 2007 from a community-dwelling cohort of older Icelandic individuals. Participants aged 67 to 93 years who underwent both brain MRI and late gadolinium enhancement cardiac MRI were included. Data analysis was performed from September 2018 to March 2019. Exposures Unrecognized MI identified by cardiac MRI. Main Outcomes and Measures Unrecognized MI was defined as cardiac MRI evidence of MI without a history of clinically evident MI. Recognized MI was defined as cardiac MRI evidence of MI with a history of clinically evident MI. Cerebral infarctions on brain MRI were included regardless of associated symptoms. Multiple logistic regression was used to evaluate the association between MI status (no MI, unrecognized MI, or recognized MI) and cerebral infarction after adjustment for demographic factors and vascular risk factors. In addition, we evaluated the association between unrecognized MI and embolic infarcts of undetermined source. Results Five enrolled participants had nondiagnostic brain MRI studies and were excluded. Among 925 participants, 480 (51.9%) were women; the mean (SD) age was 75.9 (5.3) years. There were 221 participants (23.9%) with cardiac MRI evidence of MI, of whom 68 had recognized MI and 153 unrecognized MI. There were 308 participants (33.3%) with brain MRI evidence of cerebral infarction; 93 (10.0%) had embolic infarcts of undetermined source. After adjustment for demographic factors and vascular risk factors, the likelihood (odds ratio) of having cerebral infarction was 2.0 (95% CI, 1.2-3.4; P = .01) for recognized MI and 1.5 (95% CI, 1.02-2.2; P = .04) for unrecognized MI. After adjustment for demographics and vascular risk factors, unrecognized MI was also associated with embolic infarcts of undetermined source (odds ratio, 2.0 [95% CI, 1.1-3.5]; P = .02). Conclusions and Relevance In a population-based sample, we found an association between unrecognized MI and cerebral infarction. These findings suggest that unrecognized MI may be a novel risk factor for cardiac embolism and cerebral infarction.

Debate continues about the important clinic and public health question of treating elevated blood pressure (BP) or using a specific antihypertensive medication in late-life, to reduce the risk of dementia. Long-term follow-up of large numbers of well-phenotyped people is needed to address this issue. We assessed the associations of different classes of BP-lowering drugs to incident dementia and Alzheimer's disease in older people with and without high BP. We meta-analysed 6 long-term prospective studies (Age, Gene/Environment Susceptibility-Reykjavik Study, the Atherosclerosis Risk in Communities Study, Framingham Heart Study, Honolulu-Asia Aging Study, Rotterdam Study and 3-C study), that included 31,090 dementia-free community-dwelling older adults (≥55 years) with baseline data on BP levels and use of BP-lowering drugs who were followed from 7 to 22 years. Incident dementia (n=3728) and Alzheimer's disease (n=1741) were ascertained using multi-step screening and diagnostic procedures as well as linkage systems to medical records. We examined five major drug classes: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics. Within-study Cox proportional-hazards analyses (age as time-scale) were adjusted for propensity scores to control for risk factors. A priori analyses were stratified by high baseline (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) and normal baseline BP irrespective of medication use, and APOε4 carriership. Study-specific effect estimates were meta-analysed using random-effects model. In participants with high baseline BP, those using any BP-lowering drug, regardless of drug class, had a reduced risk for developing all-cause dementia (hazard ratio 0.88, 95%confidence interval 0.79 - 0.98) and Alzheimer's disease (0.85, 0.74 - 0.99) compared to those not taking BP medication. Hazards ratios for incident dementia were likewise reduced among APOE-ε4 carriers (0.77, 0.64-0.93), which mainly reflected the associations with ACEIs (0.75, 0.57-0.98), ARBs (0.65,0.47-0.91), BBs (0.74,0.58-0.95) and diuretics (0.75,0.59-0.94). No significant associations were noted among APOE-ε4 non-carriers or in participants with normal baseline BP. Our findings suggest that antihypertensive treatment might decrease dementia risk in people with high BP, with evidence that beneficial effects may be gained by several different drug classes and vary with baseline BP level and APOE-ε4 carriership.

OBJECTIVE:To investigate olfaction in relation to incident Parkinson disease (PD) in US white and black older adults. METHODS:The study included 1,510 white (mean age 75.6 years) and 952 black (75.4 years) participants of the Health, Aging, and Body Composition study. We evaluated the olfaction of study participants with the Brief Smell Identification Test (BSIT) in 1999-2000. We retrospectively adjudicated PD cases identified through August 31, 2012, using multiple data sources. We used multivariable Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:During an average of 9.8 years of follow-up, we identified a total of 42 incident PD cases, including 30 white and 12 black participants. Overall, poor sense of smell, as indicated by a lower BSIT score, was associated with higher risk of PD. Compared with the highest tertile of BSIT (t3), the HR was 1.3 (95% CI 0.5-3.6) for the second tertile (t2) and 4.8 (95% CI 2.0-11.2) for the lowest tertile (t1) (ptrend < 0.00001). Further analyses revealed significant associations for incident PD in both the first 5 years of follow-up (HRt1/[t2+t3] 4.2, 95% CI 1.7-10.8) and thereafter (HRt1/[t2+t3] 4.1, 95% CI 1.7-9.8). This association appeared to be stronger in white (HRt1/[t2+t3] 4.9, 95% CI 2.3-10.5) than in black participants (HRt1/[t2+t3] 2.5, 95% CI 0.8-8.1), and in men (HRt1/[t2+t3] 5.4, 95% CI 2.3-12.9) than in women (HRt1/[t2+t3] 2.9, 95% CI 1.1-7.8). CONCLUSIONS:Poor olfaction predicts PD in short and intermediate terms; the possibility of stronger associations among men and white participants warrants further investigation.

Frailty is a risk factor for cardiovascular diseases (CVD), but the studies available have not considered the presence of subclinical atherosclerotic disease as potential confounders. We investigated the association between frailty and the onset of CVD independently of subclinical atherosclerotic disease. For this reason, a sample of 3818 older participants participating in the Age, Gene/Environment SusceptibilityReykjavik Study without CVD at baseline was followed for a median of 8.7 years. Frailty was defined as the presence of 3 among five Fried's criteria (unintentional weight loss, low physical activity level, weakness, exhaustion, and slow gait speed). Incident CVD was defined as onset of coronary artery disease, heart failure, stroke, and CVD-related mortality identified using hospital, medical, and death records. Subclinical atherosclerotic disease was evaluated as the maximum value of carotid intima media thickness, presence of carotid plaque (moderate or high), and total coronary calcifications (CACs). At baseline, frail participants (n=300) were more frequently obese, diabetic, and had a greater presence of metabolic syndrome than the nonfrail (n=3518). Frail participants also showed a higher presence of carotid plaques and CACs. Using a Cox's regression analysis, adjusted for clinical, biochemical, and subclinical atherosclerosis estimates, frailty increased the risk of CVD (hazard ratio [HR]=1.35; 95% confidence interval [CI]: 1.05-1.74), with results stronger for women than men (HR=1.51, p=0.006 and 1.19, p=0.44, respectively). Among Fried's criteria, exhaustion was the only criterion significantly associated with the onset of new CVD events (HR=1.30; 95% CI: 1.00-1.73). In conclusion, frailty was associated with the onset of CVD in older people even after adjusting for subclinical atherosclerotic disease.

Late-life depression increases the risk of dementia, but underlying mechanisms are still not well understood. An often proposed explanation is that high cortisol levels resulting from depression have neurotoxic effects on the brain. Yet, no studies investigated late-life depression, cortisol levels and risk of dementia in combination. We investigated whether higher levels of cortisol explained the relationship between late-life depression and incident dementia in a large population of older persons. Within the population-based AGES-Reykjavik Study, depression was assessed with the MINI diagnostic interview. Saliva samples for cortisol measures were obtained after awakening and at night in 4,354 persons (mean age 76±5 years) without dementia at baseline. Using Cox proportional hazard models we estimated the associations of current and past (remitted) depression, and evening and morning cortisol levels, respectively, with incident all-cause dementia and Alzheimer vs. non-Alzheimer dementia during on average 9 years of follow-up (range 0–13 years), adjusting for age, sex, and education. At baseline, 65 persons had a current (2-week) diagnosis of major depressive disorder (MDD) and 130 persons had a past but not current (remitted) diagnosis. Current MDD was associated with an increased risk of developing all-cause dementia (HR=2.12; 95% CI 1.30–3.44), with risks similar for AD and non-AD, while remitted MDD was not (HR=0.96; 95% CI 0.60–1.54). Higher levels of evening cortisol were also associated with increased risk of dementia (middle vs. lowest tertile HR=1.43; 95% CI 1.19–1.73, and highest vs. lowest tertile HR=1.66; 95% CI 1.38–1.99), while morning cortisol levels were not. When added together in the model, current MDD and higher levels of cortisol were independently associated with an increased risk of dementia and the risk estimates of MDD and cortisol of the joint model were very similar to those when MDD and cortisol were entered in separate models. In this population-based study of older persons, current but not past depression increased risk of incident dementia. While higher basal cortiol levels were also associated with increased risk of dementia, they did not seem to be a major mechanism underlying the relation between depression and risk of dementia.

Background— Age is the foremost risk factor for atrial fibrillation (AF), and AF has a rising prevalence in older adults. How AF may contribute to decline in physical performance in older adults has had limited investigation. We examined the associations of incident AF and 4-year interval declines in physical performance at ages 70, 74, 78, and 82 years in the Health, Aging, and Body Composition (Health ABC) Study. Methods and Results— Health ABC is a prospective cohort of community-dwelling older adults (n=3075). The study conducted serial assessments of physical performance with the Health ABC physical performance battery (scored 0–4), grip strength, 2-minute walk distance, and 400-m walking time. Incident AF was identified from the Center for Medicare and Medicaid Services and related to 4-year interval decline in physical performance. After exclusions, the analysis included 2753 Health ABC participants (52% women, 41% black race). Participants with AF had a significantly greater 4-year physical performance battery decline than those without AF at age 70, 74, 78, and 82, with mean estimated decline ranging from −0.08 to −0.10 U (95% confidence interval, −0.18 to −0.01; P <0.05 for all estimates) after multivariable adjustment. Grip strength, walk distance, and walk time similarly showed significantly greater declines at each 4-year age interval in participants with AF. Conclusions— In community-based cohort older adults, incident AF was associated with increased risk of decline in physical performance. Further research is essential to identify mechanisms and preventive strategies for how AF may contribute toward declining physical performance in older adults.

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n=15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n=21,701) and clinical vertebral fracture (n=5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]=3%) was associated with higher vBMD (=0.22, p=1.9x10(-8)) and decreased risk of radiographic vertebral fracture (odds ratio [OR]=0.75; false discovery rate [FDR] p=0.01). In 1p36.12, rs12742784 (MAF=21%) was associated with higher vBMD (=0.09, p=1.2x10(-10)) and decreased risk of clinical vertebral fracture (OR=0.82; FDR p=7.4x10(-4)). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (=0.28, FDR p=0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (=0.12, FDR p=1.7x10(-3), functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. (c) 2016 American Society for Bone and Mineral Research.

UNLABELLED:Obesity is a well-recognized risk factor for atrial fibrillation (AF), yet adiposity measures other than body mass index (BMI) have had limited assessment in relation to AF risk. We examined the associations of adiposity measures with AF in a biracial cohort of older adults. Given established racial differences in obesity and AF, we assessed for differences by black and white race in relating adiposity and AF. METHODS:We analyzed data from 2,717 participants of the Health, Aging, and Body Composition Study. Adiposity measures were BMI, abdominal circumference, subcutaneous and visceral fat area, and total and percent fat mass. We determined the associations between the adiposity measures and 10-year incidence of AF using Cox proportional hazards models and assessed for their racial differences in these estimates. RESULTS:In multivariable-adjusted models, 1-SD increases in BMI, abdominal circumference, and total fat mass were associated with a 13% to 16% increased AF risk (hazard ratio [HR] 1.14, 95% CI 1.02-1.28; HR 1.16, 95% CI 1.04-1.28; and HR 1.13, 95% CI 1.002-1.27). Subcutaneous and visceral fat areas were not significantly associated with incident AF. We did not identify racial differences in the associations between the adiposity measures and AF. CONCLUSION:Body mass index, abdominal circumference, and total fat mass are associated with risk of AF for 10years among white and black older adults. Obesity is one of a limited number of modifiable risk factors for AF; future studies are essential to evaluate how obesity reduction can modify the incidence of AF.

Objective: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. Methods: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. Results: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: −0.46, −0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: −0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: −0.85, −0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: −0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: −0.72, −0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: −1.14, −0.51). Conclusions: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary.

Introduction: Obesity is a well-recognized, modifiable risk factor for atrial fibrillation (AF). Limited studies have examined adiposity measures other than body mass index (BMI) and AF risk. We examined associations of adiposity measures with incident AF in a biracial cohort of older adults. Given the extensive racial differences between obesity and AF, we assessed for racial differences in relating adiposity and AF. Methods: The Dynamics of Health, Aging, and Body Composition Study is a prospective cohort of 3,075, community-dwelling, older adults. Adiposity measures were determined using anthropometry [BMI and abdominal circumference (AC)], CT [subcutaneous and visceral fat area (SAT, VAT)] and DXA (total and percent fat mass). AF was identified from the Center for Medicare and Medicaid Services. We determined the associations between adiposity measures and the 10-year risk of incident AF using Cox proportional hazards models. We examined for interactions between race and adiposity measures with the ou...

OBJECTIVE:The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) leads to depressive symptoms by disruption of brain structures involved in mood regulation. However, longitudinal data on the association between CSVD and depressive symptoms are scarce. The authors investigated the association between CSVD and incident depressive symptoms.METHOD:Longitudinal data were taken from the Age, Gene/Environment Susceptibility-Reykjavik Study of 1,949 participants free of dementia and without baseline depressive symptoms (mean age: 74.6 years [SD=4.6]; women, 56.6%). MRI markers of CSVD, detected at baseline (2002-2006) and follow-up (2007-2011), included white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces, and total brain parenchyma volume. Incident depressive symptoms were defined by a score ≥6 on the 15-item Geriatric Depression Scale and/or use of antidepressant medication.RESULTS:Depressive symptoms occurred in 10.1% of the participants. The association for a greater onset of depressive symptoms was significant for participants with 1 standard deviation increase in white matter hyperintensity volume over time, new subcortical infarcts, new Virchow-Robin spaces, 1 standard deviation lower total brain volume at baseline, and 1 standard deviation decreased total brain volume over time, after adjustments for cognitive function and sociodemographic and cardiovascular factors. Results were qualitatively similar when change in the Geriatric Depression Scale score over time was used as the outcome instead of incident depressive symptoms.CONCLUSIONS:Most markers of progression of CSVD over time and some markers of baseline CSVD are associated with concurrently developing new depressive symptoms. These findings support the vascular depression hypothesis.

IMPORTANCEThe spatial distribution of cerebral microbleeds (CMBs), which are asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and hypertensive vasculopathy (deep brain structures). Relatively little is known about the occurrence of and modifiable risk factors for developing CMBs, especially in a lobar location, in the general population of older people.OBJECTIVETo investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location.DESIGN, SETTING, AND PARTICIPANTSWe enrolled 2635 individuals aged 66 to 93 years from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study. Participants underwent a baseline magnetic resonance imaging (MRI) examination of the brain from September 1, 2002, through February 28, 2006, and returned for a second MRI examination from April 1, 2007, through September 30, 2011.EXPOSURESLifestyle and lipid factors assessed at baseline included smoking, alcohol consumption, body mass index, and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides.MAIN OUTCOMES AND MEASURESIncident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep.RESULTSDuring a mean follow-up of 5.2 years, 486 people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had deep CMBs. In the multivariate logarithm-binomial regression model adjusted for baseline cardiovascular risk factors, including blood pressure, antihypertensive use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94 [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location. Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95% CI, 1.02-1.25]), and a decreased triglyceride level (RR per 1-SD decrease in natural logarithm-transformed triglyceride level, 1.17 [95% CI, 1.03-1.33]) were significantly associated with an increased risk for lobar CMBs exclusively but not for deep CMBs.CONCLUSIONS AND RELEVANCELifestyle and lipid risk profiles for CMBs were similar to those for symptomatic intracerebral hemorrhage and differed for lobar and deep CMBs. Modification of these risk factors could have the potential to prevent new-onset CMBs, particularly those occurring in a lobar location.

Introduction: Atrial fibrillation (AF) is associated with significant morbidity in older adults. The effect of AF on physical function has had limited investigation. We related incident AF to prospective change in physical function across serial assessments in the Dynamics of Health, Aging, and Body Composition Study (HABC). Methods: HABC is a prospective study of older adults age 70-79 initiated in 1997-98. Physical function has been assessed in the cohort with the HABC performance battery (HABCPPB), scored 0-4, consisting of gait speed, chair stands, and balance assessments, administered at years 1, 4, 6, 8 and 10. Incident AF was ascertained from linkage with Center for Medicare and Medicaid Services, and dated by the first in-patient or second of 2 out-patient encounters. We used mixed effects regression analysis to relate incident AF to 4-year decline in the HABCPPB. Analyses incorporated age and AF as time-varying covariates and relevant multivariable adjustment (demographics; smoking, alcohol; cardiovascular disease [CVD] risk factors; prevalent CVD; and time varying hypertension, diabetes, CVD, and cancer). Results: Following exclusions, 2753 (age 73.6±2.9 years, 52% women, 41% black race) HABC participants were eligible for the analysis. We determined that older adults who developed AF at ages 74, 78, and 82 had significantly greater ( P <0.001) 4-year decline in physical function than those without AF. The Figure compares the trajectories of 4-year HABCPPB decline in those with and without AF at ages 70, 74, 78, and 82. For age centered at 74, the difference in 4-year decline in HABCPPB in those with and without AF was -0.10 (95% CI -0.21, 0.00); -0.21 (-0.31, -0.11) at age 78; and -0.32 (-0.48, -0.15) at age 82. These differences in physical function decline remained significant (P<0.001) following multivariable adjustment. Conclusions: In a community-dwelling cohort of older adults, AF was associated with significant 4-year decline in physical function.

OBJECTIVE:Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship. RESEARCH DESIGN AND METHODS:This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations. RESULTS AND CONCLUSION:One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (β=-0.99; p<0.01), decreased walking speed (β=-0.1m/s; p<0.01), decreased nerve conduction velocity (β=-1.7m/s; p<0.01), and increased neuropathy (β=0.25; p<0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF.

OBJECTIVE:The aims of this study were to evaluate and contrast the physical attributes that are associated with self-reported vs. observed ability to walk 400 m among older adults.DESIGN:Analysis of baseline and 3-yr data from 1026 participants 65 yrs or older in the InCHIANTI (Invecchiare in Chianti) study was conducted. Observed and self-reported ability to walk 400 m at baseline and at 3 yrs were primary outcomes. Predictors included leg speed, leg strength, leg strength symmetry, range of motion, balance, and kyphosis.RESULTS:Balance, leg speed, leg strength, kyphosis, leg strength symmetry, and knee range of motion were associated with self-reported ability to walk 400 m at baseline (P < 0.001, c = 0.85). Balance, leg speed, and knee range of motion were associated with observed 400-m walk (P < 0.001, c = 0.85) at baseline. Prospectively, baseline leg speed and leg strength were predictive of both self-reported (P < 0.001, c = 0.79) and observed (P < 0.001, c = 0.72) ability to walk 400 m at 3 yrs.CONCLUSIONS:The profiles of attributes that are associated with self-reported vs. observed walking ability differ. The factor most consistently associated with current and future walking ability is leg speed. These results draw attention to important foci for rehabilitation.

Background—The electrocardiographic PR interval increases with aging, differs by race, and is associated with atrial fibrillation (AF), pacemaker implantation, and all-cause mortality. We sought to determine the associations between PR interval and heart failure, AF, and mortality in a biracial cohort of older adults. Methods and Results—The Health, Aging, and Body Composition (Health ABC) Study is a prospective, biracial cohort. We used multivariable Cox proportional hazards models to examine PR interval (hazard ratios expressed per SD increase) and 10-year risks of heart failure, AF, and all-cause mortality. Multivariable models included demographic, anthropometric, and clinical variables in addition to established cardiovascular risk factors. We examined 2722 Health ABC participants (aged 74±3 years, 51.9% women, and 41% black). We did not identify significant effect modification by race for the outcomes studied. After multivariable adjustment, every SD increase (29 ms) in PR interval was associated with a 13% greater 10-year risk of heart failure (95% confidence interval, 1.02–1.25) and a 13% increased risk of incident AF (95% confidence interval, 1.04–1.23). PR interval >200 ms was associated with a 46% increased risk of incident heart failure (95% confidence interval, 1.11–1.93). PR interval was not associated with increased all-cause mortality. Conclusions—We identified significant relationships of PR interval to heart failure and AF in older adults. Our findings extend prior investigations by examining PR interval and associations with adverse outcomes in a biracial cohort of older men and women.

Findings from epidemiological studies can be used to make quantitative predictions of health impacts of new developments in a land-use planning context. In UK practice, exposures that may impact on health are described in environmental statements, but the health outcomes are rarely assessed explicitly. Methods for quantitative health impact assessments (HIA) are demonstrated in two case studies: proposals to extend an airport in south-east England and to build a waste incinerator in London. Four dimensions were assessed: particulate matter and gases, airborne carcinogens, transport accidents and noise. Calculations demonstrate that the health of the exposed populations would be affected by both developments, but that the added burden of disease would be very low in comparison with that in the existing population levels. Epidemiology provides a relevant method for extending environmental impact assessment. Quantitative assessment will allow decision-making authorities to make more informed decisions on proposed developments in the context of land-use planning.

BACKGROUNDRed cell distribution width (RDW) is a quantitative measure of variability in the size of circulating erythrocytes with higher values reflecting greater heterogeneity in cell sizes. Recent studies have shown that higher RDW is associated with increased mortality risk in patients with clinically significant cardiovascular disease (CVD). Whether RDW is prognostic in more representative community-based populations is unclear.METHODSSeven relevant community-based studies of older adults with RDW measurement and mortality ascertainment were identified. Cox proportional hazards regression and meta-analysis on individual participant data were performed.RESULTSMedian RDW values varied across studies from 13.2% to 14.6%. During 68,822 person-years of follow-up of 11,827 older adults with RDW measured, there was a graded increased risk of death associated with higher RDW values (p < .001). For every 1% increment in RDW, total mortality risk increased by 14% (adjusted hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.11-1.17). In addition, RDW was strongly associated with deaths from CVD (adjusted HR: 1.15; 95% CI: 1.12-1.25), cancer (adjusted HR: 1.13; 95% CI: 1.07-1.20), and other causes (adjusted HR: 1.13; 95% CI: 1.07-1.18). Furthermore, the RDW-mortality association occurred in all major demographic, disease, and nutritional risk factor subgroups examined. Among the subset of 1,603 older adults without major age-associated diseases, RDW remained strongly associated with total mortality (adjusted HR: 1.32; 95% CI: 1.21-1.44).CONCLUSIONSRDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases. The biologic mechanisms underlying this association merit investigation.