Antidepressant Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study.

BACKGROUND: Few studies have compared the risk of recurrent falls across various antidepressant agents-using detailed dosage and duration data-among community-dwelling older adults, including those who have a history of a fall/fracture. OBJECTIVE: To examine the association of antidepressant use with recurrent falls, including among those with a history of falls/fractures, in community-dwelling elders. METHODS: This was a longitudinal analysis of 2948 participants with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Any antidepressant medication use was self-reported at years 1, 2, 3, 5, and 6 and further categorized as (1) selective serotonin reuptake inhibitors (SSRIs), (2) tricyclic antidepressants, and (3) others. Dosage and duration were examined. The outcome was recurrent falls (≥2) in the ensuing 12-month period following each medication data collection. RESULTS: Using multivariable generalized estimating equations models, we observed a 48% greater likelihood of recurrent falls in antidepressant users compared with nonusers (adjusted odds ratio [AOR] = 1.48; 95% CI = 1.12-1.96). Increased likelihood was also found among those taking SSRIs (AOR = 1.62; 95% CI = 1.15-2.28), with short duration of use (AOR = 1.47; 95% CI = 1.04-2.00), and taking moderate dosages (AOR = 1.59; 95% CI = 1.15-2.18), all compared with no antidepressant use. Stratified analysis revealed an increased likelihood among users with a baseline history of falls/fractures compared with nonusers (AOR = 1.83; 95% CI = 1.28-2.63). CONCLUSION: Antidepressant use overall, SSRI use, short duration of use, and moderate dosage were associated with recurrent falls. Those with a history of falls/fractures also had an increased likelihood of recurrent falls.

Associations of obesity and body fat distribution with incident atrial fibrillation in the biracial health aging and body composition cohort of older adults.

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.

Association Between Unrecognized Myocardial Infarction and Cerebral Infarction on Magnetic Resonance Imaging.

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.

Age-associated declines in complex walking task performance: the Walking InCHIANTI toolkit.

OBJECTIVES: To describe a set of complex walking tasks (CWTs) that can be used to evaluate mobility and to characterize age- and sex-specific performance on these tests. DESIGN: A population-based study of persons living in the Chianti geographic area (Tuscany, Italy). SETTING: Community. PARTICIPANTS: One thousand two hundred twenty-seven persons (aged 20-95) selected from the city registries of Greve and Bagno a Ripoli (Tuscany, Italy). MEASUREMENTS: Gait velocity (m/s) was measured during 13 walking tests (Walking InCHIANTI Toolkit (WIT)) used to examine walking ability under a range of conditions and distances. Other measures included performance on the Short Physical Performance Battery and self-reported health and functional status, including disability in activities of daily living. RESULTS: Age-associated differences on the WIT were reflected in the number of older adults unable to complete CWTs and a decrease in gait velocity. For all tasks, decrements in walking speed with increasing age were significantly larger at aged 65 and older. Performance on CWTs was highly variable and could not be explained by usual gait speed measured under low-challenge conditions alone. CONCLUSION: CWTs may provide important insight into mobility function, particularly in persons with normal or near-normal usual gait speed. Further research is needed to elucidate the specific physiological mechanisms that contribute to declining performance on CWT with increasing age.

Frailty and Risk of Cardiovascular Diseases in Older Persons: The Age, Gene/Environment Susceptibility-Reykjavik Study.

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 Susceptibility-Reykjavik 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.

Atrial Fibrillation and Declining Physical Performance in Older Adults: The Health, Aging, and Body Composition Study.

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.

Walking may be related to less vascular stiffness in the Activity Counseling Trial (ACT).

BACKGROUND: The ACT was a clinical trial of various patient education and counseling interventions to increase physical activity in sedentary primary care populations. It provided the opportunity to measure the effect of increasing physical activity on aortic pulse wave velocity (APWV), a measure of vascular stiffness, in a relatively healthy middle-aged population. The effects of the interventions, as well as the impact of walking and correlates such as older age and maximal oxygen uptake (VO2max), on APWV were assessed. METHODS: The participants in this study were a subset of the 874 persons recruited for the ACT. Information about self-reported physical activity and disease status was collected at baseline (464 persons), 6-month (528 persons), and 24-month (555 persons) intervals. Physiological measures included APWV, systolic blood pressure, and other correlates. RESULTS: In multivariate analyses, the various treatment arms did not have a significant effect on APWV. However, walking in hours per day was associated with slower APWV times or less stiffness (P = .03). This was significant for women and consistent but not significant for men. In addition, age, clinic site, race, systolic blood pressure, and VO2max were independently associated with APWV. CONCLUSIONS: Increased walking frequency over a 24-month period was predictive of reduced vascular stiffness in ACT. The more significant result for walking frequency in women than in men might be caused by the presence of a low Vo2max or physical activity threshold for an effect of walking on APWV, which most women achieved but most men had surpassed at the start of the study. Although needing confirmation because this was a secondary analysis, modest physical activity may have a beneficial effect on large vessel structure.

Risk Factors Associated With Incident Cerebral Microbleeds According to Location in Older People: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

IMPORTANCE: The 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. OBJECTIVE: To investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location. DESIGN, SETTING, AND PARTICIPANTS: We 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. EXPOSURES: Lifestyle 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 MEASURES: Incident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep. RESULTS: During 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 RELEVANCE: Lifestyle 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.

Cerebral Small Vessel Disease and Association With Higher Incidence of Depressive Symptoms in a General Elderly Population: The AGES-Reykjavik Study.

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.

Diabetes, peripheral neuropathy, and lower-extremity 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 (ß=-0.99; p<0.01), decreased walking speed (ß=-0.1m/s; p<0.01), decreased nerve conduction velocity (ß=-1.7m/s; p<0.01), and increased neuropathy (ß=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.

What physical attributes underlie self-reported vs. observed ability to walk 400 m in later life? An analysis from the InCHIANTI Study.

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.

Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition study.

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.

Vitamin D and risk of cognitive decline in elderly persons.

BACKGROUND: To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. METHODS: We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. RESULTS: The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. CONCLUSION: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

Magnetization transfer imaging, white matter hyperintensities, brain atrophy and slower gait in older men and women.

OBJECTIVE: To assess whether markers of micro- and macrostructural brain abnormalities are associated with slower gait in older men and women independent of each other, and also independent of health-related conditions and of behavioral, cognitive and peripheral function. METHODS: Magnetization transfer ratio [MTR], white matter hyperintensities [WMH], brain atrophy [BA] and brain infarcts [BI] were measured in 795 participants of the AGES-Reykjavik Study cohort (mean 75.6 years, 58.9% women). RESULTS: In women, lower MTR, higher WMH and BA, but not BI, remained associated with slower gait independent of each other and of other covariates. In men, WMH and BA, but not MTR or BI, remained associated with slower gait independently of each other. Only muscle strength, executive control function and depression test scores substantially attenuated these associations. INTERPRETATIONS: MTR in older adults may be an important additional marker of brain abnormalities associated with slower gait. Studies to explore the relationship between brain micro- and macrostructural abnormalities with gait and the role of mediating factors are warranted.