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Lewis H Kuller

Publications and source records attributed to Lewis H Kuller.

At least 91 records · Page 5Linked to original sources
PubMed2004

Predictors of falling cholesterol levels in older adults: the Cardiovascular Health Study.

PURPOSE: To estimate 4-year change in serum total cholesterol levels in a population-based sample of older adults and identify independent predictors of cholesterol decline. METHODS: Prospective study of 2837 adults aged 65 years and older with serum cholesterol measured in 1992-1993 and 1996-1997. RESULTS: Mean serum cholesterol levels declined 6.3 mg/dl between the two examinations. Declines were greater in white (-7.3 mg/dl) than black (-1.4 mg/dl) participants and in those in good/excellent health (-0.9 mg/dl) vs. fair/poor health (-3.1 mg/dl; both p < 0.01). Factors associated with greater decline on multivariate analysis included age, male gender, and higher white cell count, albumin, and baseline cholesterol. Cholesterol levels declined 2.0 mg/dl per 6 year increment in baseline age and 6.8 mg/dl more in men than women after adjustment for other factors. C-reactive protein levels were unrelated to cholesterol change. CONCLUSION: Declining cholesterol levels were associated with male gender, advanced age, weight loss, and white blood cell count but not with C-reactive protein levels. The role of declining cholesterol synthesis, due to as yet undefined age-related changes or to cytokine-mediated reductions related to illness, should be examined to help clarify the mechanisms of the sometimes marked declines in cholesterol levels observed at advanced ages.

Black or African American↗
PubMed2004

Biochemical responses of healthy subjects during dietary supplementation with L-arginine.

Dietary supplements of L-arginine, a substrate for nitric oxide synthases, may promote formation of nitric oxide and thus may be of clinical benefit. However, the optimal level of L-arginine supplementation is unclear. The objective of this study was to evaluate the response of healthy individuals to increasing doses of L-arginine (as free acid). Twelve healthy subjects were recruited and instructed to take L-arginine for 1-week periods at daily doses of 3, 9, 21, and 30 g. At baseline and at the end of each week, 24-hour urine and fasting blood samples were collected, and weight, diastolic blood pressure, and systolic blood pressure were recorded. Samples were analyzed for L-arginine, L-citrulline, glycine, L-lysine, L-ornithine, asymmetric dimethy L-arginine, symmetric dimethy L-arginine, glucose, insulin (serum), creatinine, cGMP (urine), and total nitrates (serum and urine). Ten subjects reported adverse side effects at initial L-arginine doses of 21 g/day (five subjects) or 30 g/day (five subjects), respectively. Blood pressure and weight did not change during the supplementation period. Of the individual biochemical measures, only L-arginine, glycine, and L-ornithine concentrations changed significantly. The mean concentration of L-arginine reached a peak during supplementation at 9 g/d; however, individuals differed markedly in their response. Availability of L-arginine, relative to that of asymmetric dimethy L-arginine, increased significantly at both 9 g/day and 21 g/day. Mean values indicate that supplementation with 9 g/day of L-arginine, a dose associated with minimal adverse side effects, is sufficient to increase circulating L-arginine concentrations. However, subjects varied widely in their responses, indicating that L-arginine supplementation needs to be tailored to individuals.

Arginine↗
PubMed2004

Ethnic differences in atherosclerosis, cardiovascular disease and lipid metabolism.

PURPOSE OF REVIEW: Comparison of risk factors and cardiovascular disease among racial and ethnic groups is a powerful approach to study genetics and lifestyle, or environmental interactions. RECENT FINDINGS: Most, mean or median, cardiovascular risk factor levels are similar among black and white people. There are much greater differences in the distribution of risk factor level within a specific race and ethnic group than between US populations. There are also very large differences in levels of risk factors for coronary heart disease between specific ethnic migrant populations such as comparing black people in Africa with those in the US, or Japanese people in Japan with those in Hawaii and California. Differences in distribution of risk factors and disease between race and ethnic group are a function of the frequency of specific genotypes and interaction with environmental factors. Several of the most important differences between racial groups are higher blood pressure, lower triglycerides and higher HDL cholesterol among blacks, higher prevalence of diabetes and insulin resistance among Mexican Americans and American Indians, and higher triglyceride levels among the Japanese. SUMMARY: Further studies of racial and ethnic differences should focus on unique phenotypes and genotypic differences, international and migrant studies and large enough sample sizes to provide robust results. The sprinkling of a percentage of minority participants in each study is worthless. The study of racial and ethnic differences in disease and detection of risk factor levels must be based on solid hypotheses that can evaluate the interaction of lifestyle and possible genetic attributes. Many of the reported ethnic differences in risk factors and disease in US populations are primarily a function of differences in education, socioeconomic variations, and utilization of preventive and clinical treatments.

Arteriosclerosis↗
PubMed2004

Postbariatric surgery deaths, which fall under the jurisdiction of the coroner.

Obesity has attained epidemic proportions in the United States, with more than 50% of adults classified as overweight or obese. If untreated, morbidly obese patients have a 1 in 7 chance of reaching normal life expectancy. The surgical treatment of obesity has emerged as the most effective treatment modality in long-term weight control and has become increasingly popular, with attendant postoperative complications and death. We performed a cross-sectional, coroner based, 2-year retrospective review of archival case records for decedents who died following bariatric surgery for the treatment of obesity to identify underlying causes of death and forensic characteristics of this cohort. Fifteen (0.5%) out of 3097 archival cases died following bariatric surgery, with approximately 73% of decedents dying within 6 months of surgery. The underlying causes of death in 80% of decedents were natural comorbidities of obesity, with cardiovascular diseases (33%) being the most frequent causes of death, followed by gastrointestinal diseases (20%), acute pulmonary thromboembolism (13%), and acute bacterial pneumonia (13%). The majority of decedents were white females who remained morbidly obese after bariatric surgery. Only 2 decedents died of direct inadvertent/accidental surgical complications.

Acute Disease↗
PubMed2004

Incidence and prevalence of dementia in the Cardiovascular Health Study.

OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort. DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia. SETTING: Four U.S. communities. PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years. MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD. RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%). CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.

Black or African American↗
PubMed2004

Lipoprotein levels are associated with incident hypertension in older adults.

OBJECTIVES: To determine the relationship between baseline measures of serum lipoproteins and incident hypertension in older adults. DESIGN: Prospective cohort study. SETTING: Pittsburgh, Pennsylvania, site of Systolic Hypertension in the Elderly Program (SHEP). PARTICIPANTS: One hundred eighty-seven men and women (mean age 71.3), normotensive (systolic blood pressure (SBP) <160 mmHg, diastolic blood pressure (DBP) <90 mmHg) at baseline, were followed annually over 8 years as an ancillary study to the SHEP. MEASUREMENTS: Hypertension development, defined as initiation of antihypertensive therapy or SBP greater than 160 mmHg or DBP greater than 90 mmHg. Lipoprotein measures included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, triglycerides, and apolipoproteins 1, 2, and B. RESULTS: Over 8 years, 44 participants developed hypertension, for a Kaplan-Meier cumulative incidence rate of 31% (95% confidence interval (CI)=23-39%). Cumulative incidence rates were highly associated with baseline SBP, ranging from 8% in those with baseline SBP less than 120 mmHg to 70% in those with SBP of 140 to 159 mmHg. Other univariate associations included higher DBP, pulse pressure (P <.01 for both), triglycerides (P=.03), apolipoprotein B (P=.03), and lower HDL-C (P=.04) and HDL(3)-C (P=.02). In multivariate Cox regression analysis, higher baseline SBP (relative risk (RR)=1.8 per 10 mmHg, 95% CI=1.5-2.3) and lower HDL(3)-C (RR=0.8 per 5 mg/dL, 95% CI=0.42-1.0) remained significant independent predictors of time to hypertension. CONCLUSION: Older adults with abnormal serum lipoproteins are at increased risk of developing hypertension. Clinical trials exploring the effects of the modification of lipoprotein levels on hypertension incidence rates are needed.

Aged↗
PubMed2004

Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists.

OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists. DESIGN: Prospective cohort study. SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina. PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older. MEASUREMENTS: Adjudicated incident CHF. RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22% of men and 8% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5% used alpha antagonists during follow-up, with no observed increase in CHF risk. CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.

Adrenergic alpha-Antagonists↗
PubMed2004

Relationship of visceral adipose tissue to recurrence of adenomatous polyps.

OBJECTIVES: Insulin is a growth factor for colorectal cancer. Visceral adipose tissue (VAT) is strongly associated with insulin levels, and insulin and visceral obesity have been associated in cohort studies with colorectal cancer. The aim of this investigation was to determine whether VAT is associated with recurrence of adenomatous polyps, the precursor to colorectal cancer. METHODS: As an ancillary study to the Polyp Prevention Trial, a randomized clinical trial that evaluated the effect of a low-fat, high-fiber, high vegetable and fruit diet on adenomatous polyp recurrence, subjects at one clinical center underwent measurement of VAT with a single-slice CT scan through the L4-L5 interspace. The scan was performed around the time of the subject's year 4 colonoscopy that determined adenoma recurrence. RESULTS: Of 119 subjects, 44 of 84 men (52%) and 16 of 35 women (46%) had a recurrent adenoma (p= 0.51). Body mass index (BMI) and weight at baseline and at year 4 colonoscopy were unrelated to adenoma recurrence. In a multivariate model including visceral fat quartile, remote history of polyps, gender, age, and randomization group, only remote history of polyps was statistically significantly associated with recurrent adenoma with a relative risk of 4.6 (95% CI 1.7, 12.4, p= 0.001). There was no consistent monotonic trend of increased or decreased risk of recurrence as one ascended quartiles of adipose tissue for visceral, subcutaneous, or total abdominal fat. CONCLUSION: In this study, no association between visceral adipose tissue and adenomatous polyp recurrence was observed. Further study and exploration of the role of VAT in adenoma progression is required.

Adenomatous Polyps↗
PubMed2004

Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk.

Preeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Epidemiological evidence suggests that women who experience preeclampsia are at a greater risk of hypertension and heart disease later in life compared with women who had normal pregnancies. Our objective was to determine whether endothelial function is impaired in postpartum women with a history of preeclampsia in their first pregnancy. We measured forearm blood flow (FBF) by venous occlusion plethysmography in 50 healthy women: 16 with prior preeclampsia, 14 with a prior normotensive pregnancy, and 20 never pregnant controls. The postpartum women participated 6-12 mo after delivery. Heart rate (HR) and blood pressure (BP) were concurrently monitored on the contralateral arm. Hemodynamic variables were assessed at baseline and during a mental stress test known to elicit endothelium-dependent vasodilatation. We found that baseline FBF, HR, systolic BP, and diastolic BP did not significantly differ among the groups, whereas mean arterial pressure in the preeclamptic group was greater than that of the normal pregnancy group (P = 0.03). Stress-induced FBF (percent change over baseline) was reduced in the preeclamptic group compared with both the normal pregnancy and never pregnant groups (P = 0.06) and was significantly attenuated compared with women with prior normal pregnancies (91% vs. 147%, P = 0.006). These data demonstrate that women with a history of preeclampsia exhibit impaired endothelial function up to 1 yr postpartum. This observation may explain their increased risk for hypertension and cardiovascular disease.

Adolescent↗
PubMed2004

Islet cell autoimmunity in a triethnic adult population of the Third National Health and Nutrition Examination Survey.

Markers of humoral islet cell autoimmunity, such as autoantibodies (AAs) against the 65-kDa isoform of GAD (GAD65), serve as determinants of risk for autoimmune diabetes. Despite the high prevalence of diabetes in U.S. racial and ethnic minority adult populations, little is known concerning the prevalence of GAD65 AA in these groups. We estimated the prevalence of GAD65 AA in 1,064 diabetic and 1,036 nondiabetic participants who were 40-90 years of age from the Third National Health and Nutrition Examination Survey (NHANES III), which provides a representative ethnic sample of the U.S. diabetic population. The prevalence of GAD65 AA was higher in diabetic participants compared with nondiabetic participants in non-Hispanic whites (n = 920; 6.3% vs. 2.0%; P = 0.001) and non-Hispanic blacks (n = 534; 3.7% vs. 1.3%; P = 0.08) but not in Mexican Americans (n = 646; 1.2% vs. 2.6%; P = 0.18). Among diabetic non-Hispanic whites and non-Hispanic blacks, being GAD65 AA positive was associated with lower BMI and C-peptide (P < 0.05). These results may reflect the outcome of an autoimmune process leading to beta-cell destruction/dysfunction in non-Hispanic white and non-Hispanic black adult diabetic patients as it occurs in a similar manner in type 1 diabetes. Among diabetic Mexican Americans, the lower prevalence of GAD65 AA suggests a lower frequency of autoimmune-related diabetes.

Aged↗
PubMed2004

Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes.

OBJECTIVE: Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O). RESEARCH DESIGN AND METHODS: Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (-10.3 +/- 1.3 vs. -8.9 +/- 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis. RESULTS: Weight loss resulted in substantial improvement (P < 0.001) in HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 0.4 mg. min(-1). kg(-1) fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Delta-154 +/- 22 vs. Delta-51 +/- 33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87 +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32 +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (r = -0.41; P < 0.01) but not with weight loss per se. CONCLUSIONS: At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS.

Adipose Tissue↗
PubMed2004

Elevated prostate-specific antigen levels up to 25 years prior to death from prostate cancer.

OBJECTIVES: We tested the hypothesis that prostate-specific antigen (PSA) levels would be higher among prostate cancer deaths as compared with controls over time in the 25-year follow-up of the Multiple Risk Factor Intervention Trial of participants ages 35-57 at entry. METHODS: The initial stored serum samples were collected in 1973-1975 and the mean length of follow-up to prostate cancer death was 17 years. RESULTS: There were 63 prostate cancer deaths and 63 controls matched by age, clinical site, and length of follow-up. The mean PSA level for prostate cancer decedents was 2.84 ng/ml as compared with 1.10 ng/ml for controls (P = 0.002 for difference). There were nine men who died from prostate cancer and no controls with PSA levels > 4 ng/ml. Risk of prostate cancer death increased with increasing PSA levels, with increased risk observed even at moderate levels of PSA. Many of those with high PSA levels in 1973-1975 died from prostate cancer many years after the elevated PSA. CONCLUSIONS: PSA levels measured from blood obtained before the introduction of widespread PSA testing were a strong predictor of prostate cancer death over 25 years of follow-up. Studies of prostate cancer etiology and chemoprevention need to focus on middle-aged or younger men with longer follow-up.

Adult↗
PubMed2003

C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.

BACKGROUND: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT. METHODS AND RESULTS: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study. The hazard ratio of incident ischemic stroke was estimated by Cox proportional hazards regression. During 10.2 years of follow-up, 469 incident ischemic strokes occurred. The adjusted hazard ratios for ischemic stroke in the 2nd to 4th quartiles of baseline CRP, relative to the 1st quartile, were 1.19 (95% CI 0.92 to 1.53), 1.05 (95% CI 0.81 to 1.37), and 1.60 (95% CI 1.23 to 2.08), respectively. With additional adjustment for carotid IMT, there was little confounding. The association of CRP with stroke was significantly different depending on IMT (P<0.02), with no association of CRP with stroke among those in the lowest IMT tertile and a significant association among those with higher levels of IMT. CONCLUSIONS: We conclude that elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid IMT. The association of CRP with stroke is more apparent in the presence of a higher carotid IMT. CRP and carotid IMT may each be independent integrals in determining the risk of ischemic stroke.

Aged↗
PubMed2003

Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals.

OBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events. BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women. RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine. CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.

Aged↗
PubMed2003

Prospective study of alcohol consumption and risk of dementia in older adults.

CONTEXT: Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults. How alcohol consumption affects the incidence of dementia is less clear. OBJECTIVE: To determine the prospective relationship of alcohol consumption and risk of dementia among older adults. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study, a prospective, population-based cohort study in 4 US communities. The controls were frequency-matched on age, death before 1999, and their attendance of a 1998-1999 clinic. Participants in this study underwent magnetic resonance imaging (MRI) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999. MAIN OUTCOME MEASURES: Odds of incident dementia, ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption, assessed by self-reported intake of beer, wine, and liquor at 2 visits prior to the date of the MRI. RESULTS: Compared with abstention, the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 (95% confidence interval [CI], 0.41-1.02); 1 to 6 drinks, 0.46 (95% CI, 0.27-0.77); 7 to 13 drinks, 0.69 (95% CI, 0.37-1.31); and 14 or more drinks, 1.22 (95% CI, 0.60-2.49; P for quadratic term =.001). A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E epsilon4 allele. We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia. CONCLUSIONS: Compared with abstention, consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults.

Aged↗