Andrea Z. LaCroix

Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial.

CONTEXTnExercise training for patients with Alzheimer disease combined with teaching caregivers how to manage behavioral problems may help decrease the frailty and behavioral impairment that are often prevalent in patients with Alzheimer disease.nnnOBJECTIVEnTo determine whether a home-based exercise program combined with caregiver training in behavioral management techniques would reduce functional dependence and delay institutionalization among patients with Alzheimer disease.nnnDESIGN, SETTING, AND PATIENTSnRandomized controlled trial of 153 community-dwelling patients meeting National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer Disease and Related Disorders Association criteria for Alzheimer disease, conducted between June 1994 and April 1999.nnnINTERVENTIONSnPatient-caregiver dyads were randomly assigned to the combined exercise and caregiver training program, Reducing Disability in Alzheimer Disease (RDAD), or to routine medical care (RMC). The RDAD program was conducted in the patients home over 3 months.nnnMAIN OUTCOME MEASURESnPhysical health and function (36-item Short-Form Health Surveys [SF-36] physical functioning and physical role functioning subscales and Sickness Impact Profiles Mobility subscale), and affective status (Hamilton Depression Rating Scale and Cornell Depression Scale for Depression in Dementia).nnnRESULTSnAt 3 months, in comparison with the routine care patients, more patients in the RDAD group exercised at least 60 min/wk (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.25-6.39; P =.01) and had fewer days of restricted activity (OR, 3.10; 95% CI, 1.08-8.95; P<.001). Patients in the RDAD group also had improved scores for physical role functioning compared with worse scores for patients in the RMC group (mean difference, 19.29; 95% CI, 8.75-29.83; P<.001). Patients in the RDAD group had improved Cornell Depression Scale for Depression in Dementia scores while the patients in the RMC group had worse scores (mean difference, -1.03; 95% CI, -0.17 to -1.91; P =.02). At 2 years, the RDAD patients continued to have better physical role functioning scores than the RMC patients (mean difference, 10.89; 95% CI, 3.62-18.16; P =.003) and showed a trend (19% vs 50%) for less institutionalization due to behavioral disturbance. For patients with higher depression scores at baseline, those in the RDAD group improved significantly more at 3 months on the Hamilton Depression Rating Scale (mean difference, 2.21; 95% CI, 0.22-4.20; P =.04) and maintained that improvement at 24 months (mean difference, 2.14; 95% CI, 0.14-4.17; P =.04).nnnCONCLUSIONnExercise training combined with teaching caregivers behavioral management techniques improved physical health and depression in patients with Alzheimer disease.

Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women

BACKGROUNDnInhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women.nnnMETHODSnWe investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis.nnnFINDINGSnThere were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0.48 [95% CI 0.27-0.83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs.nnnINTERPRETATIONnStatins seem to be protective against non-pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

Preventing disability and falls in older adults: a population-based randomized trial

OBJECTIVESnBecause preventing disability and falls in older adults is a national priority, a randomized controlled trial was conducted to test a multicomponent intervention program.nnnMETHODSnFrom a random sample of health maintenance organization (HMO) enrollees 65 years and older, 1559 ambulatory seniors were randomized to one of three groups: a nurse assessment visit and follow-up interventions targeting risk factors for disability and falls (group 1, n = 635); a general health promotion nurse visit (group 2, n = 317); and usual care (group 3, n = 607). Data collection consisted of a baseline and two annual follow-up surveys.nnnRESULTSnAfter 1 year, group 1 subjects reported a significantly lower incidence of declining functional status and a significantly lower incidence of falls than group 3 subjects. Group 2 subjects had intermediate levels of most outcomes. After 2 years of follow-up, the differences narrowed.nnnCONCLUSIONSnThe results suggest that a modest, one-time prevention program appeared to confer short-term health benefits on ambulatory HMO enrollees, although benefits diminished by the second year of follow-up. The mechanisms by which the intervention may have improved outcomes require further investigation.

Morbidity and disability in older persons in the years prior to death.

BACKGROUNDnA large proportion of the disease and disability which affects older persons occurs in the years just prior to death. Little prospective evidence is available which quantifies the burden of morbidity and disability during these years.nnnMETHODSnIn three community-based cohorts of persons age 65 and older, chronic conditions and disability were evaluated for the three years prior to death in 531 persons who had three annual assessments and then died within one year of the third assessment. Number of chronic conditions, prevalence of disability in activities of daily living (ADLs), and prevalence of disability on a modified Rosow-Breslau scale were determined for these decedents and compared to 8821 members of the cohorts known to have survived.nnnRESULTSnPrevalence rates of disease and disability increased during the follow-up for both decedents and survivors, with decedents generally having higher rates than survivors. Disability rates prior to death, but not the number of diseases, increased with increasing age at death. The odds ratio for disability in ADLs at any of the three assessments for decedents versus survivors ranged from 3.0 to 4.2 in the three communities. In each community the odds ratio for ADL disability was higher in women decedents versus survivors than in men decedents versus survivors.nnnCONCLUSIONSnThese results have important implications for disability levels in future older populations in which death is projected to occur at increasingly higher ages.

Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial.

The lifetime risk for osteoporotic fracture in the United States is approximately 40% in women and 13% in men. One in six U.S. women 50 years of age will eventually fracture a hip (1). Age-related bone loss accelerates in elderly men and women and is a major contributing cause of osteoporosis (2, 3). Preserving bone mass in later life is a key strategy for preventing osteoporotic fractures. Large epidemiologic studies, both prospective and casecontrol, have consistently shown that thiazide treatment is associated with an approximately 30% reduction in risk for hip fracture (4-12). Thiazide has also been associated with higher bone mineral density in both women and men (13-18). Only two randomized trials, one in 63 perimenopausal women (19) and the other in 113 postmenopausal hypertensive women (20), have measured the effect of thiazide on bone mineral density, and both suggest that thiazide resulted in some benefit. No trials have examined the effects of low-dose thiazide on bone mineral density at the hip or spine, nor have any trials included normotensive older adults or men. We conducted a randomized trial to test the effects of two low doses of thiazide on rates of bone loss in later life among healthy, normotensive women and men. Methods Participants Our study was conducted at Group Health Cooperative of Puget Sound, a large staff-model health maintenance organization in Seattle, Washington, serving 370 000 people. The target population for the trial was healthy men and women 60 to 79 years of age who were normotensive, were free of serious heart disease, were not taking hormone replacement therapy or bisphosphonates, and had baseline bone mineral density at the total hip that was within two standard deviations of the normal value for their age [Z-score 2]. We excluded potential participants if they 1) had contraindications to thiazide therapy (allergy, proteinuria, abnormal serum creatinine concentration, hyponatremia, hypokalemia, gout, or low-density lipoprotein cholesterol level>4.91 mmol/L [190 mg/dL]], 2) had conditions that would complicate thiazide treatment [alcohol abuse, serious coronary artery disease, electrocardiographic evidence of moderate ischemia or arrhythmia, use of any diuretics or antihypertensive medications, hypotension, or congestive heart failure], 3) had conditions and diseases known to influence bone loss [immobility, weight>135 kg, hepatic disease, malabsorptive conditions, hypercalcemia, metabolic bone disease, or use of corticosteroids or antineoplastic drugs], or 4) had conditions and diseases that made completion of the trial unlikely (malignant cancer or other life-threatening disease, dementia, or anticipated change in residence). Age-eligible participants were recruited through direct mailings and a local media campaign from February 1993 to September 1994. Those who expressed interest were prescreened by telephone (n =3520), and potentially eligible participants were invited to a screening visit (n =865). Of these, 320 (205 women, 115 men) were enrolled, including 304 white persons (95%), 9 Asian-American persons (2.8%), 3 Hispanic-American persons (0.9%), 2 African-American persons (0.6%), and 2 persons whose ethnicity was not specified (0.6%). The Human Subjects Review Committees at Group Health Cooperative and the University of Washington, Seattle, Washington, approved the study, and each participant provided written informed consent. Study Design, Intervention, and Blinding We conducted a double-blind, randomized, placebo-controlled trial with a follow-up of 3 years. Participants were randomly assigned to one of three study groups: placebo, 12.5 mg of hydrochlorothiazide per day, or 25 mg of hydrochlorothiazide per day. We used a program written by the study statistician to randomly assign participants to study groups on an individual basis. Randomization was stratified by sex and used equal allocation with a blocking size of nine; the blocking size was known only to the statistician. A complete randomized list was prepared with study identifiers indicated, and staff at the Group Health Cooperative pharmacy labeled each vial of medication with the study identifier. The statistician kept the random assignment in a locked cabinet, and the treatment assignments were broken only for interim monitoring and final analysis. All study personnel and participants were blinded to treatment assignment for the duration of the study. Only the study statisticians and the data monitoring committee saw unblinded data, but none had any contact with study participants. Ciba-Geigy (Suffern, New York) provided active study medication and identical-appearing placebo pills that were periodically tested for active ingredients. Participants received brochures to encourage adequate intake of dietary potassium and 1000 to 1500 mg of calcium per day. Calcium intake was evaluated at baseline and at 36 months by using the Fred Hutchinson Cancer Research Center Food Frequency Questionnaire (21). Participants were given an estimate of their baseline dietary calcium. Baseline and Follow-up Measurements Participants attended clinic visits at the time of randomization (baseline) and at 6-month intervals for 3 years. To ensure safety, a 1-month visit was conducted to evaluate symptoms, blood pressure, and serum and urine electrolyte levels. Bone mineral density was measured by a trained, certified technician with dual-energy x-ray absorptiometry using a Hologic QDR 2000 densitometer (Hologic, Inc., Bedford, Massachusetts). At baseline and at each 6-month clinic visit, bone mineral density at the total hip, the primary trial outcome specified at the proposal stage, was measured twice at the proximal femur with repositioning between scans. The average of the two measurements was used in all analyses. Single measurements of bone mineral density were also made at the posterioranterior spine (L1L4) and total body at each time point. The quality control procedures of the Fracture Intervention Trial, conducted concurrently with this trial, were in place during follow-up (22). Midway through the study, the densitometer required a new calibration wheel; this resulted in a 0.49% increase in the phantom values and in vivo shifts of 0.77% at the spine, 2.4% at the total body, and 0.18% at the hip. All subsequent measurements of the spine and total body were corrected to account for this shift. At baseline and before annual clinic visits, participants completed health questionnaires designed to measure general health, physical functioning (23), physical activity (24), current smoking, caffeine intake, alcohol consumption, and occurrence of falls and fractures. At baseline and at each 6-month clinic visit, a standard 20-item symptom questionnaire adapted from the Systolic Hypertension in the Elderly Program (25) was administered by interview. This questionnaire included ascertainment of falls, fractures, fainting, dizziness, changes in sexual functioning, and nocturia. In addition, at each clinic visit nurse interviews that used open-ended questions to monitor adverse experiences and changes in calcium intake were conducted. Falls, reported by questionnaire or interview, were classified as injurious if they required medical evaluation or caused limited functioning. Two sitting and two standing blood pressure measurements were taken. Weight was measured in kilograms by using a standard balance-beam scale. Standing height was measured in millimeters by using a wall-mounted Harpenden stadiometer. Fasting blood and 24-hour urine specimens were obtained and stored frozen at 70 C for batch analysis. Urine N-telopeptide cross-links of collagen were measured at baseline and 36 months by using radioimmunoassay (Ostex International, Seattle, Washington). Serum osteocalcin was measured at baseline and at 6, 12, and 36 months by using an immunoradiometric assay (Nichols Institute Diagnostics, San Juan Capistrano, California). Vertebral and clinical fractures were considered as exploratory outcomes because the trial was not powered to detect significant differences in them. Lateral spine radiography was performed at randomization and at the 36-month visit. When the trial was completed, the two films were examined simultaneously by an experienced physician who was blinded to treatment assignment. Vertebrae with potential fractures were measured from T4 to L4, and fracture was considered present if the anterior height was less than 20% of the posterior height. No complete compressions were identified. Incident fracture was defined as a vertebra that was shown to be fractured on the final film but not the baseline film. Clinical fractures were initially ascertained by self-report at each clinic visit and were confirmed by review of treatment records and radiology reports. Statistical Analysis Baseline characteristics of the three study groups were compared by using chi-square tests for categorical variables and analysis of variance for continuous variables. Trial outcomes were evaluated by using an intention-to-treat analysis based on all available measurements of bone mineral density, regardless of participants adherence. Change in bone mineral density at the total hip was identified as the primary trial outcome at the proposal stage, and changes in bone mineral density at the spine and total body were specified as secondary end points. Two methods of analysis were prespecified at the proposal stage. First, changes in bone mineral density at the total hip, spine, and total body, expressed as mean percentage change from baseline, were compared from 0 to 6 and 0 to 36 months by using analysis of variance. Percentage change for each participant was calculated as [(bone mineral density at follow-up time baseline bone mineral density)/baseline bone mineral density] 100. The two overlapping time periods were examined separately to determine whether the effects of hydrochlorothiazide were transient, as was reported in one small previ

Coffee Consumption and the Incidence of Coronary Heart Disease

We conducted a prospective investigation of the effect of coffee consumption on coronary heart disease in 1130 male medical students who were followed for 19 to 35 years. Changes in coffee consumption and cigarette smoking during follow-up were examined in relation to the incidence of clinically evident coronary disease in comparisons of three measures of coffee intake--base-line intake, average intake, and most recent intake reported before the manifestation of coronary disease. Clinical evidence of coronary disease included myocardial infarction, angina, and sudden cardiac death. In separate analyses for each measure of coffee intake, the relative risks for men drinking five or more cups of coffee per day, as compared with nondrinkers, were approximately 2.80 for all three measures in the univariate analyses (maximum width of 95 percent confidence intervals, 1.27 to 6.51). After adjustment for age, current smoking, hypertension status, and base-line level of serum cholesterol, the estimated relative risk for men drinking five or more cups of coffee per day (using the most recent coffee intake measure), as compared with those drinking none, was 2.49 (maximum width of 95 percent confidence interval, 1.08 to 5.77). The association between coffee and coronary disease was strongest when the time between the reports of coffee intake and the coronary event was shortest. These findings support an independent, dose-responsive association of coffee consumption with clinically evident coronary heart disease, which is consistent with a twofold to threefold elevation in risk among heavy coffee drinkers.

Functional status in coronary artery disease: a one-year prospective study of the role of anxiety and depression.

PURPOSEnAlthough coronary disease is the second most common cause of work and functional disability, little is known about the relative contributions of biomedical and psychosocial factors to this disability. This study was conducted to determine the associations of depression and anxiety with self-reported physical function and activity interference in patients with coronary artery disease.nnnMETHODSnThis was a 1-year prospective cohort study of 198 HMO members who had elective cardiac catheterization for coronary artery disease in 1992. Measures included: severity of coronary artery stenosis from cardiac catheterization reports; anxiety and depression severity using interviewer-administered Hamilton Anxiety and Depression Rating Scales; and self-reported physical function and activity interference.nnnRESULTSnAt the time of catheterization, patients self-reported physical function differed significantly by number of main coronary vessels stenosed >70% (P <0.03), by anxiety quartiles (P = 0.001), and by depression quartiles (P = 0.001). At 1 year, physical function was no longer associated with the number of main coronary vessels stenosed at baseline, but still was significantly associated with baseline anxiety (P <0.001) and depression quartiles (P = 0.01). Moreover, change in physical function scores from baseline to 12 months was associated with baseline anxiety (P <0.001) or depression (P <0.001) quartiles, but not with baseline number of occluded coronaries. Results for activity interference were similar to those for physical function. These associations were largely unchanged when corrected for age, sex, education, social class, medical versus surgical management of CAD, and degree of medical comorbidity.nnnCONCLUSIONnAnxiety and depression have a significant and persistent effect on physical function in patients with coronary artery disease. Although current treatment methods appear to neutralize the influence of coronary stenosis on physical function during the year following catheterization, this is not true for anxiety and depression.

Self-efficacy and self-reported functional status in coronary heart disease: a six-month prospective study.

Objective We examine prospectively the role of specific forms of self-efficacy in the physical and role function for patients with coronary heart disease after controlling for the effects of anxiety and depression. Methods A 6-month prospective cohort study was conducted after cardiac catheterization of 198 HMO members, demonstrating clinically significant coronary disease. Coronary disease severity was assessed through cardiac catheterization; physical function, role function, anxiety, depression, and self-efficacy were assessed through questionnaires. Results The Cardiac Self-Efficacy Scale had two factors (maintain function and control symptoms) with high internal consistency and good convergent and discriminant validity. In multiple regression models, the self-efficacy scales significantly predicted physical function, social function, and family function after controlling for baseline function, baseline anxiety, and other significant correlates. Conclusions Self-efficacy to maintain function and to control symptoms helps predict the physical function and role function, after accounting for coronary disease severity, anxiety, and depression in patients with clinically significant coronary disease. Interventions to improve self-efficacy may have a broader applicability in the heart disease population than previously appreciated.

Footwear style and risk of falls in older adults.

Objectives: To determine how the risk of a fall in an older adult varies in relation to style of footwear worn.

Biomechanical properties of shoes and risk of falls in older adults

Objectives: To determine the relationships between the biomechanical properties of shoes worn in a cohort of healthy older adults and the risk of falling.