Jeanne Y. Wei

Increased gait unsteadiness in community-dwelling elderly fallers

OBJECTIVE To test the hypothesis that quantitative measures of gait unsteadiness are increased in community-dwelling elderly fallers. STUDY DESIGN Retrospective, case-control study. SETTING General community. PARTICIPANTS Thirty-five community-dwelling elderly subjects older than 70 years of age who were capable of ambulating independently for 6 minutes were categorized as fallers (age, 82.2 +/- 4.9 yrs [mean +/- SD]; n = 18) and nonfallers (age, 76.5 +/- 4.0 yrs; n = 17) based on history; 22 young (age, 24.6 +/- 1.9 yrs), healthy subjects also participated as a second reference group. MAIN OUTCOME MEASURES Stride-to-stride variability (standard deviation and coefficient of variation) of stride time, stance time, swing time, and percent stance time measured during a 6-minute walk. RESULTS All measures of gait variability were significantly greater in the elderly fallers compared with both the elderly nonfallers and the young subjects (p < .0002). In contrast, walking speed of the elderly fallers was similar to that of the nonfallers. There were little or no differences in the variability measures of the elderly nonfallers compared with the young subjects. CONCLUSIONS Stride-to-stride temporal variations of gait are relatively unchanged in community-dwelling elderly nonfallers, but are significantly increased in elderly fallers. Quantitative measurement of gait unsteadiness may be useful in assessing fall risk in the elderly.

Postprandial Reduction in Blood Pressure in the Elderly

We evaluated the effects of a meal on systolic blood pressure and heart rate in elderly institutionalized subjects (mean age +/- S.E.M., 87 +/- 1) with and without histories of syncope and in young normal subjects. Pulse and blood pressure were measured before the test meal and at intervals for up to 60 minutes afterward. By 35 minutes mean systolic blood pressure had declined a maximum of 25 +/- 5 mm Hg in 10 elderly subjects with syncope and 24 +/- 9 mm Hg in 10 elderly subjects without syncope (P less than 0.03); the level then stabilized without further change until 60 minutes. There were no changes in blood pressure in 11 young subjects or in elderly subjects not given a meal. The postprandial change in systolic pressure was not related to medications or diagnoses. Compensatory cardioacceleration was minimal in the elderly, suggesting impaired baroreflexes. Our observations show that postprandial reductions in blood pressure may predispose the elderly to symptomatic hypotension.

Footswitch system for measurement of the temporal parameters of gait

Gait analysis relies upon accurate measurement of initial and end foot contact times. These times act as a reference point for correlating all other gait data and as a mean of distinguishing normal and pathologic gait. We have developed a simple, inexpensive footswitch system that provides accurate estimates of the start and end of stance phase for sequential steps. The estimates of the beginning and end of stance phase do not require custom footwear, extensive calibration, or precise placement of the sensor within the shoe. The system is based on a commercially available transducer and can be readily reproduced for use in a laboratory setting for less than

The Power of Ageism on Physical Function of Older Persons: Reversibility of Age-Related Gait Changes

50. We describe this system, as well as its validation. To assess the accuracy of this footswitch system, we compared footswitch based estimates of initial and end foot contact times with those obtained using a force platform as 10 people took 30 steps (10 each at slow, normal and fast walking rates) across a force platform. Both estimates coincided within +/- 10 ms (mean: 0 +/- 3 ms; N = 300) for the start of stance phase and within +/- 22 ms (mean: -1 +/- 8 ms; N = 300) for the end of stance phase. For stance duration, the differences ranged from -24 to 28 ms (mean: 1 +/- 10 ms; N = 300). In combination, these measures can be used to estimate stance duration to within 3% of force plate determined values for steps with stance durations ranging from 446 to 1594 ms. Estimates of swing and stride duration also are within 5% of force plate determined values. This system should therefore prove to be a useful tool for augmenting laboratory based investigations of gait.

Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues

OBJECTIVE: To test the hypothesis that age‐associated changes in physical function, particularly walking performance, are influenced by ageism and that the activation of positive stereotypes of aging can partially reverse these changes.

Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension.

Using single-cell sequence analysis, we discovered that a high proportion of cells in tissues as diverse as buccal epithelium and heart muscle contain high proportions of clonal mutant mtDNA expanded from single initial mutant mtDNA molecules. We demonstrate that intracellular clonal expansion of somatic point mutations is a common event in normal human tissues. This finding implies efficient homogenization of mitochondrial genomes within individual cells. Significant qualitative differences observed between the spectra of clonally expanded mutations in proliferating epithelial cells and postmitotic cardiomyocytes suggest, however, that either the processes generating these mutations or mechanisms driving them to homoplasmy are likely to be fundamentally different between the two tissues. Furthermore, the ability of somatic mtDNA mutations to expand (required for their phenotypic expression), as well as their apparently high incidence, reinforces the possibility that these mutations may be involved actively in various physiological processes such as aging and degenerative disease. The abundance of clonally expanded point mutations in individual cells of normal tissues also suggests that the recently discovered accumulation of mtDNA mutations in tumors may be explained by processes that are similar or identical to those operating in the normal tissue.

Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.

BackgroundAlthough postprandial hypotension is a common cause of falls and syncope in elderly persons and in patients with autonomic insufficiency, the pathophysiology of this disorder remains unknown. Methods and ResultsWe examined the hemodynamic, splanchnic blood pool, plasma norepinephrine (NE), and heart rate (HR) power spectra responses to a standardized 400-kcal mixed meal in 11 healthy young (age, 26±5 years) and nine healthy elderly (age, 80±5 years) subjects and 10 dysautonomic patients with symptomatic postprandial hypotension (age, 65±16 years). Cardiac and splanchnic blood pools were determined noninvasively by radionuclide scans, and forearm vascular resistance was determined using venous occlusion plethysmography. In healthy young and old subjects, splanchnic blood volume increased, but supine blood pressure remained unchanged after the meal. In both groups, HR increased and systemic vascular resistance remained stable. Forearm vascular resistance and cardiac index increased after the meal in elderly subjects, whereas these responses were highly variable and of smaller magnitude in the young. Young subjects demonstrated postprandial increases in low-frequency HR spectral power, representing cardiac sympathoexcitation, but plasma NE remained unchanged. In elderly subjects, plasma NE increased after the meal but without changes in the HR power spectrum. Patients with dysautonomia had a large postprandial decline in blood pressure associated with no change in forearm vascular resistance, a fall in systemic vascular resistance, and reduction in left ventricular end diastolic volume index. HR increased in these patients but without changes in plasma NE or the HR power spectrum. Conclusion1) In healthy elderly subjects, the maintenance of blood pressure homeostasis after food ingestion is associated with an increase in HR, forearm vascular resistance, cardiac index, and plasma NE. In both young and old, systemic vascular resistance is maintained. 2) Dysautonomic patients with postprandial hypotension fail to maintain systemic vascular resistance after a meal. This impairment in vascular response to meal ingestion may underlie the development of postprandial hypotension. 3) The measurement of mean HR or plasma NE does not adequately characterize autonomic cardiac control. Power spectral analysis suggests an impairment in the postprandial autonomic modulation of HR in healthy elderly and dysautonomic subjects, possibly predisposing to hypotension when vascular compensation is inadequate.

Syncope in institutionalized elderly: The impact of multiple pathological conditions and situational stress

Cardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression of c-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of beta- to alpha-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca(2+)-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal alpha-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac alpha-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress.

Neutrophilia and congestive heart failure after acute myocardial infarction

We conducted a prospective study to identify clinical factors which predispose institutionalized elderly to syncope. Over 3 years, 97 patients (mean age = 87 +/- 6 y) developed syncope. On clinical evaluation, diagnoses fell into two categories: specific diseases including myocardial infarction (6%) and aortic stenosis (5%); and situational stresses including drug-induced hypotension (11%), postprandial syncope (8%), defecation syncope (7%) and postural hypotension (6%). Clinical variables derived from the history, physical examination, and laboratory evaluation of these patients were compared to those of 118 non-syncopal age-matched subjects evaluated in similar fashion. Multivariate analysis identified five independent statistically significant correlates of syncope: coronary artery disease (p = 0.0003), functional impairment (p = 0.006), postural blood pressure reduction (p = 0.003), aortic stenosis (p = 0.008), and insulin therapy (p = 0.03). Syncope patients were more likely than controls to have two or more coexistent factors (p = 0.0001). Syncope in institutionalized elderly is often due to the interaction of multiple coexistent clinical abnormalities which impair cardiovascular compensation for common situational stresses.

Clinical Implications of Physiological Changes in the Aging Heart

BACKGROUND Inflammation associated with acute myocardial infarction (AMI) is frequently marked by a peripheral leukocytosis and relative neutrophilia. Whether this process may contribute to the development of postinfarction congestive heart failure (CHF) is not established. The objective of this study was to examine the association between hospital admission peripheral total leukocyte count and the neutrophil percentage and the subsequent development of CHF in patients with AMI. The study was designed as a retrospective cohort study in the setting of a tertiary referral hospital. Participants included 185 patients discharged with a diagnosis of AMI between May 1 and Sept 30, 1996. METHODS AND RESULTS Outcome measures included clinical episodes of CHF with confirmatory chest roentgenogram findings and/or echocardiographic evidence of contractile dysfunction. Multivariable logistic regression analyses were performed to examine the relation between the total leukocyte count, neutrophil percentage, and the development of CHF in the first 4 days after AMI while controlling for baseline characteristics and early therapeutic interventions. Thirty-one percent of the cohort had a leukocyte count >11.0 x10(9)/L on admission to the hospital; 65% had a neutrophil percentage >65%, and 61% had a lymphocyte percentage </=25%. CHF developed in 43% of the cohort. Of these, 92. 5% had relative neutrophilia (neutrophil percentage >65%) compared with 45% of those in whom CHF did not develop. Multivariable analysis revealed a highly significant association between relative neutrophilia and the subsequent development of CHF (odds ratio 14.3; 95% confidence interval 5.2 to 39.3). CONCLUSIONS Relative neutrophilia on admission to the hospital in patients with AMI is significantly associated with the early development of CHF. This association may help in the identification of individuals at high risk who might benefit from more aggressive interventions to prevent or reduce the risk of CHF.