Larry J. Brant

Accelerated Longitudinal Decline of Aerobic Capacity in Healthy Older Adults

Background—The ability of older persons to function independently is dependent largely on the maintenance of sufficient aerobic capacity and strength to perform daily activities. Although peak aerobic capacity is widely recognized to decline with age, its rate of decline has been estimated primarily from cross-sectional studies that may provide misleading, overly optimistic estimates of aging changes. Methods and Results—To determine longitudinal rate of change in aerobic capacity and the influence of age, gender, and physical activity on these changes, we performed serial measurements of peak treadmill oxygen consumption (peak &OV0312;o2) in 375 women and 435 men ages 21 to 87 years from the Baltimore Longitudinal Study of Aging, a community-dwelling cohort free of clinical heart disease, over a median follow-up period of 7.9 years. A linear mixed-effects regression model was used to calculate the predicted longitudinal 10-year rate of change in peak &OV0312;o2, expressed in milliliters per minute, for each age decade from the 20s through the 70s after adjustment for self-reported leisure-time physical activity. A longitudinal decline in peak &OV0312;o2 was observed in each of the 6 age decades in both sexes; however, the rate of decline accelerated from 3% to 6% per 10 years in the 20s and 30s to >20% per 10 years in the 70s and beyond. The rate of decline for each decade was larger in men than in women from the 40s onward. Similar longitudinal rates of decline prevailed when peak &OV0312;o2 was indexed per kilogram of body weight or per kilogram of fat-free mass and in all quartiles of self-reported leisure-time physical activity. When the components of peak &OV0312;o2 were examined, the rate of longitudinal decline of the oxygen pulse (ie, the O2 utilization per heart beat) mirrored that of peak &OV0312;o2, whereas the longitudinal rate of heart rate decline averaged only 4% to 6% per 10 years, and accelerated only minimally with age. Conclusions—The longitudinal rate of decline in peak &OV0312;o2 in healthy adults is not constant across the age span in healthy persons, as assumed by cross-sectional studies, but accelerates markedly with each successive age decade, especially in men, regardless of physical activity habits. The accelerated rate of decline of peak aerobic capacity has substantial implications with regard to functional independence and quality of life, not only in healthy older persons, but particularly when disease-related deficits are superimposed.

γ-Glutamyltransferase as a Risk Factor for Cardiovascular Disease Mortality: An Epidemiological Investigation in a Cohort of 163 944 Austrian Adults

Background— There is evidence from recent studies that γ-glutamyltransferase (GGT) is likely to be associated with cardiovascular disease (CVD). However, few studies to date with sufficient sample size and follow-up investigated the association of GGT with CVD mortality. Methods and Results— The relation of GGT to the risk of death from CVD was examined in a cohort of 163 944 Austrian adults that was monitored for up to 17 years. To evaluate GGT as an independent predictor, Cox proportional hazards models were calculated, which adjusted for established risk factors. In both men and women, high GGT was significantly (P<0.001) associated with total mortality from CVD, showing a clear dose-response relationship. Adjusted hazard ratios (95% CI) per log GGT increase were 1.66 (1.40 to 1.98) in men and 1.64 (1.36 to 1.97) in women. In men, subgroup analyses showed that high GGT was positively associated with incident fatal events of chronic forms of coronary heart disease (P=0.009), congestive heart failure (P<0.001), and hemorrhagic (P=0.01) and ischemic stroke (P<0.001). No significant associations were observed for acute myocardial infarction (P=0.16). In women, hazard ratios suggested associations in all subgroups; however, for hemorrhagic and ischemic stroke they were not statistically significant (P=0.09 and P=0.07, respectively). In addition, subgroup analyses stratified by age revealed a stronger relationship of GGT in younger participants. Hazard ratios for total CVD were 2.03 (1.53 to 2.69) in men and 2.60 (1.53 to 4.42) in women younger than 60 years. Conclusions— This study demonstrates in a large, prospectively observed cohort that GGT is independently associated with cardiovascular mortality.

Hierarchical linear modeling analyses of the NEO-PI-R scales in the Baltimore Longitudinal Study of Aging.

The authors examined age trends in the 5 factors and 30 facets assessed by the Revised NEO Personality Inventory in Baltimore Longitudinal Study of Aging data (N=1,944; 5,027 assessments) collected between 1989 and 2004. Consistent with cross-sectional results, hierarchical linear modeling analyses showed gradual personality changes in adulthood: a decline in Neuroticism up to age 80, stability and then decline in Extraversion, decline in Openness, increase in Agreeableness, and increase in Conscientiousness up to age 70. Some facets showed different curves from the factor they define. Birth cohort effects were modest, and there were no consistent Gender x Age interactions. Significant nonnormative changes were found for all 5 factors; they were not explained by attrition but might be due to genetic factors, disease, or life experience.

Gender differences in a longitudinal study of age‐associated hearing loss

Current studies are inconclusive regarding specific patterns of gender differences in age-associated hearing loss. This paper presents results from the largest and longest longitudinal study reported to date of changes in pure-tone hearing thresholds in men and women screened for otological disorders and noise-induced hearing loss. Since 1965, the Baltimore Longitudinal Study of Aging has collected hearing thresholds from 500 to 8000 Hz using a pulsed-tone tracking procedure. Mixed-effects regression models were used to estimate longitudinal patterns of change in hearing thresholds in 681 men and 416 women with no evidence of otological disease, unilateral hearing loss, or noise-induced hearing loss. The results show (1) hearing sensitivity declines more than twice as fast in men as in women at most ages and frequencies, (2) longitudinal declines in hearing sensitivity are detectable at all frequencies among men by age 30, but the age of onset of decline is later in women at most frequencies and varies by frequency in women, (3) women have more sensitive hearing than men at frequencies above 1000 Hz but men have more sensitive hearing than women at lower frequencies, (4) learning effects bias cross-sectional and short-term longitudinal studies, and (5) hearing levels and longitudinal patterns of change are highly variable, even in this highly selected group. These longitudinal findings document gender differences in hearing levels and show that age-associated hearing loss occurs even in a group with relatively low-noise occupations and with no evidence of noise-induced hearing loss.

DNA damage and rpair with age in individual human lymphocytes

Previous biochemical studies on DNA repair competence and aging have been limited to techniques, such as alkaline elution or nucleoid sedimentation, involving mass cell populations. These techniques provide no information about the distribution of DNA damage and repair among individual cells and are unlikely to detect age-dependent changes affecting a minor fraction of the cell population. We have recently described a microgel electrophoretic assay (Singh et al., 1988) that measures, at the level of the individual cell, single-strand DNA breaks and alkali-sensitive sites. Here, we employ this method to analyze DNA damage and repair in lymphocytes isolated from the peripheral blood of 31 subjects (23 males and 8 females aged 25-91 years) and exposed in vitro to 200 rads of X-irradiation. While basal (pre-irradiation) levels of damage were independent of the age of the donor, an age-dependent increase in DNA damage was observed immediately following irradiation. For all subjects, the mean level of DNA damage was restored to pre-irradiation control levels within 2 h of incubation at 37 degrees C. However, a distribution analysis of DNA damage among cells within each sample indicated the presence of a few highly damaged cells (4-16%) in the 2-h sample, the occurrence of which was significantly more common among aged individuals. These data indicate an age-related decline in DNA repair competence among a small subpopulation of lymphocytes.

The prevalence and management of dementia and other psychiatric disorders in nursing homes.

The prevalence of psychiatric disorders among new admissions to nursing homes is unknown. Such data are needed to estimate the psychiatric needs of this population. We report the prevalence of specific psychiatric disorders in 454 consecutive new nursing home admissions who were evaluated by psychiatrists and diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised. Eighty percent had a psychiatric disorder. The commonest were dementia syndromes (67.4%) and affective disorders (10%). Also, 40% of demented patients had additional psychiatric syndromes such as delusions or depression, and these patients constituted a distinct subgroup that predicted frequent use of restraints and neuroleptics, and the greatest consumption of nursing time. These data demonstrate that the majority of nursing home residents have psychiatric disorders on admission, and that their management is often quite restrictive. Research is now needed to determine the best methods of treatment for nursing home patients with mental disorders.

Age changes in pure-tone hearing thresholds in a longitudinal study of normal human aging.

Hearing thresholds were obtained on 813 adult males (20-95 years) measured at 11 frequencies ranging from 0.125-8 kHz from pure-tone audiograms collected over a 20-year period from 1968 to 1987. Audiograms taken at two to six different ages spanning a maximum observation period of 15 years were obtained for each male belonging to one of seven different age groups (20,30,...,80 years) based on the age of initial observation. The males were participants in the Baltimore Longitudinal study of Aging (BLSA), a multidisciplinary community-based study of normal human aging. Changes in hearing thresholds occurred in all age groups during the 15-year follow-up period. For example, at 0.5 and 8 kHz for combined left and right ears there was an average longitudinal loss of 5.7-7.6 and 5.1-21.1 dB, respectively, for 20-year-olds, 10.0-12.7 and 35.2-53.0 dB for 50-year-olds, and 22.9-48.5 and 69.0-84.5 dB for 80-year-olds. As in results from previous cross-sectional studies, hearing loss in the males 70 years and older is greatest at the highest frequencies. The rate of change for these older males is faster in the speech-range frequencies 0.5-2 kHz than in the higher frequencies, since their hearing has already diminished at the high frequencies.

Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: a prospective 21-year follow-up study.

BACKGROUND The role of serum uric acid (SUA) as a risk factor for cardiovascular disease (CVD) remains controversial. Little is known about its predictive value for mortality from congestive heart failure (CHF) and stroke, particularly in elderly, post-menopausal women. METHODS The relation of SUA to risk of death from total CVD, CHF, stroke and coronary heart disease (CHD) was examined prospectively in a large cohort of 28613 elderly Austrian women (mean age 62.3 years), followed-up for a median of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independent predictor for fatal CVD events. RESULTS SUA in the highest quartile (>or=5.41 mg/dL) was significantly associated with mortality from total CVD (p<0.0001), showing a clear dose-response relationship; the adjusted hazard ratio (95%CI) in comparison to the lowest SUA quartile was 1.35 (1.20-1.52). In subgroup analyses SUA was independently predictive for deaths from acute and subacute (p<0.0001) and chronic forms (p=0.035) of CHD, yielding adjusted hazard ratios for the highest versus lowest SUA quartile of 1.58 (1.19-2.10) and 1.25 (1.01-1.56), respectively. SUA was further significantly related to fatal CHF (p<0.0001) and stroke (p=0.018); the adjusted hazard ratios for the highest versus lowest SUA quartile were 1.50 (1.04-2.17) and 1.37 (1.09-1.74), respectively. CONCLUSIONS These findings, for the first time, demonstrate that SUA is an independent predictor for all major forms of death from CVD including acute, subacute and chronic forms of CHD, CHF and stroke in elderly, post-menopausal women.

Age‐ and gender‐specific reference ranges for hearing level and longitudinal changes in hearing level

This paper presents age-specific reference ranges for hearing level and change in hearing level for men and women at 500, 1000, 2000, and 4000 Hz. The percentiles are constructed from data obtained from persons in the Baltimore Longitudinal Study of Aging who were rigorously screened for otological disorders and evidence of noise-induced hearing loss. The resulting percentile curves represent norms for changes in hearing level in the absence of any known otologic disease. These percentile curves provide a reference for detecting when a person deviates from a normal pattern of change, thus helping in diagnosing problems with hearing or in monitoring hearing in occupational settings. The smoothed means and standard deviations of the hearing levels were used to construct the longitudinal percentiles. The percentiles for cross-sectional change were constructed using the skew normal distribution to allow for the percentiles to be asymmetric on either side of the median level. These percentiles are the first reference curves that (1) provide standards for hearing level changes over periods of up to 15 years, (2) account for age differences in the distribution of hearing levels, and (3) are based on data from persons who have been systematically screened for otological disorders and evidence of noise-induced hearing loss.

Serum Erythropoietin and Aging: A Longitudinal Analysis

Objectives: To determine the changes in serum erythropoietin with age in patients with and without anemia and to assess the importance of certain comorbidities on changes in erythropoietin level and the development of anemia.