Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: A French community-based study

In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30–50% higher in men than in women) decreases with age, toward ≈20–10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor I, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a community-based population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such “treatment” are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations.

The effects of health changes on projections of health service needs for the elderly population of the United States

The 1982–1994 National Long-Term Care Surveys indicate an accelerating decline in disability among the U.S. elderly population, suggesting that a 1.5% annual decline in chronic disability for elderly persons is achievable. Furthermore, many risk factors for chronic diseases show improvements, many linked to education, from 1910 to the present. Projections indicate the proportion of persons aged 85–89 with less than 8 years of education will decline from 65% in 1980 to 15% in 2015. Health and socioeconomic status trends are not directly represented in Medicare Trust Fund and Social Security Administration beneficiary projections. Thus, they may have different economic implications from projections directly accounting for health trends. A 1.5% annual disability decline keeps the support ratio (ratio of economically active persons aged 20–64 to the number of chronically disabled persons aged 65+) above its 1994 value, 22:1, when the Hospital Insurance Trust Fund was in fiscal balance, to 2070. With no changes in disability, projections indicate a support ratio in 2070 of 8:1—63% below a cash flow balance.

Inhibition of the ubiquitin-proteasome system in Alzheimer's disease

Alzheimer's disease is the most common cause of dementia in the elderly. Although several genetic defects have been identified in patients with a family history of this disease, the majority of cases involve individuals with no known genetic predisposition. A mutant form of ubiquitin, termed Ub+1, has been selectively observed in the brains of Alzheimer's patients, including those with nonfamilial Alzheimer's disease, but it has been unclear why Ub+1 expression should be deleterious. Here we show that Ub+1 is an efficient substrate for polyubiquitination in vitro and in transfected human cells. The resulting polyubiquitin chains are refractory to disassembly by deubiquitinating enzymes and potently inhibit the degradation of a polyubiquitinated substrate by purified 26S proteasomes. Thus, expression of Ub+1 in aging brain could result in dominant inhibition of the Ub-proteasome system, leading to neuropathologic consequences.

Changes in the prevalence of chronic disability in the United States black and nonblack population above age 65 from 1982 to 1999

Survey evidence through the early 1990s generally suggests a reduction in disability in the elderly population of the United States. Because the evidence is not fully consistent, several authors have speculated about whether disability declines will continue. This paper reports results from the 1999 National Long-Term Care Survey on disability trends from 1982 through 1999. It is found that disability continued to decline in the 1994 to 1999 period, and that the decline was greater in the 1990s than in the 1980s. The disability decline from 1982 to 1989 was 0.26% per year, from 1989 to 1994 it was 0.38% per year, and from 1994 to 1999 it was 0.56% per year. In addition, disability declined by a greater percentage for blacks than for nonblacks over the 1989 to 1999 period.

Chronic stress alters the immune response to influenza virus vaccine in older adults.

To determine whether a chronic stressor (caregiving for a spouse with a progressive dementia) is associated with an impaired immune response to influenza virus vaccination, we compared 32 caregivers' vaccine responses with those of 32 sex-, age-, and socioeconomically matched control subjects. Caregivers showed a poorer antibody response following vaccination relative to control subjects as assessed by two independent methods, ELISA and hemagglutination inhibition. Caregivers also had lower levels of in vitro virus-specific-induced interleukin 2 levels and interleukin 1beta; interleukin 6 did not differ between groups. These data demonstrate that down-regulation of the immune response to influenza virus vaccination is associated with a chronic stressor in the elderly. These results could have implications for vulnerability to infection among older adults.