The evolution of menopause and human life span.

Noteworthy data is emerging to support the existence of longevity-enabling genes. Our observations of the relationship between reproductive fitness and longevity among centenarians support theories that posit strong selective forces in the determination of how fast humans age and their susceptibility to diseases associated with ageing. Current data support the idea that there is no selective advantage for humans to have a lifespan of approximately 100 years. Rather, getting to such a very old age may be a by-product of longevity-enabling genes that maximize the length of time during which women can bear children, and during which they can increase the survival probabilities of their children and grandchildren. We thus review the literature pertaining to the relationship between reproductive fitness and longevity.

Cognitive functional status of age-confirmed centenarians in a population-based study.

The New England Centenarian Study is a population-based study of all centenarians in 8 towns near Boston, MA. Age was confirmed for 43 centenarians all alive on a designated date. To determine prevalence of dementia in centenarians, the authors analyzed neuropsychological, medical, and functional status data for 34 (79%) of the centenarians. Definition of dementia was based on the Consortium to Establish a Registry for Alzheimer's Disease criteria, and a Clinical Dementia Rating (CDR) score was formulated for each participant. Seven (21%) had no dementia (CDR score 0), and an additional 4 (12%) were assigned a CDR score of 0.5, uncertain or deferred diagnosis. The remaining 22 (64%) had at least some degree of dementia. The authors calculated Barthel Index scores to determine ability to perform activities of daily living. There was a statistically significant correlation between CDR scores and Barthel Index scores (r = -0.73). Correlation was strongest for those with no or severe dementia, with the greatest range of function measured among those with moderate dementia.

Validity of reported age and centenarian prevalence in New England.

INTRODUCTION: the age reported by or on behalf of centenarians may be suspect unless proven correct. We report the validity of age reports in a population-based sample of centenarians living in New England and the prevalence of centenarians in an area within the North Eastern USA. METHODS: cohort study. All centenarians in a population-based sample detected by local censuses. Ages were confirmed by birth certificate. Type of residence and whether the subject was living independently were also recorded. RESULTS: from a population of about 450,000 people, 289 potential centenarians were reported by the censuses of the eight towns participating in the study. Of these, 186 (64%) had died at the time centenarian prevalence was determined. Of the 80 still alive, 13 (16%) had incorrect birth years recorded by the censuses. The specificity of the censuses for stating the number of centenarians alive and living in the sample was 28-31%. Using additional sources, only four more centenarians were located, indicating that the sensitivity of the censuses approached 100%. We had an 83% success rate in obtaining proof of age in those families we interviewed. In all instances, age and birth order of children were an important source of corroborative evidence and in no case did we detect inconsistencies with the families' reported ages of the centenarian subjects. Therefore, there were at least 46 centenarians or approximately 1 centenarian per 10,000 people. CONCLUSIONS: age validation can be performed for most centenarians in the North Eastern USA. Self or family reports of those between the ages of 100 and 107 years were dependable.

Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions.

Quantitative information on the cell-to-cell distribution of all possible mitochondrial DNA (mtDNA) mutations in young and aged tissues is needed to assess the relevance of these mutations to the aging process. In the present study, we used PCR amplification of full-length mitochondrial genomes from single cells to scan human cardiomyocytes for all possible large deletions in mtDNA. Analysis of more than 350 individual cells that were derived from three middle-aged and four centenarian donors demonstrates that while most of the cells contain no deletions, in certain cardiomyocytes a significant portion of the mtDNA molecules carried one particular deletion. Different affected cells contained different deletions. Although similar numbers of cells were screened for each donor, these deletion-rich cells were found only in the hearts of old donors, where they occurred at a frequency of up to one in seven cells. These initial observations demonstrate the efficiency of the method and indicate that mitochondrial mutations have the potential to play an important role in human myocardial aging.

Acute care costs of the oldest old.

Caring for elderly patients in the hospital costs less as they age. Among the reasons: Their ailments are less expensive to treat, they receive less aggressive care, and they are treated in less expensive hospitals.

Centenarians prove the compression of morbidity hypothesis, but what about the rest of us who are genetically less fortunate?

For those who believe that the longer people live into old age, the longer they will live with chronic disability (the expansion of morbidity hypothesis), the current increase in average life expectancy that we are experiencing portends an even greater increase in health care costs and morbidity associated with old age. On the other hand, other scholars assert that if medical science is able to facilitate people's living to an age near or at the maximum lifespan (by curing or markedly delaying illnesses that cause premature mortality), we should observe a compression of morbidity near the end of life. Our experience in the New England Centenarian Study indicates that compression of morbidity does occur among centenarians. Demographic selection or selective survival produces a cohort of successfully aging individuals at very old age as those with illnesses that cause premature mortality are weeded out of the aging population. Unfortunately, the majority of us who are weeded out by the early to mid-eighties (the average life expectancy), succumb to illnesses that are likely to lead to an expansion of morbidity as medical science and healthier lifestyles facilitate longer life expectancies.

Acute care costs of the oldest old: they cost less, their care intensity is less, and they go to nonteaching hospitals.

BACKGROUND: The cost of acute hospital care is often believed to increase with age among older persons. Our clinical experience in the acute hospital setting suggested that people aged 90 years and older may be a distinct cohort who have different health care needs and who use health resources differently from younger aged groups. METHODS: To determine the cost of care for the oldest old and younger old patients in Massachusetts acute care hospitals, 1992 and 1993 discharge data from all nonfederal Massachusetts hospitals were examined (678 954 discharges) according to five age groups: 60 to 69 years (n=210 270), 70 to 79 years (n=256 781), 80 to 89 years (n=171 725), 90 to 99 years (n=39 170), and 100 or more years (n=1008). Average estimated total and ancillary costs per discharge and per diagnosis related group were calculated. Differences by gender and survivorship were also examined. RESULTS: Hospitalization costs peaked in the 70- to 79-year age group and declined with age thereafter. Case mix was an important determinant of this trend. Despite lower cost per stay, average length of stay was longer for the oldest age groups. Ancillary costs accounted for 53% of the total costs per stay among the 60- to 69-year-olds and only 32% among the 100 or more-year- olds. For hospitalizations during which the patient died, the average cost per discharge decreased 61%, from $16886 for 60- to 69-year-olds to $6523 for centenarians. Costs were greater for decedents than for survivors, although these differences decreased dramatically with increasing age. Those aged 80 years and older tended to be hospitalized in nonteaching hospitals. CONCLUSIONS: In the acute hospital setting, the oldest old cost less per admission than younger elderly patients. This finding must be considered when future health care costs are predicted for this fastest growing segment of our population.

Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease.

Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is associated with a high likelihood of developing Alzheimer's disease (AD). The pathophysiologic basis of this genetic influence is unknown. We reasoned that understanding the influence of apoE epsilon 4 on the clinical course and neuropathological features of AD may provide tests of potential mechanisms. We carried out a prospective longitudinal study to compare the age of onset, duration, and rate of progression of 359 AD patients to apoE genotype. Thirty-one of the individuals who died during the study were available for quantitative neuropathological evaluation. Statistically unbiased stereological counts of neurofibrillary tangles (NFTs) and A beta deposits were assessed in a high-order association cortex, the superior temporal sulcus. Analysis of clinical parameters compared with apoE genotype showed that the epsilon 4 allele is associated with an earlier age of onset but no change in rate of progression of dementia. Quantitative neuropathological assessment revealed that NFTs were strongly associated with clinical measures of dementia duration and severity but not with apoE genotype. A beta deposition, by contrast, was not related to clinical features but was elevated in association with apoE epsilon 4. These results indicate that apoE epsilon 4 is associated with selective clinical and neuropathological features of AD and support hypotheses that focus on an influence of apoE epsilon 4 on amyloid deposition.

Higher respiratory infection rates on an Alzheimer's special care unit and successful intervention.

OBJECTIVE: To determine the rates of various types of infections on an Alzheimer's special care unit (ASCU) compared with the rates found on traditional nursing home units. Because patients on the ASCUs are allowed to wander throughout the unit and typically come into contact with each other more frequently, we hypothesized that the rate of communicable infections such as upper respiratory infections are significantly higher than on other units where patients are more easily isolated when sick. METHODS: A 4-year retrospective case control study, 1990-1993. SETTING: A metropolitan long-term care skilled nursing facility. Three floors are traditional nursing care units (123 beds), and one floor is the ASCU (41 beds). PRIMARY OUTCOME: Annual nosocomial infection rates per 10,000 patient days were measured for six types of infection during the 1990-1993 study period. Data were segregated by location of infection, either the traditional nursing units or the ASCU. In 1992, patients on the Alzheimer's unit were placed in smaller activity groups, and an education program for the control of infectious agents was provided to the unit's staff. RESULTS: The relative order of prevalence for the different infection types remained constant during the 4 years. The most common type of infection for all 4 years of the study period was urinary tract infection (UTI), followed by upper respiratory infection (URI), Lower respiratory tract infection (LRI), cutaneous infection, gastrointestinal (GI) infection, and eye infection. Of these various infections, only URI rates remained consistently higher on the ASCU versus the traditional nursing unit over the 4-year study period (in years 1990, 1991, and 1993; these differences were statistically significant, P < .05). In 1992, the year in which nursing interventions to curb the relatively high rates of URI on the ASCU took place, the rates of URI on the two unit types were not statistically different. CONCLUSIONS: This study suggests that an inherent risk of ASCUs is an increased exposure to highly contagious infections such as upper respiratory infections. An intervention program effective in decreasing this risk to the level of traditional nursing units is proposed. A prospective study is needed to confirm these findings.

Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals.

Recent genetic studies show that the apolipoprotein E epsilon 4 allele (ApoE-epsilon 4) is a risk factor for Alzheimer's disease (AD). If ApoE-epsilon 4 individuals develop AD as they get older, we would expect a decrease in ApoE-epsilon 4 allele frequency with increasing age. We found a marked decline in ApoE-epsilon 4 allele frequency with advancing age in both AD and cognitively normal controls (p < 0.003), although in all age groups the ApoE-epsilon 4 allele was overrepresented (p < 0.0001). Nonetheless, a few cognitively normal nonagenarians were ApoE-epsilon 4 positive. Thus, our data support two new conclusions: (1) the ApoE-epsilon 4 associated risk for AD is age-dependent, probably due to censoring by the earlier development of AD in ApoE-epsilon 4 individuals, and (2) despite the ApoE-epsilon 4 associated risk for AD, it is possible to reach extreme old age with normal cognition.

The relationship between age, gender and cognitive performance in the very old: the effect of selective survival.

OBJECTIVE: To determine the prevalence of cognitive disability as a function of advanced age and gender in elderly nursing home and community-dwelling populations. Since cognitive dysfunction is associated with increased mortality, we hypothesized that selective survival results in a decreased prevalence of cognitive disability in the oldest old. DESIGN: Cohort study. An analysis of 6-month longitudinal data obtained from a national probability sample of older persons in 260 nursing homes (n = 1951) and 2-year-longitudinal data obtained from a sample of community-dwelling older persons (n = 2947). MEASURES: In the nursing home sample, the primary outcome measure was cognitive performance score. In the community sample, cognitive performance was determined using the results of three orientation questions and assessment of decision-making ability. Cognitive performance and subsequent survival, controlling for various disease states and demographic factors, were examined in three age cohorts of men and women (ages 65-79, 80-89, 90-99). RESULTS: In the nursing home sample, the cognitive performance of very old men (> or = 90 years) was better than that of younger men (aged 80-89 years, P < 0.05) and very old women (age > or = 90 years, P = 0.001). Among 80-89-year-olds with poor cognitive performance, the 6-month mortality rate was higher in men than in women (38% vs 19%, P = 0.001). However, the mortality rates of men and women with good cognitive performance were not statistically different in any age group. Proportional-hazards regression analysis demonstrated that poor cognitive performance remained a powerful predictor of death among men aged 80-89 years with a relative risk of 2.7 (95% Cl, 1.19-3.17; P = 0.0006) after controlling for covariates. Results from the community sample lent support to our findings: within each age group, mortality rates for men and women with intact cognitive performance were not statistically different. However, in the two older age groups, the mortality rates of subjects with impaired cognitive performance were significantly greater for men than for women (P < 0.01 for both age groups). CONCLUSIONS: Decreased cognitive performance is significantly associated with mortality among elderly men. Survival by men who have relatively intact cognitive function results in a population of oldest men, those aged 90-99 years, with cognitive performance scores better than younger men or similarly-aged women. The same selective survival phenomenon was not observed among women. Thus, there may be less cognitive disability among very old men than previously expected.

Analysis of cutaneous delayed-type hypersensitivity reaction and T cell proliferative response in elderly nursing home patients: an approach to identifying immunodeficient patients.

Clinical experience suggests the delayed-type hypersensitivity (DTH) skin test lacks sensitivity in assessing the integrity of systemic cell-mediated immunity (CMI) or the status of recent or remote mycobacterial infections in elderly nursing home residents. In an attempt to clarify this issue, DTH reaction to purified protein derivative (PPD), tetanus toxoid and Candida albicans was compared with circulating thymus-derived lymphocyte (T cell) proliferation (TCP) to stimulation with PPD and anti-CD3 antibody in 24 randomly selected nursing home residents. The DTH reaction and the TCP response correlated reasonably well among the DTH reactors but poorly among DTH nonreactors, suggesting there may be age-related immunologic changes in the skin itself. Also, the DTH skin test to PPD alone was found to be a poor index of the integrity of systemic CMI.