Analysis of the apo E/apo C-I, angiotensin converting enzyme and methylenetetrahydrofolate reductase genes as candidates affecting human longevity.

Genetic factors are likely to affect human survival, since twin studies have shown greater concordance for age of death in monozygotic compared to dizygotic twins. Coronary artery disease is an important contributor to premature mortality in the UK. Accordingly, we have chosen genes associated with cardiovascular risk, apo E/apo C-I, angiotensin converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR), as candidates which may affect longevity/survival into old age. An association study was performed by comparing allele and genotype frequencies at polymorphic loci associated with these genes in 182 women and 100 men aged 84 years and older with 100 boys and 100 girls younger than 17 years. MTHFR allele and genotype frequencies were similar in the elderly and young populations. Apo C-I allele and genotype frequencies were significantly different in the elderly women compared to the younger sample (P < 0.05). No difference was observed in the elderly men. At the neighbouring apo E gene, we only observed a difference between genotypes in the elderly women and the young sample; however, this did not retain significance when the genotype frequencies of the young sample were adjusted to values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women. In contrast to previous studies, apo E2 was not overrepresented in the elderly men or women. Thus, the proposition that apo E2, E3 and E4 protein isoforms are themselves functionally associated with increasing risks for early death, may be too simplistic. The I/I ACE was depleted in the elderly males but not the elderly females. Furthermore, significant differences were observed between ACE genotypes in elderly men and elderly women. These data suggest that the penetrance of loci which influence survival may vary according to sex. The depletion of the ACE I/I genotype in elderly men is generally consistent with a previous study which found decreased frequencies of the I allele in French centenarians compared to younger controls. However, these results are apparently paradoxical, since others have suggested that the I allele is associated with increased cardiovascular risk. Clarification of the overall effect of a genotype on survival will be vital if therapies are to be considered which target specific genetic variants.

Analysis of alpha-1 antichymotrypsin, presenilin-1, angiotensin-converting enzyme, and methylenetetrahydrofolate reductase loci as candidates for dementia.

The genetic factors which predispose individuals to dementia in old age have not been fully defined. Although the apolipoprotein E4 allele accounts for a proportion of the genetic risk for late-onset Alzheimer disease (AD), it is neither necessary nor sufficient to cause this disease. Recent suggestions that other loci are involved in dementia risk have been supported by findings of associations of genotypes at the alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) loci with AD. We investigated these loci in two community-based aged Cambridgeshire populations: the rural Ely population (cohort 1) comprised 60 pairs of demented and nondemented elderly individuals, with a mean age of 84.2 years; and the Cambridge city population (cohort 2) comprised 81 pairs all over age 84, with a mean age of 87.3 years. Since vascular risk factors are likely to impact on dementia risk, we also examined the angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR) genes as candidates. ACE, ACT, PS-1, and MTHFR genotype and allele frequencies were not significantly different in cases and matched controls. These data support the doubts which have been raised about the involvement of the PS-1 and ACT polymorphisms in late-onset dementia.

Depression and falls among community dwelling elderly people: a search for common risk factors.

STUDY OBJECTIVE: s: Depression and falls are two common conditions that impair the health of older people. Both are relatively underdiagnosed and undertreated problems in primary care. The study objective was to investigate whether there was a common set of risk factors that could predict an increased risk of both falls and depression. DESIGN: This was a cohort study drawn from a primary care clinic, with a one year follow up. Dependent measures included: reporting two or more falls in the past year and a score of 7 or over on the S-GDS (Short Geriatric Depression Scale). A parsimonious set of risk factors was selected that predicted both outcomes based on a series of discriminant function analyses. PARTICIPANTS AND SETTING: The setting was a primary care clinic serving a mixed socioeconomic population, in Beer Sheva, Israel. The sample included 283 General Sick Fund members, aged 60 and over, who completed both baseline assessments and one year follow up interviews. MAIN RESULTS: At the one year follow up, 12% of the sample reported frequent falls in the past year and 25.5% of the sample screened positive for depressive symptoms. A set of five risk factors that included: poor self rated health, poor cognitive status, impaired ADL, two or more clinic visits in the past month, and slow walking speed (g10 seconds over five metres) was successful at discriminating between fallers and non-fallers (86% discrimination) and between those with and without depressive symptoms (76%). For every risk factor added, there was a significant increase in the proportion of respondents who had depressive symptoms. A similar result was found for falls. CONCLUSIONS: These results show that there is a common set of risk factors that increase the risk of two common outcomes in geriatric medicine, falls and depression. For a general practitioner or a geriatric physician, it might be easier to detect these risk factors than to diagnose depression or high risk for falls. When these risk factors are detected in patients the physician can then be more active in direct probing about depression and falls.

Treatment of medulloblastoma in adults.

Seventeen adult patients with medulloblastoma were treated at Rush-Presbyterian-St. Luke's Medical Center and affiliated hospital between 1969 and 1986. All patients had a surgical procedure (total excision in seven patients, partial resection in nine patients, and biopsy alone in one patient) followed by radiation therapy to the craniospinal axis. The 5-year actuarial survival rate is 77% with a disease-free survival of 58%. Five patients have relapsed in the posterior fossa, one in the brain parenchyma, and two in osseous sites. Two of the local relapses occurred more than 4 years after initial treatment. Patients undergoing "total" resection of the tumor fared better than those with partial resection or biopsy only. Local failure was uncommon with posterior fossa doses greater than 55 Gy, and there was a trend toward better local control when the radiation therapy was completed in less than 7 weeks. The histologic indicators of poor outcome were necrosis, high mitotic index, and "classical" histologic appearance.

Primary radiation therapy to T1 and T2 breast cancer following conservative surgery. Which patients should be boosted?

We reviewed 199 radiated patients at our institution (201 breasts treated) and its affiliates treated between 1978 and 1989. Of these, 157 were T1 and T2 invasive breast carcinoma. Our intent was to retrospectively compare the results of those who received standard doses of 4,500 to 5,000 cGy to the breast to those that received an additional boost to the surgical bed to a dose totaling at least 5,500 cGy. There were a total of 5 local recurrences in 159 treated breasts. (The mean follow-up time was 36 months.) Of our T1 and T2 patients with clear resection margins that were boosted, there was 1 local recurrence in 28 treated breasts. There was 1 local recurrence in the nonboosted group of 68 patients. Except for one patient, all patients with positive margins were boosted. There were 2 local recurrences in the 23 T1 and T2 breasts with positive margins that were boosted. Of the patients with uncertain margins who were not boosted, there was one local recurrence in 20 treated breasts. Of those with uncertain margins that were boosted, there were no local recurrences in 19 treated breasts. From our results, it would appear that a boost to the primary site is unnecessary if the margins of resection are negative (by either inking or if it is clearly stated in the pathology report). In those patients with uncertain margins, most were done in the years before margins were routinely inked, but generous excisional biopsies were usually done. In this latter group of patients, there also was no added benefit to boosting.

Gait and activity in the elderly: implications for community falls-prevention and treatment programmes.

Falls are the major cause of accidents in the elderly. Falls result from the interaction of medical, psychosocial and age-related changes with environmental conditions. Since many of these factors are amenable to change, theoretically many falls are preventable. As part of a multi-method community fall prevention programme we developed a gait assessment method (ELGAM). We report here on the association between ELGAM parameters and measures of social and physical activity, tested among 36 elderly community-dwelling persons. Social and physical activity were associated with only some of the gait parameters (turning head while walking and walking speed). However, the findings about gait are consistent with other research based on larger samples, and some of the findings from intervention research. Together they suggest the importance of social and physical activity in fall prevention programmes.

Validation of a fall-risk screening test, the Elderly Fall Screening Test (EFST), for community-dwelling elderly.

Falls are the most common type of injury among the elderly, and the source of both functional and psychological morbidity. The aim of this study was to validate the Elderly Fall Screening Test (EFST). In a community primary-care clinic, the members 60 years or older who were functionally independent were screened. Of the 568 elderly persons who met these criteria, 361 were interviewed once and 283 persons were re-interviewed a year later. The EFST, a five-item test, was used to divide participants into low- and high-risk groups. Concurrent criterion validity was assessed by physical examinations conducted by physicians who were blind as to the risk designation. Using data from the follow-up interview, predictive validity was assessed on both fall-related and general health measures. Based on the results of the EFST, 28% of the respondents were designated as being at high risk for falls (i.e. having a score of two or more risk items). The results of physicians' examinations corroborated the screening test results in 75% of the cases, with 83% sensitivity and 69% specificity. In the follow-up interview, the high-risk group, as compared to the low-risk group, was more likely to have high scores on EFST, a fall in the past month or year, frequent near falls, and an injurious fall. Those with high EFST scores were more likely to report four or more sick days in the past six months, a hospitalization in the past year, poor self-rated health, a decline in health in the past 6 months, and symptoms of depression. The EFST has both criterion and predictive validity. It can be useful in community-based prevention programmes with functionally independent elderly people.

Factors related to successful rehabilitation after hip fracture: a case-control study.

A case-control study was performed to evaluate factors associated with successful rehabilitation in elderly patients who sustained hip fractures. All 170 patients with fractured hips hospitalized in the geriatrics ward of the Soroka Medical Center in Beer-Sheva, Israel between 1987 and 1991 were studied. Success of rehabilitation was determined by staff evaluation of the patient's ability to walk and perform activities of daily living. The independent variables, including sociodemographic and medical variables, and mental and functional assessments, were assessed by chart reviews, staff evaluation and mental tests. One-hundred and twenty-nine patients (75.9%) were successfully rehabilitated. A normal mental state (p < 0.0001), female gender (p < 0.02) and absence of diabetes mellitus (p < 0.008) were associated significantly with successful rehabilitation.

Characterization of elderly patients in rehabilitation: stroke versus hip fracture.

PURPOSE: To compare the characteristics of elderly patients hospitalized for rehabilitation following stroke with those following hip fracture (HF). METHODS: A prospective study in a geriatrics department of a general university hospital in southern Israel. Five hundred and sixteen hospitalized elderly patients were included in the study, 221 following stroke and 295 following HF. The characteristics were compared by univariate and logistic regression analyses. RESULTS: The mean age (+/-SD) of the stroke patients was 71.7+/-7.8 years compared to 77.4+/-7.9 for HF (p < 0.000001). Fifty-three per cent of the stroke patients were women compared to 76% of the HF patients (p < 0.000001). Stroke patients had significantly lower levels of folic acid (p = 0.00002). HF patients had more hearing and visual impairments (p = 0.008 and p = 0.017, respectively), but these were related to age differences between the groups. The Folstein Minimental test result was significantly higher in the HF group (p = 0.002). There were no differences in the symptoms of depression score as measured by geriatric depression screening scale. The Functional Independent Measure scale showed a higher pre-event functional capacity among the stroke patients (p < 0.000001), but there was no difference in this scale on admission to rehabilitation or upon discharge. CONCLUSIONS: There is a difference in the nature of the stroke and HF events. When either event involves an elderly patient with a broad range of limitations and diseases, a new medical condition develops. In this condition the symptoms of depression and the functional state at admission and upon discharge are not significantly different between these groups of patients.

Junctioning adjacent fields using border films and table top measurements.

We present a technique for matching adjacent treatment fields over the spine. Our approach relies on identifying vertebral bodies and correlating their position to the table top markings present on the simulator table. The vertebral body levels are verified with films taken with the isocenter at the borders (nondivergent border films) so the "true" borders are identified. This is in contrast to using the usual divergent films, which may misrepresent the field borders with respect to the vertebral body level. An additional space between fields may be added as a precaution against overlap.

The biopsychosocial adjustment of disabled elderly: a 1-year follow-up.

The objectives of this study were to identify and compare changes in the physical, social, and structural functions and in the family relationships of elderly patients upon hospitalization in a geriatric rehabilitation unit, and 1 year after discharge to the community (in the Negev region of Israel). The study was conducted on 88 elderly people with a mean age of 74 years. The Assessment of Dependency for Long-Term Care Benefits test was used twice as the study instrument for measuring the given objectives, once during the first week following admission to the unit and once 1 year later. At the end of the year there was improvement in most activities of daily living (ADL), a decrease in social roles, an increase in the number of illnesses, greater restrictions in diet, and an increase in use of social services. Changes were observed in the structure of the family social networks, the source of the primary caregiver, and living arrangements. Changes were not observed in the perceived family relationships. In both time periods, married elderly people evaluated family relations as better than did unmarried people. However, unmarried subjects demonstrated greater improvement in physical and social functions. Also, time had a significant effect on social function. Elderly people who were ill for less than 2 months prior to admission demonstrated greater social improvement than those whose illness lasted longer.

Sociodemographic differences among members of two ethnic groups in a geriatric rehabilitation unit in Israel.

The Assessment of Dependency for Long-Term Care Benefits form was used to explore differences among 336 elderly Ashkenazi and Sephardi Jews during their first phase of recovery in a geriatric rehabilitation unit in Israel. Sephardi Jews were more likely to be younger, widowed at an earlier age, poorer, less educated, hold less prestigious jobs, and have fewer social roles. They were also more likely to be religious and to live in multigenerational households. In contrast, a higher proportion of Ashkenazi Jews owned their own houses or apartments and lived only with their spouses. No differences were observed in these two groups in terms of the number and duration of visits they received during their hospitalization; most of them had fairly extensive visits. Most of these elderly people reported having good family relationships. This perception was related to their living arrangements, number of social roles, marital situation, level of education, and identity of the main visitor during their hospitalization. Patients' social roles affected both the number of visits they received and the perceived relationships within the family.

A study of the psychosocial characteristics of patients in a geriatric rehabilitation unit in Israel.

This study characterizes the demographic backgrounds of patients in an Israeli geriatric rehabilitation unit, determines the factors associated with their family relationships and the instrumental support they received, and emphasizes the importance of social roles as a personal resource. The study population consisted of 336 low-income Jews, all of whom were immigrants. Virtually all of the subjects had a small, close support network composed mainly of their children and spouses. Their children were the most important source of instrumental support during their hospitalization. The subjects' sources of instrumental support prior to hospitalization varied, depending upon their age, gender, marital status, and social roles. Social exchange theory provided a framework for explaining their social roles. Factors found to be predictors of good family relationships were marital status, living arrangements, instrumental support, social roles, and educational level.

[Identifying the elderly at risk for falling and accompanying protocols].

Falling is one of the main problems affecting the health of the elderly. A community project was carried out to detect elderly people at high risk for falls. One of its aims was also to develop tools allowing primary care professionals to detect the elderly at risk for falling. Such a screening test in the community-dwelling elderly (EFST) and a protocol for diagnosis and treatment of the elderly at risk for falls is presented.