Alzheimer's disease in the NAS-NRC registry of aging twin veterans. II. Longitudinal findings in a pilot series. National Academy of Sciences. National Research Council Registry.

Over 3 years we followed 8 pairs of male twins one or both of whom had suspected Alzheimer's disease (AD) including 'mild/ambiguous' changes suggestive of incident AD. These pairs were screened in 1988 and 1989 from 339 pairs in the (US) National Academy of Sciences-National Research Council Registry (NASR) of aging veteran twins, then 61-72 years of age. Most of the suspected cases (10 of 12) had mild/ambiguous changes. Including these subjects, we had estimated the prevalence of AD in the NASR as about 2%. We now describe briefly the longitudinal evaluation of these 8 pairs. Only 1 of the 10 individuals with mild/ambiguous changes has progressed to show well-defined clinical symptoms of AD. Two others remain in their original research category, while 7 clearly do not have AD. Thus, we now estimate the 1988-1989 prevalence of AD in the NASR as 0.5%. These results contrast with other follow-up studies of mild cases from a university-based Alzheimer's clinic. We suggest that the contrasting findings reflect the nature of the samples studied, and we show that the present results are predicted by Bayesian reasoning.

A study of twins and stroke.

BACKGROUND AND PURPOSE: Although there are strong genetic contributions to coronary artery disease, only a few studies have considered heritable influences on stroke. METHODS: We investigated the role of genetic factors in stroke using the Twin Registry maintained by the National Academy of Sciences-National Research Council. The registry includes 15,948 male twin pairs born between 1917 and 1927. In 1985, 9,475 twins responded to a mailed questionnaire, which covered vascular risk factors, cardiac events, and stroke. RESULTS: Analysis of twin pairs in which both responded to the questionnaire, and a question on stroke, indicated proband concordance rates of 17.7% for monozygotic pairs and 3.6% for dizygotic pairs (relative risk = 4.3; chi 2 = 4.94, df = 1; p less than 0.05). CONCLUSIONS: This nearly fivefold increase in the prevalence of stroke among the monozygotic compared with the dizygotic twin pairs suggests that genetic factors are involved in the etiology of stroke. The twin study paradigm holds considerable promise for identifying both genetic and environmental influences on stroke.

Anatomic, metabolic, neuropsychological, and molecular genetic studies of three pairs of identical twins discordant for dementia of the Alzheimer's type.

Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests. The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin. DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins. Family pedigrees were negative for Alzheimer's disease. The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation.

Suicide in twins.

Suicide appears to cluster in families, suggesting that genetic factors may play a role in this behavior. We studied 176 twin pairs in which one or both twins had committed suicide. Seven of the 62 monozygotic twin pairs were concordant for suicide compared with two of the 114 dizygotic twin pairs (11.3% vs 1.8%). The presence of psychiatric disorder in the twins and their families was examined in a subsample of 11 twin pairs, two of whom were concordant for suicide. Eleven of these 13 twin suicide victims had been treated for psychiatric disorder, as had eight of their nine surviving cotwins. In addition, twins in 10 pairs had other first- or second-degree relatives who had been treated for psychiatric disorder. Thus, these twin data suggest that genetic factors related to suicide may largely represent a genetic predisposition for the psychiatric disorders associated with suicide. However, they leave open the question of whether there may be an independent genetic component for suicide.

Twin concordance for dishonorable discharge from the military: with a review of the genetics of antisocial behavior.

It has been hypothesized that there is a genetic component to antisocial behavior. To test this hypothesis, twin concordance for dishonorable discharge from the US military was examined among 15,924 twin pairs in the National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry, all of whom served in the US military. Of 62 dizygotic (DZ) twin pairs, at least one of whom had received a dishonorable discharge, one pair (1.6%) was concordant for dishonorable discharge; of 47 monozygotic (MZ) twin pairs, seven (14.9%) were concordant for dishonorable discharge. Concordance rates for dishonorable discharge were significantly greater for MZ vDZ twin pairs. Concordances for dishonorable discharge were not confounded by co-diagnoses of alcoholism. The results are discussed in light of research findings suggesting a genetic component to antisocial behavior.

The Vietnam Era Twin (VET) Registry: method of construction.

A Vietnam Era (1964-1975) Twin Registry of American male-male veterans born between 1939 and 1955 has been developed to provide a study sample for research evaluating the impact of Vietnam service on the medical and psychosocial aspects of health. In preparation for developing the Registry, several alternative sources of twins and methods for identifying twins were investigated. A computerized database of veterans discharged from the military after 1967 was selected as the source because it contains about 50% of the total Vietnam era veteran population, is reasonably unbiased, and provides a feasible method for identifying twins. Twins were identified using an algorithm which involved matching entries on the database for same last name, different first name, same date of birth, and similar social security number. Twin status was confirmed by review of military records. The registry, now complete, is composed of 7,400 twin pairs. It will be an important resource for future research projects.

The Vietnam Era Twin (VET) Registry: ascertainment bias.

An examination of ascertainment bias in identification of twin pairs in the Vietnam Era Twin Registry has been conducted. A complete listing of all male-male Vietnam era veteran twin pairs born in Connecticut between 1939 and 1955 was obtained (N = 150). An attempt was made to match these pairs with a listing of Vietnam era veteran twin pairs derived from the United States Department of Defense's Defense Manpower Data Center (DMDC) computer files. The results indicate that the DMDC files identified only 46.7% of the 150 Connecticut born Vietnam era veteran pairs. Statistically significant differences (P less than 0.05) between pairs found on the DMDC files and Connecticut veteran pairs missing from the DMDC files are observed for the following variables: a) year of discharge from military service, b) total length of active military service, c) branch of service, and d) foreign service. No consistent pattern of bias is observed for factors related to the physical and psychosocial health of veteran pairs. The implications of the ascertainment biases in the Vietnam Era Twin Registry are discussed.

Schizophrenia in the National Academy of Sciences-National Research Council Twin Registry: a 16-year update.

The authors present a 16-year update on schizophrenia in the National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry. As of October 1981, a recorded diagnosis of schizophrenia was equally common in monozygotic and dizygotic twins. However, probandwise concordance for schizophrenia was significantly greater in monozygotic (30.9%) than in dizygotic (6.5%) twins. Biases in zygosity determination, diagnosis, or ascertainment could not plausibly explain these results. Correction for selection effects in construction of the registry produced concordance rates for schizophrenia approaching those found in previous studies. According to registry data, genetic factors appear at least as important in the etiology of schizophrenia as in several common medical conditions, including diabetes and hypertension. Results from the NAS-NRC Twin Registry support the etiologic importance of genetic factors in schizophrenia.

Month of birth by zygosity in the NAS-NRC twin registry.

Previous results regarding a seasonality of twin births have been conflicting. Since the biology of monozygotic (MZ) twinning differs from that of dizygotic (DZ) twinning, it is possible that the seasonality of birth for these two twin types might differ. However, all previous studies examining the seasonality of birth by zygosity has estimated zygosity by Weinberg's method. In this report, the month of birth of all MZ and DZ veteran twins from the United States National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry are compared with that found for an unselected group of veterans. Zygosity in the registry has been individually assigned to all twin pairs by a well-validated method. Compared to unselected veterans, the distribution of births by months did not differ significantly for all the veteran twin pairs or for the MZ and DZ twin pairs considered separately. The distribution of month of birth of the MZ and DZ twin pairs did not differ significantly from one another. These results are not consistent with a significant seasonality of MZ, DZ, or all twin births in the United States.

Effects upon health of occupational exposure to microwave radiation (radar).

The effects of occupational experience with microwave radiation (radar) on the health of US enlisted Naval personnel were studied in cohorts of approximately 20,000 men with maximum opportunity for exposure (electronic equipment repair) and 208000 with minimum potential for exposure (equipment operation) who served during the Korean War period. Potential exposure was assessed in terms of occupational duties, length of time in occupation and power of equipment at the time of exposure. Actual exposure to members of each cohort could not be established. Mortality by cause of death, hospitalization during military service, later hospitalization in Veterans Administration (VA) facilities, and VA disability compensation were the health indexes studied, largely through the use of automated record systems. No adverse effects were detected in these indexes that could be attributed to potential microwave radiation exposures during the period 1950-1954. Functional and behavioral changes and ill-defined conditions, such as have been reported as microwave effects, could not be investigated in this study but subgroups of the living study population can be identified for expanded follow-up.

Splenectomy and subsequent mortality in veterans of the 1939-45 war.

A long-term follow-up of 740 American servicemen splenectomised because of trauma during the 1939-45 war showed a significant excess mortality from pneumonia and ischaemic heart-disease. Mortality from cirrhosis was also increased, but not significantly. The findings confirm that the risk of fatal infections is increased by asplenia; however, the risk of cancer was not increased, as it is in some other immunodeficiency states. Post-splenectomy thrombocytosis and hypercoagulability may account for the increased risk of fatal myocardial ischaemia in this group.

Relationship of cell type and lymph node metastasis to survival after resection of bronchial carcinoma.

In the completed adjuvant chemotherapy lung trials conducted by the Veterans Administration Surgical Group, the cell type was recorded in 2,341 of 2,349 curative resections; extent of lymph node involvement was known in all cases. Nodes were normal in 1,231 patients. Five- and ten-year survival computed by the life-table method was 33.7% and 20.4%, respectively. These rates were significantly greater than the 16.2% and 8.8% recorded in 1,118 patients whose nodes showed metastases. Among patients whose cell type was known, five-year survival in 484 with hilar node involvement was 17.4% and was not significantly different from 20.1% in 364 patients in whom only lobar nodes were involved. The survival was 8.9% in 268 patients with cancer in the mediastinal nodes; this was significantly worse than either of the aforementioned groups. A five-year survival of 26.8% in 1,482 patients with squamous cell carcinoma was greater than the 24.3% in 359 with adenocarcinoma and 22.4% in 500 with undifferentiated cell types, but the differences were not significant. Variations between these groups remained nonsignificant when nodes were normal and were of only borderline significance, at the 5% level, when they showed metastasis. When a curative resection has been accomplished, cell-type as classified in this study has little bearing on long-term survival, whereas the presence of node metastasis as well as its location is of the utmost importance.