Concomitant cerebrovascular (CV) lesions increase risk 1 and severity 2 of clinical dementia in patients meeting neuropathological criteria for Alzheimer's disease (AD).1,2 Japanese-American men participating in the Honolulu-Asia Aging Study (HAAS) had less frequent and lower densities of neuritic plaques (NPs) than similarly aged white men.3 Even among decedents in this cohort with moderate to severe dementia, NP densities were less than reported for white male dementia subjects. Whether coexistent CV lesions increase the likelihood of clinical dementia in individuals with sparse NP and neurofibrillary tangles (NFTs) is unknown.The postmortem series of the HAAS offers an ideal opportunity to study the possibility that decedents with negligible densities of NP and NFT could be at increased risk for crossing the threshold to clinical dementia if they have coexistent CV lesions. This report evaluates the presence (alone and in various combinations) of NP, NFT, and CV lesions in brains of cognitively normal, marginal, and demented decedent Japanese-American men.

Numerous case series have addressed the concern that cancer therapy may damage germ cells, leading to clinical disease in offspring of survivors. None has documented an increased risk. However, the methodological problems of small series make it difficult to draw firm conclusions regarding the potential of cancer treatments to damage the health of future offspring. We conducted a large interview study of adult survivors of childhood cancer treated before 1976. Genetic disease occurred in 3.4% of 2,198 offspring of survivors, compared with 3.1% of 4,544 offspring of controls (P=.33; not significant); there were no statistically significant differences in the proportion of offspring with cytogenetic syndromes, single-gene defects, or simple malformations. A comparison of survivors treated with potentially mutagenic therapy with survivors not so treated showed no association with sporadic genetic disease (P=.49). The present study provides reassurance that cancer treatment using older protocols does not carry a large risk for genetic disease in offspring conceived many years after treatment. With 80% power to detect an increase as small as 40% in the rate of genetic disease in offspring, this study did not do so. However, we cannot rule out the possibility that new therapeutic agents or specific combinations of agents at high doses may damage germ cells.

Neuropathologic confirmation and NP density among decedents with clinical AD in this population-based study were lower than reported by referral centers and similar to reports from two other community studies. Ethnic differences in propensity for amyloid deposition as well as differences in clinical severity and representativeness of cases might contribute to these findings.

In a retrospective cohort study of survivors of cancer and of controls, we estimated the risk of infertility after treatment for cancer during childhood or adolescence. We interviewed 2283 long-term survivors of childhood or adolescent cancer diagnosed in the period from 1945 through 1975, who were identified at five cancer centers in the United States. Requirements for admission to the study were diagnosis before the age of 20, survival for at least five years, and attainment of the age of 21. In addition, 3270 controls selected from among the survivors' siblings were interviewed. Cox regression analysis showed that cancer survivors who married and were presumed to be at risk of pregnancy were less likely than their sibling controls to have ever begun a pregnancy (relative fertility, 0.85; 95 percent confidence interval, 0.78 to 0.92). Radiation therapy directed below the diaphragm depressed fertility in both sexes by about 25 percent. Chemotherapy with alkylating agents, with or without radiation to sites below the diaphragm, was associated with a fertility deficit of about 60 percent in the men. Among the women, there was no apparent effect of alkylating-agent therapy administered alone (relative fertility, 1.02) and only a moderate fertility deficit when alkylating-agent therapy was combined with radiation below the diaphragm (relative fertility, 0.81). Relative fertility in the survivors varied considerably according to sex, site of cancer, and type of treatment; these factors should be taken into consideration in counseling survivors about the long-term consequences of disease.