Surrogate Respondents Research Articles

On the Use of Surrogate Respondents for Controls in a Case‐Control Study of Alzheimer's Disease

To examine the presence and extent of bias introduced by using surrogate respondents for healthy controls in a case-control study of Alzheimer's disease (AD). Comparative study of matched responses to questionnaire ascertaining lifestyle issues. University Hospitals/Case Western Reserve University Alzheimer Center. Controls (n = 50) were identified through the Research Registry. Surrogates (n = 50) were their healthy relatives or friends. Answers in the areas of demographic and occupational history, smoking habits, medical history, dietary intake, and leisure and work activities were recorded. The analysis was based on methods for paired data. Continuous variables were analyzed, focusing on paired differences between self and surrogate responses. For occupations and exposures, over 80% of the surrogates agreed with the subjects on over 80% of the questions. On smoking history, over 90% of the surrogates agreed with the subjects on over 70% of the questions. On leisure and work activities, over 70% of the surrogates agreed with the subjects on over 50% of the questions. There was less agreement regarding medical history. For continuous variables, most paired t-tests of zero mean difference between self and surrogate responses resulted in nonrejection of this hypothesis. Computed mean differences were not always positive or always negative. We did not find systematic under- or overreporting by the surrogates of the controls. Therefore, if there are biases in the responses of surrogates of the AD cases in our case-control study, they would not be canceled out by using surrogates for the controls.

Comparison of surrogate with self-respondents regarding medical history and prior medication use.

The self-report of medical history and medication use is a common feature of epidemiological research. In a unique re-interview study, we evaluated the concordance of medical conditions and past medication use reported in two similar interviews 5 years apart. In 196 re-interviews with the subjects themselves, and in 107 with next-of-kin of subjects who died after the first interview, agreement was good or excellent (kappa > or =0.40) for 90% (9/10) of the conditions asked about in the personal medical history for both next-of-kin and self-respondents. Agreement was excellent (kappa >0.75) for two conditions, high blood pressure and hysterectomy, among self-respondents. Self- and surrogate respondents also showed similar reproducibility for prescription medications, but next-of-kin respondents tended to have poor agreement (kappa <0.40) for over-the-counter (OTC) medications such as antacids, antihistamines, and analgesics. Next-of-kin also less reliably reported a family history of cancer. When analyses were stratified by type of surrogate respondent, concordance between the two interviews was generally higher for spouses than for other surrogate respondents. This research demonstrates that personal medical history and prescription medication use may be as reliably reported by next-of-kin as self-respondents, but suggests that additional information may be needed to validate measures of OTC medication use and family history of cancer for next-of-kin respondents, possibly through the review of hospital records.

Comparison of surrogate with self-respondents for occupational factors.

Accurate assessment of occupational history is critical in case-control studies of disease risk associated with employment. However, in some studies of rapidly fatal diseases, a surrogate or next of kin is interviewed rather than the study subject. In a unique re-interview study of subjects from a community-based case-control study originally interviewed 5 years earlier, we evaluated the level of agreement between (1) subjects and their surrogates on re-interview among those who had died since the first interview, and (2) subjects themselves and their responses at re-interview among those still living (to use as a comparison) regarding work history and specific occupational exposures. For employment start and stop dates, number of years worked, and number of jobs reported in the 1980 interview, exact agreement was poor for surrogate respondents and for self-respondents in the re-interview, with percentages ranging from 4% to 40%. Agreement was similar for surrogates and self-respondents for job and industry worked the longest, but percent of agreement among surrogates was significantly lower than among the self-respondents for job and industry worked last. Five (28%) of the kappa values for the industry in which the subject worked had high agreement (kappa > 0.75) for self-respondents and surrogates. None of the kappa statistics for materials handled by subjects in their jobs had high agreement, and 57% of the kappa statistics had poor agreement (kappa 0.0 to 0.39). This study suggests that occupational histories obtained by interview are poorly reproduced, and existing methods may need improvement to collect reliable occupational data. Further, the findings indicate that caution should be exercised when creating a job-exposure matrix based on such data.

Functional Status Before Hospitalization in Acutely Ill Older Adults: Validity and Clinical Importance of Retrospective Reports

Retrospective reports of patients' functional status before hospital admission are often used in longitudinal studies and by clinicians caring for hospitalized patients. However, the validity of these reports has not been established. Our aim was to examine the validity of retrospective reports by testing hypotheses about the relationships these measures would have with other clinical measures if they were valid. A prospective cohort study. A total of 2877 older patients (mean age 81, 36% women) hospitalized on the general medical service at two hospitals. For 1953 of the subjects, the patient was the primary respondent, whereas for 924 subjects, a surrogate was the primary respondent. Shortly after hospital admission, patients or surrogates reported whether the patient was independent in each of five activities of daily living (ADLs) on admission and at baseline 2 weeks before admission. Outcome measures included reported independence in each ADL 3 months after the hospitalization and survival to 1 year. Patients' retrospective reports of their ADL function 2 weeks before admission had a clinically plausible relationship with ADL function at the time of admission, in that patients independent in an ADL on admission rarely reported they were dependent in that ADL 2 weeks before admission (range 2-6%). Surrogates were somewhat more likely than patients to report that patients independent on admission were dependent 2 weeks before admission (range 5-14%). Retrospective reports of prehospitalization ADL function demonstrated strong evidence of predictive validity for both patients' and surrogates' reports. For example, among patients dependent in bathing on admission, patients who were reported as independent 2 weeks before admission were much more likely than those reported as dependent 2 weeks before admission to be independent 3 months after hospitalization (68% vs 20%, P < .001 for patient respondents; 30% vs 5%, P < .001 for surrogate respondents). Similarly, among patients dependent in bathing on hospital admission, survival 1 year after hospitalization was much higher in patients who were independent in bathing 2 weeks before admission than patients who were dependent 2 weeks before admission (76% vs 59%, P < .001 for patient respondents; 60% vs 45%, P < .001 for surrogate respondents). Results were similar for each of the other four ADLs. In a logistic regression model controlling for the number of ADLs reported as dependent on admission, the number of ADLs reported as dependent 2 weeks before admission was significantly associated with 1-year mortality among both patient (odds ratio (OR) = 1.39 per dependent ADL, 95% confidence interval (CI) - 1.26-1.54) and surrogate (OR = 1.14, 95% CI = 1.06-1.24) respondents. Hospitalized patients' assessments of their ability to perform ADLs before their hospitalization have evidence of face and predictive validity. These measures are strong predictors of important health outcomes such as functioning and survival. In particular, among patients dependent in ADL function on hospital admission, these results highlight the prognostic importance of inquiring about the patient's functional status before the onset of the acute illness.

Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis

A meta-analysis was carried out to calculate a pooled estimate of relative risk of lung cancer following exposure to environmental tobacco smoke (ETS) and to determine whether there was any heterogeneity in the pooled estimates according to selected characteristics of the studies. A total of 35 case-control and five cohort studies providing quantitative estimates of the association between lung cancer and exposure to ETS published between January 1981 and March 1999 were identified. Using fixed- and random-effects models, we calculated pooled estimates of relative risk for exposure to ETS from subjects’ parents (during childhood), spouses, and coworkers. As well, we investigated whether the pooled estimates of relative risk varied by study location, degree of control of potential confounding variables, proportion of cases confirmed histologically, proportion of surrogate respondents, nonresponse rates, and year of publication. The relative risk of lung cancer among non smoking women ever exposed to ETS from their husbands’ smoking was 1.20 (95% confidence interval (CI): 1.12-1.29). The pooled relative risk was 1.19 (95% CI: 1.10–1.29) for case-control studies and 1.29 (95% CI: 1.04–1.62) for cohort studies. In various subgroup and meta-regression analyses, we found no statistically significant differences by selected characteristics of the studies. In addition, we found that the risk of lung cancer increased consistently with increasing levels of exposure. The 11 studies reporting relative risks among male non smokers yielded a pooled relative risk of 1.48 (95% CI: 1.13–1.92) for ever exposed to ETS, and the relative risk of lung cancer for ever being exposed to ETS at work was a 1.16 (95% CI: 1.05–1.28). These results are consistent with the hypothesis that exposure to ETS increases the risk of lung cancer. While there may be alternative explanations to the data, it is more likely that the observed association is not an artifact and that ETS causes lung cancer in non smokers.

Study Design for a Case Control Investigation of Cellular Telephones and Other Risk Factors for Brain Tumors in Adults

The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case-control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age ≥ 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the eases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene-environment interactions.

Indicators of Nutritional Risk in a Rural Elderly Hispanic and Non-Hispanic White Population: San Luis Valley Health and Aging Study

Objective To describe the prevalence of nutritional risk factors among elderly residents in a rural Hispanic and non-Hispanic white population. Design A geographically based survey of community-dwelling elderly adults. Subjects/setting From July 1993 to July 1995, all Hispanic persons older than 65 years and an age-stratified, random sample of 69% of non-Hispanic white persons, from 2 Colorado counties, were invited to participate in a study of functional impairment and disability (81% responded). After exclusion of 184 respondents who required a surrogate respondent and 8 with missing diet data, the study consisted of 1,006 subjects. Interviews included questions similar to the Nutrition Screening Initiative checklist, a 21-item food frequency questionnaire, and anthropometric measures. Statistical analyses performed Gender- and ethnicity-specific, age-adjusted prevalence for each risk factor was estimated by use of logistic regression. Results Hispanic participants were more likely than non-Hispanic whites to report inadequate intake of vegetables, problems with teeth or dentures that limited the kinds and amounts of food eaten, difficulty preparing meals, and lack of money needed to buy food. Hispanic women reported nutritional risk factors more often than Hispanic men, although anthropometric markers indicated that Hispanic men may be at higher risk of nutritional deficiency. Applications/conclusions Hispanic men and women had a higher prevalence of nutritional risk factors than non-Hispanic whites. Intervention programs targeting rural, elderly Hispanics should aim to ensure that basic nutrition needs (access to food, help preparing meals, and adequate dental care) are being met. Community programs to increase activity levels and consumption of nutrient-dense foods are recommended. J Am Diet Assoc. 1999;99:315–322.

Wherein lies the truth? Assessment of agreement between parent proxy and child respondents.

The epidemiological study of diseases of childhood presents a special situation in that the principal respondent is almost always a person other than the index. Use of proxy respondents in paediatric epidemiology has been little studied compared with the use of surrogate respondents for adults. Agreement between responses from children and their parents to identical questions about the children was assessed in a case-control study of childhood melanoma in Queensland, Australia. Weighted kappa and log-linear modelling techniques were used to measure agreement for ordinal data. Highest agreement was found for reports of unchanging physical characteristics such as eye colour (kappa = 0.88), hair colour (kappa = 0.76), and for history of residing on a farm (kappa = 0.84). Moderate agreement was seen for density of facial freckling (kappa = 0.62), propensity to sunburn (kappa = 0.46) and tanning ability (kappa = 0.47). Variables with low levels of agreement between parent proxy and child respondents included density of freckling on the shoulders (kappa = 0.28) and degree of moliness of the skin at age 5 years (kappa = 0.24). Agreement did not vary according to age or sex of the children. Log-linear modelling was performed to determine the type and magnitude of components of agreement. Agreement between responses from children and parent proxies depends largely upon the type of information sought, rather than characteristics of the respondents.

Use of surrogate respondents in studies of stroke and dementia

A study was performed to determine the misclassification of information on exposure when surrogate informants are interviewed. Information from nondementia patients admitted to a geriatric ward was compared with that obtained from the patients' family members or friends (informants). Thirty-seven patients were recruited (17 with current or previous stroke, and 20 no history of stroke). Information on past medical and family history, cigarette smoking and alcohol consumption was collected using a questionnaire that was administered independently to patients and informants. For nonstroke patients, agreement on smoking and alcohol consumption at different ages was generally good. Informants reported slightly lower smoking and alcohol intake than patients: 1.3 fewer total pack-years (95% CI, −3.8, +6.5) and 2.7 fewer units/week (95% CI, −1.5, +6.9), respectively. For stroke patients, informants tended to report a greater smoking consumption at all ages, and a slightly higher alcohol consumption. Informants reported an excess of 7.4 total pack-years (95% CI, −1.2, +16.0) and 2.19 units/week (95% CI, −1.0, +5.3). Agreement for medical history was good, except for hypertension. There was poor agreement for family medical history. The impact of misclassification is discussed.

Familial pancreatic cancer in south Louisiana.

Previous researchers have found high mortality and incidence rates for pancreatic cancer in the Acadiana region of southern Louisiana. While lifestyle practices such as pork and alcohol consumption and a familial trend have been linked to pancreatic cancer, cigarette smoking is the only established risk factor for pancreatic cancer. Therefore, a retrospective, descriptive study was conducted to explore lifestyle risk factors and the familial trend in pancreatic cancer. The Familial Pancreatic Cancer Questionnaire (FPCQ) was used to collect data on demographics, tobacco and alcohol use, dietary history, and medical history. A surrogate respondent (family member) for 31 pancreatic cancer subjects completed the FPCQ. Race and gender specific incidence rates (IR) for pancreatic cancer in Acadiana were calculated. Results showed that mean IRs for pancreatic cancer for Caucasian and African-American males and females were higher than national SEER rates. Pancreatic cancer and lung cancer were the most frequently reported cancers among subjects' first degree relatives. The majority (65%) of the subjects smoked. A positive family history for pancreatic cancer was found in this study with five (16%) of the pancreatic cancer subjects having one or more first degree relatives with pancreatic cancer. This percent is twice that found by previous researchers.

Comparability of Information on Pesticide Use Obtained from Farmers and Their Proxy Respondents

A methodologic study in Iowa was conducted to compare information onagricultural factors obtained by interview from farmers and their proxy respondents.In-person interviews were sought from 100 farmer surrogate pairs and obtained from85 pairs. Respondents provided information on farm commodities produced, details onpesticide use, and pesticide application practices. The sensitivity and specificity ofsurrogate responses were over 90% for information such as years operating a farm oramount of corn or livestock production in recent years. Accuracy was lower forindividual pesticides used and details about pesticide application practices (sensitivitiesfrom 40 to 70% and specificities from 50 to 90%). Surrogate respondents were unableto provide as much information and reported lower prevalences of pesticide use thanthe farmers themselves. The correlation between prevalences of individual pesticidesreported by farmers and by surrogates was 0.91 for herbicides and 0.78 for livestockinsecticides. The loss of information from using proxy respondents would typically biasestimates of relative risk downward toward the null value and could result in falsenegative interpretations. Although use of surrogates undoubtedly introducesmisclassification of agricultural exposures, the degree of misclassification is generally inthe range observed for other factors obtained by interview in epidemiologic studiessuch as information on diet and details of tobacco and alcohol use.

Reliability of environmental and occupational exposure data provided by surrogate respondents in a case-control study of Parkinson's disease

This study used data provided by 40 non-demented Parkinson's disease patients and 101 community controls, and by their 110 spouses and 31 adult children to assess the reliability of surrogate-provided rural environmental and occupational exposure information on the index subjects. The level of overall raw agreement between the index subjects and the spouse or adult child surrogates varied from 50.0 to 100.0% for the case-surrogate group and from 80.6 to 96.0% for the control-surrogate group. We did not detect significant differences in overall raw agreement between the case-surrogate and control-surrogate groups or between the spouse-surrogate and adult child-surrogate groups, for any of the variables studied. Considering all index subjects and their surrogates, the level of overall raw agreement was 80.3% for well water consumption, 82.3% for farm living, 85.8% for agricultural work, 87.1% for use of pesticides, 87.9% for field crop farming and 91.9% for use of fertilizers. However, the kappa estimates were lower, varying from 0.48 (SE = 0.20) for fertilizer use to 0.66 (SE = 0.11) for crop farming. The level of specific agreement was 52.2% for fertilizer use, 64.0% for pesticide use, 71.4% for agricultural work, 73.9% for crop farming, 80.9% for farm living, and 83.6% for well water consumption. The overall findings of this study support the use, if necessary, of spouses and adult children of index subjects as surrogate respondents in case-control studies of rural environmental and occupational exposures and Parkinson's disease and, possibly, other neurologic diseases. Specific agreement seems to be a better index of reliability than overall agreement in studies where exposure is rare.

Patterns of pesticide use among farmers: implications for epidemiologic research.

Epidemiologic studies of farmers have linked pesticides with certain cancers. Information on exposures from many of these studies was obtained by interview of farmers or their next-of-kin. The reliability and validity of data on pesticide use obtained by recall, often years after the event, have been questioned. Pesticide use, however, is an integral component in most agricultural operations, and the farmers' knowledge and recall of chemicals used may be better than for many other occupations. Contrary to general belief, many farmers typically use only a few pesticides during their lifetimes and make only a few applications per year. Data from U.S. Department of Agriculture surveys indicate that herbicides are applied to wheat, corn, soybeans, and cotton and that application of insecticides to corn averages two or fewer times per year. In epidemiologic studies at the National Cancer Institute, the proportion of farmers ever reporting lifetime use of five or more different chemicals was 7% for insecticides and 20% for herbicides. Surrogate respondents have often been used in epidemiologic studies of cancer; they are able to recall pesticide use with less detail than the farmers themselves. The pesticides reported by surrogates were the same as reported by subjects themselves, but with less frequency. Comparison of reporting by cases and controls provided no evidence of case-response (differential) bias; thus, inaccurate recall of pesticide use by subjects or surrogates would tend to diminish risk estimates and dilute exposure-response gradients.

An assessment of the usefulness of demographic data provided by surrogate respondents in a case-control study of Parkinson's disease

This study, based upon data from 40 non-demented Parkinson's disease cases and 101 community controls, and similar data provided by either the spouse ( n = 110) or an adult child ( n = 31) of each index subject, attempted to assess the usefulness of various demographic data provided by the surrogate respondents for the index subjects. The data were collected by personal interview using a structured questionnaire specifically developed for this study. Ninety-one percent of the index subjects and their surrogates provided information on the annual family income and 98% provided other demographic information. The analysis was done by three groups: the case-surrogates, the control-surrogates and the combined index subject-surrogates, and within each group by the two types of surrogates for the index subjects: the spouse vs adult child. The overall percent agreement between the index subjects and their surrogates varied from moderate for annual family income (54.1%), to good for educational level (61.6%) and to excellent for ethnic origin (82.6%), for age ± 1 year (97.9%) and for marital status (100.0%). No significant differences in agreement were found for any of these demographic variables either between the case-surrogate group and the control-surrogate group, or between the spouse surrogates and the child surrogates. These findings suggest that spouses and adult children can provide valid information and are equally reliable informants concerning the demographic characteristics of index subjects in a case-control study of Parkinson's disease and, possibly, of other diseases.

Enviromental Tobacco Smoke and Lung Cancer Risk in Nonsmoking Women

Exposure to environmental tobacco smoke (passive smoking) has been suggested to be a cause of lung cancer, although early epidemiologic studies have produced inconsistent results. We conducted an epidemiologic case-control study to assess the relationship between exposure to environmental tobacco smoke and lung cancer risk among women who have never smoked (i.e., having smoked for a total of less than 6 months or having smoked less than 100 cigarettes in their lifetimes). Case patients (n = 210) were women with histologically confirmed primary carcinomas of the lung who were lifetime nonsmokers. They were identified through hospital tumor registries and the Florida Cancer Data System of the Statewide Cancer Registry. Community-based control women (n = 301) were also lifetime nonsmokers and were identified through random-digit dialing. Details on childhood and adulthood exposures to environmental tobacco smoke were ascertained through interviews with the study participants themselves or with surrogate respondents. Risks were calculated in terms of smoke-years, defined as the sum of the reported years of exposure to cigarette smoke from each smoker in the household. The risk of lung cancer more than doubled for women who reported 40 or more smoke-years of household exposure during adulthood (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1-5.3) or 22 or more smoke-years of exposure during childhood and adolescence (OR = 2.4; 95% CI = 1.1-5.4). Risks were highest for non-adenocarcinoma lung cancers, although modest elevations in risk were also observed for adenocarcinomas. When a surrogate respondent other than the patient's husband provided information on exposure, the risk estimates were considerably lower. These findings suggest that long-term exposure to environmental tobacco smoke increases the risk of lung cancer in women who have never smoked.

Relationship between alcohol intake, age of onset and duration of Alzheimer's disease: A pilot survey of 84 autopsy‐confirmed cases

AbstractLittle is known about the drinking habits of individuals who develop Alzheimer's disease. A pilot survey of 84 autopsy‐confirmed Alzheimer cases was carried out to explore a possible role of alcohol consumption in the onset and duration of Alzheimer's disease. Information on the drinking habits of deceased patients for a 15‐year period prior to the onset of the disease was obtained from a surrogate respondent (next of kin) and from the patients' medical records. Alzheimer patients' drinking patterns were comparable to those of the general population. Patients with a history of alcohol abuse did not develop Alzeimer's disease at an earlier age than abstainers or occasional, light or moderate drinkers. Although not statistically significant, duration of survival in Alzheimer's disease was a few years shorter in patients with a history of alcohol abuse.

Comparability of Data obtained from Farmers and Surrogate Respondents on Use of Agricultural Pesticides

Information from surrogates is increasingly being used in case-control studies to evaluate cancer risks from pesticides; however, little is known about the quality of this type of information. To address this concern, the authors compared interview data collected in 1987 from 95 male Iowa farmers and their wives or other surrogates on the use of specific agricultural pesticides. Agreement between direct and surrogate interviews was excellent (83-100%) for responses to dichotomous (yes/no) questions regarding past agricultural use of specific pesticides. Although there were more discrepancies for detailed questions (e.g., the number of days per year on which each pesticide was handled), responses from spouses appear to be adequate for epidemiologic studies of pesticides and cancer.

Men, women and primary lung cancer —A Saskatchewan personal interview study

In a previous study conducted by mail questionnaire and with a large proportion of surrogate responders, we found differences in smoking habits, age at diagnosis, tumour cell type distribution and occupational exposures between men and women who developed primary lung cancer. This study was designed to confirm those findings by conducting personal case interviews and extend them by examining the impact of certain biological factors. We have investigated demographic smoking, occupational and medical history sex differences in cases with primary lung cancer by interviewing 273 male and 103 female cases diagnosed between November 1983 and July 1986. The females were significantly younger at diagnosis, a pattern consistent for all cell types. Squamous cell (40%), small cell anaplastic (20%) and adenocarcinomas (16%) were the most prevalent cell types in men. In women, similar frequencies of adenocarcinomas (32%) and squamous cell carcinomas (29%) occurred. Despite a higher prevalence of physician diagnosed allergy and asthma among women, minimal sex differences in the prevalence of atopy as measured by prick skin test were found. Female cases were more likely to be lifetime non-smokers (15% vs 3%), to have started smoking on average 3 years older and to smoke 6 fewer cigarettes per day. The mean pack years of female cases was significantly lower than males' for squamous, adenocarcinoma and small cell anaplastic tumours. The majority of these women had not been occupationally exposed to any substance known to be carcinogenic or to damage the lung. However, in a small subset of cases pulmonary function variables were as depressed in women as in men with significantly higher mean pack years. Our results do not appear to be due to a cohort effect as all trends remain the same when the data were stratified by age at diagnosis. In summary, female cases were diagnosed younger; smoked less, both in terms of duration and dose; and experienced similar levels of pulmonary dysfunction at a lower dose of smoking in comparisons with men. Other factors, for example, occupational exposures and emphysema, which have been shown to increase the risk of lung cancer among males, were less prevalent in female cases.

THE ASSOCIATION BETWEEN HEAD TRAUMA AND ALZHEIMER'S DISEASE

The relation between head trauma and Alzheimer's disease was one of four major risk factors explored in a case-control study of 130 matched pairs; cases were clinically diagnosed between January 1980 and June 1985 at two geriatric psychiatric clinics in Seattle, Washington, and controls were friends or nonblood relatives of the cases. Subjects were matched by age, sex, and relationship between the case and his or her surrogate respondent. Head injuries which resulted in a loss of consciousness or which caused the subject to seek medical care were documented by means of interviews with surrogate respondents. A history of head injury was recorded for 24% of the cases and 8.5% of the controls, yielding an odds ratio of 3.5 (95% confidence interval 1.5-8.3) in conditional logistic regression analysis adjusted for age at onset of disease symptoms and family history of Alzheimer's disease. The estimated risk of Alzheimer's disease increased as the time between the last head trauma event and the onset of disease symptoms diminished (p = 0.002). This trend remained statistically significant (p = 0.006) when head injuries which occurred within 5 years of onset of the disease were excluded from the analysis. There was some difference between cases and controls for the average duration of unconsciousness in events accompanied by such a loss, but this was not statistically significant. The two groups were also similar in the circumstances surrounding the injuries and in the frequency of alcohol problems. This is the third case-control study to find a statistically significant association between head trauma and Alzheimer's disease.

The association between aluminum-containing products and Alzheimer's disease

The association between exposure to aluminum through the lifetime use of antiperspirants and antacids and Alzheimer's disease (AD) was explored in a case-control study of 130 matched pairs. Cases were clinically diagnosed between January 1980 and June 1985 at two geriatric psychiatric clinics in Seattle, Wash. Controls were friends or non-blood relatives of the case. Subjects were matched by age, sex, and the relationship between the case and his or her surrogate. For all antiperspirant/deodorant use, regardless of aluminum content, there was no association with AD (adjusted odds ratio (OR) = 1.2, 95% CI= 0.6–2.4). For aluminum-containing antiperspirants, the overall adjusted OR was 1.6 (95% CI = 1.04–2.4) with a trend toward a higher risk with increasing frequency of use ( p for trend = 0.03), the adjusted OR in the highest tertile being 3.2. For antacids regardless of aluminum content, the overall adjusted OR was 3.1 (95% CI= 1.2–7.9). Here, a steep dose-response gradient was found ( p for trend = 0.009), with an adjusted OR for the highest tertile of 11.7. However, when only aluminum-containing antacids were analyzed, the overall adjusted OR was only 0.7 (95% CI = 0.3–2.0) and there was no significant dose-response trend. These results are provocative but inconclusive due to methodologic problems relating to the necessary use of surrogate respondents and the long time period of potential exposure for this dementing disease.