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BACKGROUND: Myopia is an important public health problem because it is common and is associated with increased risk for chorioretinal degeneration, retinal detachment, and other vision- threatening abnormalities. In animals, ocular elongation and myopia progression can be lessened with atropine treatment. This study provides information about progression of myopia and atropine therapy for myopia in humans. METHODS: A total of 214 residents of Olmsted County, Minnesota (118 girls and 96 boys, median age, 11 years; range 6 to 15 years) received atropine for myopia from 1967 through 1974. Control subjects were matched by age, sex, refractive error, and date of baseline examination to 194 of those receiving atropine. Duration of treatment with atropine ranged from 18 weeks to 11.5 years (median 3.5 years). RESULTS: Median followup from initial to last refraction in the atropine group (11.7 years) was similar to that in the control group (12.4 years). Photophobia and blurred vision were frequently reported, but no serious adverse effects were associated with atropine therapy. Mean myopia progression during atropine treatment adjusted for age and refractive error (0.05 diopters per year) was significantly less than that among control subjects (0.36 diopters per year)(P<.001). Final refractions standardized to the age of 20 years showed a greater mean level of myopia in the control group (3.78 diopters) than in the atropine group (2.79 diopters) (P<.001). CONCLUSIONS: The data support the view that atropine therapy is associated with decreased progression of myopia and that beneficial effects remain after treatment has been discontinued.

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Amyotrophic lateral sclerosis (ALS), parkinsonism and/or dementia are highly prevalent among the Chamorro population of Guam. The incidence of Guamanian ALS has markedly declined in recent years, but these incidence figures may reflect underascertainment of subclinical disease. Guamanian Chamorro patients have not been systematically studied using modern clinical neurophysiological techniques. Electromyography (EMG: needle exam and nerve conduction studies) was used to study 29 patients with the major subtypes of Guamanian neurodegenerative disease, as well as 11 neurologically normal Guamanian Chamorro subjects. Central conduction was assessed by somatosensory evoked potentials (SEP's) in 16 patients. EMG evidence of peripheral neuropathy, (often subclinical) was found in 45% of Guamanian patients but no Chamorro control subjects. Diabetes mellitus, which is highly prevalent in this population, was present in some, but not all of these cases. Clinically unsuspected motor neuron disease was identified by EMG in only one of the 23 Guamanian patients with parkinsonism and/or dementia and in none of the 11 Chamorro control subjects. Two of seven patients with the clinical phenotype of Guamanian ALS had a more benign EMG pattern on the needle electrode exam with absence of fibrillation and fasciculation potentials. Three of 16 patients (all with parkinsonism and dementia) had mildly abnormal tibial SEP's. No patient had EMG evidence of myopathy or a defect of neuromuscular transmission. We conclude: (1) peripheral neuropathy may be a manifestation of Guamanian neurodegenerative disease; (2) the declining prevalence of ALS on Guam is not associated with the development of a subclinical form of motor neuron disease; (3) the substantial overlap of Guamanian ALS with parkinsonism-dementia reported in prior decades is no longer apparent; (4) abnormal central conduction, as assessed by tibial SEP's, is present in some patients with Guamanian parkinsonism-dementia.

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Controversy continues as to whether traumatic brain injury is a risk factor for Alzheimer's disease. The authors examined a related hypothesis that among persons with traumatic brain injury who develop Alzheimer's disease, time to onset of the disease is reduced. They used data on all documented episodes of traumatic brain injury that occurred from 1935 to 1984 among Olmsted County, Minnesota, residents. Community-based medical records were used to follow traumatic brain injury cases who were aged 40 years or older at last contact prior to June 1, 1988, for Alzheimer's disease until last contact, death, or June 1, 1988. The test of the hypothesis was restricted to those cases who developed Alzheimer's disease. The expected time to onset of Alzheimer's disease was derived from a life table constructed by using age-of-onset distributions within sex groups for a previously identified cohort of Rochester, Minnesota, Alzheimer's disease incidence cases without a history of head trauma. The authors found that of the 1,283 traumatic brain injury cases followed, 31 developed Alzheimer's disease, a number similar to that expected (standardized incidence ratio = 1.2, 95% confidence interval 0.8-1.7). However, the observed time from traumatic brain injury to Alzheimer's disease was less than the expected time to onset of Alzheimer's disease (median = 10 vs. 18 years, p = 0.015). The results suggest that traumatic brain injury reduces the time to onset of Alzheimer's disease among persons at risk of developing the disease.

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OBJECTIVES: To assess whether olfactory deficits are present in the general Guamanian Chamorro population and to evaluate olfaction in each of the four neurodegenerative disease syndromes of Guam: ALS, pure parkinsonism, pure dementia, and the combined parkinsonism-dementia complex (PDC). BACKGROUND: Olfactory dysfunction was previously reported in patients with PDC of Guam. METHODS: We developed a culturally adjusted olfactory test battery, derived from the original University of Pennsylvania Smell Identification Test (UPSIT), and administered this to Chamorro residents with ALS (n=9), pure parkinsonism (n=9), pure dementia (n=11), PDC (n=31), and 53 neurologically normal Chamorro and 25 North American control subjects. RESULTS: Similar, marked olfactory dysfunction was found in all four syndromes of Guamanian neurodegenerative disease. This correlated poorly with measures of parkinsonism and cognition. In the neurologically normal Chamorro control group, six subjects (11%) had very low olfactory scores; these were less than the lowest North American score, raising a question of subclinical neurodegenerative disease. CONCLUSIONS: Marked olfactory deficits are common to all four Guamanian neurodegenerative syndromes, and suggest the possibility of similar central neuropathologic substrates. The deficit in the Guamanian ALS group contrasts with idiopathic ALS, in which olfactory function has been reported to be only slightly compromised.

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OBJECTIVE: To compare the frequency of use of nonsteroidal anti-inflammatory drugs (NSAIDs) among 302 incident cases of Alzheimer's disease (AD) and age- and sex-matched control subjects. DESIGN: We undertook a retrospective case-control study, using the resources of the Rochester Epidemiology Project. MATERIAL AND METHODS: In ongoing studies of dementia in Rochester, Minnesota, we identified all incident cases of AD with onset between 1980 and 1984. From among all Rochester residents who received care at Mayo Clinic Rochester during those years, we selected one age- (within 3 years) and sex-matched control subject. For this study, exposure to a prescription NSAID was defined as prescribed use for 7 or more days during the 2-year window of time encompassing the year of onset and the year before onset among cases and the corresponding index year and the year prior for control subjects. RESULTS: The odds ratio (OR) for exposure, as described, to a prescription NSAID versus no exposure to any NSAID was 0.79 (95% confidence interval [CI], 0.45 to 1.38); the OR was 1.00 (95% CI, 0.52 to 1.92) for women and 0.40 (95% CI, 0.13 to 1.29) for men. Similarly, the overall OR for aspirin exposure versus no NSAID exposure was 0.90 (95% CI, 0.54 to 1.50). CONCLUSION: These data are suggestive but not confirmatory of a protective effect of NSAIDs for AD.

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Autonomic impairment is minor in idiopathic amyotrophic lateral sclerosis (ALS) and Alzheimer's-type dementia (D) and is usually not marked in Parkinson's disease. The autonomic status of Guamanian parkinsonism (P), ALS, and parkinsonism-dementia complex (PDC) is essentially unknown. We therefore evaluated the autonomic nervous system in Guamanian D, ALS, P, and PDC. Cardiovagal, adrenergic, and postganglionic sudomotor functions were quantitated in 16 patients and 14 paired household controls. Patients comprised PDC (N = 11), D (N = 2), P (N = 2), and ALS (N = 1). Autonomic deficit was expressed on a composite autonomic scoring scale (CASS) and its subsets that corrects for the effects of age and gender. CASS severity was rated from 0 to 10 and the maximal subset scores were 3, 3, and 4 for postganglionic sudomotor, cardiovagal, and adrenergic deficits, respectively. CASS scores for mild, moderate, and severe autonomic failure are 1 to 3, 4 to 6, and 7 to 10, respectively. Symptoms were scored by an Autonomic Symptom Profile (ASP). The affected patients were older than and had a sex distribution different from paired controls (64.2 +/- 8.0 versus 53.1 +/- 13.5; p < 0.01; male/female = 9/7 versus 2/12; p = 0.045). CASS scores were markedly increased over paired controls (6.2 +/- 2.3 versus 1.9 +/- 1.3; p < 0.001), and involvement was generalized by system. There were deficits in sudomotor, cardiovagal, and adrenergic function. Orthostatic hypotension occurred in 6 of 16 patients and 2 of 14 paired controls. Guamanian patients had more autonomic dysfunction than non-Guamanian Parkinson's disease. ASP scores were higher in patients than controls and regressed with CASS. These differences persisted when corrected for the confounding effects of age, gender, and diabetes. We conclude that Guamanian patients have autonomic failure to a greater extent than non-Guamanian Parkinson's disease or ALS. This autonomic failure suggests multisystem autonomic involvement similar to but less severe than in multiple system atrophy.

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Our goal was to use cross-sectional national mortality data to provide a multivariable statistical analysis of the factors that contribute to the decision of whether an autopsy will be performed. The identification of determinants of the autopsy is an important prerequisite for finding cost-effective alternatives for arresting or reversing the decline of autopsy rates in the circumstances in which the autopsy can continue to make a crucial contribution to clinical medicine and public health. The source of the data was 1986 National Center for Health Statistics (Washington, DC) mortality data tapes for Kentucky, Maryland, Minnesota, and Washington for the 1986 calendar year. Separate multiple logistic regressions were conducted on these data on a state-by-state basis, with a total of 139,063 individual mortality records as the unit of analysis. The dependent variable in all models was autopsy (yes/no). Odds ratios for selected explanatory variables were estimated for all four states, and the relative contribution of each explanatory variable was studied in a detailed analysis of one state. In general, the following independent variables had a statistically significant positive relationship with whether an autopsy will be performed: male sex; nonwhite ethnicity; death due to ill-defined or unknown cause; death due to accident, suicide, or homicide; presence of a nationally recognized medical center in the county of death; and death occurring in a standard metropolitan statistical area. In general, the following independent variables had a statistically significant negative relationship with whether an autopsy will be performed: older age at death; higher income level of the decedent; death in a nursing home; death at home; and residency in the county of death. The two most important variables influencing the autopsy decision were age at death (especially old age) and death due to accident, homicide, or suicide.

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On the western Pacific island of Guam, parkinsonism, dementia, and amyotrophic lateral sclerosis are highly prevalent but the cause is not known. To assess the possibility that the pathologic process extends beyond the nervous system, we studied patients with Guamanian neurodegenerative disease (N = 16) and Guamanian Chamorro control subjects (N = 16) in the Clinical Research Center of the Mayo Clinic, Rochester, MN. The principal abnormalities found in those with neurodegenerative disease included diabetes mellitus in 44%, elevated levels of serum immunoglobulin A (IgA) in 50%, and elevated IgG in 44%. The mean serum IgM level in the patient group was significantly lower than in the control group. Diabetes mellitus and elevated IgA and IgG levels were also present in 31% of neurologically normal Guamanian subjects. Some of these control subjects, however, probably have preclinical neurodegenerative disease, as found in previously published postmortem studies. Extensive serologic testing did not reveal any consistent profile of autoimmunity. Other blood and urine studies failed to identify hematologic, nutritional, renal, hepatic, or metabolic abnormalities that distinguished patients. Whether diabetes mellitus or abnormalities of immune regulation share common etiopathology with Guamanian neurodegenerative disease deserves further study.

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BACKGROUND: Local complications that require additional surgical procedures are an important problem for women with breast implants. METHODS: We studied 749 women who lived in Olmsted County, Minnesota, and received a first breast implant at the Mayo Clinic between 1964 and 1991. We identified complications that occurred after the initial procedure and after any subsequent implantation. A complication was defined as a surgical procedure performed for any of the following reasons: capsular contracture; rupture of the implant; hematoma or bleeding; infection or seroma of the wound; chronic pain; extrusion, leakage, or sweating of the implant; necrosis of the nipple, areola, or flap; malfunction of the filler port of a tissue expander; and wound dehiscence. RESULTS: During follow-up (mean, 7.8 years; range, 0 to 25.8), 208 (27.8 percent) of the women underwent 450 additional implant-related surgical procedures. Ninety-one (20.2 percent) were anticipated, staged procedures or were done because the patient requested a size change or aesthetic improvement, and 359 procedures (79.8 percent) had at least one clinical indication (thus constituting a complication). Complications occurred in 178 (23.8 percent) of the 749 women and involved 274 (18.8 percent) of the 1454 breasts with implants and 321 (18.8 percent) of the 1703 implants. The most frequent problem was capsular contraction (272 cases), followed by rupture of the implant (60), hematoma (55), and wound infection (23). The rate of complications was significantly lower (P<0.001) among women with cosmetic implants (6.5 percent at one year, 12 percent at five years) than among women who underwent implantation after mastectomy for breast cancer (21.8 percent at one year, 34 percent at five years) or prophylactic mastectomy (17.3 percent at one year, 30.4 percent at five years). CONCLUSIONS: Women who have had breast implantation frequently experience local complications during the subsequent five years. Complications were significantly less frequent among patients who received implants for cosmetic reasons than among those who received implants after mastectomy for cancer or for cancer prophylaxis.

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A historical cohort study was carried out to evaluate the effects in utero medical ionizing radiation on head circumference at birth. The nature of medical practice in Rochester, Minnesota, and the Mayo Clinic medical records linkage system enabled us to provide accurate estimates of medical radiation absorbed dose in 9,793 pregnancies of 2,980 women pregnant in Rochester between 1917 through 1973. Data were controlled for sex of the fetus, duration of pregnancy and congenital head abnormalities. It was found that medical ionizing radiation in the second and third trimesters of more than 300 mrad were related to significantly decreased head circumference. There was no significant effect of radiation exposure in the first trimester or periconceptional period. Medical ionizing radiation in the second and third trimesters of more than 300 mrad is related to a significant yet minimal, decreasing head circumference at birth. Maximum effects were seen during the midgestational and second trimester periods.

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OBJECTIVE: To examine the psychometric properties, acceptance, and screening efficacy of the Mini-Mental State Examination (MMSE) in an internal medicine practice. MATERIAL AND METHODS: The MMSE was administered more than 4,000 times by 27 internists to 3,513 elderly patients (2,299 women and 1,214 men, 60 to 102 years old) who underwent general medical examinations. The efficacy of the MMSE for screening was measured in a subsample of age- and sex-matched patients with dementia (N = 185) and control subjects (N = 227). MMSE scores were correlated with age and education in the community sample. The attitudes of physicians about the MMSE were assessed with a 12-question survey. Sensitivity, specificity, and predictive values were calculated. RESULTS: Performance on the MMSE among persons older than 59 years was influenced by age and education but not by sex. During an interval of 1 to 4 years, a change of 4 or more points in the total MMSE score is needed to indicate substantial cognitive deterioration. Participating physicians considered the MMSE of little value for routine screening in unselected populations but wanted it available for use as a clinical test. The traditional MMSE cutoff score of 23 or less had a sensitivity of 69% and a specificity of 99%. Use of age- and education-specific cutoff scores improved the sensitivity to 82% with no loss of specificity. With use of typical base rates for dementia in a general medical practice, the positive predictive value was less than 35%. CONCLUSION: The clinical utility of the MMSE and acceptance by physicians may be improved through awareness of the influences of age and education on the MMSE and by its application in settings with a high base rate of dementia. The MMSE is ineffective when used to screen unselected populations; it should be used for persons at risk of cognitive compromise.

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OBJECTIVE: To present the results of several retrospective epidemiologic studies of dementia in Rochester, Minnesota. MATERIAL AND METHODS: These studies were done by using the medical records-linkage resources of the Rochester Epidemiology Project. RESULTS: The incidence and prevalence of dementia increase sharply with advancing age. No difference is noted in overall age-adjusted incidence rates by gender. Rochester studies provide the only 25-year time trend analyses of the incidence of dementia in the United States. Time trends over three prevalence dates indicate an increase in prevalence in this community. Survival is decreased among patients with dementing illness. Case-control studies of Alzheimer's disease (AD) show that general medical conditions, previous head injury, thyroid disease, exposure to therapeutic radiation, anesthesia, and blood transfusion are generally not risk factors for AD. Patients with depression may have an increased risk for the development of AD. Sociodemographic factors such as education, occupation, marital status, and type of dwelling were not significantly different among patients with AD and their age-and gender-matched control subjects. CONCLUSION: The Rochester Epidemiology Project has proved to be an excellent resource for the study of the incidence, prevalence, and risk factors for dementia.

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OBJECTIVE: A retrospective, population-based, case-control study was carried out to evaluate episodes of prior intra-operative hypotension as a potential risk factor for Alzheimer's disease (AD). METHODS: Patients were all incident cases of AD from 1975-1984 who resided for 40 years or more in Olmsted County prior to their onset of dementia (N = 252). One age and gender-matched control for each case was selected from all registrations for care at Mayo Clinic during the year of onset in the incident case. Each case and control group had 252 individuals. RESULTS: Of these, 27 cases and 32 controls had at least one ten minute or longer episode of intra-operative hypotension of a systolic blood pressure of less than 90 mm Hg prior to the year of onset of dementia in the matched AD patient. We did not find a significantly increased risk of AD for hypotensive episodes of less than 75 or 90 mm Hg. CONCLUSIONS: It is unlikely that intra-operative hypotensive events of this degree increase the risk of AD.

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The cumulative incidence of mental retardation in a birth cohort of children born from 1976 through 1980 in Rochester, Minnesota (n = 5,919) was estimated. Rochester is the site of the Rochester Epidemiology Project, which captures virtually all medical care delivered locally. Passive follow-up through school and community medical records for criteria diagnostic of mild or severe mental retardation was undertaken. Thirty children were classified with mental retardation. The cumulative incidence of mental retardation by age 8 years was 9.1 per 1,000 (95% confidence interval = 6.2, 13.0) and was similar for boys and girls (8.3 vs. 10.0 per 1,000, respectively). The cumulative incidence for severe mental retardation in girls was more than twice that in boys; for mild retardation it was the opposite. The cumulative incidence among boys was 1.7 times greater than the cumulative incidence for girls. Results suggest that although the overall incidence of mental retardation by gender was similar, the severity may differ somewhat.

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We examined the relationship between exposure to pesticides and the subsequent development of brain tumors in adults through a critical review of the literature. The results of retrospective case-control studies are conflicting, in part because of biases in the selection of patients and controls, poor definition and ascertainment of the nature and extent of the exposure to pesticides, and a non-uniform approach to the collection of antecedent information. A number of the studies evaluated farmers as a group exposed to pesticides; however, inference about cancer incidence in farmers may reflect not only their possible exposure to pesticides, but also exposure to petrochemical products, exhaust fumes, mineral and organic dusts, and biological exposure to animals and microbes. The great majority of the cohort studies of chemical workers employed in the manufacture of pesticides did not indicate an excess of brain cancer mortality. There have been few cohort studies of pesticide applicators and these revealed elevated but non-significant relative risks for excess mortality due to brain cancer. Existing data are insufficient to conclude that exposure to pesticides is a clear risk factor for brain tumors. Given the conflicting results reported for farmers and pesticide applicators and their contrast to chemical workers, it seems more plausible that exposure to multiple agents and/or other factors, such as genetic predisposition, are most relevant with respect to brain tumor pathogenesis.

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OBJECTIVE: There is a high prevalence of neurodegenerative disease (parkinsonism, dementia, and motor neuron disease) on the western Pacific island of Guam. We sought evidence in support of the hypothesis that these conditions are triggered by nutritional deficiencies of calcium and magnesium leading to secondary hyperparathyroidism that then facilitates the entry of calcium and toxic heavy metals into the brain. METHODS: We analyzed indices of calcium metabolism plus blood-serum, urine, nail, and hair heavy metal concentrations in 12 patients with Guamanian neurodegenerative disease and 12 Chamorro control subjects. RESULTS: All 12 patients with Guamanian neurodegenerative disease had normal values for serum total and ionized calcium, 25-hydroxyvitamin D, and 24-hour urine collections for calcium. Eleven of 12 patients had normal serum parathyroid hormone values and alkaline phosphatase levels. No patient had reduced serum phosphorus or magnesium values although a minority of patients and controls had low urinary magnesium concentrations. Median blood-serum and 24-hour urine collections for heavy metals (aluminum, arsenic, cadmium, copper, iron, lead, manganese, mercury, and zinc) were statistically similar in the patient and control groups except for a slight elevation of blood, but not urine, lead in the patient group. Concentrations of heavy metals in hair and nails were similar in the two groups. CONCLUSIONS: We could find no evidence in support of abnormalities of calcium metabolism or heavy metal absorption as a major causative factor in the development of neurodegenerative disease on the island of Guam.

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Because polio and ALS are both manifestations of anterior horn cell disease, consideration of some etiologic or pathogenetic relationship continues to recur. Studies that show an association are infrequent and are greatly outnumbered by negative reports in spite of possible journal bias to report positive results. Our limited studies in Guam and Rochester, Minnesota, have added to the negative list, and support the conclusion that there is no etiologic association of these two distinct diseases. The role, if any, of nonparalytic polio and polio vaccines with respect to ALS is not clear. With such a high proportion of the population having antibodies to polio, it may not be feasible to differentiate ALS with respect to the presence or absence of polio antibodies. Although the results to date do not support a polio-ALS relationship, further long-term studies are desirable for both the classical and the Western Pacific forms of ALS with respect to past polio outbreaks and, for the future, the unknown effect of polio vaccines on the incidence of ALS.

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OBJECTIVE: The outcome of patients with mild cognitive impairment is not known, yet these patients present a difficult dilemma for the clinician. This study was designed to characterize the outcome of a group of patients with mild cognitive impairment and to determine whether the presence of the epsilon 4 allele on the apolipoprotein E gene (APOE) is a predictor of that outcome. DESIGN: A prospective, longitudinal inception cohort. SETTING: General community clinic. PARTICIPANTS: A consecutive sample of 66 patients who met criteria for a diagnosis of a mild cognitive impairment and who had at least one clinical reevaluation was identified from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry. INTERVENTIONS: We evaluated patients initially and at 12- to 18-month intervals up to 54 months using standard neurological and neuropsychological measures such as the Mini-Mental State Examination, the Dementia Rating Scale, the Wechsler Adult Intelligence Scale--Revised, the Wechsler Memory Scale--Revised, and the Free and Cued Selective Reminding Test. The APOE status of study patients was determined. MAIN OUTCOME MEASURE: The development of dementia as determined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Sixty-six individuals had been reevaluated once (mean of 18 months), 36 individuals twice (mean of 36 months), and 22 individuals on three occasions (mean of 54 months), with conversion rates to dementia at these intervals of 24%, 44%, and 55%, respectively. A multivariate Cox regression model demonstrated that possession of an APOE epsilon 4 allele was the strongest predictor of clinical outcome. CONCLUSIONS: These data suggest the following: (1) patients with mild cognitive impairment can be clinically defined, (2) many members of this group progress to Alzheimer's disease, and (3) APOE epsilon 4 allele status appears to be a strong predictor of clinical progression.

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Using the unique data resources of the Rochester Epidemiology Project, we have designed a population-based retrospective cohort study to examine the risks and complications of silicone breast implants among 749 Olmsted County, Minnesota, women who received these devices between 1964 and 1991, and 1498 control women who did not receive such devices. In this paper, we present data describing the population-based trends in the utilization of these devices from 1964 to 1991. In addition, we discuss the case ascertainment, outcome assessment, and reliability of the data collection for the outcomes study. The utilization of breast implants increased markedly over the past 30 yr with the rate of new implants per 100,000 women (> or = 15 years of age) rising from 3.5 in 1964 to 95 in 1979, remaining stable thereafter. The prevalence of breast implants among Olmsted County women > or = 15 years of age on 1 January 1992 was approx. 1%. An examination of the characteristics of these women reveals that recent utilization of breast implants has increased more rapidly among rural than among urban women, that the proportion of women receiving implants for breast cancer mastectomy reconstruction has increased in recent years, and that the great majority of women receiving implants are married at the time of implant. These trends also revealed that the average age of women who receive implants is rising and that in more recent years both much younger and much older women are receiving implants.

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