APOE alleles in Alzheimer's disease and vascular dementia in a population aged 85+.

Apolipoprotein E genotyping was carried out in a stratified random sample of 52 patients with Alzheimer's disease, 48 patients with vascular or mixed dementia, and 49 nondemented controls in a population-based study of people aged 85 and older (the Vantaa 85+ Study). Our results indicate that the apolipoprotein E epsilon 4 allele is associated with approximately a twofold increase in clinically diagnosed Alzheimer's disease in this very old general population aged 85+. When combined with previous studies, our data also suggest that the association is decreasing with age. In contrast, there appears to be no relation between apolipoprotein E alleles and clinically diagnosed vascular dementia.

Creutzfeldt-Jakob disease: possible medical risk factors.

To explore possible risk factors in the past medical history of patients with Creutzfeldt-Jakob disease (CJD), we conducted a case-control study among 26 cases and 40 matched controls. Statistically significant odds ratios were obtained for intraocular pressure testing; injury to or surgery on the head, face or neck; and trauma to other parts of the body. The odds ratios were nearly significant for head trauma and procedures requiring sutures. These data suggest that the CJD agent may be acquired by inoculation through injury or during surgery, and perhaps on certain absorbable sutures of animal origin. The tonometer used for glaucoma testing may also be a vehicle of transmission.

Elevated risk of Alzheimer's disease among workers with likely electromagnetic field exposure.

We conducted a case-control study of the possible association of occupations with likely exposure to electromagnetic fields and Alzheimer's disease (AD) with patients from the Alzheimer Disease Treatment and Diagnostic Center, Rancho Los Amigos Medical Center, Downey, CA. Patients with definite or probable AD were the case subjects (86 male, 240 female). Patients with cognitive impairment/dementia other than vascular dementia were control subjects (76 male, 76 female). The study was limited to patients who were at least age 65 at the time of their first examination at Rancho Los Amigos. The odds ratio for both sexes combined was adjusted for sex, education, and age at onset. The odds ratio for males was adjusted only for age at onset, and the odds ratio for females was adjusted for both education and age at onset. The adjusted odds ratio for both sexes was 3.93 (p = 0.006), 95% CI = (1.5 to 10.6). For males the adjusted odds ratio was 4.90 (p = 0.01), 95% CI = (1.3 to 7.9), and for females the adjusted odds ratio was 3.40 (p = 0.10), 95% CI = (0.8 to 16.0). These results are consistent with previous findings regarding the hypothesis that electromagnetic field exposure is etiologically associated with the occurrence of AD.

Stroke in the Lehigh Valley: combined risk factors for recurrent ischemic stroke.

We used the Lehigh Valley Stroke Register and a logistic regression model for the odds ratio to study the relative contribution of several factors, considered jointly, to the risk of recurrent ischemic stroke. The factors were hypertension (HT), transient ischemic attack (TIA), myocardial infarction (MI), other heart diseases (OHD), diabetes mellitus (DM), age, and sex. Among these factors MI, OHD, and TIA constituted significantly greater risk than HTN, DM, age, or sex for ischemic stroke recurrence.

Multiple sclerosis and childhood infections.

Migration from an area where MS is common to an area where it is rare (and vice versa) affects the risk of MS, provided migration occurs in childhood. A childhood infection might explain this effect. Therefore, the age pattern of infectious diseases in different regions was examined. A higher proportion of children showed positive titers to many viral diseases early in life in areas where MS is rare compared with those where MS is common. Also, mortality rates from a variety of infectious diseases correlated negatively with the MS mortality. Thus, infection early in life may "protect" against MS, and conversely, later infection, when the immune system has partially matured, may increase risk. MS may be an age-dependent, host-immune response to childhood infection.

Risk factors for Creutzfeldt-Jakob disease: a reanalysis of case-control studies.

To review the evidence for risk factors of Creutzfeldt-Jakob disease (CJD), we pooled and reanalyzed the raw data of three case-control studies. The pooled data set comprised 178 patients and 333 control subjects. The strength of association between CJD and putative risk factors was assessed by computing the odds ratio as estimate of the relative risk. The risk of CJD was statistically significantly increased for subjects with a family history of CJD (odds ratio = 19.1; 95% CI 1.1 to 348.0). Further, there was a significant association between the risk of CJD and a history of psychotic disease (odds ratio = 9.9; 95% CI 1.1 to 86.1). Although not significantly increased, there was an elevated risk of CJD for subjects with a family history of dementia, a history of poliomyelitis, subjects employed as health professionals, and subjects ever exposed to cows and sheep. No association could be shown with organ meat consumption, including brain. The negative results of this reanalysis reassures the absence of a common risk factor in all CJD patients. However, the ongoing epidemiologic surveillance of CJD in several European countries may provide more evidence to exclude any environmental exposure early in childhood.

Lack of association of apolipoprotein E allele epsilon 4 with late-onset Alzheimer's disease among Finnish centenarians.

No association between Alzheimer's disease (AD) and apolipoprotein E type epsilon 4 (ApoE epsilon 4) phenotype was found among centenarians in Finland (N = 179). The data are based on ascertainment of all centenarians in Finland in 1991. All examinations were conducted during 1991. The diagnoses of dementia and AD were based on clinical grounds, conforming to DSM-III-R and NINCDS-ADRDA criteria. The percentage of ApoE epsilon 4 alleles among the centenarians was 8.7% (31 of 358 alleles). This is significantly lower than percentages found in younger Finnish populations. Thirty (16.8%) of the 179 centenarians were epsilon 4 allele carriers. One hundred fifty-one (84.4%) of the centenarians were women. Twenty-eight (18.5%) of the women had at least one epsilon 4 allele, as did two (7.1%) of the men. The prevalence of clinically diagnosed AD was 26.8%; 44% of the subjects were cognitively normal, 23% had signs of cognitive decline or at most mild dementia (with no differential diagnosis), and 6% had a dementia clinically diagnosed as being due to some cause other than AD. For AD cases versus cognitively normal subjects, the odds ratio associated with being a carrier of the epsilon 4 allele was 1.34 (p = 0.64; 95% CI = [0.5, 3.3]). Among women, the odds ratio was 0.99 (p = 1.0; 95% CI = [0.4, 2.6]). There were fewer, but not significantly so, epsilon 4 carriers among subjects with cognitive decline or at most mild dementia (12.2%) than there were among the cognitively normal subjects (16.5%). The AD patients had no evidence of difficulty standing on a flat stationary surface unless the surface suddenly moved.(ABSTRACT TRUNCATED AT 250 WORDS)

Stroke in the Lehigh Valley: risk factors for recurrent stroke.

Age-specific risk of recurrent stroke for various risk factors, calculated independently, was estimated using the first year of data from the Lehigh Valley Stroke Register. The register is based on a population of more than one-half million. Among the risk factors examined, the highest overall risk of recurrent stroke, 41.4, occurred with a history of at least one transient ischemic attack (TIA). After myocardial infarction (MI), the relative risk of a recurrent stroke was 8.0, while with all other heart diseases combined it was 8.4. With diabetes, the relative risk of a recurrent stroke was 5.6; with hypertension, it was 4.5. The relative risk increased with age after TIA and MI, but not for other heart disease, diabetes, and hypertension, except in the 85+-year-old age group.

Creutzfeldt-Jakob disease.

There has been significant advance in our understanding of CJD and similar spongiform encephalopathies in recent years. The range in clinical expression of the disease is better appreciated, and the existence of "atypical" cases of CJD is increasingly recognized. New ideas about the possible modes of natural transmission have been derived from case-control studies in different parts of the world.

Changes in selected biochemical constituents of blood collected from horses participating in a 50-mile endurance ride.

The effects of strenuous exercise on serum electrolytes, blood metabolites, and serum enzymes were studied in a group of 13 horses participating in a 50-mile endurance ride. Blood samples were collected before, during, and at the end of the ride, as well as 1 hour and 16 hours after the completion of the ride. There were significant changes in these values when preride values were compared with those of samples taken at different sample-collection periods. Significant (P less than 0.001) decreases were observed in serum concentrations of chloride, potassium, and calcium. A significant increase in the serum concentration of phosphorous also was observed. The mean concentrations of chloride and calcium remained significantly reduced in the 16-hour postride sample. A small, but significant (P less than 0.05), increase in sodium and decrease in glucose concentrations were observed at the midride sample. Although midride samples did not reflect a significant change in blood pyruvate concentration, a significant (P less than 0.05) increase was observed at the end of the ride. Changes in the hematocrit and the total protein concentration were statistically significant at levels of P less than 0.001 and P less than 0.01, respectively. The horses showed highly significant increases in concentrations of free fatty acids, serum enzymes (P less than 0.001), and lactate (P less than 0.005) during the ride. The elevated values of creatine kinase and lactic dehydrogenase decreased, while the aspartate aminotransferase values remained increased long after completion of the ride. The lactate and free fatty acids, which rose significantly during the ride, decreased to approximately preride values by 16 hours after the ride was completed. We conclude that the changes in serum electrolytes, enzymes, and blood metabolites reflect the sweating, muscle damage, and increased dependency on anaerobic glycolysis and lipid mobilization that these horses experienced during the competitive endurance ride.

Smoking and stroke.

The purpose of this review is to evaluate literature published since 1978 on the association between smoking and stroke. Two cohort studies found a dose-response relationship between the amount of cigarettes smoked per day and the relative risk of stroke. Also, two of the cohort studies found that when smoking ceased, the risk of stroke lessened (p less than 0.001). Nine case-control studies found a significant association between smoking and stroke for men and women. The biological association between smoking and stroke is plausible and several epidemiologic studies are supportive of this thesis. Additional, well-designed epidemiologic studies with a sufficient sample size to detect reasonably small odds ratios or relative risks (thus providing adequate statistical power) are warranted.

Genetic analysis of late-onset diseases using first-degree relatives.

We consider the problem of testing that a disease with variable age at onset is an autosomal dominant or recessive genetic trait. Specific reference is made to Alzheimer's disease and recent publications proposing an autosomal dominant inheritance pattern. The pedigree structure allowed is restricted to first-degree relatives of the proband for the dominant and to sibs of the proband for the recessive hypotheses, respectively, in addition to the proband. The sampling method assumed is the one most often used in practice: single ascertainment or sampling pedigrees with probability proportional to size (pps), i.e., to the number of affected individuals within a pedigree who are in the sampling frame. The statistical methodology developed takes the sampling procedure into account and is a generalization of the Kaplan-Meier method of estimating survival functions to pps sampling.

Sheep consumption: a possible source of spongiform encephalopathy in humans.

A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania.

Hearing problems in Mexican American elderly.

OBJECTIVE: To investigate hearing problems in a sample of elderly Mexican Americans. STUDY DESIGN: A longitudinal field study of a cohort of 3,050 subjects with in-person baseline and a 2-year follow-up. Population-based, cross-sectional, weighted data were analyzed. SETTINGS AND SUBJECTS: Hispanic Established Populations for Epidemiologic Studies of the Elderly (H-EPESE) consisting of Mexican Americans aged 65 and older provided basic health data using area probability sampling in five southwestern states during 1993 and 1994. MAIN OUTCOME MEASURES: Information was collected regarding demographics, medical conditions, smoking, and alcohol consumption. Hearing problems were identified through a series of self-perceived hearing problem questions, hearing aid use, and inability to hear a normal voice. RESULTS: A hearing problem was identified in 24.5% of this cohort (weighted, 748/3,049). Statistical analysis using a multiple logistic regression model was performed to identify factors jointly associated with hearing problems. Age group (odds ratio [OR] = 2.7, p<0.0001), male sex (OR = 1.9, p< 0.0001), hypertension (OR = 1.4, p<0.001), arthritis (OR = 1.5, p<0.0005), significant depressive symptomatology (OR = 1.4, p<0.002), and ever having consumed alcohol (OR = 1.4, p<0.005) were jointly statistically significantly associated with hearing problems. Number of cigarettes smoked daily (e.g., 0, 1-10, 11-20, etc.) was nearly significantly associated with a hearing problem in the multivariate model (OR = 1.1 for each increased in category, p<0.07). CONCLUSIONS: Hearing problems are common in this population. Control of hypertension, an amelioration of arthritis, and decreasing the consumption of alcohol and cigarettes may lower the likelihood of development of a hearing problem. Initial depressive symptomatology may have occurred subsequent to the hearing loss. A longitudinal study would allow determination of the direction of causation.

Prolonged, progressive dementia with spongiform encephalopathy: a variant of Creutzfeldt-Jakob disease?

A 46-year-old female is described with prolonged, progressive dementia and a brain biopsy consistent with Creutzfeldt-Jakob disease (CJD). She had neither myoclonic jerks nor an electroencephalogram with periodic spikes and suppression. Five of her close relatives were also demented. The nosology of CJD was discussed in the light of this case in which histopathology was characteristic of spongiform encephalopathy but the clinical features were atypical. We concluded that it would be premature to expand the traditional diagnostic criteria to include such cases as having CJD but, at the same time, it would be prudent to handle tissue, linens and surgical instruments as if they were contaminated by the resistant agent of CJD.

Amyotrophic lateral sclerosis and occupational exposure to electromagnetic fields.

In an hypothesis-generating case-control study of amyotrophic lateral sclerosis, lifetime occupational histories were obtained. The patients (n = 28) were clinic based. The occupational exposure of interest in this report is electromagnetic fields (EMFs). This is the first and so far the only exposure analyzed in this study. Occupational exposure up to 2 years prior to estimated disease symptom onset was used for construction of exposure indices for cases. Controls (n = 32) were blood and nonblood relatives of cases. Occupational exposure for controls was through the same age as exposure for the corresponding cases. Twenty (71%) cases and 28 (88%) controls had at least 20 years of work experience covering the exposure period. The occupational history and task data were used to classify blindly each occupation for each subject as having high, medium/high, medium, medium/low, or low EMF exposure, based primarily on data from an earlier and unrelated study designed to obtain occupational EMF exposure information on workers in "electrical" and "nonelectrical" jobs. By using the length of time each subject spent in each occupation through the exposure period, two indices of exposure were constructed: total occupational exposure (E1) and average occupational exposure (E2). For cases and controls with at least 20 years of work experience, the odds ratio (OR) for exposure at the 75th percentile of the E1 case exposure data relative to minimum exposure was 7.5 (P < 0.02; 95% CI, 1.4-38.1) and the corresponding OR for E2 was 5.5 (P < 0.02; 95% CI, 1.3-22.5). For all cases and controls, the ORs were 2.5 (P < 0.1; 95% CI, 0.9-8.1) for E1 and 2.3 (P = 0.12; 95% CI, 0.8-6.6) for E2. This study should be considered an hypothesis-generating study. Larger studies, using incident cases and improved exposure assessment, should be undertaken.

A case-control study of Creutzfeldt-Jakob disease. Dietary risk factors.

The mode of natural transmission of Creutzfeldt-Jakob disease remains unknown. In a case-control study conducted in 1981-1983 to evaluate possible dietary and other sources of the disease, 26 cases were ascertained in the mid-Atlantic region of the United States, 23 of which were obtained from accumulated records of the Laboratory of Central Nervous System Studies of the National Institutes of Health. Controls included 18 family members and 22 hospital-matched individuals (total sample size, 66). An increased consumption among patients was found for roast pork, ham, hot dogs (p less than 0.05), roast lamb, pork chops, smoked pork, and scrapple (p less than 0.1). An excess consumption of rare meat (p less than 0.01) and raw oysters/clams (p less than 0.1) was also reported among the patients. Liver consumption, among organ foods, was greater (p less than 0.1) among the cases. If Creutzfeldt-Jakob disease is acquired through ingestion of foods containing the agent, then the food items identified may be among those which need to be evaluated more intensively. Larger case-control studies with more focused dietary questions are warranted.

Does delay in acquiring childhood infection increase risk of multiple sclerosis?

Multiple sclerosis (MS) appears to be more common in technically advanced countries than in underdeveloped regions and migration from one area to another at a young age affects the risk of acquiring MS. One way of explaining both the peculiar frequency distribution and the effect of migration while young is to postulate that an infection early in life decreases the chance of central demyelination. However, no specific infection has been implicated consistently. Alternatively, an aberrant host response to infection in childhood might induce central demyelination. Thus, the aberrant host response could be age-dependent. In seeking associations between age of infection and risk of MS, we observed a direct relationship: where childhood diseases were acquired early in life, the frequency of MS in that population was low; where childhood diseases tended to occur nearer adolescence, MS frequency in that population was high. Since immune responsiveness to antigenic challenges matures through early adolescence, we reason that early infection might be protective and delay in acquiring childhood infections might increase the risk of developing MS. Indeed, in experimental models, the chance of inducing chronic relapsing central demyelination is increased by using adolescent rather than newborn or mature animals. In this paper, epidemiologic evidence showing the strong association between age of infection and risk of MS is presented.

Does delay in acquiring childhood infection increase risk of multiple sclerosis?

Multiple sclerosis (MS) appears to be more common in technically advanced countries than in underdeveloped regions, and migration from one area to another at a young age affects the risk of acquiring MS. One way of explaining both the peculiar frequency distribution and the effect of migration while young is to postulate that an infection early in life decreases the chance of central demyelination. However, no specific infection has been implicated consistently. Alternatively, an aberrant host response to infection in childhood might induce central demyelination. Thus, the aberrant host response could be age-dependent. In seeking associations between age of infection and risk of MS, we observed a direct relationship: where childhood diseases were acquired early in life, the frequency of MS in that population was low; where childhood diseases tended to occur nearer adolescence, MS frequency in that population was high. Since immune responsiveness to antigenic challenges matures through early adolescence, we reason that early infection might be protective and that delay in acquiring childhood infections might increase the risk of developing MS. Indeed, in experimental models, the chance of inducing chronic relapsing central demyelination is increased by using adolescent rather than newborn or mature animals. In this paper, epidemiologic evidence showing the strong association between age of infection and risk of MS is presented.