1 Aging Research Center, Division of Geriatric Epidemiology and Medicine, Neurotec, Karolinska Institutet, Stockholm, Sweden.
2 Stockholm Gerontology Research Center, Stockholm, Sweden.
3 Department of Occupational and Environmental Health, Stockholm County Council, and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Received for publication June 7, 2002; accepted for publication July 21, 2003.
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ABSTRACT |
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aged; Alzheimer disease; dementia; education; social class
Abbreviations: Abbreviations: CI, confidence interval; SES, socioeconomic status.
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INTRODUCTION |
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It is known that education is an indicator of socioeconomic status (SES). Different studies have shown high (11) to moderate (2) correlations between education and occupation-based SES. Nevertheless, these two variables represent different aspects of and periods in the life course and may generate differences in health through various mechanisms (11, 12). Lynch and Kaplan describe education as "the transition from a socio-economic position largely received from parents to an achieved socio-economic position as an adult" (13, p. 22).
Socioeconomic factors acting over the life course have been found to affect health and premature death, as well as risk of cardiovascular disease (14, 15). Cumulative economic hardship has been found to lead to poorer cognitive functioning (16). Recently, Turrell et al. (17) examined the relation between socioeconomic mobility and cognitive function among Finish men in late middle age and suggested that all stages of the life course play a role in influencing adult cognitive function.
Few studies have reported an association between adult SES based on occupation and the incidence of Alzheimers disease or dementia. Evans et al. (2) found that all of the investigated markers of SES (education, occupational prestige, and income) predicted the development of Alzheimers disease. It has been reported that manual work, when it involves production of goods, could increase the risk of clinical Alzheimers disease or dementia (18). However, these studies focused on principal occupation, not all occupational periods. In addition, the relation of social mobility through different socioeconomic levels over the life course to the risk of dementia in old age has not been studied.
The general aim of this study was to determine whether the reported association between low education and increased risk of Alzheimers disease and dementia could be explained by occupation-based SES. Specifically, we examined how the risk of Alzheimers disease and dementia varied by different combinations of 1) education and main occupation-based SES and 2) education and lifetime number of years spent in a low occupation-based SES. Since education and occupation-based SES are interrelated, special attention was given to the categories that deviated from the expected pattern, that is, the combinations of high education/low occupation-based SES and low education/high occupation-based SES. Furthermore, we investigated social mobility patterns to explore whether later advancement or setbacks in occupation-based SES may affect the relation between education and Alzheimers disease incidence.
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MATERIALS AND METHODS |
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Identification of incident cases of Alzheimers disease and dementia
At follow-up, all subjects were clinically examined by physicians, neuropsychologically assessed by psychologists, and interviewed by nurses. Incident cases of dementia were defined as those that developed during the follow-up period. The diagnosis of clinical dementia was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (20), using a three-step procedure. First, a preliminary diagnosis was made by the examining physician. Second, all cases were independently reviewed by a specialized clinician, and a second diagnosis was made. If the diagnoses were in agreement, they were accepted as final. In cases of disagreement, a third opinion was obtained, and the concordant diagnosis was accepted. The diagnosis of dementia was made when the subject completely fulfilled the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised.
The diagnosis of Alzheimers disease in particular required gradual onset and progressive deterioration of cognitive functioning and exclusion of all other specific causes of dementia. Neuroimaging and autopsy data were not available. Our clinical diagnosis of Alzheimers disease corresponds to the diagnosis of "probable Alzheimers disease" according to the NINCDS-ADRDA [National Institute of Neurological and Communicative Disorders and StrokeAlzheimers Disease and Related Disorders Association] criteria (21). For the 161 deceased subjects, a preliminary diagnosis was made by a physician who consulted medical records and death certificates, and the diagnosis was then reviewed by a senior clinician. When only discharge diagnoses from hospitals (n = 50) or only death certificates (n = 11) were available, the reported diagnosis was accepted. When we repeated the analyses in the survivors cohort, the results were similar.
Measurement of educational attainment
Information on total years of formal education was collected at baseline. In this study, educational level was divided into two main categories: 27 years (6 years of primary school and, in some cases, 1 extra year of practical vocational training) and 8 years (intermediate and university levels). This dichotomization was based on a previous analysis (4) in which different levels of education were examined in relation to Alzheimers disease. Persons with an intermediate amount of education (810 years of schooling) did not differ from university-educated subjects (
11 years of schooling) in terms of Alzheimers disease risk. Data on educational background were missing for three persons. These subjects were omitted from all analyses concerning education.
Assessments of occupation-based SES
Main occupation-based SES
Specially trained nurses interviewed a relative or another person significant to the subject about the subjects full lifetime work history. The questionnaire was developed by an occupational hygienist. Up to eight occupational periods with specific information regarding time and place were listed. The subjects longest-held job was considered his or her main occupation. Occupations were grouped according to the socioeconomic classification system developed by Statistics Sweden (22). The Swedish socioeconomic classification system primarily contains dimensions of ownership of the means of production and division into blue-collar and white-collar occupations as assessed by normal trade-union affiliation. It also contains aspects of skills in the subdivisions inside blue-collar and white-collar occupational categories. However, customary educational requirements for the respective occupations are used, not information about education at the individual level.
Quite a few women (21 percent) were homemakers during their longest occupational period. Information on husbands occupation, which is frequently used to estimate the SES of wives, was not available. Instead of including homemakers in a category of their own, we used their second-longest-held job to estimate their SES. Eighteen subjects had been housewives throughout their working lives and were excluded from the analyses involving main occupation.
We first analyzed the relation of SES to incidence of Alzheimers disease and dementia by using three categories (blue-collar workers, white-collar employees, and self-employed persons plus those in academic professions). Since the two last categories had similar risks, the two groups were merged.
Lifetime occupational SES
Data were gathered about the length of each occupational period over the subjects lifetime, and all occupations were classified as described above, with the exception that no substitutions from other occupational periods could be made for the homemaker work periods. Instead they were classified as nonmanual periods, because 1) these women often held nonmanual jobs in their other occupational periods and 2) they were generally more highly educated than the nonhousewives. Finally, we added up the numbers of years in all periods of manual labor to obtain the sum of years spent in a low occupation-based SES. In the current study, we report results from analyses in which the number of years in a low SES was less than or equal to 25 versus more than 25 (the median amount of time spent in a low SES by the low-SES fraction of the population).
Socioeconomic mobility
We computed occupation-based SES at ages 20, 40, and 60 years in order to estimate individual socioeconomic mobility patterns. When information about a particular time period was missing, we substituted an equal number of years from the two closest work periods. Sixty-three persons lacked information about occupational position at 60 years of age; instead, information concerning the occupational period prior to that was chosen to represent it.
Covariates
We used all covariates with available information from our database that may have acted as confounding factors. As major possible confounders, we considered age, gender, vascular diseases, and alcohol data.
Information on age and gender was derived from the Swedish National Population Register. Information on cerebrovascular and heart diseases and diabetes mellitus was derived from the computerized Stockholm Inpatient Registry System, in which all admission and discharge diagnoses from every hospital in Stockholm are recorded. In the current study, all diagnoses made at any time from 1969 to the baseline examination were used. Diseases were diagnosed according to the International Classification of Diseases, Eighth Revision (codes 430438 for cerebrovascular disease, codes 410414 for coronary disease, code 428 for heart failure, code 427 for arrhythmia, and code 250 for diabetes mellitus). Information on diabetes from the in-patient register was integrated with self-reports of a doctors diagnosis of diabetes, use of oral hypoglycemic medication or insulin, or a blood glucose level greater than 11 mmol/liter. Arterial blood pressure was measured at baseline with a mercury sphygmomanometer by trained nurses. If the first reading was abnormal (systolic pressure 160 mmHg or diastolic pressure
95 mmHg), two additional readings were made. The mean of the second and third readings was used for analyses (23). Furthermore, we created a simple additive index ranging from 0 to 5 for the vascular diseases or risk factors described above.
Information on alcohol use was collected from relatives, who specified how many glasses of wine, bottles of beer, and/or glasses of liquor the proband consumed weekly. Since consumption of alcohol in this predominantly female elderly population was found to be particularly low (82.4 percent of the persons with available data on alcohol reported that they used no alcohol at all, and only 3.5 percent consumed an amount corresponding to more than five glasses of wine per week), we decided to divide the alcohol data into three categories: no use, any use, and no information. The latter category was included in the analyses because reporting on alcohol use can sometimes be a sensitive matter, and we found it relevant to investigate whether the absence of information was associated with the risk of dementia.
Other covariates, which were controlled for in further analyses, were: 1) cognitive status at baseline, measured by the Mini-Mental State Examination (24); 2) social network at baseline, measured with a four-grade index (poor, limited, moderate, and rich social network) as defined in a previous study (25); and 3) engagement in mental and physical activities at baseline, graded in three frequency categories (26).
Statistical analysis
Logistic regression was used to evaluate the differences in baseline characteristics between participants and dropouts. Cox proportional hazards regression analyses were used to estimate the relative risk of incident Alzheimers disease and dementia associated with different combinations of education and occupation-based SES, as well as socioeconomic mobility. The follow-up time for nondemented persons was estimated from the date of the baseline interview to the date of follow-up examination or death. For the demented persons, half of this time was calculated, since dementia onset was assumed to be the midpoint between baseline and follow-up examination.
Age, gender, vascular disease index, and alcohol use were entered into all models. Additional models were used to verify the possible confounding effect of baseline Mini-Mental State Examination score, social network, and leisure activities. We also repeated all analyses after excluding the stroke cases, with the purpose of examining whether stroke might obscure or increase diagnostic difficulties in dementia due to cognitive dysfunction in subjects with previous stroke.
The interrelation between education and SES was explored using two stratifications. First, the study population was divided into four strata characterized by 1) high education and high SES; 2) high education and low SES; 3) low education and high SES; and 4) low education and low SES. Second, we used four strata by combining low and high education as defined above, with permanence in low SES for less than or equal to 25 years versus more than 25 years.
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RESULTS |
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A total of 101 subjects developed clinically definite dementia during the follow-up period. Among dementia cases of all types, 76 persons were diagnosed with clinically definite dementia of the Alzheimers type. Table 1 provides characteristics of the participants by dementia status at follow-up.
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Low education in combination with either low or high occupation-based SES was associated with increased risk of Alzheimers disease and dementia, even after adjustment for the major covariates. The combination of high education and low occupation-based SES was not associated with any increased risk of Alzheimers disease and dementia (table 3).
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Table 4, model 1, shows the relative risks of Alzheimers disease in relation to eight social mobility patterns after controlling for age and gender. Having a low occupation-based SES at ages 20, 40, and 60 years resulted in a borderline-significant elevated risk of Alzheimers disease compared with the reference category of high SES at all three ages. Having a low occupation-based SES at ages 20 and 40 years but not at age 60 years was also associated with significantly elevated risks of Alzheimers disease. Furthermore, low occupation-based SES at 20 years of age, regardless of whether SES was high at age 40 and/or age 60, was associated with elevated Alzheimers disease risks, though not statistically significantly. However, after additional adjustment for education, none of the significant associations remained. Twenty-eight percent of the subjects with high occupational SES at ages 20, 40, and 60 years but 91 percent of the subjects with low SES at ages 20, 40, and 60 years had a low educational level. Analyses of all-type dementia showed similar results.
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DISCUSSION |
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Our results are in agreement with previous findings of a positive association between a low level of education and increased risk of Alzheimers disease and dementia (110). Evans et al. (2) reported that each of the socioeconomic measures (education, income, and occupational prestige) predicted Alzheimers disease risk. However, when they included all three measures in the same model, only education (not income or occupational prestige) retained a significant association with Alzheimers disease. Recently, investigators from the Nurses Health Study (27) reported a strong association between low education and cognitive decline but little association with other markers of SES.
The fact that the association between low education and increased risk of Alzheimers disease and dementia in general was present independently of main occupation-based SES, and the fact that the association of SES with Alzhei-mers disease and dementia was mainly due to SES in early work life, seems to indicate that unknown education-related factors acting during the first two decades of life may be involved in the development of Alzheimers disease and dementia. This interpretation is in agreement with a number of previous reports. In a recent article, Kaplan et al. (28) concluded that higher childhood socioeconomic position, as well as greater educational attainment, was associated with better cognitive function in adulthood. In a study of education and dementia in an Italian population with a middle-to-high socioeconomic level, the first decade of life was suggested to be a critical period for development of dementia later in life (29). Hall et al. (30) discussed the possibility that low education by itself is not a major risk factor for Alzhei-mers disease but rather a marker for other accompanying deleterious socioeconomic or environmental influences in childhood. Poor-quality childhood or adolescent environments have been suggested to prevent the brain from reaching complete levels of maturation, which in turn may put people at higher risk of Alzheimers disease (31, 32). Results from the PAQUID Study (33) showed that occupation did not change the risk of Alzheimers disease, which instead was related to cognitive abilities in childhood and adolescence. The early-life factors in question may be early socioeconomic factors, mental stimulation, or cognitive abilities. The cognitive abilities may be affected by both environmental (34) and genetic influences (9). Since many studies, like ours, lack an independent measure of intelligence, the importance of early-life cognitive abilities is difficult to evaluate.
A number of studies have given special attention to the effect of early-life circumstances on health and mortality in general. Early-life SES has been reported to be connected with cardiovascular diseases and general health status later in life (3537). Disadvantaged childhood living conditions have been hypothesized to trigger unhealthy life trajectories, where increased illness risk is the sum of several health-damaging factors (38). New results from a random Swedish national sample indicate that occupational class differences in adult mortality depend, to a fairly large extent, on childhood conditions (39). We examined the relation between SES and Alzheimers disease and dementia from a lifetime perspective, ranging from school to retirement, but unfortunately we lacked specific data on the SES of the family of origin. Thus, we can only suggest the involvement of early-life factors in the development of Alzheimers disease and dementia as a hypothesis.
An alternative explanation for our findings is that education may be a better indicator of adult lifestyle and habits than occupational SES, and that lifestyle and habits such as alcohol use and smoking may explain the detected association. However, when our data were adjusted for alcohol use, and additionally when current social network index and engagement in physical and mental activities were entered into the model as covariates, we obtained similar results. Smoking was not related to Alzheimers disease or dementia in our population (40).
With regard to cognitive function in late middle age, Turrell et al. (17) reported that disadvantaged socioeconomic circumstances in childhood may, to some extent, be overcome by later upward mobility. However, in our study, low education remained associated with an increased risk of Alzheimers disease even after adjustment for adult social mobility.
Some potential limitations of this study must be considered. Persons who dropped out of the study were less educated than participants. Since low education was related to Alzheimers disease and dementia, this may have affected our results, but it is more likely to have skewed our findings towards underestimation of the association than towards overestimation. The occupational data were obtained through informants. However, a single open-ended question about occupation (without any specification of time, place, or number of years) had already been posed to the participants during the baseline interview, and it was possible to compare these responses with the informant data regarding the subjects main job. When information from the two different sources was used to estimate SES, agreement was 80 percent. The Swedish system for classification of SES from occupation is well established and has been evaluated (41). However, it remains that occupation-based SES is more difficult to evaluate than education. Estimation of SES from occupation was difficult for the housewives in the cohort (21 percent). Our approximations were likely to create nondifferential misclassification of SES, leading to a dilution of the association. We performed additional analyses (data not shown) treating the housewives as a third occupational category, and this did not affect our results.
Finally, we must be cautious in interpreting our findings as reflecting a direct effect of education on Alzheimers disease risk and not one that is mediated by occupation-based SES. In fact, there is the possibility of unmeasured confounders being responsible for the patterns of associations found in the study. For example, work-related stress may be associated with occupation-based SES but not with education and may increase the risk of Alzheimers disease and dementia, though there is currently no clear evidence in the literature concerning such an association.
The main conclusion that can be drawn from this study is that a low level of education is more directly associated with increased Alzheimers disease incidence and is not mediated by low adult occupation-based SES, regardless of whether the low-SES occupational period was extended over a substantial number of years (25 years) and regardless of adult socioeconomic mobility pattern. The results are not inconsistent with the already-suggested hypotheses of cognitive or brain reserves (5, 6). Alternatively, these findings may partly reflect a detection bias by which subjects with a low level of education tend to be clinically diagnosed with Alzheimers disease and dementia at an earlier point in time (4). However, the possibility that factors related to early-life SES may play a role in the development of Alzheimers disease and dementia should not be disregarded. Our findings support this hypothesis and stress the importance of collecting data on early life conditions when studying dementia in old age.
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ACKNOWLEDGMENTS |
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The authors thank all members of the Kungsholmen Project study group for their cooperation in data collection and management.
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NOTES |
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REFERENCES |
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