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RESEARCH AND PRACTICE |
Marcus Richards, Neil Thompson, and Michael E. J. Wadsworth are with the Medical Research Council, National Survey of Health and Development, University College London, London, England. Martin J. Jarvis is with the Cancer Research UK Health Behaviour Unit, University College London.
Correspondence: Requests for reprints should be sent to Marcus Richards, PhD, MRC National Survey of Health and Development, Royal Free and University College London Medical School, University College London, Department of Epidemiology and Public Health, 1-19 Torrington Pl, London WC1E 6BT, England (e-mail: m.richards{at}ucl.ac.uk).
| ABSTRACT |
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Objectives. The authors investigated the effects of cigarette smoking on midlife cognitive performance.
Methods. Multiple regression was used to test the association between cigarette smoking and changes in cognitive test scores among male and female members of the British 1946 birth cohort aged between 43 and 53 years.
Results. Smoking was associated with faster declines in verbal memory and with slower visual search speeds. These effects were largely accounted for by individuals who smoked more than 20 cigarettes per day and were independent of sex, socioeconomic status, previous (adolescent) cognitive ability, and a range of health indicators.
Conclusions. The present results show that heavy smoking is associated with cognitive impairment and decline in midlife. Smokers who survive into later life may be at risk of clinically significant cognitive declines.
| INTRODUCTION |
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In the present study, we investigated the association between smoking and cognitive function in midlife among the British 1946 birth cohort, controlling for socioeconomic status and a range of health indicators, including maternal smoking, respiratory and cardiovascular disease, forced expiratory volume in 1 second (FEV1), blood pressure, affective disturbances, and potential alcohol abuse. Because data had been gathered previously on cohort members cognitive functioning in adolescence, we also were able to control for the possibility that smoking initiation in adolescence is mediated by cognitive ability.
| METHODS |
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The most recent follow-up (n = 3035) occurred in 1999, when the participants were aged 53 years. In 1989, the cohort was shown to comprise a representative sample of the UK population legitimately and singly born in the immediate postwar era.11 Exceptions were overrepresentations among nonresponders of individuals who had never married, those at the lowest education levels, those in manual-occupational social class, and those with psychiatric disturbances.
Smoking Frequency
Interview-based prospective information on cigarette smoking frequency at ages 36, 43, and 53 years was obtained by research nurses. At each age, frequency was categorized as 0, 1 to 20, or more than 20 cigarettes smoked per day.
Cognitive Measures
Measures of verbal memory and measures of speed and concentration were repeated at ages 43 and 53 years. Verbal memory was assessed with a 15-item word-learning task devised by the NSHD. Each word was shown for 2 seconds. When all 15 words had been shown, the cohort member was asked to write down as many of the words as possible. The total number of words correctly recalled over 3 identical trials was summed to provide an overall score (maximum: 45).
Speed and concentration were assessed with a visual search task in which participants were required to cross out the letters P and W, randomly embedded within a page of other letters, as quickly as possible within 1 minute. Scores were computed as total number of letters searched (maximum: 600) minus number of targets missed. Both tests were administered by research nurses.
Background Variables
Potential confounding variables were sex, educational attainment (in tables, categorized as none, vocational only, ordinary secondary, advanced secondary, higher), occupational social class (in tables, categorized as I, II, III: manual, III: nonmanual, IV, V), previous (adolescent) cognitive ability, and a range of health indicators. Previous cognitive ability was represented as summed verbal and nonverbal ability scores, reading comprehension, and mathematical ability12 at age 15 years from tests administered by the NHSD.
Several health indicators were considered. Early life indicators were maternal smoking, based on recall of the survey member at age 53 years; low birthweight (2.5 kg or less), obtained from medical records; and occurrence of lower respiratory disease in infancy, as reported by respondents mothers. Indicators at age 53 years were (1) self-reported bronchitis, angina, heart attack, abnormal blood pressure, stroke, and cancer and (2) measured FEV1, adjusted for adult height, systolic and diastolic blood pressure levels, and resting pulse. Affective disturbances, assessed with the General Health Questionnaire,13 and potential alcohol abuse, defined by at least 2 positive item scores on the CAGE alcohol abuse screen,14 also were assessed at the 53-year follow-up.
Statistical Analyses
We investigated the associations between smoking and verbal memory and visual search speed using linear regression models. First, we assessed the association between smoking at age 43 years and both cognitive outcomes at age 43 years. Second, to examine whether smoking at age 43 years was associated with rates of change in cognition between ages 43 and 53 years, we conducted analyses using cognitive scores at age 53 years, adjusting for corresponding scores at age 43 years. To investigate the possible effect of an additional 10 years of smoking, we repeated these models, using smoking at age 53 years instead of age 43 years. We adjusted all of the regression models for sex, educational attainment, occupational social class (all entered as categorical variables), and cognitive ability at age 15 years. We then adjusted the models for each of the study health indicators in turn.
| RESULTS |
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Smoking Patterns at Age 36 to Age 53 Years
A trend toward reduction and cessation is evident. The frequency of non-smoking was 1352 (69.7%) at 36 years, 1420 (73.2%) at 43 years, and 1516 (78.1%) at 53 years. For those smoking 1-20 cigarettes per day these figures were 455 (23.4%) at 36 years, 386 (19.9%) at 43 years, and 338 (17.4%) at 53 years. For those smoking more than 20 per day these figures were 134 (6.9%) at 36 years, 135 (7.0%) at 43 years, and 87 (4.5%) at 53 years. On the other hand, consistent levels of exposure to cigarettes over time within each smoking frequency category were observed, with non-smokers at 53 years having smoked a mean (SD) of 2.32 (6.48) cigarettes at 36 years, and 1.56 (5.62) at 43 years. It can be seen that cigarette consumption at age 53 years reflected consistent levels of exposure to cigarettes over the previous 17 years.
Smoking at Age 43 Years and Memory
Table 1
shows beta coefficients representing mean respondent differences in memory scores at age 43 years and mean declines in memory between ages 43 and 53 years, after control for sex, educational attainment, occupational social class, and previous cognitive ability. Beta coefficients for these control variables are shown as well. There was no association between smoking at age 43 years and memory at age 43 years. However, smoking at age 43 years was associated with a more rapid decline in memory from 43 to 53 years.
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Smoking at Age 43 Years and Timed Visual Search
Table 2
shows a model, identical to that presented in Table 3
, for timed visual search. Smoking was associated with slower search speeds at age 43 years. Although inspection of the coefficients suggests a doseresponse effect, supported by a trend test significant at the 5% level, this effect was again largely accounted for by individuals who smoked more than 20 cigarettes per day. There was no association between smoking and change in search speed from 43 to 53 years. Sex x Smoking interactions were not significant at the 5% level for this measure. As with memory, associations between previous cognitive ability and search speed were evident, as was a female advantage on this measure; however, the contributions of educational attainment and adult social class were far less pronounced than for memory.
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Control for Health Indicators
The association between smoking at age 53 years and change in search speed from 43 to 53 years was slightly reduced after additional adjustment for FEV1 and low birthweight, although it should be noted that this association was already of relatively low magnitude before this adjustment. When adjusted in turn, none of the other health indicators modified the associations between smoking and cognition to any notable extent. In each case, the effect of smoking more than 20 cigarettes per day at age 53 years on search speed at age 43 years and the effect on change in memory from 43 to 53 years remained significant at the .001 level.
Smoking Cessation and Cognitive Functioning
To investigate whether the effects of smoking on cognition were modified by smoking cessation, we reclassified participants into those who did not smoke at age 36, 43, or 53 years; those who were smoking at age 36 years only; those who were smoking at age 36 and 43 years only; and those who were smoking at all 3 ages. In the case of 127 of the participants, irregular smoking patterns could not be classified in this way. Cigarette consumption was relatively light in this group (means of 8.8 [SD = 8.58], 9.05 [SD = 9.88], and 2.90 [SD = 6.92] cigarettes smoked per day at age 53, 43, and 36 years, respectively).
Table 4
shows that participants who smoked at all 3 ages had significantly lower scores, and exhibited significantly greater declines, on both cognitive tests at age 53 years compared with those smoking at none of these ages. This effect was almost certainly accounted for by individuals who smoked more than 20 cigarettes per day, because most of these participants were classified with those who smoked at all 3 ages. There was, in addition, a trend toward a slowing of memory decline among those who stopped smoking (particularly those who did not smoke at age 43 and 53 years) relative to those who had never smoked. Participants who stopped smoking had slower visual search speeds than did those who had never smoked, but this effect was relatively weak. As before, all analyses were adjusted for sex, educational attainment, occupational social class, and cognitive ability at age 15 years.
| DISCUSSION |
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We should highlight several potential limitations of this study. First, smoking measures were self-reported, and measures of cotinine were not available to quantify inhaled doses. Second, there was a disproportionate loss to follow-up among participants at lower cognitive ability levels, limiting the generalizability of the results and possibly leading to underestimations of the true effect of smoking on cognition. However, we have no reason to believe that this loss to follow-up had any impact on the patterns of associations themselves. This limitation is balanced, furthermore, by the relatively young age of the participants, among whom premature death from smoking was unlikely to have reached a level that would cause significant survival bias.
Third, participants were required to abstain from smoking during their interviews. It is therefore possible that some smokers were in a state of incipient nicotine withdrawal during cognitive testing (approximately 90 minutes into the interview), which could have led to reductions in performance.15
With these limitations in mind, we must ask: What is the nature of the association between smoking and cognitive impairment in this population? The inability of the physical health indicators (e.g., cardiovascular and respiratory functioning) to explain the association between smoking and cognition raises the possibility of a direct effect of smoking on the central nervous system. In this regard, smoking was identified as a risk factor for perfusional decline, cerebral atrophy, and leukoaraiosis in a sample of individuals at increased risk of cognitive decline16 whose mean age (59 years) was similar to that of the NSHD cohort.
A second possibility concerns the role of nutrition. Smokers have been found to have lower intakes of antioxidant vitamins and higher levels of triglycerides, fibrinogen, and serum cholesterol compared with nonsmokers.17 The implications of such findings for the cognitive functioning of the NSHD cohort will be a matter for detailed investigation.
Two further aspects of our results deserve attention. First, the association between smoking and memory was not observed at age 43 years but emerged as a change in functioning between ages 43 and 53 years. This finding implies a possible temporal window of action in terms of smoking effects on central nervous system processes underlying memory. The effect of smoking on psychomotor speed was already evident by age 43 years, however, and thus such a window for this area of functioning cannot be inferred from the results of the present study.
Second, the association between smoking and memory observed at age 53 years was far stronger than that observed at age 43 years. This finding represents either the effect of a further 10 years of smoking exposure or an uncontrolled characteristic of the subgroup that persisted in smoking heavily throughout midlife.
What are the public health implications of this study? Peto et al. have estimated that in developed countries, tobacco use causes approximately 30% of all mortality among individuals between ages 35 and 69 years, making it the largest single cause of premature death in the industrialized world.8 Because memory impairment has been shown to predict dementia,18,19 our results suggest that even if smokers survive into later life, they may be at high risk of clinically significant cognitive decline. Continued follow-up of the NSHD cohort will determine this risk with greater precision.
| Acknowledgments |
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Ethical clearance for this research was obtained from multicenter and local research ethics committees across the United Kingdom. Informed consent was obtained from all participants.
| Footnotes |
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M. Richards initiated the core study ideas, and M. J. Jarvis, N. Thompson, and M. E. J. Wadsworth helped to develop these ideas. M. Richards designed and performed the statistical analysis. The article was written jointly by all authors.
Accepted for publication January 12, 2003.
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