Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based stud
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《英国医生杂志》
1 Aging Research Center, Division of Geriatric Epidemiology, Neurotec, Karolinska Institutet, Box 6401, 11382 Stockholm, Sweden, 2 Department of Public Health and General Practice, University of Kuopio, Box 1627, 70211 Kuopio, Finland, 3 Division of Geriatric Medicine, Neurotec, Karolinska Institutet, Karolinska University Hospital, Huddinge, 14186 Stockholm, 4 Department of Neuroscience and Neurology, University of Kuopio, Kuopio, 5 Department of Epidemiology and Health Promotion, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland
Correspondence to: Miia Kivipelto Miia.Kivipelto@uku.fi
Abstract
Alcohol drinking has been proposed as a possible risk factor for cognitive impairment and dementia, though understanding the association has proved difficult. Some studies have found no association between alcohol drinking and cognitive impairment1-3 or Alzheimer's disease,4 5 whereas others have found an association between heavy drinking and increased risk of dementia.6 7 Some have claimed there is a J or U shaped relation between alcohol drinking and cognitive impairment8-10 or dementia11-14; that is, light to moderate alcohol drinking might have a protective effect compared with total abstention and heavy drinking. The apolipoprotein e4 allele, which is the only genetic risk factor for dementia with an established risk for the general population, may modify the effects of alcohol on the risk of developing cognitive impairment15 16 or dementia.12 17 However, the observed pattern of the effect modification has been different across the studies.
Earlier studies of alcohol drinking and cognition defined cognitive impairment in terms of performance in a variety of neuropsychological tests and did not validate it by any clinical or diagnostic concepts such as the criteria defining mild cognitive impairment.18 Mild cognitive impairment is considered to be a clinically identifiable entity and to carry a high risk for progression to dementia.19 20 Studies of alcohol drinking and dementia have mainly been either cross sectional or carried out in elderly cohorts with relatively short follow up times, making them prone to biases caused by subclinical dementia and other factors.
In order to clarify the role of alcohol in the development of dementia, one needs prospective studies with data on earlier alcohol drinking and long follow up. Given that midlife risk factors contribute to the onset of the dementing disease processes,21 we investigated whether alcohol drinking in middle age could influence the subsequent risk of dementia. The aim of this study was to evaluate the association between midlife alcohol drinking and the risk of mild cognitive impairment and dementia in old age. We also investigated whether the apolipoprotein e4 allele modifies this association.
Participants and methods
Characteristics of the participants according to their midlife alcohol drinking
About 30% of the participants never drank alcohol, 40% drank it infrequently, and 30% drank frequently (table 1). Among the frequent drinkers, about 68% drank alcohol once or twice a month, 24% once a week, about 8% twice a week, and 1% daily. Among the infrequent drinkers, more than 40% drank alcohol twice a year or less frequently, and about 60% reported drinking three to six times a year.
Table 1 Sociodemographic and clinical characteristics of 1018 participants from eastern Finland according to their midlife alcohol consumption. Values are means (standard deviations) unless stated otherwise
Non-drinkers were the oldest group at the follow up examination, and frequent drinkers were the youngest (table 1). Non-drinkers were less educated than the other two groups. Women were more likely to be non-drinkers or infrequent drinkers, whereas men were more likely to be frequent drinkers. Smoking was most common among frequent drinkers. Body mass index and total cholesterol concentration tended to be lower among infrequent drinkers than in the other two groups. The proportion of people with a history of myocardial infarction and stroke did not differ significantly according to drinking frequency either at middle age (a few cases only, data not shown) or old age. Mild cognitive impairment in old age was most common among non-drinkers and least common in infrequent drinkers. The frequency of old age dementia did not significantly differ with drinking frequency (table 1).
Alcohol consumption in middle age and cognitive impairment in old age
Participants who reported never drinking alcohol and those who reported drinking alcohol frequently were both more than twice as likely to have mild cognitive impairment in old age than those who drank infrequently, even after we controlled for age, sex, and years of education (table 2). The results remained essentially the same when we repeated the analyses with additional adjustment for factors related to alcohol drinking or increased risk of dementia, including follow up time, smoking, total serum cholesterol concentration, body mass index, systolic and diastolic blood pressure, and vascular diseases in old age. The risk of dementia did not significantly differ between alcohol drinking categories (table 2). Adding apolipoprotein E genotype to this second model provided only slightly different odds ratios for dementia (non-drinkers 0.81 (95% confidence interval 0.34 to 1.93), infrequent drinkers 1 (reference), frequent drinkers 1.57 (0.70 to 3.50)) and for mild cognitive impairment (non-drinkers 2.03 (0.95 to 4.34), infrequent drinkers 1, frequent drinkers 2.60 (1.19 to 5.69)).
Table 2 Results of multiple logistic regression analyses showing influence of participants' midlife alcohol consumption on their cognitive status in old age. Values are odds ratios (95% confidence intervals)
Effect of apolipoprotein e4 allele
To investigate whether apolipoprotein E genotype modified the effect of midlife alcohol drinking on the risk of dementia in old age, we performed analyses stratified by apolipoprotein e4 carrier status. Because our results indicated that the risk of dementia increased with increasing alcohol drinking frequency (see table 2), we used the group who never drank as the reference group. Among carriers of the apolipoprotein e4 allele, the risk of dementia increased with increasing alcohol consumption after all the adjustments (odds ratio for never drinking 1 (reference), for infrequent drinking 4.08 (95% confidence interval 0.98 to 16.91), and for frequent drinking 7.07 (1.37 to 36.60)). Among non-carriers of apolipoprotein e4, the risk of dementia did not change significantly with alcohol drinking categories (odds ratio for never drinking 1, for infrequent drinking 0.45 (0.13 to 1.60), and for frequent drinking 0.75 (0.19 to 2.99)).
To detect the combined effect of apolipoprotein E genotype and alcohol drinking in relation to dementia, we introduced the interaction term "drinking frequency*apolipoprotein e4" into the logistic regression model together with apolipoprotein e4, drinking frequency, and other covariates. This showed a significant interaction between apolipoprotein E and alcohol drinking frequency, with the overall interaction term being significant (P = 0.04). The interaction terms "infrequent drinking*apolipoprotein e4" and "frequent drinking*apolipoprotein e4" were also significant (P = 0.02 and P = 0.03, respectively). The figure shows the odds ratios derived from this model for each of the six possible combinations between apolipoprotein e4 and drinking frequency. Compared with the participants who never drank and did not carry the apolipoprotein e4 allele, e4 carriers who drank infrequently were 2.3 times more likely to develop dementia, and carriers who drank frequently were 3.6 times more likely. However, the risk of dementia for e4 carriers who never drank was not different from that for non-carriers who never drank. Among the non-carriers, there was no association between alcohol drinking and the risk of dementia.
Combined effect of midlife alcohol drinking and apolipoprotein e4 allele on risk of dementia in old age. Values are odds ratios from one logistic regression analysis with alcohol drinking frequency, apolipoprotein e4, and the interaction term "drinking frequency*apolipoprotein e4" in the model and fully adjusted (see methods). Non-carriers of apolipoprotein e4 who never drank were the reference group. P value for the overall interaction "drinking frequency*apolipoprotein e4" is 0.04. The odds ratio for the interaction term "infrequent drinking*apolipoprotein e4" is 8.52 (P=0.02) and for "frequent drinking*apolipoprotein e4" is 7.64 (P=0.03)
The effect modification by apolipoprotein e4 for the association between alcohol drinking and mild cognitive impairment in the interaction model did not reach significance (P = 0.54 for the overall interaction term, P = 0.39 for "never drinking*apolipoprotein e4," and P = 1.00 for "frequent drinking*apolipoprotein e4," with non-carriers of apolipoprotein e4 who drank infrequently as the reference group).
As mild cognitive impairment and dementia can be seen as points on the same cognitive continuum, we analysed how apolipoprotein e4 modified the association between alcohol drinking and cognitive impairment (including both mild cognitive impairment and dementia). We found similar results as those seen for dementia alone: there was a significantly increased risk among e4 carriers who drank alcohol, more so among frequent drinkers than infrequent drinkers. For the entire interaction between alcohol drinking and apolipoprotein e4, the P value was 0.045. The odds ratio for the interaction term "infrequent drinking*apolipoprotein e4" was 3.87 (P = 0.02), and for "frequent drinking*apolipoprotein e4" it was 3.00 (P = 0.05).
Among men, frequent alcohol drinking was related to an increased risk of mild cognitive impairment (odds ratio = 5.03, P = 0.02) compared with infrequent drinking, but never drinking did not significantly increase the risk (odds ratio = 3.84, P = 0.12). Among women, neither frequent drinking nor never drinking was significantly associated with an increased risk of mild cognitive impairment (odds ratios 1.63 (P = 0.43) and 1.41 (P = 0.44) respectively). Nevertheless, there was no interaction between sex and alcohol drinking frequency for the risk of mild cognitive impairment. Alcohol drinking was not significantly related to risk of dementia in the analyses when we included sex interactions (data not shown).
The results concerning the risk of dementia remained unchanged when we repeated the analyses with the dementia diagnoses derived from the patient registries also taken into account.
Alcohol consumption in old age and cognitive impairment
Alcohol consumption in old age was in agreement with midlife consumption ( = 0.36, P < 0.01). In the analyses of the association between old age drinking and the prevalence of mild cognitive impairment, we found again that non-drinkers more often had mild cognitive impairment than did infrequent drinkers, even after we adjusted for age, education, and sex (data not shown). However, frequent alcohol drinking was no longer associated with mild cognitive impairment. Old age drinking was not associated with dementia. Further adjustments did not change these results. The apolipoprotein e4 allele did not significantly modify the association between old age drinking and mild cognitive impairment or dementia.
Non-participants
Non-participants at the follow up visit (1998) were, at the midlife assessment, older than the participants (mean age 49.1 v 48.0 years, P = 0.01); had spent less time in education (7.7 v 8.7 years, P < 0.01); and had higher systolic blood pressure (148.9 v 143.4 mm Hg, P < 0.01), diastolic blood pressure (92.3 v 90.1 mm Hg, P < 0.01), total serum cholesterol concentration (7.0 v 6.8 mmol/l, P < 0.01), and body mass index (26.9 v 26.3, P < 0.01). They also had dementia in old age (data from patient records) more often than the participants (8.0% v 5.1%, P = 0.03). However, their midlife alcohol consumption did not differ significantly from that of the participants (non-drinkers 34.8% v 29.5%, infrequent drinkers 37.9% v 41.6%, and frequent drinkers 27.4% v 29.0%, P = 0.13), and the prevalence of smoking was similar (47.7% v 44.3%, P = 0.23). The sex distribution of non-participants was no different from that of participants (64.3% v 62.1% women, P = 0.42).
Discussion
Cervilla JA, Prince M, Mann A. Smoking, drinking and incident cognitive impairment: a cohort community based study included in the Gospel Oak project. J Neurol Neurosurg Psychiatry 2000;68: 622-6.
Launer LJ, Feskens EJ, Kalmijn S, Kromhout D. Smoking, drinking, and thinking. The Zutphen elderly study. Am J Epidemiol 1996;143: 219-27.
Hébert LE, Scherr PA, Beckett LA, Albert MS, Rosner B, Taylor JO, et al. Relation of smoking and low-to-moderate alcohol consumption to change in cognitive function: a longitudinal study in a defined community of older persons. Am J Epidemiol 1993;137: 881-91.
Graves AB, van Duijn CM, Chandra V, Fratiglioni L, Heyman A, Jorm AF, et al. Alcohol and tobacco consumption as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20(suppl 2): S48-57.
Hébert LE, Scherr PA, Beckett LA, Funkenstein HH, Albert MS, Chown MJ, et al. Relation of smoking and alcohol consumption to incident Alzheimer's disease. Am J Epidemiol 1992;135: 347-55.
Saunders R, Copeland JRH, Dewey ME, Davidson IA, McWilliam C, Sharma V, et al. Heavy drinking as a risk factor for depression and dementia in elderly men. Br J Psychiatry 1991;159: 213-6.
Thomas VS, Rockwood KJ. Alcohol abuse, cognitive impairment, and mortality among older people. J Am Geriatr Soc 2001;49: 415-20.
Kalmijn S, van Boxtel MPJ, Verschuren MVM, Jolles J, Launer LJ. Cigarette smoking and alcohol consumption in relation to cognitive performance in middle age. Am J Epidemiol 2002;156: 936-44.
Galanis DJ, Joseph C, Masaki KH, Petrovich H, Ross GW, White L. A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia aging study. Am J Public Health 2000;90: 1254-9.
Leroi I, Sheppard J-M, Lyketsos CG. Cognitive function after 11.5 years of alcohol use: relation to alcohol use. Am J Epidemiol 2002;156: 747-52.
Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris) 1997;153: 185-92.
Ruitenberg A, van Swieten JC, Wittemann JCM, Mehta KM, van Duijn CM, Hofman A, et al. Alcohol consumption and risk of dementia: the Rotterdam study. Lancet 2002;359: 281-6.
Huang W, Qiu C, Winblad B, Fratiglioni L. Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. J Clin Epidemiol 2002;55: 959-64.
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Dufouil C, Tzourio C, Brayne C, Berr C, Amouyel P, Alpérovitch A. Influence of apolipoprotein E genotype on the risk of cognitive deterioration in moderate drinkers and smokers. Epidemiology 2000;11: 280-4.
Mukamal KJ, Kuller LH, Fitzpatrick AL, Longstreth WT Jr, Mittleman MA, Soscovick DS. Prospective study of alcohol consumption and risk of dementia in older adults. JAMA 2003;289: 1405-13.
Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al. Current concepts in mild cognitive impairment. Arch Neurol 2001;58: 1985-92.
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56: 303-8.
Larrieu S, Letenneur L, Orgogozo JM, Fabrigoule C, Amieva H, Le Carret N, et al. Incidence and outcome of mild cognitive impairment in a population-based prospective cohort. Neurology 2002;59: 1594-9.
Braak E, Griffing K, Arai K, Bohl J, Bratzke H, Braak H. Neuropathology of Alzheimer's disease: what is new since A. Alzheimer? Eur Arch Psychiatry Clin Neurosci 1999;249(suppl 3): 14-22.
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Correspondence to: Miia Kivipelto Miia.Kivipelto@uku.fi
Abstract
Alcohol drinking has been proposed as a possible risk factor for cognitive impairment and dementia, though understanding the association has proved difficult. Some studies have found no association between alcohol drinking and cognitive impairment1-3 or Alzheimer's disease,4 5 whereas others have found an association between heavy drinking and increased risk of dementia.6 7 Some have claimed there is a J or U shaped relation between alcohol drinking and cognitive impairment8-10 or dementia11-14; that is, light to moderate alcohol drinking might have a protective effect compared with total abstention and heavy drinking. The apolipoprotein e4 allele, which is the only genetic risk factor for dementia with an established risk for the general population, may modify the effects of alcohol on the risk of developing cognitive impairment15 16 or dementia.12 17 However, the observed pattern of the effect modification has been different across the studies.
Earlier studies of alcohol drinking and cognition defined cognitive impairment in terms of performance in a variety of neuropsychological tests and did not validate it by any clinical or diagnostic concepts such as the criteria defining mild cognitive impairment.18 Mild cognitive impairment is considered to be a clinically identifiable entity and to carry a high risk for progression to dementia.19 20 Studies of alcohol drinking and dementia have mainly been either cross sectional or carried out in elderly cohorts with relatively short follow up times, making them prone to biases caused by subclinical dementia and other factors.
In order to clarify the role of alcohol in the development of dementia, one needs prospective studies with data on earlier alcohol drinking and long follow up. Given that midlife risk factors contribute to the onset of the dementing disease processes,21 we investigated whether alcohol drinking in middle age could influence the subsequent risk of dementia. The aim of this study was to evaluate the association between midlife alcohol drinking and the risk of mild cognitive impairment and dementia in old age. We also investigated whether the apolipoprotein e4 allele modifies this association.
Participants and methods
Characteristics of the participants according to their midlife alcohol drinking
About 30% of the participants never drank alcohol, 40% drank it infrequently, and 30% drank frequently (table 1). Among the frequent drinkers, about 68% drank alcohol once or twice a month, 24% once a week, about 8% twice a week, and 1% daily. Among the infrequent drinkers, more than 40% drank alcohol twice a year or less frequently, and about 60% reported drinking three to six times a year.
Table 1 Sociodemographic and clinical characteristics of 1018 participants from eastern Finland according to their midlife alcohol consumption. Values are means (standard deviations) unless stated otherwise
Non-drinkers were the oldest group at the follow up examination, and frequent drinkers were the youngest (table 1). Non-drinkers were less educated than the other two groups. Women were more likely to be non-drinkers or infrequent drinkers, whereas men were more likely to be frequent drinkers. Smoking was most common among frequent drinkers. Body mass index and total cholesterol concentration tended to be lower among infrequent drinkers than in the other two groups. The proportion of people with a history of myocardial infarction and stroke did not differ significantly according to drinking frequency either at middle age (a few cases only, data not shown) or old age. Mild cognitive impairment in old age was most common among non-drinkers and least common in infrequent drinkers. The frequency of old age dementia did not significantly differ with drinking frequency (table 1).
Alcohol consumption in middle age and cognitive impairment in old age
Participants who reported never drinking alcohol and those who reported drinking alcohol frequently were both more than twice as likely to have mild cognitive impairment in old age than those who drank infrequently, even after we controlled for age, sex, and years of education (table 2). The results remained essentially the same when we repeated the analyses with additional adjustment for factors related to alcohol drinking or increased risk of dementia, including follow up time, smoking, total serum cholesterol concentration, body mass index, systolic and diastolic blood pressure, and vascular diseases in old age. The risk of dementia did not significantly differ between alcohol drinking categories (table 2). Adding apolipoprotein E genotype to this second model provided only slightly different odds ratios for dementia (non-drinkers 0.81 (95% confidence interval 0.34 to 1.93), infrequent drinkers 1 (reference), frequent drinkers 1.57 (0.70 to 3.50)) and for mild cognitive impairment (non-drinkers 2.03 (0.95 to 4.34), infrequent drinkers 1, frequent drinkers 2.60 (1.19 to 5.69)).
Table 2 Results of multiple logistic regression analyses showing influence of participants' midlife alcohol consumption on their cognitive status in old age. Values are odds ratios (95% confidence intervals)
Effect of apolipoprotein e4 allele
To investigate whether apolipoprotein E genotype modified the effect of midlife alcohol drinking on the risk of dementia in old age, we performed analyses stratified by apolipoprotein e4 carrier status. Because our results indicated that the risk of dementia increased with increasing alcohol drinking frequency (see table 2), we used the group who never drank as the reference group. Among carriers of the apolipoprotein e4 allele, the risk of dementia increased with increasing alcohol consumption after all the adjustments (odds ratio for never drinking 1 (reference), for infrequent drinking 4.08 (95% confidence interval 0.98 to 16.91), and for frequent drinking 7.07 (1.37 to 36.60)). Among non-carriers of apolipoprotein e4, the risk of dementia did not change significantly with alcohol drinking categories (odds ratio for never drinking 1, for infrequent drinking 0.45 (0.13 to 1.60), and for frequent drinking 0.75 (0.19 to 2.99)).
To detect the combined effect of apolipoprotein E genotype and alcohol drinking in relation to dementia, we introduced the interaction term "drinking frequency*apolipoprotein e4" into the logistic regression model together with apolipoprotein e4, drinking frequency, and other covariates. This showed a significant interaction between apolipoprotein E and alcohol drinking frequency, with the overall interaction term being significant (P = 0.04). The interaction terms "infrequent drinking*apolipoprotein e4" and "frequent drinking*apolipoprotein e4" were also significant (P = 0.02 and P = 0.03, respectively). The figure shows the odds ratios derived from this model for each of the six possible combinations between apolipoprotein e4 and drinking frequency. Compared with the participants who never drank and did not carry the apolipoprotein e4 allele, e4 carriers who drank infrequently were 2.3 times more likely to develop dementia, and carriers who drank frequently were 3.6 times more likely. However, the risk of dementia for e4 carriers who never drank was not different from that for non-carriers who never drank. Among the non-carriers, there was no association between alcohol drinking and the risk of dementia.
Combined effect of midlife alcohol drinking and apolipoprotein e4 allele on risk of dementia in old age. Values are odds ratios from one logistic regression analysis with alcohol drinking frequency, apolipoprotein e4, and the interaction term "drinking frequency*apolipoprotein e4" in the model and fully adjusted (see methods). Non-carriers of apolipoprotein e4 who never drank were the reference group. P value for the overall interaction "drinking frequency*apolipoprotein e4" is 0.04. The odds ratio for the interaction term "infrequent drinking*apolipoprotein e4" is 8.52 (P=0.02) and for "frequent drinking*apolipoprotein e4" is 7.64 (P=0.03)
The effect modification by apolipoprotein e4 for the association between alcohol drinking and mild cognitive impairment in the interaction model did not reach significance (P = 0.54 for the overall interaction term, P = 0.39 for "never drinking*apolipoprotein e4," and P = 1.00 for "frequent drinking*apolipoprotein e4," with non-carriers of apolipoprotein e4 who drank infrequently as the reference group).
As mild cognitive impairment and dementia can be seen as points on the same cognitive continuum, we analysed how apolipoprotein e4 modified the association between alcohol drinking and cognitive impairment (including both mild cognitive impairment and dementia). We found similar results as those seen for dementia alone: there was a significantly increased risk among e4 carriers who drank alcohol, more so among frequent drinkers than infrequent drinkers. For the entire interaction between alcohol drinking and apolipoprotein e4, the P value was 0.045. The odds ratio for the interaction term "infrequent drinking*apolipoprotein e4" was 3.87 (P = 0.02), and for "frequent drinking*apolipoprotein e4" it was 3.00 (P = 0.05).
Among men, frequent alcohol drinking was related to an increased risk of mild cognitive impairment (odds ratio = 5.03, P = 0.02) compared with infrequent drinking, but never drinking did not significantly increase the risk (odds ratio = 3.84, P = 0.12). Among women, neither frequent drinking nor never drinking was significantly associated with an increased risk of mild cognitive impairment (odds ratios 1.63 (P = 0.43) and 1.41 (P = 0.44) respectively). Nevertheless, there was no interaction between sex and alcohol drinking frequency for the risk of mild cognitive impairment. Alcohol drinking was not significantly related to risk of dementia in the analyses when we included sex interactions (data not shown).
The results concerning the risk of dementia remained unchanged when we repeated the analyses with the dementia diagnoses derived from the patient registries also taken into account.
Alcohol consumption in old age and cognitive impairment
Alcohol consumption in old age was in agreement with midlife consumption ( = 0.36, P < 0.01). In the analyses of the association between old age drinking and the prevalence of mild cognitive impairment, we found again that non-drinkers more often had mild cognitive impairment than did infrequent drinkers, even after we adjusted for age, education, and sex (data not shown). However, frequent alcohol drinking was no longer associated with mild cognitive impairment. Old age drinking was not associated with dementia. Further adjustments did not change these results. The apolipoprotein e4 allele did not significantly modify the association between old age drinking and mild cognitive impairment or dementia.
Non-participants
Non-participants at the follow up visit (1998) were, at the midlife assessment, older than the participants (mean age 49.1 v 48.0 years, P = 0.01); had spent less time in education (7.7 v 8.7 years, P < 0.01); and had higher systolic blood pressure (148.9 v 143.4 mm Hg, P < 0.01), diastolic blood pressure (92.3 v 90.1 mm Hg, P < 0.01), total serum cholesterol concentration (7.0 v 6.8 mmol/l, P < 0.01), and body mass index (26.9 v 26.3, P < 0.01). They also had dementia in old age (data from patient records) more often than the participants (8.0% v 5.1%, P = 0.03). However, their midlife alcohol consumption did not differ significantly from that of the participants (non-drinkers 34.8% v 29.5%, infrequent drinkers 37.9% v 41.6%, and frequent drinkers 27.4% v 29.0%, P = 0.13), and the prevalence of smoking was similar (47.7% v 44.3%, P = 0.23). The sex distribution of non-participants was no different from that of participants (64.3% v 62.1% women, P = 0.42).
Discussion
Cervilla JA, Prince M, Mann A. Smoking, drinking and incident cognitive impairment: a cohort community based study included in the Gospel Oak project. J Neurol Neurosurg Psychiatry 2000;68: 622-6.
Launer LJ, Feskens EJ, Kalmijn S, Kromhout D. Smoking, drinking, and thinking. The Zutphen elderly study. Am J Epidemiol 1996;143: 219-27.
Hébert LE, Scherr PA, Beckett LA, Albert MS, Rosner B, Taylor JO, et al. Relation of smoking and low-to-moderate alcohol consumption to change in cognitive function: a longitudinal study in a defined community of older persons. Am J Epidemiol 1993;137: 881-91.
Graves AB, van Duijn CM, Chandra V, Fratiglioni L, Heyman A, Jorm AF, et al. Alcohol and tobacco consumption as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 1991;20(suppl 2): S48-57.
Hébert LE, Scherr PA, Beckett LA, Funkenstein HH, Albert MS, Chown MJ, et al. Relation of smoking and alcohol consumption to incident Alzheimer's disease. Am J Epidemiol 1992;135: 347-55.
Saunders R, Copeland JRH, Dewey ME, Davidson IA, McWilliam C, Sharma V, et al. Heavy drinking as a risk factor for depression and dementia in elderly men. Br J Psychiatry 1991;159: 213-6.
Thomas VS, Rockwood KJ. Alcohol abuse, cognitive impairment, and mortality among older people. J Am Geriatr Soc 2001;49: 415-20.
Kalmijn S, van Boxtel MPJ, Verschuren MVM, Jolles J, Launer LJ. Cigarette smoking and alcohol consumption in relation to cognitive performance in middle age. Am J Epidemiol 2002;156: 936-44.
Galanis DJ, Joseph C, Masaki KH, Petrovich H, Ross GW, White L. A longitudinal study of drinking and cognitive performance in elderly Japanese American men: the Honolulu-Asia aging study. Am J Public Health 2000;90: 1254-9.
Leroi I, Sheppard J-M, Lyketsos CG. Cognitive function after 11.5 years of alcohol use: relation to alcohol use. Am J Epidemiol 2002;156: 747-52.
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