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M X Tang

Publications and source records attributed to M X Tang.

At least 19 recordsLinked to original sources

Familial Alzheimer disease in Latinos: interaction between APOE, stroke, and estrogen replacement.

BACKGROUND: Factors that modify risk related to APOE variants have been examined primarily in unrelated patients and controls, but seldom in family-based studies. Stroke, vascular risk factors, estrogen replacement therapy (ERT), head injury (HI), and smoking have been reported to influence risk of sporadic but not familial Alzheimer disease (AD). OBJECTIVES: To examine the potential relationship between these risk factors and APOE, the authors used a family study design in a population in which the APOE-epsilon4 variant is strongly associated with risk of AD. METHODS: Latino families primarily from the Caribbean Islands in which two or more living relatives had dementia were identified in the New York City metropolitan area, the Dominican Republic, and Puerto Rico. A total of 1,498 participants from 350 families underwent a clinical interview, medical and neurologic examinations, neuropsychological testing, and APOE genotyping. Diagnosis was made by consensus using research criteria for AD. RESULTS: APOE-epsilon4 was associated with a nearly twofold increased risk of AD. A history of stroke was also associated with a fourfold increased risk. A statistical interaction between APOE-epsilon4 and stroke was observed. Women with an APOE-epsilon4 who took ERT did not have an increased risk of AD, but in women with a history of stroke ERT was a deleterious effect modifier. CONCLUSIONS: APOE-epsilon4 and stroke independently increase risk of familial Alzheimer disease (AD) among Latinos, and may interact to further increase AD risk. Among women, the risk of AD associated with APOE-epsilon4 may be attenuated by a history of ERT.

Aged↗

Aggregation of vascular risk factors and risk of incident Alzheimer disease.

BACKGROUND: The prevalence of Alzheimer disease (AD) is increasing in the elderly, and vascular risk factors may increase its risk. OBJECTIVE: To explore the association of the aggregation of vascular risk factors with AD. METHODS: The authors followed 1,138 individuals without dementia at baseline (mean age 76.2) for a mean of 5.5 years. The presence of vascular risk factors was related to incident possible and probable AD. RESULTS: Four risk factors (diabetes, hypertension, heart disease, and current smoking) were associated with a higher risk of AD (p < 0.10) when analyzed individually. The risk of AD increased with the number of risk factors (diabetes + hypertension + heart disease + current smoking). The adjusted hazards ratio of probable AD for the presence of three or more risk factors was 3.4 (95% CI: 1.8, 6.3; p for trend < 0.0001) compared with no risk factors. Diabetes and current smoking were the strongest risk factors in isolation or in clusters, but hypertension and heart disease were also related to a higher risk of AD when clustered with diabetes, smoking, or each other. CONCLUSIONS: The risk of Alzheimer disease (AD) increased with the number of vascular risk factors. Diabetes and current smoking were the strongest risk factors, but clusters including hypertension and heart disease also increased the risk of AD. These associations are unlikely to be explained by misclassification of the outcome, given strong associations when only probable AD is considered.

Aged↗

Association between mild parkinsonian signs and mild cognitive impairment in a community.

BACKGROUND: Mild parkinsonian signs (MPS) are associated with prevalent and incident dementia but it is not known whether they are associated with mild cognitive impairment (MCI). OBJECTIVE: To determine whether MPS and specific MPS (changes in axial function, rigidity, tremor) are associated with MCI in nondemented community-dwelling older people in northern Manhattan, NY. METHODS: Participants underwent neurologic assessment, including a modified motor portion of the Unified Parkinson Disease Rating Scale. MCI was diagnosed in nondemented participants who had cognitive impairment based on neuropsychological testing and no functional impairment. Participants with MCI were classified as having MCI with memory impairment (MCI+M) vs MCI without memory impairment (MCI-M). RESULTS: MCI was present in 608 (27.3%) of 2,230 participants, including 255 participants with MCI+M and 353 with MCI-M; 1,622 participants did not have MCI. MPS were present in 369 (16.5%) of 2,230 participants. In a univariate logistic regression model, odds of MCI+M (vs no MCI) were 51% higher in participants with MPS compared to those with no MPS (OR = 1.51, 95% CI = 1.09 to 2.09, p = 0.01). Multivariate models yielded similar results (OR = 1.45, 95% CI = 1.03 to 2.05, p = 0.03). Rigidity was present in a higher proportion of participants with MCI+M compared to participants without MCI. CONCLUSIONS: Mild parkinsonian signs, especially rigidity, are associated with amnestic mild cognitive impairment. Mild parkinsonian signs and mild cognitive impairment may share similar pathogeneses. Whether this involves Alzheimer-type pathology, Lewy bodies, or vascular changes in the basal ganglia or basal ganglia circuitry deserves further investigation in postmortem studies.

Age Factors↗

Influence of leisure activity on the incidence of Alzheimer's disease.

OBJECTIVE: To determine whether leisure activities modify the risk for incident dementia. BACKGROUND: Although high educational and occupational attainments have been associated with reduced risk of incident dementia, the relation between leisure activities and dementia risk has not been adequately investigated. METHODS: A total of 1,772 nondemented individuals aged 65 years or older, living in northern Manhattan, New York, were identified and followed longitudinally in a community-based cohort incidence study. Subjects' leisure activities at baseline were assessed, annual examinations with the same standardized neurologic and neuropsychological measures were performed for up to 7 years (mean 2.9 years), and incident dementia was assessed as the main outcome measure. Cox proportional hazards models, adjusting for age, ethnic group, education, and occupation, were used to estimate the relative risk (RR) of incident dementia associated with high leisure activities. RESULTS: Of the 1,772 subjects, 207 became demented. The risk of dementia was decreased in subjects with high leisure activities (RR, 0.62; 95% CI 0.46 to 0.83). The association of high leisure with decreased RR of incident dementia was present even when baseline cognitive performance, health limitations interfering with desired leisure activities, cerebrovascular disease, and depression were considered. CONCLUSIONS: The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the disease.

Age Factors↗

Mortality and apolipoprotein E in Hispanic, African-American, and Caucasian elders.

To investigate whether mortality risk is influenced by apolipoprotein E (APOE) genotype and whether the risk differs by ethnicity, we compared the mortality risk in 2,112 individuals > or = 65 years of age residing in northern Manhattan in New York. Mortality risks associated with the APOE genotype, adjusted for sex, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, differed significantly by ethnic group. Among Caucasian and Hispanics, the E2/E3 genotype was associated with the lowest mortality risk in the multivariate Cox proportional hazards modeling, adjusted for lipid levels, whereas mortality risk did not differ substantially between the E4/E3 and E3/E3 genotypes. Among African-Americans, the E2/E3 genotype was not associated with the lowest mortality risk, but the E4/E3 genotype was. Adjustment for heart disease, diabetes, and stroke reduced mortality risk associated with each genotype by about 50% for all ethnic groups, but the patterns remained the same. Although we cannot rule out the possibility of a healthy survival bias, our analyses designed to examine healthy survival by comparing risk of mortality in groups who were younger or older at entry do not support this possibility. Our findings suggest that the APOE genotype is associated with mortality and that the genotypic risks differ by ethnic group. Nearly 50% of the mortality risk associated with the APOE genotype appears to act through major chronic diseases, but those diseases only partially explain the mechanism by which the genotypic risk acts. To better understand the observed ethnic differences in mortality risk by genotype, a detailed prospective study is needed to examine the relationships among APOE, other candidate genes, health conditions, and eventual death.

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Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort.

Research on the relation between diabetes mellitus and dementia has produced conflicting results, and the relation has not been investigated among Blacks and Hispanics. In this study, Cox proportional hazards models were used to analyze longitudinal data from 1,262 elderly subjects without dementia at baseline (1991-1996) who were followed for an average of 4.3 years between 1992 and 1997. Outcomes were incident Alzheimer's disease and dementia associated with stroke. The prevalence of diabetes was 20% at baseline. The adjusted relative risk of Alzheimer's disease among persons with diabetes as compared with those without diabetes was 1.3 (95% confidence interval (CI): 0.8, 1.9). The adjusted relative risk for the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) in subjects with diabetes was 1.6 (95% CI: 1.2, 2.1). The adjusted relative risk of stroke-associated dementia in persons with diabetes was 3.4 (95% CI: 1.7, 6.9). Among Blacks and Hispanics, approximately one third of the risk of stroke-associated dementia was attributable to diabetes (33% (95% CI: 31, 36) and 36% (95% CI: 33, 37), respectively), as compared with 17% (95% CI: 13, 22) among Whites. The finding of an association between diabetes and the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) is consistent with prior reports of a modest relation between diabetes and Alzheimer's disease.

Black or African American↗

Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan.

OBJECTIVE: To compare the incidence rates for AD among elderly African-American, Caribbean Hispanic, and white individuals and to determine whether coincident cerebrovascular disease contributes to the inconsistency in reported differences among ethnic groups. METHODS: This was a population-based, longitudinal study over a 7-year period in the Washington Heights and Inwood communities of New York City. Annual incidence rates for AD were calculated and compared by ethnic group, and cumulative incidence adjusted for differences in education, diabetes, cardiovascular risk factors, and stroke was calculated. RESULTS: The age-specific incidence rate for probable and possible AD was 1.3% (95% CI, 0.8 to 1.7) per person-year between the ages of 65 and 74 years, 4.0% (95% CI, 3.2 to 4.8) per person-year between ages 75 and 84 years, and 7.9% (95% CI, 5.5 to 10.5) per person-year for ages 85 and older. Compared to white individuals, the cumulative incidence of AD to age 90 years was increased twofold among African-American and Caribbean Hispanic individuals. Adjustment for differences in number of years of education, illiteracy, or a history of stroke, hypertension, heart disease, or diabetes did not change the disproportionate risks among the three ethnic groups. CONCLUSION: The incidence rate for AD was significantly higher among African-American and Caribbean Hispanic elderly individuals compared white individuals. The presence of clinically apparent cardiovascular or cerebrovascular disease did not contribute to the increased risk of disease. Because the proportion of African-American and Caribbean Hispanic individuals reaching ages 65 and older in the United States is increasing more rapidly than the proportion of white individuals, it is imperative that this disparity in health among the elderly be understood.

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An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease.

BACKGROUND: Studies of patients meeting clinical and pathologic criteria for Alzheimer disease (AD) have not consistently found associations between the presence of Lewy bodies (LBs) at postmortem examination and a higher frequency during life of the clinical features of dementia with LBs. OBJECTIVE: To evaluate the clinical correlates of LBs in patients with AD. DESIGN AND METHODS: Fifty-one patients were diagnosed as having probable AD during life and met pathologic criteria for AD. Semiquantitative ratings for LBs were obtained in 4 brain regions: substantia nigra, cingulate, insular cortex, and hippocampus. The patients had been followed up semiannually for up to 9.9 years before death, and clinical features associated with dementia with LBs, including extrapyramidal signs and visual hallucinations, were assessed at each study visit. Logistic regression analyses determined whether patients who had LBs were more likely than those without LBs to express specific clinical signs during follow-up. Cox analyses determined whether patients with LBs developed clinical signs or died earlier. Generalized estimating equations were used to compare rates of cognitive or functional change. RESULTS: Nineteen of the 51 patients had at least 1 LB in one of the studied regions. In no case was a significant relation noted between LBs and the presence of a measured clinical sign. No LB measure was associated with an increased risk of developing any of the evaluated clinical signs earlier in the disease. There was no association between the presence of LBs and more rapid mortality or more rapid disease progression. CONCLUSIONS: In patients diagnosed as having AD during life, we did not observe a relation of LBs noted during postmortem examination with the presence of any clinical feature that we assessed or with the rapidity of disease progression. The relation between LBs and specific clinical manifestations may be tenuous in these patients.

Aged↗

Autoantibodies to amyloid-beta and Alzheimer's disease.

Immunization against amyloid-beta has been suggested as a possible preventive or therapeutic treatment for Alzheimer's disease. We hypothesized that some individuals may have autoantibodies to amyloid-beta and that this may be protective. We analyzed the plasma of 365 individuals, drawn from a larger longitudinal epidemiological study, for the presence of antibodies to amyloid-beta. There were detectable but very low levels of anti-amyloid-beta antibodies in just over 50% of all samples and modest levels in under 5% of all samples. However, neither the presence nor the level of anti-amyloid-beta antibodies correlated with the likelihood of developing dementia or with plasma levels of amyloid-beta peptide. These data suggest that low levels of anti-amyloid-beta autoantibodies are frequent in the elderly population but do not confer protection against developing dementia.

Aged↗

Motor impairment in PD: relationship to incident dementia and age.

OBJECTIVE: To analyze the relationship of specific motor impairment in idiopathic PD to incident dementia. BACKGROUND: The total Unified PD Rating Scale (UPDRS) motor score at baseline has been associated with an increased risk of developing dementia in PD. METHODS: A cohort of 214 nondemented community-dwelling patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of baseline motor impairment with incident dementia was analyzed using Cox proportional hazards models. Facial expression, tremor, rigidity, and bradykinesia were analyzed as part of subscore A (indicative of dopaminergic deficiency); speech and axial impairment were analyzed as part of subscore B (indicative of predominantly nondopaminergic deficiency). The correlation between the six motor domains and age was also analyzed. RESULTS: Of 173 patients followed for at least 1 year, 50 became demented according to the Diagnostic and Statistical Manual of Mental Disorders, revised 3rd edition (DSM III-R) criteria (mean follow-up, 3.6 +/- 2. 2 years). When both subscores A and B were entered into the Cox model, subscore B was associated with incident dementia (relative risk = 1.19; 95% CI, 1.09 to 1.30; p = 0.0001), in addition to gender, age, and education, whereas subscore A was not (relative risk = 1.03; 95% CI, 0.99 to 1.07; p = 0.19). Of the six motor domains, speech and bradykinesia were associated with incident dementia (p < 0.05), and axial impairment approached significance (p = 0.06). Only axial impairment was correlated with age (correlation coefficient = 0.32; p < 0.001). CONCLUSION: The findings suggest that motor impairment mediated predominantly by nondopaminergic systems is associated with incident dementia in PD. Axial impairment may be the result of a combined effect of the disease and the aging process.

Age Factors↗

The deletion polymorphism and Val1000Ile in alpha-2-macroglobulin and Alzheimer disease in Caribbean Hispanics.

The association between polymorphisms in the alpha-2-macroglobulin (a2m) gene and Alzheimer's disease remains in doubt because of conflicting results in independent case-control and family studies. We examined the association between Alzheimer's disease and alpha2m polymorphisms in Caribbean Hispanic families. The odds of having the alpha2m deletion/insertion polymorphism was increased 3-fold for family members with Alzheimer's disease compared to healthy family members, rising to 5-fold after adjusting for APOE-epsilon4. In contrast, there was no relationship between the alpha2m Val1000Ile polymorphism and Alzheimer's disease in these families. The inconsistencies in studies cited above and the modest association between alpha2m and Alzheimer's disease found in the Caribbean Hispanic families reported here, suggest that the overall effect of this gene on susceptibility is small and may be limited to certain populations or families.

Adult↗

Familial aggregation of Alzheimer disease among whites, African Americans, and Caribbean Hispanics in northern Manhattan.

BACKGROUND: Alzheimer disease (AD) aggregates in families. OBJECTIVE: To compare the familial aggregation and lifetime risk of AD to the age of 90 years in the first-degree relatives of patients with AD and unrelated controls among Caribbean Hispanics, African Americans, and whites in Washington Heights, Manhattan, New York, NY. METHODS: Family history of AD and demographic information were obtained from informants of 435 patients with probable or possible AD concerning 1577 siblings and parents and from 1094 controls without dementia concerning 3952 siblings and parents. RESULTS: Lifetime risk of AD to the age of 90 years was 25.9% in relatives of patients and 19.1% in relatives of controls. Rate ratio (RR) for AD in relatives of patients compared with relatives of controls was 1.5 overall (95% confidence interval [CI], 1.2-1.9), and was greater for siblings (RR, 1.8; 95% CI, 1.2-2.5) than for parents (RR, 1.2; 95% CI, 0.9-1.8). Within ethnic groups, RR for AD among relatives was significantly elevated in whites (RR, 2.0; 95% CI, 1.2-3.3) and Hispanics (RR, 1.5; 95% CI, 1.1-2.1), but the difference did not reach statistical significance in African Americans (RR, 1.4; 95% CI, 0.7-2.7). Risk of AD was greater among relatives who were women compared with men (RR, 1.5; 95% CI, 1.2-1.9). CONCLUSIONS: Familial aggregation of AD was increased among families of patients compared with those of controls in all 3 ethnic groups. Risk of AD was highest among siblings and women relatives.

Aged↗

No association between a presenilin 1 polymorphism and Alzheimer disease.

BACKGROUND: Homozygosity of allele 1 of a presenilin 1 intron 8 polymorphism (PS1-1) has been associated with doubling of the risk of sporadic late-onset Alzheimer disease (LOAD), in some, but not all studies. OBJECTIVE: To genotype the PS1 intron 8 polymorphism in predominantly Hispanic families with LOAD to test for association and for linkage between this polymorphism and LOAD. DESIGN: A family-based, case-control, genetic-linkage study. SETTING: Predominantly Hispanic families were selected from probands who were part of a random sample of 2128 Medicare beneficiaries aged 65 years or older who were residing in the community of Washington Heights, which is located in the northern part of Manhattan, NY. PARTICIPANTS: Fifty-one families with 103 affected family members, 67 unaffected family members, and 7 family members with other diagnoses were genotyped for the PS1 polymorphism. All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for either probable or possible Alzheimer disease. Age was truncated at 55 years or older. MAIN OUTCOME MEASURES: Association analyses, conditional logistic regression, and traditional linkage methods were applied to the families for the PS1 polymorphism and for the presence of the gene for apolipoprotein E (APOE). Results of the association and conditional logistic regression analyses of PS1 intron 8 polymorphism were subsequently adjusted for the effect of APOE-epsilon4, sex, age, and education of each sibling. RESULTS: No association between the PS1 intron 8 polymorphism and LOAD was observed (relative risk, 0.99; 95% confidence interval, 0.3-3.4). An association between presence of the APOE-epsilon4 allele and LOAD (relative risk 4.05; 95% confidence interval, 1.3-12.5) was observed. CONCLUSION: We could not confirm the relationship between the PS1 intron 8 polymorphism and LOAD in this collection of families.

Aged↗

Rate of memory decline in AD is related to education and occupation: cognitive reserve?

OBJECTIVE: To determine whether the rate of decline in performance on a memory test is more rapid in AD patients with higher versus lower educational and occupational attainment. BACKGROUND: Epidemiologic and imaging studies have suggested that, given comparable clinical severity of dementia, AD pathology is more advanced in patients with higher educational and occupational attainment. Because educational and occupational attainment should not influence the progression of AD pathology, and because severe AD pathology will eventually produce a mortality-causing condition, people with higher attainment might experience clinical AD for a shorter time and have a more rapid clinical progression. METHODS: A total of 177 AD patients were tested yearly for up to four study visits with the Selective Reminding Test (a memory test). Analysis of prospective change in the total recall score was performed by applying generalized estimating equations to regression analyses with repeated measures. RESULTS: At the initial visit, scores were comparable in the high- and low-education and the high- and low-occupation groups. Overall, memory scores declined by approximately 1 point yearly (p<0.01). There was a more rapid decline in memory scores in patients with higher educational (p<0.057) and higher occupational attainment (p<0.02). The authors then stratified patients based on their initial memory scores. The more rapid decline in memory scores associated with higher educational and occupational attainment was noted only in the group with low initial scores (p<0.05 for both). The full group and stratified group analyses were also repeated controlling for other potentially relevant variables including age, gender, race, ethnicity, and the presence of extrapyramidal signs, stroke, or at least one apolipoprotein E-epsilon4 allele. The results remained unchanged. CONCLUSIONS: Memory declined more rapidly in AD patients with higher educational and occupational attainment. This adds support to the idea that the discontinuity between the degree of AD pathology and the observed clinical severity of AD is mediated through some form of reserve.

Aged↗

APOE genotype, plasma lipids, lipoproteins, and AD in community elderly.

BACKGROUND: Genetic variation at the APOE locus has a major influence on both plasma lipid levels and the risk of AD. The relationship between APOE genotype and plasma lipids may influence the risk of AD. OBJECTIVE: In a community-based study of white, African American, and Caribbean Hispanic elderly in New York City, we investigated the relationship between plasma lipids and AD as well as the possible influence of APOE genotype on this relationship. METHODS: Total plasma cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were investigated in a cross-sectional study of nondemented elderly and patients with AD and in a prospective study of incident AD. Analyses included APOE genotype, gender, ethnicity, body mass index, and other potential confounders such as a history of hypertension, smoking, aspirin use, previous stroke, or ischemic heart disease. RESULTS: Compared with nondemented elderly, decreased TC level had a weak but significant inverse association with incident AD, independent of APOE genotype. No other lipoprotein fragment was associated with either prevalent or incident AD. CONCLUSION: Our results suggest that no consistent relationship exists between APOE genotype, plasma lipoproteins, and AD.

Aged↗

Low-density lipoprotein cholesterol and the risk of dementia with stroke.

CONTEXT: Next to Alzheimer disease, vascular dementia is the second most common form of dementia in the elderly, yet few specific risk factors have been identified. OBJECTIVE: To investigate the relationship of plasma lipids and lipoproteins to dementia with stroke. DESIGN AND SETTING: Prospective longitudinal community-based study over a 7-year period (1991-1998). PARTICIPANTS: A total of 1111 nondemented participants (mean [SD] age, 75.0 [5.9] years) were followed up for an average of 2.1 years (range, 1-7.8 years). MAIN OUTCOME MEASURE: Incident dementia with stroke according to standardized criteria, by baseline levels of total plasma cholesterol and triglycerides, low-density lipoprotein (LDL) cholesterol, LDL levels corrected for lipoprotein(a), high-density lipoprotein cholesterol, lipoprotein(a), and apolipoprotein E genotype. RESULTS: Two hundred eighty-six (25.7%) of the 1111 subjects developed dementia during follow-up; 61 (21.3%) were classified as having dementia with stroke and 225 (78.7%) as having probable Alzheimer disease. Levels of LDL cholesterol were significantly associated with an increased risk of dementia with stroke. Compared with the lowest quartile, the highest quartile of LDL cholesterol was associated with an approximately 3-fold increase in risk of dementia with stroke, adjusting for vascular risk factors and demographic variables (relative risk [RR], 3.1; 95% confidence interval [CI], 1.5-6.1). Levels of LDL corrected for lipoprotein(a) were an even stronger predictor of dementia with stroke in the adjusted multivariate analysis. Compared with the lowest quartile, the RR of dementia with stroke for the highest quartile of lipoprotein(a)-corrected LDL cholesterol was 4.1 (95% CI, 1.8-9.6) after adjusting for vascular factors and demographic variables. Lipid or lipoprotein levels were not associated with the development of Alzheimer disease in our cohort. CONCLUSIONS: Elevated levels of LDL cholesterol were associated with the risk of dementia with stroke in elderly patients. Further study is needed to determine whether treatment of elevated LDL cholesterol levels will reduce the risk of dementia with stroke.

Aged↗

The influence of smoking on the risk of Alzheimer's disease.

OBJECTIVE: To investigate the relationship between cigarette smoking and Alzheimer's disease (AD) in a prospective community-based study in northern Manhattan. BACKGROUND: Results from previous case-control studies suggest that there is a protective effect of smoking on AD. However, the recent prospective Rotterdam Study found that there was an increased risk of AD for smokers, particularly those without an apolipoprotein E (APOE)-epsilon4 allele. METHODS: The authors examined data from a community-based longitudinal study of local elders residing in northern Manhattan to determine whether tobacco use increases or decreases the risk of AD. Information regarding the frequency of tobacco use was obtained in structured interviews at the baseline assessment. Standardized clinical assessments were subsequently completed on each subject at annual visits during which incident cases of AD were identified. RESULTS: The relative risk (RR) of AD among former smokers was 0.7 (95% CI, 0.5 to 1.1). The RR among current smokers was 1.9 (95% CI, 1.2 to 3.0). Smokers without an APOE-epsilon 4 allele had the highest risk of AD (RR = 2.1; 95% CI, 2.1 to 3.7) compared with those with an APOE-epsilon 4 allele (RR = 1.4; 95% CI, 0.6 to 3.3). CONCLUSIONS: Our results are consistent with the observation that smoking increases the risk of AD. However, we found that among previous smokers who quit smoking, there may be a slight reduction in the risk of AD.

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