The Third National Health and Nutrition Examination Survey (NHANES III) was conducted in 1988–1994 on a nationwide multi-stage probability sample of 39,695 persons from the civilian, non-institutionalized population aged 2 months and over of the United States [
6]. Persons aged 60 and over, African Americans, and Mexican Americans were over-sampled. Details of the plan, sampling, operation, response and institutional review board approval have been published as have procedures used to obtain informed consent and to maintain confidentiality of information obtained [
6]. The personal interviews and physical and laboratory examinations of NHANES III subjects provided the baseline data for the study. This analysis was based on the public-use version of the NHANES III linked-mortality file with mortality data through 2000. Of 33,994 persons with baseline interview data, 13,944 were under age 17 and 26 lacked data for matching leaving 20,024 eligible for mortality follow-up. The NHANES III linked mortality file contains information based upon the results from a probabilistic match between NHANES III and the NCHS National Death Index records. The NHANES III linked mortality file provides mortality follow-up data from the date of NHANES III survey participation (1988–1994) through 31 December 2000. Of the 20,022 interviewed persons with mortality follow-up, 6,588 were aged 60 years and over and eligible to have cognitive function testing performed, 6,339 of whom had valid cognitive function data. After excluding persons with missing data for any of the variables shown in the tables, 4,916 persons aged 60 and over with complete data remained for mortality analyses (1,919 deaths). The length of follow-up of survivors averaged 8.5 years.
Questions assessing mental cognition were asked only of respondents aged 60 years or older and not to proxy respondents [
7]. These questionnaires were designed for administration in a bilingual (English/Spanish) format so that respondents could be interviewed in their preferred language. The neuropsychological measures used in the NHANES III study, were selected to assess cognitive functions typically affected in dementia. A short cognitive function index (SICF) was constructed for this analysis from these items administered at home interview and/or at a Mobile Examination Center to assess orientation, recall and attention (
Appendix 1) [
7]. Cronbach’s alpha for the index was 0.82 (n = 4916). Participants were asked, “Have you smoked at least 100 cigarettes in your entire life?” (If yes) “Do you smoke cigarettes now?” (If yes) “About how many cigarettes do you smoke per day?” Responses were used to classify persons as current, former and never smokers. Serum cotinine levels were measured by high-performance liquid chromatography and atmospheric-pressure chemical ionization tandem mass spectrometry [
8–
10]. Previous researchers have used the serum cotinine value of <14 ng/mL to identify non-smokers. Serum cotinine is directly proportional to absorbed nicotine and has a half-life of approximately 20 hours [
8]. It is considered a better marker of smoking status than self-reported tobacco use. It has been used in a number of reports to document underreporting of smoking in various groups [
8]. Cotinine data were available for 2,415 of the 4,916 persons for the validity sub-analysis. Compared to persons in the analysis (
Table 1,
Appendix 2), persons aged 60 and greater excluded were older (mean age 72.65 years) and more likely to be female (62%), black (10.5%), and not married (47%) but did not differ in Mexican ethnicity or region of residence.
Estimates of the risk of death from Cox proportional hazards regression models with time-to-event as the time scale and other statistics were computed using the survey weights and survey analysis procedures in Stata release 11. Survivors were censored at the date of the end of mortality follow-up. Proportional hazards assumptions were assessed by graphical methods. Logistic regression models were utilized to further examine the effect of smoking and SICF on the odds of death.