CHS, a multi-site observational study of 5,888 adults age 65 years and older (26
), was initiated in 1989. The CHS recruited 5201 participants during its initial wave from Medicare eligibility lists in four U.S. communities: Forsyth County, NC, Washington County, MD, Sacramento County, CA, and Pittsburgh, PA (27
). In 1992/93 687 African-Americans were recruited. From its baseline (1989/90) until 1998/99, up to ten annual clinic visits were completed. Data collected at these examinations each year included demographics, anthropometry, vital signs, cognitive function, psychosocial interviews, depression, medical history, and physical function. Phlebotomy was performed for laboratory analyses. Surveillance and collection of events data is ongoing (28
). All participants completed an informed consent and Institutional Review Board approvals were received at all sites. A separate DNA consent was obtained for genetic studies.
In 1998/99, dementia was classified in 3,602 CHS participants as a part of the CHS Cognition Study (29
). Inclusion into the Cognition cohort required completion of a cranial MRI and the Modified Mini-Mental Status Exam or 3MSE in 1992/94. These participants were screened using data collected at the visit closest to the MRI to identify those at higher risk who were asked to return to the clinic for additional cognitive testing. An individual was considered to be at high risk of dementia if he/she had previously scored less than 80 or had a decrease of 5 or more points on the 3MSE administered at previous exams, a previous Telephone Interview for Cognitive Status (TICS) score <28 or an Informant Questionnaire on Cognitive Decline in the Elderly (IQCode) score of > 3.6, incident stroke, or currently residing in a nursing home. A battery of neuropsychiatric tests was administered to those agreeing to return to the clinic or to receive a home-visit using the following exams: the America version of the National Reading test, Raven’s Couloured Progressive Matrices, California Verbal Learning Test, Rey-Osterreith figure, Immediate and Delayed Recall, modified Boston Naming test, Verbal fluency test, Block design (modified from the Wechsler Adult Intelligence Scale-revised), Stroop Neuropsychological Screening Test, Trail Making, Digit Spans, and the Baddeley & Papagno Divided Attention Task. Methods to evaluate persons who declined the neuropsychiatric battery or were no longer living included a medical record review of all hospitalizations, questionnaires sent to his/her personal physician, and standardized interviews by phone with the participants (if living) or a designated informant (TICS, Neuropsychiatric Inventory, and/or IQCode). In addition, all prospectively collected data from the CHS’s inception were reviewed to provide additional information on cognitive decline over the ten years of follow-up including repeated measures of the 3MSE, Digit Symbol Substitution Test (DSST), Benton Visual Retention Test (BVRT), Trails A and B, CESD-Depression, medications inventory, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADLs), other physical function measures (gait speed, balance tests, grip strength, etc), and documentation of hospitalized medical events such as strokes, myocardial infarctions, etc. All data were compiled into packets for review during the classification process.
Dementia classification was completed by consensus of neurologists and psychiatrists using data from the neuropsychiatric tests or by other data as noted above for deceased participants or those unable to come into the clinic. Cranial MRIs were used for classification of dementia subtype. AD was classified by National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer Disease and Related Disorders Association criteria (31
). VaD was classified by State of California Alzheimer’s Disease Diagnostic and Treatment Centers (ADDTC) criteria (32
). Dementia onset was determined by review of the longitudinal data collected during the 10 years of study follow-up and by family input using the NPI. If date of onset was determined to be prior to entry into the cognition cohort, the participant was determined to have prevalent dementia at baseline.
Anthropometric measurements in late-life were collected in-person at the clinic visit occurring closest to the CHS MRI. These measures included standing height measured in cm, weight measured in kg, waist and hip circumference measured in cm in 1992/93 (baseline for the Cognition Study). Mid-life weight, however, relied upon self-report of weight at age 50 collected in the Medical History form. Mid-life BMI was estimated using this self-report of participants’ “usual” weight at age 50 years and height measured at study baseline. BMI was calculated as weight divided by height squared (kg/m2
), and WHR, as the ratio of waist to hip circumference. BMI was also categorized into four groups as follows: underweight (< 20), normal (20
), overweight (>25-30) and obese (> 30) based on recommendations for older adults (33
). Time to dementia was calculated in days from entry into the Cognition cohort until dementia onset, death, or July 1, 1999 (end of dementia follow-up).
Covariates examined included self-reported age, race (white vs non-white), gender and education (in years); diabetes was ascertained by American Diabetes Association definition. Hypertension was defined as a systolic blood pressure above 140 or diastolic over 190 mm/Hg. Coronary heart disease was based upon a history of myocardial infarction, angina, coronary bypass surgery, or angioplasty. Total cholesterol, C-reactive protein, interleukin-6, and apolipoprotein E (ApoE) genotype were assayed by the CHS Central Laboratory (34
). Smoking status was self-reported (current, previous or never). Ankle-Arm Index was calculated using blood pressure at the brachial artery and ankle (35
Of the 3,602 participants in the CHS Cognition Study, 227 participants with prevalent dementia at the MRI and 577 with mild cognitive impairment (MCI) were excluded. We calculated descriptive statistics for demographics and comorbidities by category of BMI. Chi-square tests and analyses of variance determined bivariate differences. The sample size for these analyses included 2,798 persons, 480 classified with dementia and 2,318 persons without dementia throughout follow-up. Cox proportional hazards regression estimated the risk of dementia associated with BMI at mid- and late-life as continuous and categorical variables. We also examined WHR as an exposure. Models were adjusted for demographics (age, gender, race, and education), cardiovascular and dementia risk factors including history of hypertension, diabetes, coronary heart disease, total cholesterol, ankle-arm blood pressure, C-reactive protein, Interleukin-6, smoking, kilocalories expended per week, and ApoE genotype. For dementia subtype, persons were censored at onset of VaD in models evaluating AD and for AD in models of VaD. All analyses were done using SPSS (version 13.0, Chicago, IL).