Demographic and lifestyle characteristics of the participants were collected via an interviewer-administered questionnaire, consisting of the following measures: personal demographic data, childhood environment, lifestyle, including occupational history, physical exercise (during the adolescent period, around 50 years old and over the past 2 years), cigarette smoking, passive smoking, alcohol consumption, tea drinking, and dietary habits measured by a food frequency questionnaire (FFQ). The questionnaire was designed to capture information on the consumption of major nutrients as well as specific Chinese foods over the las 12 months. The Zung Self-Rating Anxiety Scale (ZSAS) and the Center for Epidemiologic Studies Depression Scale (CESD) were used to determine mood for each subject, the Pittsburgh Sleep Quality Index (PSQI) was used to measure the sleep quality, the EQ-5D to measure the health outcome, and finally, items from the Lawton and Brody Activity of Daily Living (ADL) scale-16 was used to elicit physical self-maintenance and instrumental activities of daily living.

Clinical interviews were conducted for all participants. Participants were asked about their medical histories, reproductive history and hormone use (for women). Medications taken during the previous 2 weeks and during the previous year were also recorded. After each clinical assessment, study neurologists and neuropsychologists reviewed the functional, medical, neurologic, psychiatric, and neuropsychological data and reached a consensus regarding the presence or absence of dementia using DSM-IV criteria.

The neurological examination included motor responses and reflexes assessments for each participant. Subjects also were asked if their parents or siblings have or had been diagnosed with dementia or severe memory impairment. Neurologists administered the Clinical Dementia Rating (CDR) scale to a proxy and elicited memory complaints. Participants were considered to have memory complaints if they, or their proxy, a nurse or physician indicated that they had problems with memory or thinking.

Neuropsychological translated tests from western countries harmonized to Chinese culture were used to collect information about the domains of global cognition, executive function, spatial construction function, memory, language, and attention using the Mini-Mental State Examination (MMSE), Conflicting Instructions Task (Go/No Go Task),the Stick Test, the Modified Common Objects Sorting Test, the Auditory Verbal Learning Test, the Modified Fuld Object Memory Evaluation, the Trail-making test A&B,and the Renminbi (official currency of China) Test.

Participants were examined in the morning upon testing for fasting glucose, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Blood pressure and anthropometry (height and weight, seated height, hip, waist and head circumference) were measured . Body mass index (BMI) was calculated. An electrocardiogram was also conducted for each participant to detect undiagnosed heart disease.

Urine samples, fasting blood, mouth-rinse samples with saliva were collected.

All the information collected during the clinical interview was confirmed from the participants' medical records, maintained by them.

DNA was extracted from blood or saliva samples.

A clinical interview was conducted face-to-face to participants with the mild cognitive impairment (MCI) detected in baseline. Non-demented participants from baseline were also contacted for a cognitive function assessment using the same neuropsychological battery used at baseline. Participants were asked about their cognitive complaints which they, their proxy, or a nurse or physician indicated that they had problems with memory or thinking. The Lawton and Brody Activity of Daily Living (ADL) scale was used to measure physical self-maintenance and instrumental activities of daily living of participants. Participants who suffered with newly onset of hypertension, diabetes mellitus, stroke, and heart disease were examined and confirmed from the medical records.

Neuropsychological translated tests from western countries harmonized to Chinese culture were used to evaluate the cognitive function of participants. The test comprised: the Mini-Mental State Examination (MMSE), Conflicting Instructions Task (Go/No Go Task), the Stick Test, the Modified Common Objects Sorting Test, the Auditory Verbal Learning Test, the Modified Fuld Object Memory Evaluation, the Trail-making Test A&B, and the Renminbi (official currency of China) Test.

For the deceased participants from baseline, the cause and date of death were provided by their family members via the telephone call and confirmed by the death certificates from the Center of Disease Control.