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Non-Steroidal Anti-Inflammatory Drugs
Cache County Study
Average Follow-up Time Detail
The first wave of the study began in 1995, with follow-up in 1998-2000 (wave II), 2002-2003 (wave III), and 2005-2006 (wave IV).
Between waves I and II, participants completed the Women's Health Questionnaire (WHQ), a supplemental telephone questionnaire about reproductive history and use of hormone therapy.
HRT users included both users of unopposed estrogen and users of estrogen combined with a progestin (59.7% took unopposed, 37.0% took opposed, and 3.3% had unknown formulation status). Of the HRT users, 93.6% took an oral form, 11% used a cream, and 6% used a patch (Percentages exceed 100% because some reported using multiple routes of administration).
Results are reported for separate exposure categories in this paper:
1) Any v. No HRT use
2) Time between menopause and HRT initiation (≤ 5y, > 5y)
3) Time between menopause and HRT initiation, broken down by duration (<3y, 3-10y, >10y)
4) HRT formulation (No HRT, any unopposed, any opposed)
5) HRT formulation, broken down by time between menopause and HRT initiation (≤ 5y, > 5y)
6) HRT formulation, broken down by both time between menopause and HRT initiation and time of initiation relative to baseline
The results reported here compare formulation of HRT use (estrogen with progestin, estrogen without progestin) to no HRT use, broken down further by time between menopause and HRT initiation (≤ 5 years, > 5 years).
Not reported in this paper. All participants were residents of Cache County, Utah, USA. Ethnicity information is based on a
of the cohort.
Age data in the paper provide ages at the study baseline.
Screening and Diagnosis Detail
Dementia Questionnaire (Silverman 1986)
Informant Questionnaire for Cognitive Decline in the Elderly (Jorm 1989)
Modified Mini-Mental State Examination (Teng 1987)
Modified NINCDS ADRDA
"Modified" National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria
Total dementia definition:
"Participants were evaluated at each wave for dementia using a multistage assessment procedure described previously.
They were screened for cognitive impairments using the Modified Mini-Mental State Examination(3MS),
or the Informant Questionnaire for Cognitive Decline in the Elderly,
followed (in waves I and II) by the Dementia
Questionnaire with a proxy informant.
Participants with evidence of cognitive dysfunction received a clinical assessment including a clinical history and review of systems, brief physical examination, and 1-hour battery of neuropsychological tests.
Based on this information, working diagnoses of cognitive disorders were assigned. Estimated age at onset of dementia was recorded as the year in which participants met DSM-III-R criteria. Participants with apparent cognitive disorders were re-examined by a study physician and underwent standard laboratory tests and a brain MRI. Finally, a panel of expert clinicians reviewed all available information and assigned differential diagnoses of dementia using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria
Covariates & Analysis Detail
Cox proportional hazards regression
APOE e4 genotype
APOE e4 genotype
The results for total dementia are reported in supplementary Table e-1.
The propensity score was created using predicted probabilities from a logistic regression model of HRT use (any) related to the following covariates: parity, age at menarche, age at menopause, history of hysterectomy, history of oopherectomy, history of alcohol/tobacco use, self-rated health status during the past week, body mass index, history of hypertension, high cholesterol, diabetes, stroke, heart attack, or coronary artery bypass graft surgery, family history of AD in a first degree relative, number of vitamins or supplements taken, physical activity, social activity, and dietary scores for the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diet.