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AlzRisk Paper Detail

Reference: Waring, 1999
Cohort: Rochester Epidemiology Project
Risk Factor: Hormone Therapy

Average Follow-up Time Detail
The Mayo Clinic, which provides care to many Olmsted County residents, began using a system of medical record keeping in 1910, and in 1966, this system was expanded to encompass non-Mayo health care providers serving county residents. As a result, nearly all county residents are represented in some form within the REP. The study includes women who developed AD between 1980 and 1984, and matched controls of the same age ( + or - 3 years) who resided in Rochester in the year of onset of dementia in the matched case (index year).

This study and Roberts et al., 2006 are from the same cohort (i.e., Rochester Epidemiology Project), but they cover different intervals (1980-84 vs 1985-89).

Exposure Detail
HRT exposure was defined as use of any form of estrogen (oral, parenteral, topical suppository) for 6 months or longer. The majority used oral estrogen alone or in combination with topical preparations (90% among case patients and 90% among control subjects). The most common preparation was oral conjugated estrogens. Exposure information was collected by a trained nurse abstractor, who was unaware of the study hypotheses and case status.

Results are reported for three separate exposure categories in this paper:

1) Any v. minimal or no use use ( < 6 months, ≥ 6 months)
2) Duration of use ( never, < 6 months, ≥ 6 months)
3) Total cumulative dose (0 mg, ≤ 20 mg, 21-500 mg, > 500 mg)

The results reported here are for duration of HRT use (categorized in three classes: never, <6 months, and ≥6 months).

Ethnicity Detail
In 1990, 96% of the Olmsted County population were white, many of northern European origin.

Age Detail
"The median age at onset of AD was 82 years (range, 57 to 96); it was later for patients taking ERT than for those not taking ERT (82 years versus 84 years; p = 0.78)."

Screening and Diagnosis Detail
Screening Method:

AD Diagnosis:
DSM IIIR Diagnostic and Statistical Manual III-Revised
NINCDS ADRDA National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (McKhann 1984)

"A retrospective review of all records of potential cases was undertaken, and a diagnosis was made by a neurologist (E.K.) using criteria for dementia and AD previously reported (21-24). Our diagnostic criteria are essentially equivalent to those of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition—Revised (25) for dementia and those of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association for AD (26). However, because our diagnoses were based on a retrospective review of medical records, we were unable to standardize the clinical evaluation of all patients. For example, not all patients examined for dementia underwent neuropsychological testing or imaging tests, and some were never evaluated by either a neurologist or a psychiatrist. The differential diagnosis of AD from other types of dementia was based on all clinical and laboratory information available in the medical record; however, no standard differential diagnosis scale, such as the Hachinski ischemic score or its modifications (27), was used routinely for each patient. Autopsy reports were used whenever available."

Covariates & Analysis Detail
Analysis Type:
Conditional logistic regression

AD Covariates:

Controls were matched to cases based on age (+ or - 3 years) and approximate length of enrollment in the records-linkage system. They were also residents of Rochester, MN during the index year (year of onset of AD in the matched case patient).

It is unclear which covariates (if any) were included in the final models, but authors report that the odds ratio did not change noticeably after controlling for the effects of education, age at menopause, and parity, and when conducting stratified analyses in women who had undergone natural menopause or who used estrogen for > 1 year.