Alzforum: AlzRisk Paper Detail

AlzRisk Paper Detail

Risk Factors

Alcohol

Inflammatory Biomarkers

Non-Steroidal Anti-Inflammatory Drugs

Nutritional Antioxidants

Obesity

Physical Activity

Statin use

Reference:	Shao, 2012

Cohort:	Cache County Study

Risk Factor:	Hormone Therapy

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).

The number of subjects in the analysis does not always add up to 1,768 in all cases because of missing data on timing, duration, or type of hormone therapy.

Exposure Detail
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 time between menopause and HRT initiation (≤ 5 years, > 5 years) and no HRT use, and are broken down by how long HRT was used (<3y, 3-10y, >10y).

Ethnicity Detail
Not reported in this paper. All participants were residents of Cache County, Utah, USA. Ethnicity information is based on a description of the cohort.

Age Detail
Age data in the paper provide ages at the study baseline.

Screening and Diagnosis Detail
Screening Method:

DQ	Dementia Questionnaire (Silverman 1986)
IQ-CODE	Informant Questionnaire for Cognitive Decline in the Elderly (Jorm 1989)
3MSE	Modified Mini-Mental State Examination (Teng 1987)

AD Diagnosis:

Modified NINCDS ADRDA	"Modified" National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria
Brain Imaging

Total dementia definition: DSM-III-R

"Participants were evaluated at each wave for dementia using a multistage assessment procedure described previously.^9,¹⁰ They were screened for cognitive impairments using the Modified Mini-Mental State Examination(3MS),¹³ or the Informant Questionnaire for Cognitive Decline in the Elderly,¹⁴ followed (in waves I and II) by the Dementia
Questionnaire with a proxy informant.¹⁵ 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.¹⁶ 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 criteria¹⁷ for AD."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

AD Covariates:

A	age
E	education
APOE4	APOE e4 genotype
PS	propensity score

TD Covariates:

A	age
E	education
APOE4	APOE e4 genotype
PS	propensity score

Results for total dementia are reported in supplementary Table e1.

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.