# Presentation: 042300

## Ancillary Studies of the WHI on Hormones & Cognition

- Sally A. Shumaker, Ph.D.
- Wake Forest University School of Medicine
- October, 2002

## Definition of Terms

***Normal Cognitive Aging:*** age-related changes in cognitive processes, particularly verbal memory.
***Mild Cognitive Impairment (MCI): *** a   detectable decline in one or more core cognitive function.
***Dementia: *** a clinical designation where more than one core cognitive function is significantly impaired.

## TRAJECTORIES OF COGNITIVE FUNCTION OVER LIFE SPAN

**Hi**

**Low**

**Years**

**Cognitive**
**Function**

**CLINICAL**
**(Dementia)**

**SUB-CLINICAL**
** ****(Mild Cognitive Impairment)**

**TRAJECTORIES OF COGNITIVE FUNCTION OVER LIFE SPAN**

**NORMAL**

## Cognition-related WHI Ancillary Studies

- Women’s Health Initiative - Memory Study (WHIMS) (Wyeth Ayerst Contract)
- Women’s Health Initiative Study of Cognitive Aging (WHISCA) (NIA Contract)
- Cognitive Study of Tamoxifen and Raloxifene (Co-STAR) (NIA Contract)

## Study Relationships

- WHI
- HRT=27,348

- WHIMS
- N=7,480

- CO-STAR
- N= 1600

- WHISCAN= 2,302

## WHIMS

- Designed to test the effects of hormone  therapy (ET and Progesterone + ET vs Placebo) on:
- All-cause probable dementia.
- Mild cognitive impairment.
- Progression of probable dementia.
- Of the 18,520 women participating in the Hormone Therapy trial of the WHI, 7480 women, 65 years of age and older, at 39 WHI clinical sites were enrolled into WHIMS.

## WHIMS Protocol

- Annual screening of all participants w/ Modified Mini-Mental
- Women scoring below cut-points complete detailed neuropsychological testing battery, and clinical exam by trained clinician
- Women diagnosed “probable dementia” complete CAT scan and further work-up
- Central adjudication and classification of all dementia cases

## WHISCA

- Designed to determine whether  Hormone Therapy (ET and/or Progesterone + ET):
- Protects against age-associated memory and cognitive decline in women over 65.
- If the addition of progesterone to ET modifies the effects of estrogen on memory and other cognitive abilities.
- Detailed neuropsychological assessment performed annually in 2302 women enrolled from 14 WHIMS sites; women followed annually for up to 6 years

## Co-STAR

- Designed to assess:
- The rate of change in memory and other cognitive abilities in women receiving tamoxifen compared to women receiving raloxifene.
- Whether tamoxifen and raloxifene have beneficial, neutral, or detrimental effects on age-associated memory and cognitive decline in women age 65 & over.
- How the cognitive effects of tamoxifen and raloxifene compare to those of ET, Progesterone + ET, and placebo (i.e., compare to WHISCA cohort).

## Co-STAR, Design

- Ancillary to the Study of Tamoxifen and Raloxifene (STAR) breast cancer prevention trial (NCI/NSABP)
- Women age 65 and older, randomized in STAR are eligible
- Detailed neuropsychological assessment performed annually
- 1,600 women to be recruited from throughout the United States

## CURRENT STATUS OF COGNITIVE 

***STUDIES IN WHI***

## WHIMS & WHISCA 

- Progesterone + ET arm of HT ended June, 2002;  surveillance of dementia (WHIMS) & normal cognitive aging (WHISCA) ongoing.
- Expedited data clean-up (WHIMS & WHISCA) and adjudication of dementia events (WHIMS)
- Plan to publish effects of P+ET on dementia (WHIMS) and cognitive aging (WHISCA) by early, 2003
- ET arm continued as designed with analysis of effects of ET on dementia and cognitive aging  resulting paper produced at end of WHI

## Co-Star

- Early stages of study implementation
- Training and certifying technicians
- Recruiting women into the study