Ancillary Studies of the WHI on Hormones

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Ancillary Studies of the WHI on Hormones
Cognition

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

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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.

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TRAJECTORIES OF COGNITIVE FUNCTION OVER LIFE SPAN
Hi
NORMAL
Cognitive Function
SUB-CLINICAL (Mild Cognitive Impairment)
CLINICAL (Dementia)
Low
Years
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Cognition-related WHI Ancillary Studies

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

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Study Relationships
WHI HRT27,348
WHIMS N7,480
CO-STAR N 1600
WHISCAN 2,302
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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.

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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

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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

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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).

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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

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CURRENT STATUS OF COGNITIVE STUDIES IN WHI
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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 PET 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

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Co-Star

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