Sally A Shumaker Ph D Wake Forest University

							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




                                   NORMAL
Cognitive
Function
                                 SUB-CLINICAL
                            (Mild Cognitive Impairment)
                                    CLINICAL
                                   (Dementia)
      Low

                                    Years
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
    WHISCA
                             CO-STAR
    N= 2,302
                             N= 1600
                  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