Tony WAEGEMANS, MD

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Tony WAEGEMANS, MD UCB Pharma, Belgium
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• MCI as implemented in our study
• MCI is a very early stage of dementia with as
  main characteristic a
• progressive
• cognitive
• impairment
• (a decline from former premorbid level), leading
  in the vast majority of patients to more severe
  and overt forms of dementia (AD, VaD, mixed
  dementia,).
• Mild is not equivalent to benign MCI is
  malignant in prognosis.

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• MCI is not a "psychometric construct" but a
  clinical entity.
• It can be diagnosed using established clinical
  techniques
• e.g. dementia staging instruments such as
• CDR 0.5
• GDS 3
• Such clinical diagnostic measures include
• clinical interview
• "bedside mental tests
• collateral source information.

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• Additional specific psychometric tests may be
  used
• to confirm the diagnosis
• or
• to increase the proportions of patients
  declining
• (delayed recall and executive functions or
  control
• processes - Orgogozo, 2000).

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• Operational definition of MCI
• Although specific psychometric tests were used as
  a scientific tool in defining the MCI concept,
• it is not an ideal instrument for diagnosis
• No reliable reference to pre-morbid level
  possible
• Inclusion of perpetual underachievers
• Exclusion of subjects declining from a high
  pre-morbid level
• Thus a clinical diagnosis is preferred
• In line with how a disease is diagnosed -
  face validity
• Can better assess a decline from pre-morbid
  functioning
• Can identify extraneous influences (physical
  illness, etc)

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• The use of cognitive testing in MCI studies
• Cognitive testing is the ideal endpoint for
  longitudinal follow-up (detailed and repeated
  measures of a condition over time).
• Sensitive to change
• Correlates very closely with
• the increasing clinical severity of dementia
• cerebral atrophy (the Braak staging)
• volumetric MRI measures
• It can be done using standardized and
  well-validated methods

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• The endpoint is an assessment of the core problem
  of such patients cognitive decline over time.
• Although in early stages of dementia memory
  problems may seem predominant, other cognitive
  functions are also deteriorating in various
  proportions and varying speeds in individual
  patients.
• Thus, evaluations must cover a full range of
  cognitive aspects
• The tests should be choosen to measure the
  functions in decline in this early stages.
• The ADAS used in established dementia has
• ceiling effect
• is not sufficiently sensitive in very mild
  cognitive decline

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• Principal endpoint
• A complete cognitive battery measuring each key
  aspect of cognition should be done.
• Tests of free and cued recall
• Delayed recall
• Working memory
• Executive functions (planning and problem
  solving)
• Semantic category fluency
• Praxis and spatial ability
• Attention and concentration
• more global cognitive functioning
• Such cognitive battery should result in one
  composite score covering the global
  deterioration.

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Parallel to studies in established dementia,
there should be a global change evaluation (CIBIC
like) and an assessment of instrumental/complex
activities of daily living (IADL-MCI). Additional
endpoints - CIBIC - GDS - MMSE -
IADL Inventory - MCI-version - Scale for
emotional distress (BSI - Brief Symptom
Inventory)
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Design
Active
Placebo run-in
Placebo
Screening Baseline
6 months
1 year
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Run-in to control for a learning effect, if any.
Congrès

Mémoire
28-30 Sept., 2000
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• Conclusion
• These are the different elements that we and our
  Expert Advisory Board propose to be appropriate
  for evaluating drug effects in MCI, and therefore
  should be included in potential guidelines.
• Design parallel group, placebo-controlled study
  of 1 year duration.
• Diagnosis clinical diagnosis based on staging
  instruments.
• Efficacy endpoints
• cognitive decline documented by using a
  composite score
• from a global cognitive test battery
• supported by a global clinical measure of
  change, and/or an
• impact on instrumental or complex activities
  of daily living