Speed of processing, the missing measure in early detection of MCI?

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Speed of processing, the missing measure in
early detection of MCI?
Yogesh Shah

• Ruth OHara
• March 13th 2001

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MCI

• Introduction
• Early detection
• Speed of processing
• Study
• Conclusions

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2001 and beyond

• 100 Billion/year
• Delay 2 years 2 million less AD
• Delay 6 months 6 billion/year

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Early Detection

• Detection of preclinical cognitive deficits is
  important for identifying those at risk for
  Alzheimers
• Neuropsychological measures may not be
  sufficiently sensitive to preclinical cognitive
  impairment

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Normal Speed of Processing Decline
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Millisecond Difference

• the speed of memory performance may be the
  first aspect of the memory system to decline as
  the system begins to fail. Intl Jnl Ger
  Psychiatry, Vol. 10 199-206 (95)
• traditional tests for dementia were relatively
  ineffective for identifying its early forms. The
  only effective assessment is one that measures
  both speed accuracy. Int Psychogeriatr,
  19968(3)397-411

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Millisecond Difference

• research suggests that speed of performance may
  reflect the efficiency of mental processes.
  Nature Neuroscience 2000 3509-515
• speed scores identify impairments that would
  otherwise be missed using traditional measures.
  speed scores on measures of attention memory
  identify patients with MCI.
  Research Practice
  In Alzheimers Disease, Vol. 3, 2000

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Millisecond Difference

• A few 100ms in processing speed may spell the
  difference between healthy unhealthy brain

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Slower Reaction Time on Memory Tasks is
Associated with Presence of the Apolipoprotein E4
allele A Brief Report

• Ruth OHara, Ph.D.,1 Barbara Sommer, M.D., 1
  Helena C. Kraemer, Ph.D., 1 Jerome Yesavage,
  M.D., 1,2 Joy Taylor, Ph.D., 1,2 Kevin Morgan,
  B.A., 1 and Greer Murphy, M.D., Ph.D. 1
• 1 Department of Psychiatry and Behavioral
  Sciences, Stanford University School of Medicine,
  Stanford University, Stanford, CA
• 2 VA Palo Alto Health Care System, Palo Alto, CA

Info_at_cogcare.com
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Reaction Time

• The ability of a computerized battery of
  neurocognitive tests (Cognometer) to
  differentiate between the cognitive performance
  of subjects with and without the e4 allele.

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Abstract   Detection of preclinical cognitive
deficits is important for identifying those at
risk for Alzheimers disease, but available
neuropsychological measures may not be
sufficiently sensitive to preclinical cognitive
impairment, particularly in high functioning,
younger older adults. Utilizing a battery of
computerized cognitive tests designed to provide
a more sensitive measure of age-related cognitive
performance, we compared the performance of 10
older adults with the AD risk-factor
Apolipoprotein e4 allele with 17 older adults
without the e4 allele. This battery includes
measures of attention, sensory-motor,
visuospatial, working memory (executive) and
delayed memory function, which incorporate
reaction time components that reflect
information-processing speed. The e4 group was
significantly slower in performing all delayed
memory and specific working memory tasks,
although no significant differences were observed
between the groups with respect to accuracy on
almost all these measures. This suggests that
reaction time performance on such memory and
working memory measures might be able to detect
subtle cognitive deficits, particularly in
younger, older adults.
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Abstract

• The e4 group was significantly slower in
  performing all delayed memory and specific
  working memory tasks, although no significant
  differences were observed between the groups with
  respect to accuracy.

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Abstract

• Reaction time performance on memory measures
  might be able to detect subtle memory deficits,
  particularly in younger, older adults

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Method

• 10 older adults with Apolipoprotein e4 allele
  with 17 older adults without the e4 allele
• AGE- 74.6
• EDU- 16.2
• MMSE-26

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Stanford Apolipoprotein E4 allele Cognometer
Study
Executive decision-making, set switching task
 
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Individuals with the Apolipoprotein E4 allele
Exhibit Significantly Slower Reaction Times on
Cognometer Tests
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Reaction Time-conclusion

• Individuals with the e4 allele have greater
  difficulty with the information processing
  involved in executive and memory functions

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Reaction Time-conclusion

• Reaction time performance on memory measures
  might be able to detect subtle memory deficits,
  particularly in younger, older adults

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Current issues -MCI

• Is there a frontal, executive deficit in MCI?
• Are standard neuro-psych instruments sensitive to
  working memory deficits?
• Can reaction time measures be meaningful outcome
  in anti-dementia drug trials?

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MCI is there also a frontal, executive deficit?

• ADCS patients with MCI perform worse on
  memory measures. But equal to healthy people in
  other cognitive areas.
• Stanford ApoE4 study (et al) suggests working
  memory processing speed may also be a
  meaningful MCI measure.

Alzheimers Disease Cooperative Study speed
scores on measures of attention memory
identify patients with MCI Research Practice
In Alzheimers Disease, Vol. 3, 2000
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experience with cholinesterase inhibitors shows
that other outcome measures may be more sensitive
to drug effects reaction time measures can be
meaningful outcome measures in anti-dementia drug
trials.Lancet, Vol. 356, December 16, 2000
Dr. Jeffrey Cummings, Dept. of Neurology, UCLA