Value of Neuropsychological Tests, Neuroimaging, and Biomarkers for Diagnosing Alzheimer

1
Value of Neuropsychological Tests, Neuroimaging,
and Biomarkers for Diagnosing Alzheimers Disease
in Younger and Older Age Cohorts

• Ben Schmand, PhD Piet Eikelenboom, MD, PhD
  Willem A. van Gool, MD, PhD and the Alzheimers
  Disease Neuroimaging Initiative
• The American Geriatrics Society 591705-1710, 2011

Lindsay Drevlow, PA-S2 November 21, 2011
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Overview

• Alzheimers Disease is a progressive neurologic
  disease of the brain that leads to the
  irreversible loss of neurons and dementia
• Cause unknown
• Amyloid protein precursors
• Multiple E4 genes

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Overview

• Neuropathology
• Diffuse atrophy w/ flattened cortical sulci and
  enlarged cerebral ventricles
• Microscopic findings
• Senile plaques, neurofibrillary tangles, neuronal
  loss, synaptic loss, and granulovascular
  degeneration of the neurons
• Neurotransmitters
• Acetylecholine and norepinephrine

4
Overview

• Most clinical studies are done in people about 75
  years old
• Only 7 of people with AD are younger than 75
• Increasing age Less specific pathologic
  characteristics of AD
• Plaques/tangles
• CSF
• ApoE
• Mixed dementia

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Objective

• To examine the influence of age on the value of
  four techniques for diagnosing Alzheimers
  disease

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Design and Setting

• Observational cohort study
• Launched in 2003
• Alzheimers Disease Neuroimaging Initiative

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Participants
Normal Controls Mild Cognitive Impairment Alzheimers Disease
Number of Participants 105 179 91
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Inclusion Criteria

• Good physical and mental state
• Normal intact memory (WMS-R), MMSE gt 23, CDR
  0
• MCI subjective memory complaints, abnormal
  WMS-R, MMSE gt 23, CDR 0.5
• AD abnormal WMS-R, MMSE 20 - 26, CDR 0.5 - 1
  AND satisfied criteria of probable AD

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Exclusion Criteria

• Those using drugs with anticholinergic or opioid
  properties

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Techniques Evaluated

1. Neuropsychological Evaluation
2. Cerebrospinal Fluid Biomarkers
3. MRI
4. FDG-PET

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Statistical Analyses

• All variables corrected for age, sex education
  based on regression weights in the normal
  control group
• Logistic regressions
• Age
• Median age
• ROCs to compare each technique
• Significance p lt 0.05

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Results

• Selection of Variables
• Neuropsychological testing
• A posteriori classification success 99
• Explained variance 98
• AUC 0.998 (90 CI)
• CSF--total tauamyloid-beta
• A posteriori classification success 78
• Explained variance 47
• AUC 0.86

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Results

• Selection of Variables
• MRI
• A posteriori classification success 88
• Explained variance 73
• AUC 0.94
• FDG-PET
• A posteriori classification success 81
• Explained variance 57
• AUC 0.89

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Results

• Effects of Age
• MRI and neuropsychological assessment
• NO statistical difference b/t younger and older
  age cohorts
• CSF and FDG-PET
• Significantly higher in younger than older
  participants

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Conclusion

• Structural MRI and neuropsychological assessment
  are the prime methods of diagnostic examination
  if AD is suspected
• FDG-PET neuroimaging and CSF biomarkers add very
  little, especially in adults over age 75.

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Limitations

• Artificial discrimination
• AD patients were uncomplicated cases at the
  beginning stages of the disease
• Limited s consented to LP and FDG-PET
• Decreased statistical power
• Circularity

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Level of Evidence
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References

• Schmand, B., Eikelenboom, P., van Gool, W. A. and
  the Alzheimer's Disease Neuroimaging Initiative
  (2011), Value of Neuropsychological Tests,
  Neuroimaging, and Biomarkers for Diagnosing
  Alzheimer's Disease in Younger and Older Age
  Cohorts. Journal of the American Geriatrics
  Society, 59 17051710. doi 10.1111/j.1532-5415.2
  011.03539.x
• Sadock, Benjamin J., and Virginia A. Sadock.
  "7.3." Kaplan Sadock's Concise Textbook of
  Clinical Psychiatry. Philadelphia Wolters
  Kluwer/Lippincott Williams Wilkins, 2008. Print.