Lindsay Drevlow, PA-S2 November 21, 2011
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Transcript of Lindsay Drevlow, PA-S2 November 21, 2011
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Value of Neuropsychological Tests, Neuroimaging, and Biomarkers for Diagnosing Alzheimer’s Disease in
Younger and Older Age Cohorts
Ben Schmand, PhD; Piet Eikelenboom, MD, PhD; Willem A. van Gool, MD, PhD;
and the Alzheimer’s Disease Neuroimaging Initiative
The American Geriatrics Society 59:1705-1710, 2011
Lindsay Drevlow, PA-S2
November 21, 2011QuickTime™ and a
decompressorare needed to see this picture.
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Overview Alzheimer’s 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
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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 Alzheimer’s disease
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Design and Setting Observational cohort study
Launched in 2003
Alzheimer’s Disease Neuroimaging Initiative
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Participants
Normal Controls
Mild Cognitive
Impairment
Alzheimer’s Disease
Number of Participants 105 179 91
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Inclusion Criteria Good physical and mental state “Normal”: intact memory (WMS-R), MMSE >
23, CDR = 0 “MCI”: subjective memory complaints,
abnormal WMS-R, MMSE > 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 Evaluated1. Neuropsychological Evaluation2. Cerebrospinal Fluid Biomarkers3. MRI4. 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 < 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 tau:amyloid-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: 1705–1710. doi: 10.1111/j.1532-5415.2011.03539.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.