lindsay drevlow, pa-s2 november 21, 2011

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.

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

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

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

Objective To examine the influence of age on the value

of four techniques for diagnosing Alzheimer’s disease

Design and Setting Observational cohort study

Launched in 2003

Alzheimer’s Disease Neuroimaging Initiative

Participants

Normal Controls

Mild Cognitive

Impairment

Alzheimer’s Disease

Number of Participants 105 179 91

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

Exclusion Criteria Those using drugs with anticholinergic or

opioid properties

Techniques Evaluated1. Neuropsychological Evaluation2. Cerebrospinal Fluid Biomarkers3. MRI4. FDG-PET

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

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

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

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

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.

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

Level of Evidence

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.