Lindsay Drevlow, PA-S2 November 21, 2011

1. 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, 2011

2. 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

3. 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

5. Objective • To examine the influence of age on the value of four techniques for diagnosing Alzheimer’s disease

6. Design and Setting • Observational cohort study • Launched in 2003 • Alzheimer’s Disease Neuroimaging Initiative

7. Participants

8. 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

9. Exclusion Criteria • Those using drugs with anticholinergic or opioid properties

10. Techniques Evaluated • Neuropsychological Evaluation • Cerebrospinal Fluid Biomarkers • MRI • FDG-PET

11. 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

12. 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

13. 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

14. 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

15. 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.

16. 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

17. Level of Evidence

18. 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.