1. Structural and Functional Neuroimaging in the Diagnosis of Dementia John M. Ringman, M.D. Assistant Professor UCLA Department of Neurology

2. Neuroimaging in Dementia Outline What is Dementia and Alzheimer’s Disease? How Do We Diagnose It? Clinical Evaluation Structural Neuroimaging Functional Neuroimaging

3. MRI studies brain anatomy. Functional MRI (fMRI) studies brain function. MRI vs. fMRI Source: Jody Culham’s fMRI for Dummies web sitefMRI for Dummies

4. Dementia - DSM-IV Definition Multiple cognitive deficits Memory loss must be present One or more other deficit (aphasia, apraxia, agnosia, executive functions) Decline from prior level of function Deficits do not occur exclusively in the presence of delirium

5. Neuroimaging in Dementia Background Prevalence of Degenerative Dementias Alzheimer’s disease (“AD” - 47-66%) Dementia with Lewy Bodies (5-20%) Frontotemporal dementia (12-17%) Other Vascular dementia (20-47%) HIV, CJD, B 12 deficiency, Normal Pressure Hydrocephalus, neurosyphilis, EtOH, head trauma Clinical diagnosis of AD is imperfect (81% sensitivity, 70% specificity) (Knopman et al, ‘01)

6. Early Alzheimer’s Disease - Clinical Evaluation History and Physical/Neurological Examination Mini Mental Status Exam (MMSE) Insensitive to mild cognitive decline Influenced by language, education Memory subtest inadequate Verbal fluency - (Benson) Number of “F” words named in a minute (should produce 10-20) Clock Drawing Test (Shulman, 2000) Quick way to assess executive function

7. Classic and primitive A  deposits in AD brain (Armstrong et al, 2002)

8. Neuroimaging in Dementia - When to Obtain Neuroimaging A CT or MRI recommended by the American Academy of Neurology during the work-up for dementia (Knopman et al, Neurology, ‘01) Rule out other causes of dementia (stroke, brain tumor) Precise diagnosis assists in prognosis and family counseling Helps make decisions regarding treatment

9. Neuroimaging in Dementia - Structural Neuroimaging Computerized Axial Tomography (CT scan) Produces a 3-dimensional reconstruction of X- ray information Magnetic Resonance Imaging (MRI) Uses magnetic properties of the protons in water molecules in your body to make images of soft tissues (such as the brain)

11. Grade 1, 2, 3, and 4 medial temporal lobe atrophy (Scheltens et al., ‘95)

12. Positron Emission Tomography (PET scans) Fluorodeoxyglucose (FDG) PET scans measure metabolism Ligands that label specific pathological changes FDDNP and PIB may label Alzheimer’s pathology Single Photon Emission Tomography (SPECT) Typically measures blood flow Functional magnetic resonance imaging (fMRI) Measures areas of increased blood flow during a mental task Neuroimaging in Dementia - Functional Neuroimaging

13. (Silverman et al, ‘99)

14. (Klunk et al, ‘04)

15. FMRI BOLD activation during recall and learning (Bookheimer et al, ‘00) May represent compensatory increase in blood flow