Normal Aging, Diagnosis of Dementia,Best done with multiple clinical and neuropsychological exams over years • Accuracy of clinical diagnosis 60% depending on stage • MRI is normal or shows non-specific atrophy/focal lesions • FDG-PET often shows characteristic pattern for different dementias Imaging Alzheimer’s Disease • Hypometabolism / hypoperfusion – High biparietal – Posterior cingulate – Bitemporal - often asymmetric – Frontal (orbital and cingulate) • Decreased activity is not just atrophy – Seen independent of atrophy – Neural markers often unchanged – Likely due to local damage and deafferentation PET-FDG Patterns in Dementia Dementia Metabolic Deficits •Alzheimer’s Disease •Vascular Dementia •Pick’s Disease •Dementia with Lewy Bodies •Primary Progressive Aphasia Dementia with Lewy Bodies • Associated with PD and α-synuclein plaques • High rate of plaques & tangles • Has bilateral parietal-temporal hypometabolism • Unlike AD, DLB also shows occipital cortex hypometabolism S. Gilman et al. / Experimental Neurology 191 (2005) S95–S103 Clinical Prognostic Value of PET • 88 dementia patients followed clinically for 3 years after PET –52% progressed, 38% stable, 10% improved • FDG-PET criteria for progressive or nonprogressive dementia defined a priori • Baseline PET predicted 94% of patients who progressed • Only 9% of patients with negative scans progressed (negative predictive value = 91%) • FDG-PET criteria in pathological cases – 88% accurate: 94% sensitive, 73 % specific for AD – Restricted to only those with mild or questionable symptoms, overall accuracy was 89% – 94% sensitive, 78% specific to predict any type of degenerative disease • FDG-PET criteria in follow up – 91% sensitive, 75% specific in predicting progression Proposed Utility of PET Evaluation in Dementia • Improve early diagnostic accuracy. • Increase recognition of Alzheimer’s disease and other neurodegenerative dementias. • Remove time of ambiguity for patient & physician. • Facilitate early treatment leading to disease stabilization and improved quality of life.

1. “ Imaging in Dementia” & incorporating a short primer to Functional Neuroimaging Dr Himadri S. Das. Dr P.Hatimota,Dr.P.Hazarika,Dr.C.D.Choudhury MATRIX Guwahati

6. Cerebral Hemorrhage Mixed acute/chronic subdural hematoma Acute intraparenchymal hematoma

7. Tumor or Other Masses Arachnoid Cyst Abscess “ Tumefactive” MS GBM

17. DWI , DTI & FA

20. Perfusion fMRI

29. 3D FUSION fMRI

30. FDG PET Co-registration with MRI

31. The image Healthy brain areas need glucose and thus appear bright on the scan Damaged brain areas are not working and therefore do not pick up glucose

33. MEG TMS transcranial magnetic stimulator uses PET scanner

34. TMS TMS

35. ALZHEIMER’S DISEASE(AD)

37. PATHOLOGY: Senile plaques, Neurofibrillary tangles, decreased synaptic density, neuron loss & cerebral atrophy. Plaques Vs tangles? Genetic evidence implicates derangement in amyloid metabolism Tau protein found by breakdown of microtubules are the pathologic substrate of NF tangles Neuritic (senile) plaque consisting of central beta amyloid core with inflammatory cells & dystrophic neurites

38. IMAGING IN AD: Atrophy : Hemispheric & specific anatomic sites like etorhinal cortex,medial temporal lobe & hippocampus. Volm & linear measurements of hippocampus, interuncal distance & medial temporal lobe limbic structures correlating with age matched controls MR volume measurement of hippocampal atrophy is a sensitive marker of the pathology of AD ,early in the disease.

40. IMAGING IN AD: Prediction of AD by a single imaging study(Mayo clinic AD study) using MR measurements : During longitudinal follow up of 32.6 months of 80 patients with MCI , 27 developed AD Most studies show median rate of atrophy of upto 1.5 percent against 0.2 percent in comparable control groups

41. Magnetic Resonance Spectroscopy in Alzheimer's Disease MRS • Increase in the NAA/creatine ratio in the frontal cortex (1.23 at baseline vs 1.3 after treatment; p = 0.026) and • Increase in the myo-inositol/creatine ratio in the occipital cortex (0.61 vs 0.65; p = 0.009) • DWI: Increase in diffusion values are seen in AD pts compared to controls

42. Magnetic resonance image in a patient with posterior cortical atrophy

43. IMAGING IN AD IMAGING IN AD MR PERFUSION, 18FDG PET & SPECT : shows bilateral temporal parietal perfusion/metabolism defects Considerable research ongoing for functional activation of the medial temporal lobes in AD patients using memory paradigms as “stress test”. Functional changes in early AD pathology precedes gross architextural changes.

44. 18F-fluorodeoxyglucose PET of the patient with posterior cortical atrophy Hypometabolism in posterior cingulate,parietotemporal, and visual (lateral and primary) cortex. The frontal, sensor motor cortex, cerebellum and caudate nucleus were relatively preserved

46. Comparison of brain perfusion SPECT images for moderate AD and moderate DLB DLB showed lower perfusion in occipital cortex than AD (arrows). In contrast, AD showed lower perfusion in medial temporal areas (arrowheads) Hiroshi Matsuda, J Nucl Med. Aug 2007

48. Pick's Disease Brain show circumscribed atrophy of frontal & anterior temporal lobes with sparing of motor cortex & medial temporal lobe. Frontal lobe degeneration: Second MC FTD syndrome. Grossly same as Pick’s however histopathologically shows spongiform degeneration & microvacuolation FTD WITH ALS: Third MC FTD syndrome. Histologically shows overlap between Pick”s & FLD. Unique feature is loss of neurons & gliosis in substantia nigra & loss of motor neurons in the trigeminal & hypoglossal nuclei.

50. Imaging in FTD

58. Thank you