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Dementia

Dr. Peter J. Nestor from the University of Cambridge explores the role of MRI and PET imaging in assessing focal lesions in the mesial temporal lobe, a key area in Alzheimer's disease linked to amnesia. This research focuses on the pathological changes in Alzheimer's, including neurofibrillary tangles and hippocampal atrophy. We investigate how different patterns of temporal lobe atrophy can help distinguish between Alzheimer's disease and other dementias, such as semantic dementia. Innovations in imaging techniques, such as FDG-PET co-registration, provide crucial insights into metabolic pathways and neuronal loss.

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Dementia

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  1. UNIVERSITY OF CAMBRIDGE Dementia Dr Peter J Nestor peter.nestor@mrc-cbu.cam.ac.uk

  2. Imaging challenging patients

  3. Focal lesions to the mesial temporal lobe cause amnesiaAmnesia is the first feature of Alzheimer’s diseaseNeurofibrillary tangle (t) pathology occurs earliest and most severely in the mesial temporal lobe

  4. MRI in established AD Hippocampal atrophy Healthy elderly AD

  5. Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia C. J. Galton, MRCP(UK);, K. Patterson, PhD;, K. Graham, PhD;, M.A. Lambon-Ralph, PhD;, G. Williams, PhD;, N. Antoun, FRCR, FRCP;, B.J. Sahakian, PhD and J.R. Hodges, MD, FRCPNeurology 2001 57: 216-225

  6. 18FDG: a PET tracer analogue of glucose glucose-6-phosphate glucose Energy FDG-6-phosphate FDG blood vessel Brain cells Metabolic pathways of glucose and 18Fluorodeoxyglucose

  7. 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

  8. Alzheimer’s disease Co-registration Spatial normalisation to standard template Smoothing Statistics

  9. Very mild Alzheimer’s-Isolated memory impairment Posterior cingulate hypometabolism

  10. Retrosplenial cortex is the first area universally affected Nestor et al, Eur J Neurosci 2003

  11. 60 year old male, recent onset memory impairment, MMSE = 30/30

  12. Anatomy Cingulum bundle

  13. Regions of interest traced onto 3T volumetric MRI. FDG-PET co-registered onto MRI CMRglc calculated Normalised to cerebellum 3-compartment partial volume correction Method

  14. Co-registration

  15. Nestor et al, Ann Neurol, 2003

  16. Pathology Neuronal loss Amyloid deposition ACh activity loss NFT (t) Marker [18F]FDG [11C]PIB [11C]PMP In development Alzheimer’s disease and positron emission tomography

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