Dementia Research

Professor Andrew Blamire

brain scan imagesUnderstanding the processes affecting the ageing brain is central to unlocking the secrets of dementia. A major project is developing a multi-parameter approach to defining brain tissue structure, organisation and several aspects of function.  To allow effective and acceptable study of people with early dementia we have developed very rapid scanning techniques. These allow measurement of the six major parameters in the same patient (Figure: top row - structural scan, T1 and T2 relaxation maps providing details on tissue microenvironment; bottom row - tissue microsctructure revealed by mean water diffusion, diffusion anisotropy and cerebral blood flow). 

Understanding the relationship between these measurements will shed new light on disease progression of Alzheimer’s disease and other forms of dementia. Clinical studies are ongoing.

Dementia Research

Dr John-Paul Taylor

The Brain Ageing and Dementia research group within the Institute of Neuroscience is one of the leading international centres for research into dementias, especially non-Alzheimer dementias such as vascular dementia, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) and hosts the NIHR Biomedical Research Unit specialising in clinical research into Lewy body dementia. Newcastle, jointly with the Institute of Neurology in London, will be the co-ordinating Centre for the Department of Health funded Neurodegenerative Disease and Dementia Clinical Research Networks. In the North East of England research across the basic to clinical interface has the major advantage of unparalleled access to such patient groups.

Using our 3T magnet we have described cross-sectional and longitudinal structural and spectroscopic changes associated with vascular dementia, DLB and PDD. We have defined key imaging changes characteristic of DLB and PDD, and shown clear separation from AD. Regions of ongoing white matter damage in AD; brain activation during attentional task; regions of greater brain tissue loss in prodromal AD vs DLBWe have also identified subcortical vascular disease and frontal grey matter changes as major correlates of cognitive impairment after stroke (the figure shows regions of ongoing white matter damage in AD; brain activation during attentional task; regions of greater brain tissue loss in prodromal AD vs DLB).

Current studies include functional, spectroscopic and diffusion studies investigating the neural basis of symptom formation (especially fluctuating consciousness and visual hallucinations) in DLB and PDD and investigation of the contribution of Alzheimer and vascular pathology to the development of cognitive impairment after stroke. Serial studies are assessing subjects from both 'at risk' groups and those at the earliest stages of illness to define predictors of subsequent development of dementia and to assess imaging changes as surrogate outcome measures for clinical trials. Development of MR biomarkers in dementia is a central theme of our work and we are exploring the inter-relationships between MR structural and functional changes in dementia and other biomarker modalities e.g. amyloid and metabolic PET imaging, cerebrospinal fluid tau/amyloid etc.

We are also part of national imaging collaborations, including the MRC/NIHR funded Deep and Frequent phenotyping study, and clinical trials for vascular dementia and Alzheimer’s disease. Newcastle is one of the academic partners in the MRC funded Dementia Platforrms UK.

Dementia Projects at the MR Centre

Dementia Publications from the MR Centre

Year 2016

  • Chen AQ, Akinyemi RO, Hase Y, Firbank MJ, Ndung'u MN, Foster V, Craggs LJL, Washida K, Okamoto Y, Thomas AJ, Polvikoski TM, Allan LM, Oakley AE, O'Brien JT, Horsburgh K, Ihara M, Kalaria RN. Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia. Brain 2016;139:242-258. doi: 10.1093/brain/awv328 PMID: 26667280.
  • Firbank MJ, Watson R, Mak E, Aribisala B, Barber R, Colloby SJ, He JB, Blamire AM, O'Brien JT. Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease. Parkinsonism Relat Disord. 2016;24:76-80. doi: 10.1016/j.parkreldis.2016.01.003 PMID: 26792342.
  • Firbank M, Kobeleva X, Cherry G, Killen A, Gallagher P, Burn DJ, Thomas AJ, O'Brien JT, Taylor JP. Neural correlates of attention-executive dysfunction in lewy body dementia and Alzheimer's disease. Hum Brain Mapp. 2016;37(3):1254-1270. doi: 10.1002/hbm.23100 PMID: 26705763.
  • Mak E, Su L, Williams GB, Watson R, Firbank M, Blamire A, O'Brien J. Differential Atrophy of Hippocampal Subfields: A Comparative Study of Dementia with Lewy Bodies and Alzheimer Disease. Am J Geriatr Psychiatry 2016;24(2):136-143. doi: 10.1016/j.jagp.2015.06.006 PMID: 26324541.
  • Su L, Blamire AM, Watson R, He J, Aribisala B, O’Brien J. Cortical and subcortical changes in Alzheimer’s disease: a longitudinal and quantitative MRI study. Current Alz Res. 2016 2016;13(5):534-44 doi: 10.2174/1567205013666151116141416 PMID: 26567737.

Year 2015

  • Peraza LR, Taylor JP, Kaiser M. Divergent brain functional network alterations in dementia with Lewy bodies and Alzheimer's disease. Neurobiol Aging 2015;36(9):2458-2467. doi: 10.1016/j.neurobiolaging.2015.05.015 PMID: 26115566.
  • Peraza LR, Colloby SJ, Firbank MJ, Greasy GS, McKeith IG, Kaiser M, O'Brien J, Taylor JP. Resting state in Parkinson's disease dementia and dementia with Lewy bodies: commonalities and differences. Int J Geriatr Psychiatry 2015;30(11):1135-1146. doi: 10.1002/gps.4342 PMID: 26270627.
  • McAleese KE, Firbank M, Dey M, Colloby SJ, Walker L, Johnson M, Beverley JR, Taylor JP, Thomas AJ, O'Brien JT, Attems J. Cortical tau load is associated with white matter hyperintensities. Acta Neuropathol Commun. 2015;3. doi: 10.1186/s40478-015-0240-0 PMID: 26419828.
  • Blanc F, Colloby SJ, Philippi N, de Petigny X, Jung B, Demuynck C, Phillipps C, Anthony P, Thomas A, Bing F, Lamy J, Martin-Hunyadi C, O'Brien JT, Cretin B, McKeith I, Armspach JP, Taylor JP. Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages. Plos One 2015;10(6). doi: 10.1371/journal.pone.0127396 PMID: 26061655.
  • Mak E, Su L, Williams GB, Watson R, Firbank M, Blamire AM, O’Brien JT. Whole brain atrophy rates differentiate Alzheimer’s disease from dementia with Lewy bodies. In Press Neuroimage:Clinical (2015).
  • Su L, Blamire AM, Watson R, He J, Aribisala B, O’Brien J. Cortical and subcortical changes in Alzheimer’s disease: a longitudinal and quantitative MRI study. In press, Current Alz Res. (2015).
  • Mak E, Su L, Williams GB, Watson R, Firbank MJ, Blamire AM, O'Brien JT. Progressive cortical thinning and subcortical atrophy in dementia with Lewy bodies and Alzheimer's disease. Neurobiol Aging. 2015 Apr;36(4):1743-50. doi: 10.1016/j.neurobiolaging.2014.12.038. Epub 2015 Jan 8. PMID: 25649023.
  • Watson R, Colloby SJ, Blamire AM, O'Brien JT. Assessment of regional gray matter loss in dementia with Lewy bodies: a surface-based MRI analysis. Am J Geriatr Psychiatry. 2015 Jan;23(1):38-46. doi: 10.1016/j.jagp.2014.07.005. Epub 2014 Jul 23. PMID: 25218360.
  • Su L, Blamire AM, Watson R, He J, Aribisala B, O'Brien JT. Tissue microstructural changes in dementia with Lewy bodies revealed by quantitative MRI. J Neurol. 2015 Jan;262(1):165-72. doi: 10.1007/s00415-014-7541-2. Epub 2014 Oct 30. PMID: 25355453.

Year 2014

  • O'Donovan J, Watson R, Colloby SJ, Blamire AM, O'Brien JT. Assessment of regional MR diffusion changes in dementia with Lewy bodies and Alzheimer's disease. Int Psychogeriatr 2014;26(4):627-635. doi: 10.1017/s1041610213002317 PMID: 24331205.
  • Colloby SJ, O'Brien JT, Taylor JP. Patterns of cerebellar volume loss in dementia with Lewy bodies and Alzheimer's disease: A VBM-DARTEL study. Psychiatry Research-Neuroimaging 2014;223(3):187-191. doi: 10.1016/j.pscychresns.2014.06.006 PMID: 25037902.
  • Lowther ER, O'Brien JT, Firbank MJ, Blamire AM. Lewy body compared with Alzheimer dementia is associated with decreased functional connectivity in resting state networks. Psychiatry Res. 2014 Sep 30;223(3):192-201. doi: 10.1016/j.pscychresns.2014.06.004. Epub 2014 Jun 27. PMID: 25035300.
  • Peraza LR, Kaiser M, Firbank M, Graziadio S, Bonanni L, Onofrj M, Colloby SJ, Blamire A, O'Brien J, Taylor JP. fMRI resting state networks and their association with cognitive fluctuations in dementia with Lewy bodies. Neuroimage Clin. 2014 Mar 28;4:558-65. doi: 10.1016/j.nicl.2014.03.013. eCollection 2014. PMID: 24818081.

Year 2013

  • O'Donovan J, Watson R, Colloby SJ, Firbank MJ, Burton EJ, Barber R, Blamire AM, O'Brien JT.  Does posterior cortical atrophy on MRI discriminate between Alzheimer's disease, dementia with Lewy bodies, and normal aging? Int Psychogeriatr. 2013 Jan;25(1):111-9. doi: 10.1017/S1041610212001214. PMID: 22809815.
  • Kenny ER, O'Brien JT, Firbank MJ, Blamire AM. Subcortical connectivity in dementia with Lewy bodies and Alzheimer's disease. British Journal of Psychiatry 2013;203(3):209-214. doi: 10.1192/bjp.bp.112.108464 PMID: 23846997.
  • Wood JS, Watson R, Firbank MJ, Mosimann UP, Barber R, Blamire AM, O’Brien JT. Longitudinal testing of visual perception in dementia with Lewy bodies and Alzheimer’s disease. International Journal of Geriatric Psychiatry. 2013, 28(6):567-572 doi: 10.1002/gps.3860 PMID: 22821711.

Year 2012

  • Kenny ER, Blamire AM, Firbank MJ, O'Brien JT. Functional connectivity in cortical regions in dementia with Lewy bodies and Alzheimer's disease. Brain. 2012 Feb;135:569-81. doi: 10.1093/brain/awr327 PMID: 22189566.
  • Taylor JP, Firbank MJ, He J, Barnett N, Pearce S, Livingstone A, Vuong Q, McKeith IG, O'Brien JT. Visual cortex in dementia with Lewy bodies: magnetic resonance imaging study. Br J Psychiatry. 2012 200(6):491-498. doi: 10.1192/bjp.bp.111.099432 PubMed PMID: 22500014.
  • Lopes MA, Firbank MJ, Widdrington M, Blamire AM, Kalaria RN and O'Brien JT. Post-stroke dementia: the contribution of thalamus and basal ganglia changes, International Psychogeriatrics, 2012, 24(4), pp. 568-576.
  • Firbank MJ, Teodorczuk A, van der Flier WM, Gouw AA, Wallin A, Erkinjuntti T, Inzitari D, Wahlund LO, Pantoni L, Poggesi A, Pracucci G, Langhorne P, O'BrienJT; the LADIS group. Relationship between progression of brain white matter changes and late-life depression: 3-year results from the LADIS study. Br J Psychiatry. 2012 201(1):40-45. doi: 10.1192/bjp.bp.111.098897 PubMed PMID: 22626634.
  • Vasudev A, Saxby BK, OʼBrien JT, Colloby SJ, Firbank MJ, Brooker H, Wesnes K, Thomas AJ. Relationship Between Cognition, Magnetic Resonance White MatterHyperintensities, and Cardiovascular Autonomic Changes in Late-Life Depression.Am J Geriatr Psychiatry. 2012 20(8):691-699. doi: 10.1097/JGP.0b013e31824c0435 PubMed PMID: 22609766.
  • Watson R, O'Brien JT, Barber R and Blamire AM.  Patterns of gray matter atrophy in dementia with Lewy bodies: a voxel-based morphometry study', International Psychogeriatrics, 2012 24(4), pp. 532-540.
  • Taylor JP and O'Brien JT. Neuroimaging of Dementia with Lewy Bodies, Neuroimaging Clinics of North America, 2012, 22(1), pp. 67-81.
  • Colloby SJ, Firbank MJ, He J, Thomas AJ, Vasudev A, Parry SW and O'Brien, JT. Regional cerebral blood flow in late-life depression: arterial spin labelling magnetic resonance study , Br J Psychiatry. 2012 Feb;200(2):150-5. Epub 2011 Dec 22. PubMed PMID: 22194184.
  • Watson R, Blamire AM, Colloby SJ, Wood JS, Barber R, He J and O’Brien JT. (2012) Characterising dementia with Lewy bodies by means of diffusion tensor imaging. Neurology 79(9): 906-14.

Year 2011

  • Wood JS, Firbank MJ, Mosimann UP, Barber R, Watson R, Blamire AM, O’Brien JT. Testing visual perception in dementia with Lewy bodies and Alzheimer’s disease. American Journal of Geriatric Psychiatry 2011; 24:73-83
  • Wood J, Firbank MJ, Mosimann UP, Taylor J-P, O’Brien JT. Development of a novel fMRI compatible visual perception prototype battery to test older people with and without dementia. Journal of Geriatric Psychiatry and Neurology 2011; 24(2) 73-83.
  • Firbank MJ, He Jiabao, Blamire AM, Singh B, Danson P, Rajesh N. Kalaria, et al. Cerebral blood flow by arterial spin labelling in post stroke dementia. Neurology 2011; 76: 1478-1484
  • Firbank MJ, Blamire AM, Teodorczuk A, Teper E, Mitra D, O'Brien JT. Diffusion tensor imaging in Alzheimer's disease and dementia with Lewy bodies. Psychiatry Res. 2011 194(2):176-83
  • Marcos AL, Firbank MJ Widdrington M, Blamire AM, Kalaria RN, O’Brien JT.  Post-stroke dementia: the contribution of thalamus and basal ganglia changes. Int Pyschogeriatrics, in press (2011).

Year 2010

  • Firbank MJ, Blamire AM, Teodorczuk A, Teper E, Burton EJ, Mitra D, O’Brien JT. High resolution imaging of the medial temporal lobe in Alzheimer’s disease and dementia with Lewy bodies. J Alz Disease 2010; 21: 1129-1140.
  • Kenny ER, O’Brien JT, Cousins D, Richardson J, Thomas A, Firbank MJ, Blamire AM. Functional Connectivity in Late-life Depression using Resting-state Functional Magnetic Resonance Imaging. Am J Geriatric Psychiatry 2010 Jul;18(7):643-51.

Year 2009

  • Watson R, Blamire AM, O’Brien JT. Magnetic resonance imaging in Lewy body dementias.  Dementia and Geriatric Cognitive Disorders 2009; 28:493-506

Year 2008

  • Firbank MJ, Barber, R., Burton, E.J., O’Brien, J.T., 2008. Validation of a fully automated hippocampal segmentation method on patients with dementia. Human Brain Mapping 29(12), 1442-1449.

Year 2007

  • Firbank MJ, Blamire AM, Krishnan MS, Teodorczuk A, English P, Gholkar A, et al. Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer's disease. Neuroimage. 2007;36(1):1-7.
  • Firbank MJ, Blamire AM, Krishnan MS, Teodorczuk A, English P, Gholkar A, et al. Diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease. Psychiatry Research-Neuroimaging. 2007;155(2):135-45.