Understanding 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.
The Brain Ageing and Dementia research group within the Institute for Ageing and Health 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). 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. We have also identified subcortical vascular disease and frontal grey matter changes as major correlates of cognitive impairment after stroke.
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 (MRC funded NeuroGrid; the NIHR funded Translational Research Collaboration in dementia), International (EU funded LADIS study) imaging collaborations aimed at developing common methods and protocols for image acquisition and analysis and data sharing.
Dementia Projects at the MR Centre
Dementia Publications from the MR Centre
- Mak E, Su L, Williams GB, Watson R, Firbank M, Blamire AM, O’Brien JT. Differential atrophy of hippocampal subfields: a comparative study of dementia with Lewy bodies and Alzheimer’s disease. Am J Ger Psych. In press, (2015).
- 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.
- 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.
- 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. Epub 2012 Jul 19
- 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.
- 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 Apr 12. [Epub ahead of print] PubMed PMID: 22500014.
- 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. In Press (2012)
- 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 May 24. [Epub ahead of print] 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 May 17. [Epub ahead of print] 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.
- 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).
- 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.
- Watson R, Blamire AM, O’Brien JT. Magnetic resonance imaging in Lewy body dementias. Dementia and Geriatric Cognitive Disorders 2009; 28:493-506
- 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.
- 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.