Professor of Cerebrovascular Pathology (Neuropathology)
Lead PI, MRC Vascular Factors in Dementia programme; Director, Cerebrovascular Laboraoty, Institute for Ageing and Health
Associate Professor of Neurology, Neurosciences and Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Royal College of Pathologists (Fellow), British Neuroscience Association (Hon Sec), International Brain Research Organisation (Executive Committee), Society for Neuroscience (ordinary member), International Society for Vascular Behavioural and Cognitive Disorders (Chair, Scientific and Nominating Committees)
Gold medal from President Diouf of Senegal, appointed Officier L’Ordre National du Lion for services to promote research and teaching of neurosciences in Africa
Neuropathology of Dementia and Cerebroavascular disease, Vascular Demetia, Alzheimer's disease, Stroke
Neuropathology of Cerebrovascular Disease; CADASIL
Member, Scientific Advisory Board, Alzheimer's Research Trust (UK)
Member, Scientific Advisory Board- Medical Research Council, London
MRC (UK), NIH (NINDS), Alzheimer's Research Trust (UK), EU-1999, Alzheimer's Assocation (USA)and CADASIL Trust (UK).
Interests: Increasing age is the strongest risk factor for cognitive dysfunction, which may result from primary cerebrovascular or neurodegenerative mechanisms, such as those involved in vascular dementia or Alzheimer’s disease (AD), or both. Like neurodegenerative disease, cerebrovascular disease (CVD) leads to high morbidity and mortality and is the second most common cause of dementia. Over the past 17 years, Prof Kalaria and his team in Newcastle have collected abundant evidence from epidemiological, genetic, clinical-pathological and animal studies to demonstrate the impact of systemic vascular and cerebrovascular diseases on cerebral neural processes and cognitive function.
We have also contributed to diagnostic criteria guidelines for vascular dementia and vascular cognitive disorders (DSM V). The NRG has also built a reputation for students to publish at 2-3 peer-reviewed papers prior to completion of their doctoral studies.
Potential Project(s) for students:
In collaboration with colleagues in Edinburgh and Japan (Kyoto and Osaka), the NRG has worked to share their expertise in human ageing, dementias and animal models (mice) of disease to probe mechanistic insights into the effects of altered brain perfusion and downstream consequences. Through these efforts, we have developed rigorous models in order to demonstrate how CVD causes nerve cell degeneration and affect dementia.
The student will test the hypothesis that reduced brain perfusion in genetically altered mice, bred for their suitability to track specific modifications, leads to microvascular changes and subsequent damage to nerve cells, synapses and communication tracts between brain regions, which manifests as white matter disease. He/She will explore how reduced local cerebral blood flow (CBF) leads to neurodegeneration and culminates in cognitive impairment and dementia. Synaptic and dendritic structures are particularly vulnerable targets of ischaemic or hypoperfusive (oligaemic) insults, and likely contribute to cognitive impairment.
The student will also explore how improved perfusion through readily implemented interventions (physical exercise or active lifestyle) protects cortical (and strategic subcortical) structures from degeneration of their neuronal, synaptic, and microvascular network. This research will have impact on the global burden of dementia; identifying strategies, which will enable to reduce common dementing illnesses of old age.
The project is ideally suited to students from a physics based, mathematical or similar background, as they will join a team whose purpose will be to develop and refine the use of multiphoton (MP) laser imaging and its related technology to monitor CBF (laser speckle), blood rheology, perfusion across cerebral capillaries and assess synaptic/neuronal networks in live rodents. The data will be derived from a depth of ~900μm in specified regions of live mouse brains by the interaction of two photon collisions at the site of in vivo fluorochromes. This exciting project has only recently become possible due mainly to current understanding of multiphoton collision at increased tissue depth and the advent of innovative MP equipment design. The development of in vivo imaging using MP microscopy also affords a tremendous opportunity for the IoN and the Wellcome Trust Centre on Translation Research.
Supervision of doctoral and MRes students and fellows (last 2 years):
Primary supervisor :
M Burke (PhD 2013), Elizabeth Gemmell (PhD 2014), R Akinyemi (PhD 2014), Felicity Dewhurst (MD 2013), V Foster (PhD 2015), Stella-Maria Paddick (MD 2015).
Kirsty McAlleese (PhD 2014), Laura Barratt (PhD 2014), S McParland (PhD expected 2014)
Jennifer Horn (MRes 2014); Phoebe J Meyer (MRes 2013), Georgia Raey-Robinson (MRes 2013), R Fenwick (MRes 2013), S Tiwari (MRes 2013). Secondary; Natalie Shek (MRes 2014), M Li (MRes 2014), Noreen Ishaq (MRes 2014)
J Eklid (2014), Shobana Analapakhan (2014)
Dr Lucy Craggs (UK), Dr Yoshiki Hase (Japan), Dr Rufus Akinyemi (Nigeria)
MRES Medical and Molecular Biosciences. Neuroscience module