Professor Raj Kalaria
Professor of Cerebrovascular Pathology (Neuropathology)
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 248 1352
- Fax: +44 (0) 191 208 1301
- Address: Institute of Neuroscience
NIHR Biomedical Research Building
Campus for Ageing and Vitality
Newcastle upon Tyne, NE4 5PL
Roles and Responsibilities
Professor of Cerebrovascular Pathology (Neuropathology), personal chair appointed 1997
Lead PI, Newcastle Cognitive Function After Stroke (CogFAST) Longitudinal Study
Director, Neurovascular Research Group (NRG), Institute of Neuroscience
Co-ordinator, Newcastle NE ARUK Network Centre, Alzheimer's Research UK (ARUK)
Secretary-General, International Society for Vascular Behavioural and Cognitive Disorders (VasCog)
Associate Professor of Neurology, Neurosciences and Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
Royal College of Pathologists (Fellow), Society of Biology (Fellow), International Society for Vascular Behavioural and Cognitive Disorders (Secretary-General), British Neuroscience Association (past Hon Sec), International Brain Research Organisation (past member of Executive Committee),
Honours and Awards
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
Cerebrovascular diseases, Vascular Dementia, Alzheimer's disease, Post-Stroke Dementia
Neuropathology of Cerebrovascular Disease; CADASIL and Small Vessel Diseases of the Brain
Member, Centres of Excellence (CoE), Academy of Finland, Review panel, 2009-2012.
Member, Canadian Excellence Research Chairs (CERC) Review panel, Social Sciences and Humanities Research Council of Canada, 2008-2011.
Member, Scientific Advisory Board, Alzheimer's Research UK, 2000-2010, (2011, also Fellowships)
Member (and chair) Scientific Review panel, Fogarty NIH Brain Disorders Across the Life Span, 2003- 2011.
Member, MRC Clinical Pharmacology and Pathology Fellowships Board, 2009-2010.
Chair, Steering Group, MRC Brain Banks (Sudden death, HIV and CJD), Edinburgh, UK, 2007-2010.
Medical Research Council UK (MRC), Dunhill Medical Trust (UK), Alzheimer's Research UK (ARUK)
Neurovascular Research Group (NRG)
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 2015)
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. Scientific Basis of Neurological Disease module
MRes Ageing and Health module. Neuropathology Lectures
MRCPsyh Parts I and II, Neuroanatomical localization and Neuropathology of Dementia
- Sachdev P, Kalaria R, O'Brien J, Skoog I, Alladi S, Black SE, Blacker D, Blazer DG, Chen C, Chui H, Ganguli M, Jellinger K, Jeste DV, Pasquier F, Paulsen J, Prins N, Rockwood K, Roman G, Scheltens P. Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement. Alzheimer Disease & Associated Disorders 2014, 28(3), 206-218.
- Gemmell E, Tam E, Allan L, Hall R, Khundakar A, Oakley AE, Thomas A, Deramecourt V, Kalaria RN. Neuron Volumes in Hippocampal Subfields in Delayed Poststroke and Aging-Related Dementias. Journal of Neuropathology and Experimental Neurology 2014, 73(4), 305-311.
- Burke MJC, Nelson L, Slade JY, Oakley AE, Khundakar AA, Kalaria RN. Morphometry of the hippocampal microvasculature in post-stroke and age-related dementias. Neuropathology and Applied Neurobiology 2014, 40(3), 284-295.
- Datta A, Qian J, Chong R, Kalaria RN, Francis P, Lai MKP, Chen CP, Sze SK. Novel pathophysiological markers are revealed by iTRAQ-based quantitative clinical proteomics approach in vascular dementia. Journal of Proteomics 2014, 99, 54-67.
- Lam SM, Wang Y, Duan X, Wenk MR, Kalaria RN, Chen CP, Lai MKP, Shui G. The brain lipidomes of subcortical ischemic vascular dementia and mixed dementia. Neurobiology of Aging 2014, 35(10), 2369-2381.
- Ihara M, Kalaria RN. Understanding and preventing the development of post-stroke dementia. Expert Review of Neurotherapeutics 2014, 14(9), 1067-1077.
- Craggs LJL, Yamamoto Y, Ihara M, Fenwick R, Burke M, Oakley AE, Roeber S, Duering M, Kretzschmar H, Kalaria RN. White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Neuropathology and Applied Neurobiology 2014, 40(5), 591-602.
- Rannikmae K, Kalaria RN, Greenberg SM, Chui HC, Schmitt FA, Samarasekera N, Al-ShahiSalman R, Sudlow CL. APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis. Journal of Neurology, Neurosurgery & Psychiatry 2014, 85, 300-305.
- Yamamoto Y, Craggs LJL, Watanabe A, Booth T, Attems J, Low RWC, Oakley AE, Kalaria RN. Brain Microvascular Accumulation and Distribution of the NOTCH3 Ectodomain and Granular Osmiophilic Material in CADASIL. Journal of Neuropathology and Experimental Neurology 2013, 72(5), 416-431.
- Craggs LJL, Oakley A, Kalaria R. CADASIL: Intracytoplasmic Granular Osmiophilic Material Deposits Are Pseudoinclusions Reply. Journal of Neuropathology and Experimental Neurology 2013, 72(8), 801-803.
- Paddick S-M, Longdon AR, Kisoli A, Dotchin C, Gray WK, Dewhurst F, Chaote P, Kalaria R, Jusabani AM, Walker R. Dementia prevalence estimates in sub-Saharan Africa: comparison of two diagnostic criteria. Global Health Action 2013, 6, 19646.
- Kalaria RN, Ihara M. Dementia: Vascular and neurodegenerative pathways - will they meet?. Nature Reviews Neurology 2013, 9(9), 487-488.
- Allan LM, Rowan EN, Thomas AJ, Polvikoski JT, O'Brien JT, Kalaria RN. Long-term incidence of depression and predictors of depressive symptoms in older stroke survivors. British Journal of Psychiatry 2013, n/a, n/a.
- Craggs LJL, Hagel C, Kuhlenbaeumer G, Borjesson-Hanson A, Andersen O, Viitanen M, Kalimo H, McLean CA, Slade JY, Hall R, Oakley AE, Yamamoto Y, Deramecourt V, Kalaria RN. Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases. Brain Pathology 2013, 23(5), 547-557.
- Hawkes CA, Gatherer M, Sharp MM, Dorr A, Yuen HM, Kalaria R, Weller RO, Carare RO. Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid- from the mouse brain. Aging Cell 2013, 12(2), 224-236.
- Carare RO, Hawkes CA, Jeffrey M, Kalaria RN, Weller RO. Review: Cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathology and Applied Neurobiology 2013, 39(6), 593-611.
- Mukaetova-Ladinska EB, Andras A, Milne J, Abdel-All Z, Bohr I, Jaros E, Perry RH, Honer WG, Cleghorn A, Doherty J, McIntosh G, Perry EK, Kalaria RN, McKeith IG. Synaptic proteins and choline acetyltransferase loss in visual cortex in dementia with Lewy bodies. Journal of Neuropathology and Experimental Neurology 2013, 72(1), 53-60.
- Akinyemi R, Mukaetova-Ladinska E, Attems J, Ihara M, Kalaria RN. Vascular Risk Factors and Neurodegeneration in Ageing related Dementias: Alzheimer's Disease and Vascular Dementia. Current Alzheimer Research 2013, 10(6), 642-653.
- Kalaria RN, Perry RH, O'Brien J, Jaros E. Atheromatous disease in small intracerebral vessels, microinfarcts and dementia. Neuropathology and Applied Neurobiology 2012, 38(5), 505-508.
- Ndung'u M, Hartig W, Wegner F, Mwenda JM, Low RWC, Akinyemi RO, Kalaria RN. Cerebral amyloid beta(42) deposits and microvascular pathology in ageing baboons. Neuropathology and Applied Neurobiology 2012, 38(5), 487-499.
- Okamoto Y, Yamamoto T, Kalaria RN, Senzaki H, Maki T, Hase Y, Kitamura A, Washida K, Yamada M, Ito H, Tomimoto H, Takahashi R, Ihara M. Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathologica 2012, 123(3), 381-394.
- Kalaria RN, Mukaetova-Ladinska EB. Delirium, dementia and senility. Brain 2012, 135(9), 2582-2584.
- Kalaria RN, Akinyemi R, Ihara M. Does vascular pathology contribute to Alzheimer changes?. Journal of the Neurological Sciences 2012, 322(1-2), 141-147.
- Huey ED, Ferrari R, Moreno JH, Jensen C, Morris CM, Potocnik F, Kalaria RN, Tierney M, Wassermann EM, Hardy J, Grafman J, Momeni P. FUS and TDP43 genetic variability in FTD and CBS. Neurobiology of Aging 2012, 33(5), 1016.e9–1016.e17.
- Gemmell E, Bosomworth H, Allan L, Hall R, Khundakar A, Oakley AE, Deramecourt V, Polvikoski TM, O'Brien JT, Kalaria RN. Hippocampal Neuronal Atrophy and Cognitive Function in Delayed Poststroke and Aging-Related Dementias. Stroke 2012, 43(3), 808-814.
- Mukaetova-Ladinska EB, Abdel-All Z, Andrade J, McNally RJ, James PW, Kalaria RN, O'Brien JT. Increase in platelet immunoglobulin in Alzheimer's disease is lowered following cholinesterase inhibitor treatment: preliminary results. Journal of Alzheimer's Disease 2012, 32(2), 431-436.
- Ekonomou A, Johnson M, Perry RH, Perry EK, Kalaria RN, Minger SL, Ballard CG. Increased neural progenitors in individuals with cerebral small vessel disease. Neuropathology and Applied Neurobiology 2012, 38(4), 344-353.
- Lax NZ, Pienaar IS, Reeve AK, Hepplewhite PD, Jaros E, Taylor RW, Kalaria RN, Turnbull DM. Microangiopathy in the cerebellum of patients with mitochondrial DNA disease. Brain 2012, 135(6), 1736-1750.
- Firbank MJ, Allan LM, Burton EJ, Barber R, O'Brien JT, Kalaria RN. Neuroimaging predictors of death and dementia in a cohort of older stroke survivors. Journal of Neurology, Neurosurgery and Psychiatry 2012, 83(3), 263-267.
- Giwa MO, Williams J, Elderfield K, Jiwa NS, Bridges LR, Kalaria RN, Markus HS, Esiri MM, Hainsworth AH. Neuropathologic evidence of endothelial changes in cerebral small vessel disease. Neurology 2012, 78(3), 167-174.
- Mukaetova-Ladinska EB, Abdel-All Z, Dodds S, Andrade J, AlvesdaSilva J, Kalaria RN, O'Brien JT. Platelet immunoglobulin and amyloid precursor protein (APP) as potential peripheral biomarkers for Alzheimer’s Disease. Findings from a pilot study. Age and Ageing 2012, 41(3), 408-412.
- Lopes MA, Firbank MJ, Widdrington M, Blamire AM, Kalaria RN, O'Brien JT. Post-stroke dementia: the contribution of thalamus and basal ganglia changes. International Psychogeriatrics 2012, 24(4), 568-576.
- Kitamura A, Fujita Y, Oishi N, Kalaria RN, Washida K, Maki T, Okamoto Y, Hase Y, Yamada M, Takahashi J, Ito H, Tomimoto H, Fukuyama H, Takahashi R, Ihara M. Selective white matter abnormalities in a novel rat model of vascular dementia. Neurobiology of Aging 2012, 33(5), 1012.e25.
- Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA, Kalaria RN. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012, 78(14), 1043-1050.
- Narayan SK, Gorman G, Kalaria RN, Ford GA, Chinnery PF. The minimum prevalence of CADASIL in northeast England. Neurology 2012, 78(13), 1025-1027.
- Allan LM, Rowan EN, Firbank MJ, Thomas AJ, Parry SW, Polvikoski TM, O'Brien JT, Kalaria RN. Long term incidence of dementia, predictors of mortality and pathological diagnosis in older stroke survivors. Brain 2011, 134(12), 3716-3727.
- Chen A, 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, e-pub ahead of print.
- Craggs L, Taylor J, Slade JY, Chen A, Hagel C, Kuhlenbaeumer G, Borjesson-Hanson A, Viitanen M, Kalimo H, Deramecourt V, Oakley AE, Kalaria RN. Clusterin/Apolipoprotein J immunoreactivity is associated with white matter damage in cerebral small vessel diseases. Neuropathology and Applied Neurobiology 2015, (epub ahead of print).
- Pienaar IS, Lee CH, Elson JL, McGuinness L, Gentleman SM, Kalaria RN, Dexter DT. Deep-brain stimulation associates with improved microvascular integrity in the subthalamic nucleus in Parkinson's disease. Neurobiology of Disease 2015, 74, 392–405.
- Chen A, Akinyemi RO, Washida K, Foster V, Firbank MJ, Oakley AE, Okamoto Y, O'Brien JT, Allan LM, Ihara M, Kalaria RN. Frontal white matter clasmatodendrosis and cognitive dysfunction in the elderly. In: 116th Meeting of the British Neuropathological Society Institute of Child Health. 2015, London, UK: Wiley-Blackwell Publishing Ltd.
- Craggs LJL, Fenwick R, Oakley AE, Ihara M, Kalaria RN. Immunolocalization of platelet-derived growth factor receptor-β (PDGFR-β) and pericytes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Neuropathology and Applied Neurobiology 2015, 41(4), 557-570.
- Akinyemi RO, Firbank M, Ogbole GI, Allan LM, Owolabi MO, Akinyemi JO, Yusuf BP, Ogunseyinde O, Ogunniyi A, Kalaria RN. Medial temporal lobe atrophy, white matter hyperintensities and cognitive impairment among African stroke survivors. BMC Research Notes 2015, 8, 625.
- Mukaetova-Ladinska EB, Abdel-All Z, Andrade J, da Silva JA, O'Brien JT, Kalaria RN. Plasma and platelet clusterin ratio is altered in Alzheimer's disease patients with distinct neuropsychiatric symptoms: findings from a pilot study. International Journal of Geriatric Psychiatry 2015, 30(4), 368-375.
- Hattori Y, Okamoto Y, Nagatsuka K, Takahashi R, Kalaria RN, Kinoshita M, Ihara M. SIRT1 attenuates severe ischemic damage by preserving cerebral blood flow. NeuroReport 2015, 26(3), 113-117.
- Akinyemi RO, Ovbiagele B, Akpalu A, Jenkins C, Sagoe K, Owolabi L, Sarfo F, Obiako R, Gebreziabher M, Melikam E, Warth S, Arulogun O, Lackland D, Ogunniyi A, Tiwari H, Kalaria RN, Arnett D, Owolabi MO, SIREN, H3Africa Consortium. Stroke genomics in people of African ancestry: charting new paths. Cardiovascular Journal of Africa 2015, 26(2 Suppl. 1), S39-S49.
- Mukaetova-Ladinska EB, Li M, Kalaria RN. Tau protein, ischemic injury and vascular dementia. Future Neurology 2015, 10(6), 559-575.
- Mukaetova-Ladinska EB, Abdel-All Z, Mugica ES, Li M, Craggs LJ, Oakley AE, Honer WG, Kalaria RN. Tau proteins in the temporal and frontal cortices in patients with vascular dementia. Journal of Neuropathology & Experimental Neurology 2015, 72(2), 148-157.
- Paddick SM, Kalaria RN, Mukaetova-Ladinska EB. The prevalence and clinical manifestations of delirium in sub-Saharan Africa: A systematic review with inferences. Journal of the Neurological Sciences 2015, 348(1-2), 6-17.
- Banik A, Brown RE, Bamburg J, Lahiri DK, Khurana D, Friedland RP, Chen W, Ding Y, Mudher A, Padjen AL, Mukaetova-Ladinska E, Ihara M, Srivastava S, Srivastava MVP, Masters CL, Kalaria RN, Anand A. Translation of Pre-Clinical Studies into Successful Clinical Trials for Alzheimer's Disease: What are the Roadblocks and How Can They Be Overcome?. Journal of Alzheimer's Disease 2015, 47(4), 815-843.
- Mukaetova-Ladinska EB, Abdel-All Z, Craggs LJL, Oakley AE, Honer WG, Kalaria RN. Brain tau in ischaemic injury and vascular dementia. In: Meeting of the British Neuropathological Society. 2014, Institute of Child Health, London, UK: Wiley-Blackwell Publishing Ltd.
- Mulugeta E, Vallortigara J, Francis PT, Hye A, Kalaria RN, Perry EK, Lovestone S, Ballard CG. Dynamin protein in stroke and vascular dementia. Neuroscience Letters 2014, 563, 118-122.
- Washida K, Ihara M, Kalaria RN. Glial activation and white matter change in baboon brain with chronic cerebral hypoperfusion. In: 9th World Stroke Congress. 2014, Istanbul, Turkey: Wiley-Blackwell Publishing.
- Craggs LJL, Yamamoto Y, Deramecourt V, Kalaria RN. Microvascular Pathology and Morphometrics of Sporadic and Hereditary Small Vessel Diseases of the Brain. Brain Pathology 2014, 24(5), 495-509.
- Akinyemi RO, Allan L, Ogunniyi A, Kalaria RN. Profile and determinants associated with vascular cognitive impairment in African stroke survivors: The CogFAST - Nigeria study. In: 9th World Stroke Congress. 2014, Istanbul, Turkey: Wiley-Blackwell Publishing.
- Akinyemi RO, Allan L, Owolabi MO, Akinyemi JO, Ogbole G, Ajani A, Firbank M, Ogunniyi A, Kalaria RN. Profile and determinants of vascular cognitive impairment in African stroke survivors: The CogFAST Nigeria Study. Journal of the Neurological Sciences 2014, 346(1-2), 241-249.
- Foster V, Oakley AE, Slade JY, Hall R, Polvikoski TM, Burke M, Thomas AJ, Khundakar A, Allan LM, Kalaria RN. Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias. Brain 2014, 137(9), 2509-2521.
- Hattori Y, Okamoto Y, Maki T, Yamamoto Y, Oishi N, Yamahara K, Nagatsuka K, Takahashi R, Kalaria RN, Fukuyama H, Kinoshita M, Ihara M. Silent Information Regulator 2 Homolog 1 Counters Cerebral Hypoperfusion Injury by Deacetylating Endothelial Nitric Oxide Synthase. Stroke 2014, 45(11), 3403-3411.