Room 233, Sanders-Brown Center On Aging
800 South Limestone Street
Lexington, KY 40536-0230
Neurology and Sanders-Brown Center on Aging
While mild cognitive impairment (MCI) has largely been considered a pre-Alzheimer’s disease state, clinical and pathologic heterogeneity is common. Subtypes of MCI likely represent preclinical Dementia with Lewy Bodies, Vascular Dementia, Fronto-temporal Dementia, and others. Clinical investigations focus on the unique presentation and clinical course for each subtype of MCI and correlate this with final neuropathologic outcome to further refine and develop more accurate antemortem diagnosis of predementia degenerative disease states.
Clinico-neuropathologic studies are also focused on defining the additive or synergistic roles of complex pathologic processes (cerebrovascular, Lewy body, and argyrophilic grain disease) in the development of dementia. Building collaborative efforts with researchers in neuropsychology, radiology, and the basic sciences (biomarker development) are a major focus of our bench-to-bedside translational research aims.
Studies investigating angiogenic dysregulation in our lab have identified alterations in capillary density in Alzheimer’s disease (AD) that is associated with both decreased progranulin expression and increased amyloid burden in cerebral blood vessels (cerebral amyloid angiopathy, CAA). Extensive work characterizing CAA has allowed the development of a neocortical staging system based on both severity and anatomic distribution of this unique pathological feature. Both soluble and membrane bound VEGF receptors also show abnormal cellular localization in AD suggesting that aberrant angiogenesis may play a critical role in the development of disease. Future work will further define and characterize these changes in both human autopsy and transgenic mouse models allowing for preclinical testing of angiogenic regulators as novel therapies for AD.
Ongoing collaborations with Kentucky Telecare are focused on developing, validating, and implementing clinical telemedicine evaluations for the assessment of MCI and dementia, building a translational (tertiary care to community) model system to improve access to high quality subspecialty healthcare throughout rural and remote areas of Kentucky. The establishment of this rural cohort is providing unique insights into risk factors for and clinical phenotype of cognitive decline in rural Appalachia. Other ongoing translational collaborative efforts include a partnership with the Department of Family Medicine to develop, validate, and implement ecologically-valid clinical tools for the diagnosis of MCI in the primary care setting. We intend to build a clinical cohort in this setting for the longitudinal evaluation of this population in an effort to demonstrate that we can reliably integrate the diagnosis of MCI and improve healthcare outcomes for cognitive decline in the primary care setting.
Clinical trials in Alzheimer’s disease as part of the Alzheimer’s Disease Cooperative Study Group and pharmaceutical company-sponsored trials are a major focus of ongoing research efforts and activities. We are actively engaged in several state-of-the-art clinical trials in an effort to find better treatments and investigate potential cures for Alzheimer’s disease and other degenerative dementias. From early Phase I development through Phase II & III, and potential FDA approval, our research team is focused on finding better medicines that may prove to be disease-modifying, eventually paving the way for the development of cures for Alzheimer’s disease and related disorders.
Our focus is on building a foundation for translational research in degenerative diseases, from bench to bedside, from bedside to practice, from medical centers to communities, in an effort to improve health care outcomes for all who suffer from Alzheimer’s and other degenerative diseases.
GA Jicha & WR Markesbery. Omega 3 fatty acids : potential role in the management of early Alzheimer's Disease.Clinical Interventions in Aging, Clin Interv Aging. 2010 Apr 7;5:45-61. Review. PMID: 20396634.
Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol. 2010 Oct 8.
BT Gold,Y Jiang, GA Jicha, CD Smith. Functional response in ventral temporal cortex differentiates mild cognitive impairment from normal aging.Human Brain Mapping, 2010 Aug;31(8):1249-59. PMID: 20063353.
GA Jicha & SA Carr. Conceptual evolution in Alzheimer’s disease: Implications for our understanding of the clinical phenotype of progressive neurodegenerative disease. JAD,2009 Oct 8. [Epub ahead of print]PMID: 19815973
SA.Carr, R Davis, D Spencer, M Smart, J Hudson, S Freeman, GE Cooper, FA Schmitt, WR Markesbery, D Danner, GA Jicha. Comparison of Recruitment Efforts Targeted at Primary Care Physicians versus the Community At Large for Participation in Alzheimer’s Disease Clinical Trials. Alz Dis Assoc Dis, 2009 Jun 30.
WR Markesbery, GA Jicha, H Liu, FA Schmitt. Lewy Body Pathology in Normal Elderly Subjects.JNEN, 2009 Jun 16.
GA Jicha. Is passive immunization for Alzheimer’s disease “alive and well” or “dead and buried”. Exp Opin Biol Ther, 2009 Apr;9(4):481-91.
PT Nelson, E Abner, FA Schmitt, RJ Kryscio, GA Jicha, CD Smith, DG Davis, JW Poduska, E Patel, MS Mendiondo, WR Markesbery. Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathology, Nov 19, 2008 [E-Pub ahead of print]
GA Jicha, FA Schmitt, E. Abner, P. Nelson, GE Cooper, CD Smith, WR Markesbery. Prodromal clinical manifestations of neuropathologically confirmed neocortical Lewy body disease.Neurobiol Aging, Nov 19, 2008 [E-Pub ahead of print]
Nelson PT, Kryscio, RJ, Abner, EA, Schmitt, FA, Jicha, GA, Mendiondo, MS, Cooper, G, Smith, CB, and Markesbery, WR, Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer’s disease and AD+DLB.Journal of Alzheimer’s Disease, 2008 (In Press).
GA Jicha, E. Abner, FA Schmitt, GE Cooper, N. Stiles, R. Hamon, S. Carr, C.D. Smith, W.R. Markesbery. Clinical features of Mild Cognitive Impairment (MCI) differ in the research and tertiary clinic settings.Dem Geriat Cog Dis, Dement Geriatr Cogn Disord 2008;26:187-192.
GA Jicha, JE Parisi, DW Dickson, R Cha, K Johnson, GE Smith, BF Boeve, RC Petersen, DS Knopman. Age and apoE associations with complex pathologic features in Alzheimer's disease. J Neurol Sci.2008 Oct 15;273(1-2):34-9. Epub 2008 Jul 23.
Nelson PT, Jicha GA,Schmitt FA, Liu H, Davis DG, Mendiondo MS, Abner EL, Markesbery WR. Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severity. J Neuropathol Exp Neurol 66: 1136-1146, 2007.
Smith CD, Chebrolu H, Wekstein DR, Schmitt FA, Jicha GA,Cooper G, Markesbery WR. Brain structural alterations before mild cognitive impairment. Neurology 68: 1268-1273, 2007.
Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha GA, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 6: 734-746, 2007.