1030 S Broadway
Lexington, KY 40536-0230
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.