Gene E Alexander

Gene E Alexander

Professor, Psychology
Professor, Psychiatry
Professor, Evelyn F Mcknight Brain Institute
Professor, Neuroscience - GIDP
Professor, Physiological Sciences - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-1704

Work Summary

My research focuses on advancing our understanding of how and why aging impacts the brain and associated cognitive abilities. I use neuroimaging scans of brain function and structure together with measures of cognition and health status to identify those factors that influence brain aging and the risk for Alzheimer's disease. My work also includes identifying how health and lifestyle interventions can help to delay or prevent the effects of brain aging and Alzheimer's disease.

Research Interest

Dr. Alexander is Professor in the Departments of Psychology and Psychiatry, the Evelyn F. McKnight Brain Institute, and the Neuroscience and Physiological Sciences Graduate Interdisciplinary Programs of the University of Arizona. He is Director of the Brain Imaging, Behavior and Aging Lab, a member of the Internal Scientific Advisory Committee for the Arizona Alzheimer’s Consortium, and a member of the Scientific Advisory Board for the Arizona Evelyn F. McKnight Brain Institute. He received his post-doctoral training in neuroimaging and neuropsychology at Columbia University Medical Center and the New York State Psychiatric Institute. Prior to coming to Arizona, Dr. Alexander was Chief of the Neuropsychology Unit in the Laboratory of Neurosciences in the Intramural Research Program at the National Institute on Aging. Dr. Alexander has over 20 years experience as a neuroimaging and neuropsychology researcher in the study of aging and age-related neurodegenerative disease. He is a Fellow of the Association for Psychological Science and the American Psychological Association (Division 40) Society for Clinical Neuropsychology. His research has been supported by grants from the National Institutes of Health, the Evelyn F. McKnight Brain Research Foundation, the State of Arizona, and the Alzheimer’s Association. He uses structural and functional magnetic resonance imaging (MRI) and positron emission tomography (PET) combined with measures of cognition and behavior to investigate the effects of multiple health and lifestyle factors on the brain changes associated with aging and the risk for Alzheimer’s disease. Keywords: "Aging/Age-Related Disease", "Brain Imaging", "Cognitive Neurosicence", "Alzheimer's Disease"

Publications

Furey-Kurkjian, M. L., Pietrini, P., Graff-Radford, N. R., Alexander, G. E., Freo, U., Szczepanik, J., & Schapiro, M. B. (1996). Visual variant of Alzheimer disease: Distinctive neuropsychological features. Neuropsychology, 10(2), 294-300.

Abstract:

A subgroup of patients with probable Alzheimer disease (AD) reported a history of isolated visual disturbances (VS) early in the course of disease, without the characteristic memory complaints. Brain imaging and neuropathologic studies indicated that this subgroup had larger involvement of visual cortical areas and relative sparing of temporal, frontal, and limbic structures compared with classic AD. Consistent with these Endings, the authors hypothesized that the cognitive deficits in this subgroup would be distinctly different from those seen in more typical AD patients. The authors studied 10 probable AD patients with VS (AD+VS), 22 patients without VS (AD-), and 25 healthy controls with a neuropsychological test battery. Compared with AD-, AD+VS patients performed significantly better on tests of verbal memory and had greater impairment on tests of visuospatial skills, suggesting a distinct pattern of cognitive dysfunction consistent with metabolic and neuropathologic reports.

Alexander, G. E., Mentis, M. J., Horn, J. V., Grady, C. L., Berman, K. F., Furey, M. L., Pietrini, P., & Moeller, J. R. (1997). Association of task performance with regional PET activation patterns during face-matching: A "pixelated" scaled subprofile model (SSM) analysis. NeuroImage, 5(4 PART II), S118.
Alexander, G. E., Furey, M. L., Grady, C. L., Pietrini, P., Brady, D. R., Mentis, M. J., & Schapiro, M. B. (1997). Association of premorbid intellectual function with cerebral metabolism in Alzheimer's disease: Implications for the cognitive reserve hypothesis. American Journal of Psychiatry, 154(2), 165-172.

PMID: 9016263;Abstract:

Objective: Clinical heterogeneity in Alzheimer's disease has been widely observed. One factor that may influence the expression of dementia in Alzheimer's disease is premorbid intellectual ability. It has been hypothesized that premorbid ability, as measured by educational experience, reflects a cognitive reserve that can affect the clinical expression of Alzheimer's disease. The authors investigated the relation between estimates of premorbid intellectual function and cerebral glucose metabolism in patients with Alzheimer's disease to test the effect of differing levels of premorbid ability on neurophysiological dysfunction. Method: In a resting state with eyes closed and ears occluded, 46 patients with Alzheimer's disease were evaluated with positron emission tomography and [ 18F]-2- fluoro-2-deoxy-D-glucose to determine cerebral metabolism. Premorbid intellectual ability was assessed by a demographics-based IQ estimate and performance on a measure of word-reading ability. Results: After the authors controlled for demographic characteristics and dementia severity, both estimates of premorbid intellectual ability were inversely correlated with cerebral metabolism in the prefrontal, premotor, and left superior parietal association regions. In addition, the performance-based estimate (i.e., reading ability) was inversely correlated with metabolism in the anterior cingulate, paracentral, right orbitofrontal, anti left thalamic regions, after demographic and clinical variables were controlled for. Conclusions: The results suggest that higher levels of premorbid ability are associated with greater pathophysiological effects of Alzheimer's disease among patients of similar dementia severity levels. These findings provide support for a cognitive reserve that can alter the clinical expression of dementia and influence the neurophysiological heterogeneity observed in Alzheimer's disease.

Giovacchini, G., Alexander, G. E., Furey, M. L., Ricciardi, E., Horwitz, B., Solaini, G., Guazzelli, M., Schapiro, M. B., Rapoport, S. I., & Pietrini, P. (1999). Brain metabolism at rest and during passive audiovisual stimulation in young and older healthy human subjects. NeuroImage, 9(6 PART II), S262.
Pietrini, P., Dani, A., Furey, M. L., Alexander, G. E., Freo, U., Grady, C. L., Mentis, M. J., Mangot, D., Simon, E. W., Horwitz, B., Haxby, J. V., & Schapiro, M. B. (1997). Low glucose metabolism during brain stimulation in older Down's syndrome subjects at risk for Alzheimer's disease prior to dementia. American Journal of Psychiatry, 154(8), 1063-1069.

PMID: 9247390;Abstract:

Objective: Down' s syndrome is characterized by the genetically programmed accumulation of substantial Alzheimer's disease neuropathology after age 40 and the development of early dementia years later, providing a unique human model to investigate the preclinical phases of Alzheimer's disease. Older nondemented adults with Down's syndrome show normal rates of regional cerebral glucose metabolism at rest before the onset of dementia, indicating that their neurons maintain function at rest. The authors hypothesized that an audiovisual stimulation paradigm, acting as a stress test, would reveal abnormalities in cerebral glucose metabolism before dementia in the neocortical parietal and temporal areas most vulnerable to Alzheimer' s disease. Method: Regional cerebral glucose metabolism was assessed by means of positron emission tomography (PET) with [18F]fluorodeoxyglucose in eight younger (mean age=35 years, SD=2) and eight older (mean age=50, SD=7) healthy, nondemented adults with trisomy 21 Down's syndrome. PET scans were performed at rest and during audiovisual stimulation in the same scanning session. Levels of general intellectual functioning and compliance were similar in the two groups. Results: At rest the two groups showed no difference in glucose metabolism in any cerebral region. In contrast, during audiovisual stimulation the older subjects with Down' s syndrome had significantly lower glucose metabolic rates in the parietal and temporal cortical areas. Conclusions: Abnormalities in cerebral metabolism during stimulation appeared in the first cortical regions typically affected in Alzheimer's disease. These results indicate that a stress test paradigm can detect metabolic abnormalities in the preclinical stages of Alzheimer's disease despite normal cerebral metabolism at rest.