Gene E Alexander
Professor, BIO5 Institute
Professor, Evelyn F Mcknight Brain Institute
Professor, Neuroscience - GIDP
Professor, Physiological Sciences - GIDP
Professor, Psychiatry
Professor, Psychology
Primary Department
Department Affiliations
(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

Goldman, R. G., Alexander, G. E., Zemishlany, Z., Mukherjee, S., Sackeim, H., & Prohovnik, I. (1996). Acute effects of haloperidol on cerebral cortex blood flow in normal and schizophrenic subjects. Biological Psychiatry, 40(7), 604-608.

PMID: 8886293;Abstract:

To evaluate the effects of neuroleptic medications on cerebral blood flow (CBF), cortical perfusion was quantified by the 133xenon technique in 8 unmedicated schizophrenics and 9 healthy controls before, and 1 and 3 hours after, administration of haloperidol (5 mg per os). At 3 hours, the normal subjects, but not schizophrenic patients, showed a significant increase in global mean perfusion (17 ± 13%). Changes in CBF were not associated with plasma haloperidol levels or the presence of extrapyramidal side effects, and remained significant after controlling for pCO2. The lack of change in CBF in schizophrenic patients following acute haloperidol administration may be due to prior neuroleptic exposure, absence of anxiety, or other nonspecific factors, or may reflect a more fundamental feature of underlying pathophysiology in schizophrenia.

Ibáñez, V., Pietrini, P., Alexander, G. E., Furey, M. L., Teichberg, D., Rajapakse, J. C., Rapoport, S. I., Schapiro, M. B., & Horwitz, B. (1998). Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease. Neurology, 50(6), 1585-1593.

PMID: 9633698;Abstract:

Objective: To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AID) is due entirely to brain atrophy. Background: Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET. Methods: Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects. Results: Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients. Conclusion: Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue.

Stern, Y., Alexander, G. E., Prohovnik, I., Stricks, L., Link, B., Lennon, M. C., & Mayeux, R. (1995). Relationship between lifetime occupation and parietal flow: Implications for a reserve against Alzheimer's disease pathology. Neurology, 45(1), 55-60.

PMID: 7824135;Abstract:

We previously reported an inverse relation between parietal cerebral blood flow and years of education in Alzheimer's disease (AD) patients matched for clinical severity. This suggested that the clinical manifestation of advancing AD pathology is delayed in patients with higher educational attainment. Other aspects of life experience may also provide a reserve against the clinical expression of AD. To test this hypothesis, we classified the primary lifetime occupations of 51 AD patients using the Dictionary of Occupational Titles, published by the US Department of Labor, and derived six factor scores describing intellectual, interpersonal, and physical job demands. Regional cerebral blood flow was measured using the xenon-133 inhalation method. After controlling for age, clinical dementia severity, and education, there was less relative perfusion in the parietal region in subjects whose occupations were associated with higher interpersonal skills and physical demands factor scores. We conclude that independent of education, aspects of occupational experience may provide a reserve that delays the clinical manifestation of AD.

Bokde, A. L., Ibáñez, V., Pietrini, P., Furey, M. L., Alexander, G. E., Graff-Radford, N., Rapoport, S. I., Schapiro, M. B., & Horwitz, B. (1998). Cerebral glucose hypometabolism in the visual variant of Alzheimer's disease after correcting for brain atrophy. NeuroImage, 7(4 PART II), S628.
Carlin, D., Bonerba, J., Phipps, M., Alexander, G., Shapiro, M., & Grafman, J. (2000). Planning impairments in frontal lobe dementia and frontal lobe lesion patients. Neuropsychologia, 38(5), 655-665.

PMID: 10689042;Abstract:

Patients with frontal lobe brain damage are reportedly impaired on tasks that require plan development and execution. In this study, we examined the performance of 15 patients diagnosed with frontal lobe dementia and 14 patients with focal frontal lobe lesions on the Tower of London planning task. Patients with frontal lobe dementia committed a significantly higher number of rule violations, made more moves, and demonstrated longer solution time latencies compared to their matched controls. Patients with frontal lobe lesions demonstrated significantly delayed solution times and also made more moves compared to their matched controls. Frontal lobe lesion patient performance suggests an impairment in execution-related processes, while frontal lobe dementia patients appear to be impaired in both plan development and execution. Despite these findings, the identification of a specific cognitive impairment that induces these planning problems remains elusive. (C) 2000 Elsevier Science Ltd.