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

Dimitrov, M., Granetz, J., Peterson, M., Hollnagel, C., Alexander, G., & Grafman, J. (1999). Associative learning impairments in patients with frontal lobe damage. Brain and Cognition, 41(2), 213-230.

PMID: 10590820;Abstract:

The performance of 18 frontal lobe lesion (FL) and 10 frontal lobe dementia (FLD) patients on an associative memory test was compared with the performance of their matched normal controls. The FL group was severely impaired on cued and free recall and was moderately impaired on a recognition condition. Left FL patients performed the poorest on the cued and free recall conditions. The FLD patients were moderately impaired on the free recall condition only but there was a subgroup of FLD patients with additional left temporal atrophy who appeared severely impaired on both cued and free recall. These findings indicate that both left frontal and temporal lobe damage can impair associative learning and that this impairment is more strikingly seen with free rather than cued recall.

Reiman, E. M., Chen, K., Liu, X., Bandy, D., Meixiang, Y. u., Lee, W., Ayutyanont, N., Keppler, J., Reeder, S. A., B., J., Alexander, G. E., Klunk, W. E., Mathis, C. A., Price, J. C., Aizensteini, H. J., DeKosky, S. T., & Caselli, R. J. (2009). Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 106(16), 6820-6825.

PMID: 19346482;PMCID: PMC2665196;Abstract:

Fibrillar amyloid-beta (Aβ) is found in the brains of many cogni-tively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar Aβ burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar Aβ burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) ε4 allele. The 8 ε4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar Aβ was significantly associated with APOE ε4 carrier status and ε4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar Aβ burden in cognitively normal older people is associated with APOE ε4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar Aβ accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar Aβ, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar Aβ imaging in primary prevention trials.

Stonnington, C., Lee, W., Thiyyagura, P., Bauer, R., Sharieff, S., Chen, Y., Alexander, G. E., Casellli, R., Locke, D., Reiman, E., & Chen, K. (2017). Predicting progression to the clinical stages of Alzheimer’s disease using volumetric magnetic resonance imaging and fluorodeoxyglucose positron emission tomography. Journal of Alzheimer's Disease.
Bokde, A. L., Pietrini, P., Ibáñez, V., Furey, M. L., Alexander, G. E., Graff-Radford, N., Rapoport, S. I., Schapiro, M. B., & Horwitz, B. (2001). The effect of brain atrophy on cerebral hypometabolism in the visual variant of Alzheimer disease. Archives of Neurology, 58(3), 480-486.

PMID: 11255453;Abstract:

Background: Brain glucose metabolic rates measured by positron emission tomography can be more affected by partial volume effects in Alzheimer disease (AD) than in healthy aging because of disease-associated brain atrophy. Objective: To determine whether the distinct distribution of cerebral metabolic lesions in patients with the visual variant of AD (AD + VS) represents a true index of neuronal/synaptic dysfunction or is the consequence of brain atrophy. Setting: Government research hospital. Design: Resting cerebral metabolic rate for glucose was measured with positron emission tomography in a cross-sectional study of AD and AD + VS groups and in healthy control subjects. Segmented magnetic resonance images were used to correct for brain atrophy. Patients: Patients with AD + VS had prominent visual and visuospatial symptoms. There were 15 patients with AD, 10 with AD + VS, and 37 age-matched control subjects. Main Outcome Measure: Measurement of the rate of cerebral glucose metabolism. Results: Before atrophy correction, the AD + VS group, compared with the control subjects, showed hypometabolism in primary and extrastriate visual areas and in parietal and superior temporal cortical areas. Compared with the AD group, the AD + VS group showed hypometabolism in visual association areas. After atrophy correction, hypometabolism remained significantly different between patients and controls and between the 2 AD groups. Conclusions: The reductions in cerebral hypometabolism represent a true loss of functional activity and are not simply an artifact caused by brain atrophy. The different patterns of hypometabolism indicate the differential development of the lesions between the AD and AD + VS groups.

Chen, K., Reiman, E. M., Alexander, G. E., Caselli, R. J., Gerkin, R., Bandy, D., Domb, A., Osborne, D., Fox, N., Crum, W. R., Saunders, A. M., & Hardy, J. (2007). Correlations between apolipoprotein E epsilon4 gene dose and whole brain atrophy rates.. American Journal of Psychiatry.

Study demonstrating a gene dose relationship between APOE e4 and brain atrophy in cognitive normal late middle aged adults.;Your Role: Contributed to analysis, aspects of study design, and revision of manuscript.;Full Citation: Chen, K., Reiman, E.M., Alexander, G.E., Caselli, R.J., Gerkin, R., Bandy, D., Domb, A., Osborne, D., Fox, N., Crum, W.R., Saunders, A.M., Hardy, J. (2007). Correlations between apolipoprotein E epsilon4 gene dose and whole brain atrophy rates. American Journal of Psychiatry, 164, 916-21.;Collaborative with faculty member at UA: Yes;