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
(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"


Alexander, G. E., Caselli, R. J., Reiman, E. M., Locke, D. E., Hutton, M. L., Hentz, J. G., C, H., Woodruff, B. K., Alexander, G. E., & D., O. (2007). Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment.. Archives of Neurology.

Study investigating the pre-mild cognitive impairment effects of Alzheiemer's disease.;Your Role: Contributed to analysis, aspects of study design, and revision of manuscript;Full Citation: Caselli RJ, Reiman EM, Locke DE, Hutton ML, Hentz JG, Hoffman-Snyder C, Woodruff BK, Alexander GE, Osborne D. Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment.Arch Neurol. 2007 Sep;64(9):1306-11.;Collaborative with faculty member at UA: Yes;

Liang, W. S., Dunckley, T., Beach, T. G., Grover, A., Mastroeni, D., Walker, D. G., Caselli, R. J., Kukull, W. A., McKeel, D., Morris, J. C., Hulette, C., Schmechel, D., Alexander, G. E., Reiman, E. M., Rogers, J., & Stephan, D. A. (2007). Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiological Genomics, 28(3), 311-322.

PMID: 17077275;PMCID: PMC2259385;Abstract:

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer's disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders. Copyright © 2007 the American Physiological Society.

Xia, W. u., Chen, K., Yao, L., Ayutyanont, N., Langbaum, J. B., Fleisher, A., Reschke, C., Lee, W., Liu, X., Alexander, G. E., Bandy, D., Foster, N. L., Thompson, P. M., Harvey, D. J., Weiner, M. W., Koeppe, R. A., Jagust, W. J., & Reiman, E. M. (2010). Assessing the reliability to detect cerebral hypometabolism in probable Alzheimer's disease and amnestic mild cognitive impairment. Journal of Neuroscience Methods, 192(2), 277-285.

PMID: 20678521;PMCID: PMC2952503;Abstract:

Fluorodeoxyglucose positron emission tomography (FDG-PET) studies report characteristic patterns of cerebral hypometabolism in probable Alzheimer's disease (pAD) and amnestic mild cognitive impairment (aMCI). This study aims to characterize the consistency of regional hypometabolism in pAD and aMCI patients enrolled in the AD neuroimaging initiative (ADNI) using statistical parametric mapping (SPM) and bootstrap resampling, and to compare bootstrap-based reliability index to the commonly used type-I error approach with or without correction for multiple comparisons. Batched SPM5 was run for each of 1000 bootstrap iterations to compare FDG-PET images from 74 pAD and 142 aMCI patients, respectively, to 82 normal controls. Maps of the hypometabolic voxels detected for at least a specific percentage of times over the 1000 runs were examined and compared to an overlap of the hypometabolic maps obtained from 3 randomly partitioned independent sub-datasets. The results from the bootstrap derived reliability of regional hypometabolism in the overall data set were similar to that observed in each of the three non-overlapping sub-sets using family-wise error. Strong but non-linear association was found between the bootstrap-based reliability index and the type-I error. For threshold p= 0.0005, pAD was associated with extensive hypometabolic voxels in the posterior cingulate/precuneus and parietotemporal regions with reliability between 90% and 100%. Bootstrap analysis provides an alternative to the parametric family-wise error approach used to examine consistency of hypometabolic brain voxels in pAD and aMCI patients. These results provide a foundation for the use of bootstrap analysis characterize statistical ROIs or search regions in both cross-sectional and longitudinal FDG-PET studies. This approach offers promise in the early detection and tracking of AD, the evaluation of AD-modifying treatments, and other biologically or clinical important measurements using brain images and voxel-based data analysis techniques. © 2010 Elsevier B.V.

Caselli, R. J., Reiman, E. M., Hentz, J. G., Osborne, D., Alexander, G. E., & Boeve, B. F. (2002). A distinctive interaction between memory and chronic daytime somnolence in asymptomatic APOE e4 homozygotes. Sleep, 25(4), 447-453.

PMID: 12071547;Abstract:

Study Objectives: To correlate memory measures with a trait measure of chronic daytime somnolence in cognitively normal individuals with different gene doses of the apolipoprotein E (APOE) e4 allele, a common Alzheimer's disease susceptibility gene. Design: Cross-sectional, exploratory study of cognitive abilities in APOE e4 homozygotes (HMZ) (n=42), heterozygotes (HTZ), (n=42) and noncarriers (NC) (n=42) who are matched for age, gender, educational level, and family history of dementia. Setting: Tertiary care academic medical center Participants: Cognitively normal residents of Maricopa County, Arizona who are 30-70 years of age, genotyped for APOE, and have no history of a sleep disorder Interventions: N/A Measurements: Epworth Sleepiness Scale (ESS) and a battery of neuropsychological tests Results: Age, education, gender, and insomnia complaints did not significantly differ among groups. Despite normal baseline memory scores, memory declined with increasing ESS on all eight memory measures in the HMZ, two of eight in the HTZ, and one of eight in the NC. Differences between HMZ and NC on the slope of memory decline with increasing ESS reached statistical significance on two verbal memory measures, AVLT Long-Term Memory (p=0.048) and Percent Delayed Recall (p=0.035). Conclusions: Chronic daytime somnolence is associated with a distinctive decline in verbal memory in cognitively normal APOE e4 HMZ, a group at particularly high risk of Alzheimer's disease. Additional studies are needed to confirm these exploratory findings and to determine the effects of acute somnolence on cognition in these genetic subgroups.

Alexander, G. E., Mentis, M. J., D., J., Grady, C. L., Berman, K. F., Furey, M. L., Pietrini, P., Rapoport, S. I., Schapiro, M. B., & Moeller, J. R. (1999). Individual differences in PET activation of object perception and attention systems predict face matching accuracy. NeuroReport, 10(9), 1965-1971.

PMID: 10501542;Abstract:

We sought to investigate how individual differences in the regional patterns of cerebral blood flow (rCBF) relate to task performance during the perceptual matching of faces. We analyzed rCBF data obtained by PET and H215O from nine young healthy, right-handed, adult males (mean age 29 ± 3 years) using a statistical model of regional covariance, the Sealed Subprofile Model (SSM). SSM analysis performed on a voxel-basis for scan substractions comparing face-matching and control tasks extracted two patterns whose subject expression in a multiple regression analysis was highly predictive of task accuracy (R2 = 0.87, p