Alexander, G. E., Saunders, A. M., Szczepanik, J., Strassburger, T. L., Pietrini, P., Dani, A., Furey, M. L., Mentis, M. J., Roses, A. D., Rapoport, S. I., & Schapiro, M. B. (1997). Relation of age and apolipoprotein E to cognitive function in Down syndrome adults. NeuroReport, 8(8), 1835-1840.
PMID: 9223061;Abstract:
TO test the cognitive effects of aging and apolipoprotein E (APOE) in individuals at high risk for Alzheimer's disease (AD), we assessed APOE genotypes and performance on a battery of neuropsychological tests in 41 non- demented, Down syndrome (DS) adults. Old DS subjects (ages 41-61 years) showed poorer memory and orientation scores than young DS adults (ages 22-38 years), but the groups did not differ in other measures after we controlled for intellectual function. Language ability was inversely related to APOE genotype, even after age was controlled for, with the presence of the ε2 allele corresponding to better language skills than ε4. Age-related cognitive changes in non-demented DS adults are consistent with the early effects of AD. The relationship between basic linguistic skills and APOE genotype supports this genetic factor in influencing the development of dementia and AD neuropathology in DS.
Alexander, G., Caselli, R. J., Reiman, E. M., Hentz, J. G., Osborne, D., & Alexander, G. E. (2004). A distinctive interaction between chronic anxiety and problem solving in asymptomatic APOE e4 homozygotes. The Journal of neuropsychiatry and clinical neurosciences, 16(3).
We correlated measures of problem solving (Wisconsin Card Sorting Test [WCST] categories, total errors, and perseverative errors) and chronic anxiety (Personality Assessment Inventory Anxiety Scale [ANX]) in asymptomatic apolipoprotein E (APOE) e4 homozygotes (HMZs), heterozygotes, and noncarriers (NC) (n = 42 in each group) matched for age, education, and gender. Differences between HMZ and NC in the slope of the regression of WCST scores on ANX reached statistical significance on all three WCST measures. Chronic anxiety adversely affects cognitive skills in all groups, and is associated with significantly greater decline in problem solving skills in cognitively normal APOE e4 HMZ.
Henry, M. L., Beeson, P. M., Alexander, G. E., & Rapcsak, S. Z. (2012). Written language impairments in primary progressive aphasia: A reflection of damage to central semantic and phonological processes. Journal of Cognitive Neuroscience, 24, 261-75.
Hua, X., Gutman, B., Boyle, C. P., Rajagopalan, P., Leow, A. D., Yanovsky, I., Kumar, A. R., Toga, A. W., Jack, C. R., Schuff, N., Alexander, G. E., Chen, K., Reiman, E. M., Weiner, M. W., & Thompson, P. M. (2011). Accurate measurement of brain changes in longitudinal MRI scans using tensor-based morphometry. NeuroImage, 57(1), 5-14.
PMID: 21320612;PMCID: PMC3394184;Abstract:
This paper responds to Thompson and Holland (2011), who challenged our tensor-based morphometry (TBM) method for estimating rates of brain changes in serial MRI from 431 subjects scanned every 6. months, for 2. years. Thompson and Holland noted an unexplained jump in our atrophy rate estimates: an offset between 0 and 6. months that may bias clinical trial power calculations. We identified why this jump occurs and propose a solution. By enforcing inverse-consistency in our TBM method, the offset dropped from 1.4% to 0.28%, giving plausible anatomical trajectories. Transitivity error accounted for the minimal remaining offset. Drug trial sample size estimates with the revised TBM-derived metrics are highly competitive with other methods, though higher than previously reported sample size estimates by a factor of 1.6 to 2.4. Importantly, estimates are far below those given in the critique. To demonstrate a 25% slowing of atrophic rates with 80% power, 62 AD and 129 MCI subjects would be required for a 2-year trial, and 91 AD and 192 MCI subjects for a 1-year trial. © 2011 Elsevier Inc.
Alexander, G., Gmitro, A. F., & Alexander, G. E. (1993). Use of a projection reconstruction method to decrease motion sensitivity in diffusion-weighted MRI. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, 29(6).
Diffusion-weighted MRI is a clinically useful technique, but its utility is compromised by high sensitivity to patient motion. Use of radial-scan data acquisition and projection reconstruction, rather than the conventional Fourier imaging method, can substantially reduce the sensitivity to global translational motion of the object. The basis of this concept and a demonstration of the technique in an animal imaging experiment are presented.
