Caselli, R. J., Osborne, D., Reiman, E. M., Hentz, J. G., Barbieri, C. J., Saunders, A. M., Hardy, J., Graff-Radford, N. R., Hall, G. R., & Alexander, G. E. (2001). Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: A replication study. Journal of the Neurological Sciences, 189(1-2), 93-98.
PMID: 11535238;Abstract:
In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9±5.9 years), gender (60% women), and education (15.9±2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup. Copyright © 2001 Elsevier Science B.V.
Zemishlany, Z., Alexander, G. E., Prohovnik, I., Goldman, R. G., Mukherjee, S., & Sackeim, H. (1996). Cortical blood flow and negative symptoms in schizophrenia. Neuropsychobiology, 33(3), 127-131.
PMID: 8776740;Abstract:
An association between negative symptoms and frontal cortex abnormalities has been suggested in schizophrenic patients. We tested whether this association can be found when patients' task performance is good and while controlling for possible cortical atrophy. We investigated regional cerebral blood flow with the xenon-133 inhalation method in 9 unmedicated schizophrenic patients at rest and during performance of the Continuous Performance Test. Negative symptoms were quantified with the Scale for Assessment of Negative Symptoms. All patients could attend to the test and performed it successfully with mean accuracy of 91 ± 8%. Changes of the left hemisphere hyperfrontality ratio were significantly correlated with severity of negative symptoms, especially for the subscales of attention (r = -0.83) and anhedonia (r = -0.70). These results lend further support to the putative association between negative symptoms and physiological abnormalities of the frontal cortex in schizophrenic patients.
Krasuski, J. S., Alexander, G. E., Horwitz, B., Rapoport, S. I., & Schapiro, M. B. (2002). Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: Implications for the prodromal phase of Alzheimer's disease. American Journal of Psychiatry, 159(1), 74-81.
PMID: 11772693;Abstract:
Objective: In Down's syndrome (trisomy 21), a dementia syndrome occurs that is phenotypically similar to Alzheimer's disease; the initial phase is characterized by memory loss. The authors used an in vivo structural technique in the predementia stage of Alzheimer's disease in adults with Down's syndrome to investigate whether atrophy of medial temporal lobe structures occurs in these subjects and whether volumes of these structures correlate specifically with performance on memory tests. Method: The subjects were 34 nondemented Down's syndrome adults (mean age=41.6 years, 17 women and 17 men) and 33 healthy comparison subjects (mean age=41.3, 15 women and 18 men). By using T 1-weighted magnetic resonance imaging slices taken perpendicular to the Sylvian fissure, volumes of the hippocampus, amygdala, anterior and posterior parahippocampal gyrus, and temporal pole CSF were measured in both hemispheres. These data were normalized to the total intracranial volume. Results: For Down's syndrome, smaller volumes of the right and left amygdala, hippocampus, and posterior parahippocampal gyrus were significantly associated with greater age; this association was not seen in the anterior parahippocampal gyrus. The amygdala and hippocampus volumes were positively correlated with memory measures. For the comparison group, there was no relationship between volume and age in any region. Conclusions: In the predementia phase of Down's syndrome, significant volume changes in medial temporal lobe structures occur with age and are related to memory. These structures are affected early in Alzheimer's disease in Down's syndrome, and their evaluation may help identify people in the preclinical stages of Alzheimer's disease.
Raichlen, D. A., Bharadwaj, P., Fitzhugh, M., Haws, K., Torre, G., Trouard, T. P., & Alexander, G. E. (2016). Differences in resting state functional connectivity between young adult endurance athletes and healthy controls. Frontiers in Human Neuroscience, 10, 610.
Teipel, S. J., Hampel, H., Alexander, G. E., Schapiro, M. B., Horwitz, B., Teichberg, D., Daley, E., Hippius, H., Möller, H., & Rapoport, S. I. (1998). Dissociation between corpus callosum atrophy and white matter pathology in Alzheimer's disease. Neurology, 51(5), 1381-1385.
PMID: 9818864;Abstract:
Objective: To determine whether the size of the corpus callosum is related to the extent of white matter pathology in patients with AD and age- matched healthy control subjects. Methods: White matter hyperintensity load and corpus callosum size were compared between 20 clinically diagnosed AD patients and 21 age-matched healthy control subjects. We investigated the effect of age and disease severity on corpus callosum size and white matter hyperintensity, in addition to the relation between corpus callosum areas and white matter hyperintensity load. Results: We found significant regional atrophy of the corpus callosum in AD when compared with control subjects, although the groups did not differ in their white matter hyperintensity load. We further showed a region-specific correlation between corpus callosum size and white matter hyperintensity in the control group but not in AD patients. In the AD group, corpus callosum size correlated with age and dementia severity, whereas white matter hyperintensity correlated only with age. Conclusion: Corpus callosum atrophy in AD can occur independent of white matter degeneration, likely reflecting specific AD pathology in projecting neurons.
