Ricciardi, E., Alexander, G. E., Furey, M. L., Giovacchini, G., Horwitz, B., Dani, A., Guazzelli, M., Rapoport, S. I., Schapiro, M. B., & Pietrini, P. (1999). Coupling between regional cerebral glucose metabolism and blood flow at rest in young and older healthy subjects. NeuroImage, 9(6 PART II), S265.
Chen, K., Reiman, E. M., Alexander, G. E., Bandy, D., Renaut, R., Crum, W. R., Fox, N. C., & Rossor, M. N. (2004). An automated algorithm for the computation of brain volume change from sequential MRIs using an iterative principal component analysis and its evaluation for the assessment of whole-brain atrophy rates in patients with probable Alzheimer's disease. NeuroImage, 22(1), 134-143.
PMID: 15110003;Abstract:
This article introduces an automated method for the computation of changes in brain volume from sequential magnetic resonance images (MRIs) using an iterative principal component analysis (IPCA) and demonstrates its ability to characterize whole-brain atrophy rates in patients with Alzheimer's disease (AD). The IPCA considers the voxel intensity pairs from coregistered MRIs and identifies those pairs a sufficiently large distance away from the iteratively determined PCA major axis. Analyses of simulated and real MRI data support the underlying assumption of a linear relationship in paired voxel intensities, identify an outlier distance threshold that optimizes the trade-off between sensitivity and specificity in the detection of small volume changes while accounting for global intensity changes, and demonstrate an ability to detect changes as small as 0.04% of brain volume without confounding effects of between-scan shifts in voxel intensity. In eight patients with probable AD and eight age-matched normal control subjects, the IPCA was comparable to the established but partly manual digital subtraction (DS) method in characterizing annual rates of whole-brain atrophy: resulting rates were correlated (Spearman rank correlation = 0.94, P 0.0005) and comparable in distinguishing probable AD from normal aging (IPCA-detected atrophy rates: 2.17 ± 0.52% per year in the patients vs. 0.41 ± 0.22% per year in the controls [Wilcoxon-Mann-Whitney test P = 7.8 × 10-4]; DS-detected atrophy rates: 3.51 ± 1.31% per year in the patients vs. 0.48 ± 0.29% per year in the controls [P = 7.8 × 10-4]). The IPCA could be used in tracking the progression of AD, evaluating the disease-modifying effects of putative treatments, and investigating the course of other normal and pathological changes in brain morphology. © 2004 Elsevier Inc. All rights reserved.
Greenwood, P. M., Parasuraman, R., & Alexander, G. E. (1997). Controlling the focus of spatial attention during visual search: Effects of advanced aging and Alzheimer disease. Neuropsychology, 11(1), 3-12.
PMID: 9055265;Abstract:
It was hypothesized that slowed visual search in healthy adult aging arises from reduced ability to adjust the size of the attentional focus. A novel, cued-visual search task manipulated the scale of spatial attention in a complex field in healthy elderly individuals and patients with dementia of the Alzheimer type (DAT). Precues indicated with varying validity the size and location of the area to be searched. Location precues exerted the strongest effects on conjunction search and the weakest effects on feature search. As the size of valid location cues decreased, conjunction search was facilitated. These effects declined progressively with advanced age and the onset of DAT. As the size of invalid cues increased, conjunction search was first facilitated, then slowed, but neither age nor DAT altered this effect. These results indicate that both Alzheimer's disease and, to a lesser degree, advanced aging, reduce control of the spatial focus of attention.
Hampel, H., Teipel, S. J., Alexander, G. E., Horwitz, B., Pietrini, P., Hippius, H., Möller, H., Schapiro, M. B., & Rapoport, S. I. (2000). Corpus callosum measurement as an in vivo indicator for neocortical neuronal integrity, but not white matter pathology, in Alzheimer's disease. Annals of the New York Academy of Sciences, 903, 470-476.
Caselli, R. J., Chen, K., Bandy, D., Smilovici, O., Boeve, B. F., Osborne, D., Alexander, G. E., Parish, J. M., Krahn, L. E., & Reiman, E. M. (2006). A preliminary fluorodeoxyglucose positron emission tomography study in healthy adults reportinq dream-enactment behavior. Sleep, 29(7), 927-933.
PMID: 16895260;Abstract:
Study Objectives: To test the hypothesis that healthy adults reporting dream-enactment behavior (DEB+) have reduced cerebral metabolic rate for glucose (CMRgI) in regions preferentially affected in patients with dementia with Lewy bodies (DLB). Design: Automated brain-mapping algorithms were used to compare regional fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements from previously evaluated DEB cases and controls. Setting: Tertiary-care academic medical centers. Participants: Seventeen cognitively normal patients with DEB+ and 17 control subjects (DEB-) who were individually matched for age (59 ± 11 years), education level (16 ± 4 years), sex (67% women), body mass index (26 ± 4.8 kg/m2), first-degree relative with dementia (85%), and proportion of apolipoprotein E (APOE) e4 carriers (13 e4 carriers, 4 noncarriers). Interventions: FDG-PET. Measurements and Results: DEB was associated with significantly lower CMRgI in several brain regions known to be preferentially affected in both DLB and Alzheimer disease (parietal, temporal, and posterior cingulate cortexes) and in several other regions, including the anterior cingulate cortex (p .001, uncorrected for multiple comparisons). The DEB-associated CMRgI reductions were significantly greater in the APOE e4 noncarriers than in the carriers. Conclusions: These preliminary findings suggest that cognitively normal persons with DEB have reduced CMRgI in brain regions known to be metabolically affected by DLB, supporting further study of DEB as a possible risk factor for the development of DLB.
