Gene E Alexander

PMID: 19948227;PMCID: PMC2919751;Abstract:

Previously, a standard theory of systems level memory consolidation was developed to describe how memory recall becomes independent of themedial temporal memory system. More recently, an extended consolidation theory was proposed that predicts seven changes in regional neural activity and inter-regional functional connectivity. Using longitudinal event-related functional magnetic resonance imaging of an associate memory task, we simultaneously tested all predictions and additionally tested for consolidation-related changes in recall of associate memories at a sub-trial temporal resolution, analyzing cue, delay and target periods of each trial separately. Results consistent with the theoretical predictions were observed though two inconsistent results were also obtained. In particular, while medial temporal recall related delay period activity decreased with consolidation as predicted, visual cue activity increased for consolidated memories. Though the extended theory of memory consolidation is largely supported by our study, these results suggest that the extended theory needs further refinement and the medial temporal memory system has multiple, temporally distinct roles in associate memory recall. Neuroimaging analysis at a sub-trial temporal resolution, as used here, may further clarify the role of the hippocampal complex in memory consolidation. Published by Elsevier Inc.

Study identifying the relation between genetic factors associated with cholesterol and cerebral metabolism assessed by positron emission tomography;Your Role: Co-author involved in analysis, study design, and critical review of manuscript;Full Citation: Reiman EM, Chen K, Caselli RJ, Alexander GE, Bandy D, Adamson JL, Lee W, Cannon A, Stephan EA, Stephan DA, & Papassotiropoulos A. (2008). Cholesterol-related genetic risk scores are associated with hypometabolism in Alzheimer's-affected brain regions. Neuroimage,40, 1214-21.;Other collaborative: Yes;Specify other collaborative: Part of ongoing collaboration with Banner Good Samaritan Medical Center, Phoenix, AZ;

PMID: 11843695;Abstract:

Background: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). Objectives: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. Methods: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 ± 8.5 months) and 10 age-and sex-matched healthy controls (mean observation time, 24.1 ± 6.8 months). Results: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (p = 0.52, P.02). The load of subcortical lesions at baseline (P.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. Conclusions: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.

PMID: 10838147;Abstract:

A cued visual search task was used to examine the dynamic range over which spatial attention affects target identification during visual search. Precues varied in validity (valid, invalid, or neutral) and in precision (cue size) of target localization. Participants were 'young-old' (65-74 years) and 'old-old' (75-85 years) elderly adults and individuals in the mild stage of dementia of the Alzheimer type (DAT). For all participants, search was speeded as the precision with which a precue surrounding the location of a subsequently appearing target increased (precue size decreased). The cue size effect was evident in both feature and conjunction search, but was greatly reduced in both old-old and DAT groups compared to the young-old. However, whereas all non-demented adults showed a progressive modulation of search efficiency over the entire range of cue sizes, the dynamic range of spatial attention was restricted to the most precise cue in the DAT group. The restriction in the dynamic range of spatial attention may represent an underlying component of the impairment in perceptual and memory functioning found in early-stage DAT. Copyright (C) 2000 Elsevier Science Ltd.

Abstract:

Having approved fluorodeoxyglucose positron emission tomography (FDG PET) for the diagnosis of Alzheimer's disease (AD) in some patients, the Centers for Medicare and Medicaid Services suggested the need to develop and test analysis techniques to optimize diagnostic accuracy. We developed an automated computer package comparing an individual's FDG PET image to those of a group of normal volunteers. The normal control group includes FDG-PET images from 82 cognitively normal subjects, 61.89±5.67 years of age, who were characterized demographically, clinically, neuropsychologically, and by their apolipoprotein E genotype (known to be associated with a differential risk for AD). In addition, AD-affected brain regions functionally defined as based on a previous study (Alexander, et al, Am J Psychiatr, 2002) were also incorporated. Our computer package permits the user to optionally select control subjects, matching the individual patient for gender, age, and educational level. It is fully streamlined to require minimal user intervention. With one mouse click, the program runs automatically, normalizing the individual patient image, setting up a design matrix for comparing the single subject to a group of normal controls, performing the statistics, calculating the glucose reduction overlap index of the patient with the AD-affected brain regions, and displaying the findings in reference to the AD regions. In conclusion, the package automatically contrasts a single patient to a normal subject database using sound statistical procedures. With further validation, this computer package could be a valuable tool to assist physicians in decision making and communicating findings with patients and patient families.