Gene E Alexander

PMID: 9227693;Abstract:

Background and Purpose: Advanced age and hypertension have each been associated with changes in brain morphology and cognitive function. To investigate the interaction of age and hypertension with structural brain changes and neuropsychological performance in otherwise healthy patients with essential hypertension, we compared young-old (ages 56 to 69 years) and old- old (ages 70 to 84 years) hypertensive patients (n=27) with 20 age-matched normotensive healthy control subjects, using quantitative volumetric MRI and a battery of neuropsychological tests. Methods: Quantitative regions of interest and segmentation analyses were applied to MRI scans of brain to measure volumes of different brain structures and of cerebrospinal fluid (CSF). Severity of white matter hyperintensities (WMHs) was qualitatively rated in the MRI scans. A battery of neuropsychological tests was administered to each subject. Results: The combined hypertensive group (young-old and old-old) had smaller volumes of thalamic nuclei and larger volumes of CSF in the cerebellum and temporal lobes and showed poorer performance in memory and language tests than did the control subjects. Main effects for age were significant in multiple brain regions of interest. The old-old hypertensive patients and age-matched control subjects demonstrated volume reductions in brain structures and increases in ventricular and peripheral CSF volumes compared with the younger subjects. There was a significant group x age-group interaction in temporal and occipital CSF, not related to WMH, with the old-old hypertensive patients having significantly larger CSF volumes in these regions than the young-old hypertensives and both healthy control groups. Conclusions: Hypertension exacerbates the morphological changes accompanying advanced age. Temporal and occipital regions appear most vulnerable to brain atrophy due to the interactive effects of age and hypertension.

PMID: 7626962;Abstract:

To evaluate the pathophysiology of frontal lobe dementia (FLD), the authors compared regional cerebral blood flow (rCBF) in matched groups of FLD, probable Alzheimer's disease (AD), and major depression patients and normal control subjects (n = 7 each). The planar xenon-133 technique allowed full quantification of cortical perfusion and estimates of the relative weight of gray matter (wg). FLD patients showed lower blood flow and wg in the frontal cortex than the other groups. Mean cortical perfusion was correlated with cortical wg in the FLD group only. These findings 1) suggest that matched reductions of frontal gray matter weight and perfusion occur in FLD and 2) support the use of rCBF in distinguishing FLD from AD and severe depression.

Article on findings in subjects with the very early age-related cognitive impairment in relation to PET cerebral metabolism. Figure from paper selected for the cover of the journal issue.;Your Role: Co-author involved in study design, analysis, and critical review of manuscript;Full Citation: Caselli RJ, Chen K, Lee W, Alexander GE, & Reiman EM. (2008). Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. Archives of Neurology, 65, 1231-6.;Other collaborative: Yes;Specify other collaborative: Part of ongoing collaboration with Banner Good Samaritan Medical Center and Mayo Clinic Scottsdale;

PMID: 18029993;Abstract:

We previously developed a noninvasive technique for the quantification of fluorodeoxyglucose (FDG) positron emission tomography (PET) images using an image-derived input function obtained from a manually drawn carotid artery region. Here, we investigate the use of independent component analysis (ICA) for more objective identification of the carotid artery and surrounding tissue regions. Using FDG PET data from 22 subjects, ICA was applied to an easily defined cubical region including the carotid artery and neighboring tissue. Carotid artery and tissue time activity curves and three venous samples were used to generate spillover and partial volume-corrected input functions and to calculate the parametric images of the cerebral metabolic rate for glucose (CMRgl). Different from a blood-sampling-free ICA approach, the results from our ICA approach are numerically well matched to those based on the arterial blood sampled input function. In fact, the ICA-derived input functions and CMRgl measurements were not only highly correlated (correlation coefficients >0.99) to, but also highly comparable (regression slopes between 0.92 and 1.09), with those generated using arterial blood sampling. Moreover, the reliability of the ICA-derived input function remained high despite variations in the location and size of the cubical region. The ICA procedure makes it possible to quantify FDG PET images in an objective and reproducible manner. © 2007 IOP Publishing Ltd.

PMID: 9177249;PMCID: PMC21081;Abstract:

Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H2¹⁵O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.