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G E Alexander

Publications and source records attributed to G E Alexander.

At least 19 recordsLinked to original sources
PubMed2002

In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET.

Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, (18)FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with (18)FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.

Alzheimer Disease↗
PubMed2001

Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Aged↗
PubMed2001

Brain metabolite concentration and dementia severity in Alzheimer's disease: a (1)H MRS study.

OBJECTIVE: (1)H-MRS studies have shown abnormalities in brain levels of myo-inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these abnormalities with dementia severity was not examined. The authors sought to determine whether altered brain levels of mI and other metabolites occur in mild AD and whether they change as dementia severity worsens. METHODS: The authors used (1)H-MRS with external standards to measure absolute brain concentrations of mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21 subjects with AD and 17 age- and sex-matched controls in occipital and left and right parietal regions. RESULTS: Concentrations of NAA were significantly decreased, whereas mI and Cr concentrations were significantly increased in all three brain regions in subjects with AD compared with controls. Higher concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of the (1)H-MRS data combined with CSF volume measurements distinguished subjects with AD, ranging from mild to severe dementia, from controls with 100% correct classification. NAA concentration, though not other metabolites, was positively correlated with Mini-Mental State Examination score. CONCLUSION: The measurements with (1)H-MRS of absolute metabolite concentrations in the neocortex showed abnormal concentrations of brain metabolites in AD; these metabolite concentrations do not necessarily correlate with disease severity. Although changes in myo-inositol and creatine occur in the early stages of AD, abnormalities of N-acetyl aspartate do not occur in mild AD but progressively change with dementia severity. Further, subjects with mild AD can be differentiated from controls with (1)H-MRS.

Aged↗
PubMed2001

Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study.

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.

Age of Onset↗
PubMed2001

Functional anatomy of nonvisual feedback loops during reaching: a positron emission tomography study.

Reaching movements performed without vision of the moving limb are continuously monitored, during their execution, by feedback loops (designated nonvisual). In this study, we investigated the functional anatomy of these nonvisual loops using positron emission tomography (PET). Seven subjects had to "look at" (eye) or "look and point to" (eye-arm) visual targets whose location either remained stationary or changed undetectably during the ocular saccade (when vision is suppressed). Slightly changing the target location during gaze shift causes an increase in the amount of correction to be generated. Functional anatomy of nonvisual feedback loops was identified by comparing the reaching condition involving large corrections (jump) with the reaching condition involving small corrections (stationary), after subtracting the activations associated with saccadic movements and hand movement planning [(eye-arm-jumping minus eye-jumping) minus (eye-arm-stationary minus eye-stationary)]. Behavioral data confirmed that the subjects were both accurate at reaching to the stationary targets and able to update their movement smoothly and early in response to the target jump. PET difference images showed that these corrections were mediated by a restricted network involving the left posterior parietal cortex, the right anterior intermediate cerebellum, and the left primary motor cortex. These results are consistent with our knowledge of the functional properties of these areas and more generally with models emphasizing parietal-cerebellar circuits for processing a dynamic motor error signal.

Adult↗
PubMed2001

Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease.

Cross-sectional positron emission tomography (PET) studies find that cognitively normal carriers of the apolipoprotein E (APOE) epsilon4 allele, a common Alzheimer's susceptibility gene, have abnormally low measurements of the cerebral metabolic rate for glucose (CMRgl) in the same regions as patients with Alzheimer's dementia. In this article, we characterize longitudinal CMRgl declines in cognitively normal epsilon4 heterozygotes, estimate the power of PET to test the efficacy of treatments to attenuate these declines in 2 years, and consider how this paradigm could be used to efficiently test the potential of candidate therapies for the prevention of Alzheimer's disease. We studied 10 cognitively normal epsilon4 heterozygotes and 15 epsilon4 noncarriers 50-63 years of age with a reported family history of Alzheimer's dementia before and after an interval of approximately 2 years. The epsilon4 heterozygotes had significant CMRgl declines in the vicinity of temporal, posterior cingulate, and prefrontal cortex, basal forebrain, parahippocampal gyrus, and thalamus, and these declines were significantly greater than those in the epsilon4 noncarriers. In testing candidate primary prevention therapies, we estimate that between 50 and 115 cognitively normal epsilon4 heterozygotes are needed per active and placebo treatment group to detect a 25% attenuation in these CMRgl declines with 80% power and P = 0.005 in 2 years. Assuming these CMRgl declines are related to the predisposition to Alzheimer's dementia, this study provides a paradigm for testing the potential of treatments to prevent the disorder without having to study thousands of research subjects or wait many years to determine whether or when treated individuals develop symptoms.

Aged↗
PubMed2001

The effect of brain atrophy on cerebral hypometabolism in the visual variant of Alzheimer disease.

BACKGROUND: Brain glucose metabolic rates measured by positron emission tomography can be more affected by partial volume effects in Alzheimer disease (AD) than in healthy aging because of disease-associated brain atrophy. OBJECTIVE: To determine whether the distinct distribution of cerebral metabolic lesions in patients with the visual variant of AD (AD + VS) represents a true index of neuronal/synaptic dysfunction or is the consequence of brain atrophy. SETTING: Government research hospital. DESIGN: Resting cerebral metabolic rate for glucose was measured with positron emission tomography in a cross-sectional study of AD and AD + VS groups and in healthy control subjects. Segmented magnetic resonance images were used to correct for brain atrophy. PATIENTS: Patients with AD + VS had prominent visual and visuospatial symptoms. There were 15 patients with AD, 10 with AD + VS, and 37 age-matched control subjects. MAIN OUTCOME MEASURE: Measurement of the rate of cerebral glucose metabolism. RESULTS: Before atrophy correction, the AD + VS group, compared with the control subjects, showed hypometabolism in primary and extrastriate visual areas and in parietal and superior temporal cortical areas. Compared with the AD group, the AD + VS group showed hypometabolism in visual association areas. After atrophy correction, hypometabolism remained significantly different between patients and controls and between the 2 AD groups. CONCLUSIONS: The reductions in cerebral hypometabolism represent a true loss of functional activity and are not simply an artifact caused by brain atrophy. The different patterns of hypometabolism indicate the differential development of the lesions between the AD and AD + VS groups.

Aged↗
PubMed2000

Functional adaptation of reactive saccades in humans: a PET study.

It is known that the saccadic system shows adaptive changes when the command sent to the extraocular muscles is inappropriate. Despite an abundance of supportive psychophysical investigations, the neurophysiological substrate of this process is still debated. The present study addresses this issue using H2(15)O positron emission tomography (PET). We contrasted three conditions in which healthy human subjects were required to perform saccadic eye movements toward peripheral visual targets. Two conditions involved a modification of the target location during the course of the initial saccade, when there is suppression of visual perception. In the RAND condition, intra-saccadic target displacement was random from trial-to-trial, precluding any systematic modification of the primary saccade amplitude. In the ADAPT condition, intra-saccadic target displacement was uniform, causing adaptive modification of the primary saccade amplitude. In the third condition (stationary, STAT), the target remained at the same location during the entire trial. Difference images reflecting regional cerebral-blood-flow changes attributable to the process of saccadic adaptation (ADAPT minus RAND; ADAPT minus STAT) showed a selective activation in the oculomotor cerebellar vermis (OCV; lobules VI and VII). This finding is consistent with neurophysiological studies in monkeys. Additional analyses indicated that the cerebellar activation was not related to kinematic factors, and that the absence of significant activation within the frontal eye fields (FEF) or the superior colliculus (SC) did not represent a false negative inference. Besides the contribution of the OCV to saccadic adaptation, we also observed, in the RAND condition, that the saccade amplitude was significantly larger when the previous trial involved a forward jump than when the previous trial involved a backward jump. This observation indicates that saccade accuracy is constantly monitored on a trial-to-trial basis. Behavioral measurements and PET observations (RAND minus STAT) suggest that this single-trial control of saccade amplitude may be functionally distinct from the process of saccadic adaptation.

Adaptation, Physiological↗
PubMed2000

Alzheimer disease constricts the dynamic range of spatial attention in visual search.

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.

Adult↗
PubMed2000

Time course of pharmacodynamic and pharmacokinetic effects of physostigmine assessed by functional brain imaging in humans.

In imaging studies of brain functions using pharmacological probes, identification of the time point at which central effects of intravenously infused drugs become stable is crucial to separate the effects of experimental variables from the concomitant changes in drug effects over time. We evaluated the time courses of the pharmacokinetics and pharmacodynamics, including butyrylcholinesterase inhibition and central neural responses, of physostigmine in healthy young subjects. Ten positron emission tomography (PET) scans that alternated between a rest condition (eyes open, ears unplugged) and a working memory for faces (WM) task were acquired in healthy subjects. Subjects in the drug group received a saline infusion for the first two scans, providing a baseline measure, then received an infusion of physostigmine for all subsequent scans. Subjects in the control group received a placebo infusion of saline for all scans. Physostigmine plasma levels and percent butyrylcholinesterase inhibition increased over time (p < 0. 0001), and both became stable by 40 min. Physostigmine decreased reaction time (RT) (p = 0.0005), and this effect was detected after 20 min of infusion and stable thereafter. Physostigmine also decreased regional cerebral blood flow (rCBF) in right prefrontal cortex during task (p = 0.0002), and this effect was detected after 40 min of infusion and stable thereafter. No change in RT or rCBF was observed in the control group. These results indicate that a 40-min infusion of physostigmine was necessary to obtain stable central effects. More generally, we have demonstrated that experimental effects can vary with time, especially during the initial phases of a drug infusion, indicating that it is critical that these changes are controlled.

Adult↗
PubMed2000

The neurometabolic landscape of cognitive decline: in vivo studies with positron emission tomography in Alzheimer's disease.

Alzheimer's disease, the most common form of dementia in the elderly, is characterized by the progressive, global and irreversible deterioration of cognitive abilities. The development of positron emission tomography (PET) methodologies has made it possible to study the in vivo brain metabolic correlates of human cognitive and behavioral functions. Moreover, as PET scan examinations can be repeated, the progression of the neuropathological process and its relation to cognitive dysfunction can be followed over time. In an effort to understand the changes in neural function that precede and accompany onset of dementia and their relation to clinical manifestations, in the last several years, we have conducted clinical, neuropsychological and brain metabolic studies in groups of Alzheimer's disease patients at different stages of dementia severity or with distinct clinical pictures and in populations at risk for developing the disease. Here, we discuss the main findings and implications obtained from these studies.

Alzheimer Disease↗
PubMed2000

Cholinergic enhancement improves performance on working memory by modulating the functional activity in distinct brain regions: a positron emission tomography regional cerebral blood flow study in healthy humans.

Previously, we have shown that physostigmine, an acetylcholinesterase inhibitor, improved performance on a working memory for faces task, as reflected by reduced reaction time (RT), and reduced task-specific regional cerebral blood flow (rCBF) in right prefrontal cortex and, further, that these reductions in RT and right frontal rCBF were significantly correlated. Here we investigated the relation between the effects of physostigmine on task performance and task-specific functional brain response throughout the cortex by examining correlations between physostigmine-related changes in rCBF in all brain areas and changes in RT. In subjects who received an infusion of physostigmine, reduced RT correlated (p<0.001) positively with reduced rCBF in right frontal cortex, left temporal cortex, anterior cingulate, and left hippocampus; and correlated with increased rCBF in medial occipital visual cortex. In subjects who received a placebo infusion of saline, no significant correlations between changes in RT and cortical rCBF were observed. The results show that cholinergically induced improvements in working memory performance are related to alterations in neural activity in multiple cortical regions, including increased neural activity in regions associated with early perceptual processing and decreased neural activity in regions associated with attention, memory encoding, and memory maintenance.

Adult↗
PubMed2000

Cerebral metabolic response to passive audiovisual stimulation in patients with Alzheimer's disease and healthy volunteers assessed by PET.

UNLABELLED: Alzheimer's disease is associated with reductions in resting-state brain metabolism, as measured by PET, progressing with dementia severity. The purpose of this study was to see to what extent brain regions with reduced resting-state metabolic rates in Alzheimer patients could be activated by a passive audiovisual stimulation test and to compare the result with activation in age-matched healthy volunteers. The extent of activation in Alzheimer's disease is considered to reflect the integrity of synaptic function, or inherent viability, and the potential responsiveness of the Alzheimer brain to drug therapy. METHODS: Regional cerebral metabolic rates for glucose (rCMRglc, in mg/ 100 g tissue/min) were measured in the resting state (eyes and ears covered) and during passive audiovisual stimulation (watching a movie) in 15 otherwise healthy Alzheimer patients of differing dementia severity (Mattis Dementia Rating Scale score, 23-128) and in 14 age-matched healthy volunteers (score, 141 +/- 3) using PET with 2 sequential injections of FDG. RESULTS: In the volunteers, audiovisual stimulation caused significant rCMRglc increases in visual and auditory cortical areas but significant decreases in frontal areas. In the mildly demented patients, rCMRglc responses were within 2 SDs of the mean in volunteers. However, the magnitude of the rCMRglc responses during stimulation declined significantly with dementia severity in the right occipitotemporal, right and left occipital association, and left calcarine cortical regions. CONCLUSION: Functional brain responsiveness, evaluated by a passive audiovisual stimulation paradigm with PET, is within normal limits in mildly demented Alzheimer patients but fails with worsening dementia severity. Declining responsiveness may account for the limited success of neurotransmitter replacement therapy in Alzheimer patients with moderate-to-severe dementia.

Acoustic Stimulation↗
PubMed1999

Individual differences in PET activation of object perception and attention systems predict face matching accuracy.

We sought to investigate how individual differences in the regional patterns of cerebral blood flow (rCBF) relate to task performance during the perceptual matching of faces. We analyzed rCBF data obtained by PET and H2150 from nine young healthy, right-handed, adult males (mean age 29i3 years) using a statistical model of regional covariance, the Scaled Subprofile Model (SSM). SSM analysis performed on a voxel-basis for scan subtractions comparing face-matching and control tasks extracted two patterns whose subject expression in a multiple regression analysis was highly predictive of task accuracy (R2 = 0.87, p < 0.002). The pattern reflecting this linear combination was principally characterized by higher rCBF in regions of bilateral occipital and occipitotemporal cortex, right orbitofrontal cortex, left thalamus, basal ganglia, midbrain, and cerebellum with relatively lower rCBF in anterior cingulate, regions in bilateral prefrontal and temporal cortex, right thalamus, and right inferior parietal cortex. The results indicate that individual subject differences in face matching performance are specifically associated with the functional interaction of cortical and subcortical brain regions previously implicated in aspects of object perception and visual attentional processing.

Adult↗
PubMed1999

Regional cerebral blood flow in Down syndrome adults during the Wisconsin Card Sorting Test: exploring cognitive activation in the context of poor performance.

BACKGROUND: Prior studies have indicated abnormal frontal lobes in Down syndrome (DS). The Wisconsin Card Sorting Test (WCST) has been used during functional brain imaging studies to activate the prefrontal cortex. Whether this activation is dependent on successful performance remains unclear. To determine frontal lobe regional cerebral blood flow (rCBF) response in DS and to further understand the effect of performance on rCBF during the WCST, we studied DS adults who perform poorly on this task. METHODS: Initial slope (IS), an rCBF index, was measured with the 133Xe inhalation technique during a Numbers Matching Control Task and the WCST. Ten healthy DS subjects (mean age 28.3 years) and 20 sex-matched healthy volunteers (mean age 28.7 years) were examined. RESULTS: Performance of DS subjects was markedly impaired compared to controls. Both DS and control subjects significantly increased prefrontal IS indices compared to the control task during the WCST. CONCLUSIONS: Prefrontal activation in DS during the WCST was not related to performance of that task, but may reflect engagement of some components involved in the task, such as effort. Further, these results show that failure to activate prefrontal cortex during WCST in schizophrenia is unlikely to be due to poor performance alone.

Adult↗
PubMed1999

Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease.

BACKGROUND: Positron emission tomographic studies of patients with Alzheimer disease (AD) suggest a loss of metabolic functional interactions between different cortical regions. Atrophy of the corpus callosum as the major tract of intracortical connective fibers may reflect decreased cortical functional integration in AD. OBJECTIVES: To investigate whether regional atrophy of the corpus callosum is correlated with regional reductions of cortical glucose metabolism, as shown by positron emission tomography, and whether primary white matter degeneration is a possible cofactor of corpus callosum atrophy in AD. PATIENTS AND METHODS: We measured total and regional cross-sectional areas of the corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients with AD and 15 age-matched control subjects. Regional cerebral metabolic rates for glucose in cortical lobes were measured by positron emission tomography using fludeoxyglucose F 18. White matter hyperintensities were rated in T2-weighted magnetic resonance imaging scans. RESULTS: The total cross-sectional area of corpus callosum was significantly reduced in patients with AD, with the most prominent changes in the rostrum and splenium and relative sparing of the body of the corpus callosum. Frontal and parietal lobe metabolism was correlated with the truncal area of the corpus callosum in AD. The ratios of frontal to parietal and of frontal to occipital metabolism were correlated with the ratio of anterior to posterior corpus callosum area in the group with AD. White matter hyperintensities did not correlate with corpus callosum atrophy in the patients with AD. CONCLUSION: The regional pattern of corpus callosum atrophy correlated with reduced regional glucose metabolism independently of primary white matter degeneration in the patients with AD.

Aged↗
PubMed1999

Cerebral blood flow patterns underlying the differential impairment in category vs letter fluency in Alzheimer's disease.

Verbal fluency tasks are used to assess language functioning in Alzheimer's disease (AD), and performance typically declines as the disease progresses. However, several studies have shown that Category Fluency performance (produce words from a category) declines faster than Letter Fluency performance (produce words beginning with a certain letter), which is not the case for other dementias. The purpose of this study was to determine if each of these two types of fluency tasks was associated with different patterns of cerebral blood flow abnormality in AD. A resting, Xenon-inhalation regional cerebral blood flow measurement (133Xe rCBF) and neuropsychological evaluation was administered to 25 patients with probable AD and 24 healthy elderly controls. Stepwise regression using rCBF measures as predictor variables was used to predict Category and Letter Fluency performance, in both a combined group of patients and controls, and in the patient group alone. Correlations were also computed between rCBF variables and the difference between normatively corrected scores on each task for each subject, which characterized the extent of the discrepancy between them. In full sample regressions, both Category and Letter Fluency were predicted by education and the decline in left inferior parietal flow, a focal AD-related deficit. Additional variance in Category fluency, however, was predicted by global mean flow, while additional variance in Letter Fluency was predicted by frontal flow. Within the patient sample, in turn, the primary predictor of Category Fluency was mean flow; the primary predictor of Letter Fluency was left-sided frontal flow. Analysis of the fluency difference score revealed that relatively greater impairment of Category Fluency was associated with more typical, AD-related deficits in posterior temporal and parietal perfusion. When the two were equivalently impaired, typical AD-related deficits were accompanied by marked deficits in frontal perfusion. These findings are consistent with the underlying neuropsychology of these tasks, and suggest that Category Fluency's stronger association to the most typical CBF deficits of AD account for its greater sensitivity to this disease. Letter Fluency deficits, on the other hand, carry significant information about the degree to which perfusion deficits have spread to frontal cortex.

Aged↗