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Objective: To study the effects of moderate to severe traumatic brain injury (TBI) on the functional neuroanatomy supporting memory retrieval., Methods: Subjects were six patients who had sustained a moderate to severe TBI about four years before scanning and had since made a good recovery. Eleven healthy young adults matched to the patients for age and education served as controls. An established H(2)(15)0 positron emission tomography paradigm was used to elicit brain activations in response to memory retrieval. TBI patients' patterns of brain activation were compared statistically with those of control subjects. Both group and individual case data were analysed., Results: Both TBI patients and controls engaged frontal, temporal, and parietal regions known to be involved in memory retrieval, yet the TBI patients showed relative increases in frontal, anterior cingulate, and occipital activity. The hemispheric asymmetry characteristic of controls was attenuated in patients with TBI. Reduced activation was noted in the right dorsomedial thalamus. Although local aspects of this pattern were affected by the presence of focal lesions and performance differences, the overall pattern was reliable across patients and comparable to functional neuroimaging results reported for normal aging, Alzheimer's disease, and other patients with TBI., Conclusions: The TBI patients performed memory tasks using altered functional neuroanatomical networks. These changes are probably the result of diffuse axonal injury and may reflect either cortical disinhibition attributable to disconnection or compensation for inefficient mnemonic processes.

Age-related differences in brain activity mediating face recognition were examined using positron emission tomography. Participants encoded faces using a pleasant-unpleasant judgment, a right-left orientation task, and intentional learning. Scans also were obtained during recognition. Both young and old groups showed signficant effects of encoding task on recognition accuracy, but older adults showed reduced accuracy overall. Increased brain activity in older adults was similar to that seen in young adults during conditions associated with deeper processing, but was reduced during the shallow encoding and recognition conditions. Left prefrontal activity was less in older adults during encoding, but greater during recognition. Differential correlations of brain activity and behavior were found that suggest older adults use unique neural systems to facilitate face memory.

In response to the recent increase in the number of laboratories engaged in the use of functional and structural neuroimaging to study cognitive aging, this special section has been compiled to serve as an entry into this area for the readers of Psychology and Aging. These articles are representative of the field and cover many of the issues faced by researchers in this area. This introduction presents some background into the techniques that are used and provides an overview of the articles.

Encoding and recognition of unfamiliar faces in young adults were examined using positron emission tomography to determine whether different encoding strategies would lead to encoding/retrieval differences in brain activity. Three types of encoding were compared: a 'deep' task (judging pleasantness/unpleasantness), a 'shallow' task (judging right/left orientation), and an intentional learning task in which subjects were instructed to learn the faces for a subsequent memory test but were not provided with a specific strategy. Memory for all faces was tested with an old/new recognition test. A modest behavioral effect was obtained, with deeply-encoded faces being recognized more accurately than shallowly-encoded or intentionally-learned faces. Regardless of encoding strategy, encoding activated a primarily ventral system including bilateral temporal and fusiform regions and left prefrontal cortices, whereas recognition activated a primarily dorsal set of regions including right prefrontal and parietal areas. Within encoding, the type of strategy produced different brain activity patterns, with deep encoding being characterized by left amygdala and left anterior cingulate activation. There was no effect of encoding strategy on brain activity during the recognition conditions. Posterior fusiform gyrus activation was related to better recognition accuracy in those conditions encouraging perceptual strategies, whereas activity in left frontal and temporal areas correlated with better performance during the 'deep' condition. Results highlight three important aspects of face memory: (1) the effect of encoding strategy was seen only at encoding and not at recognition; (2) left inferior prefrontal cortex was engaged during encoding of faces regardless of strategy; and (3) differential activity in fusiform gyrus was found, suggesting that activity in this area is not only a result of automatic face processing but is modulated by controlled processes.

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.

To define brain regions involved in feature extraction or elementary form perception, regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in subjects viewing two classes of achromatic textures. Textures composed of local features (e.g. extended contours and rectangular blocks) produced activation or increased rCBF along the occipitotemporal pathway relative to textures with the same mean luminance, contrast, and spatial-frequency content but lacking organized form elements or local features. Significant activation was observed in striate, extrastriate, lingual, and fusiform cortices as well as the hippocampus and brain stem. On a scan-by-scan basis, increases in rCBF shifted from the occipitotemporal visual cortices to medial temporal (hippocampus) and frontal lobes with increased exposure to only those textures containing local features. These results suggest that local feature extraction occurs throughout the occipitotemporal (ventral) pathway during extended exposure to visually salient stimuli, and may indicate the presence of similar receptive-field mechanisms in both occipital and temporal visual areas of the human brain.

We evaluate regional cerebral blood flow (rCBF) in 19 healthy elderly subjects, mean age 64 +/- 11 (SD, years), during a passive visual stimulus in which pattern-flash frequency was parametrically manipulated. Using goggles with a grid of red lights imbedded into each lens, we performed five positron emission tomography (PET) H2(15)O water scans on each subject at alternating (left to right eye) flash frequencies of 0, 1, 4, 7, and 14 Hz. We found a biphasic rising and falling rCBF response in the striate cortex (7 Hz peak) and left anterior cingulate (4 Hz peak), 1 Hz activation in left middle temporal gyrus (V5), monotonically increasing rCBF in posterior areas (lateral and inferior visual association areas, Brodmann 18 and 19), and monotonically decreasing rCBF in anterior areas (frontal, cingulate, and superior temporal) predominantly in right hemisphere. We suggest the striate rCBF changes at all frequencies primarily reflect lateral geniculate input, the middle temporal activation at 1 Hz reflects perception of apparent motion, and the posterior extrastriate rCBF monotonic increase represents a neural response to increasing luminance intensity and form and color complexity that occur as pattern-flash frequency increases. The anterior monotonic rCBF decrease may represent active cross-modal functional suppression of brain areas irrelevant for processing the passive visual stimulus. Pattern-flash rCBF responses were highly reproducible (no series effect), more so in posterior than in anterior brain regions. The reproducibility and systematically changing rCBF responses to this passive stimulus suggest that it could be successfully used as a disease probe to evaluate neural function and drug effects in cognitively impaired patients.

Positron emission tomography (PET) was used to compare regional cerebral blood flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they were encoding, recognizing, and recalling word pairs. A multivariate partial-least-squares (PLS) analysis of the data was used to identify age-related neural changes associated with (1) encoding versus retrieval and (2) recognition versus recall. Young subjects showed higher activation than old subjects (1) in left prefrontal and occipito-temporal regions during encoding and (2) in right prefrontal and parietal regions during retrieval. Old subjects showed relatively higher activation than young subjects in several regions, including insular regions during encoding, cuneus/precuneus regions during recognition, and left prefrontal regions during recall. Frontal activity in young subjects was left-lateralized during encoding and right-lateralized during recall [hemispheric encoding/retrieval asymmetry (HERA)], whereas old adults showed little frontal activity during encoding and a more bilateral pattern of frontal activation during retrieval. In young subjects, activation in recall was higher than that in recognition in cerebellar and cingulate regions, whereas recognition showed higher activity in right temporal and parietal regions. In old subjects, the differences in blood flow between recall and recognition were smaller in these regions, yet more pronounced in other regions. Taken together, the results indicate that advanced age is associated with neural changes in the brain systems underlying encoding, recognition, and recall. These changes take two forms: (1) age-related decreases in local regional activity, which may signal less efficient processing by the old, and (2) age-related increases in activity, which may signal functional compensation.

Background: There are significant age and sex effects in cognitive ability and brain disease. However, sex differences in aging of human brain areas associated with nonreproductive behavior have not been extensively studied. We hypothesized that there would be significant sex differences in aging of brain areas that subserve speech, visuospatial, and memory function., Methods: We investigated sex differences in the effect of aging on human brain morphometry by means of volumetric magnetic resonance imaging and on regional cerebral metabolism for glucose by positron emission tomography. In the magnetic resonance imaging study, we examined 69 healthy right-handed subjects (34 women and 35 men), divided into young (age range, 20 to 35 years) and old (60 to 85 years) groups. In the positron emission tomography study, we investigated 120 healthy right-handed subjects (65 women and 55 men) aged 21 to 91 years., Results: In the magnetic resonance imaging study, age-related volume loss was significantly greater in men than women in whole brain and frontal and temporal lobes, whereas it was greater in women than men in hippocampus and parietal lobes. In the positron emission tomography study, significant sex differences existed in the effect of age on regional brain metabolism, and asymmetry of metabolism, in the temporal and parietal lobes, Broca's area, thalamus, and hippocampus., Conclusions: We found significant sex differences in aging of brain areas that are essential to higher cognitive functioning. Thus, our findings may explain some of the age-sex differences in human cognition and response to brain injury and disease.

Objective: Visual-processing abnormalities commonly contribute to typical Alzheimer's disease symptoms, but their detailed pathophysiology remains unknown. To investigate why patients with Alzheimer's disease have greater difficulty performing visuoconstructive (magnocellular-dominated) tasks than face- or color-perception (parvocellular-dominated) tasks, the authors measured brain activation in response to a temporally graded visual stimulus (neural stress test) during positron emission tomography., Method: The stress test measured regional cerebral blood flow (CBF) in response to a patterned flash stimulus in the resting state (0 Hz in the dark) and at frequencies of 1, 2, 4, 7, and 14 Hz. Ten patients with Alzheimer's disease and 12 age- and sex-matched comparison subjects were studied., Results: The striate response at 7 Hz and 14 Hz (the degree of regional CBF increase from that at 0 Hz) was significantly less in the patients than in the comparison subjects, whereas the change in regional CBF at the lower frequencies did not differ between groups. In bilateral middle temporal association areas activated by motion and dominated by magnocellular input, regional CBF at 1 Hz (the frequency with maximal apparent motion) was significantly greater than at 0 Hz in the comparison subjects but not in the patients., Conclusions: The magnocellular visual system normally responds to high-frequency input and motion; the failure of response in the striate cortex at high but not low frequencies in the Alzheimer's patients suggests greater magnocellular than parvocellular dysfunction at these levels. Activation failure in the middle temporal areas in the patients supports magnocellular dysfunction. The finding that the Alzheimer's disease group had abnormal visual cortical function emphasizes the importance of clinical visuospatial evaluation of patients with Alzheimer's disease to fully understand symptom production and to plan interventions.

Functional neuroimaging has become a powerful tool for investigating the neurobiological foundations of cognition. An overview is presented of the two major strategies by which such data are currently analyzed. One strategy compares the pattern of activity between two (or more) tasks, looking for those brain areas that show significant changes. The second investigates the functional relationships between regional activities in an attempt to determine the systems-level neural networks mediating the tasks. Object and spatial visual processing tasks are used to illustrate each of these strategies.

The functional dissociation of human extrastriate cortical processing streams for the perception of face identity and location was investigated in healthy men by measuring visual task-related changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H2(15)O. Separate scans were obtained while subjects performed face matching, location matching, or sensorimotor control tasks. The matching tasks used identical stimuli for some scans and stimuli of equivalent visual complexity for others. Face matching was associated with selective rCBF increases in the fusiform gyrus in occipital and occipitotemporal cortex bilaterally and in a right prefrontal area in the inferior frontal gyrus. Location matching was associated with selective rCBF increases in dorsal occipital, superior parietal, and intraparietal sulcus cortex bilaterally and in dorsal right premotor cortex. Decreases in rCBF, relative to the sensorimotor control task, were observed for both matching tasks in auditory, auditory association, somatosensory, and midcingulate cortex. These results suggest that, within a sensory modality, selective attention is associated with increased activity in those cortical areas that process the attended information but is not associated with decreased activity in areas that process unattended visual information. Selective attention to one sensory modality, on the other hand, is associated with decreased activity in cortical areas dedicated to processing input from other sensory modalities. Direct comparison of our results with those from other PET-rCBF studies of extrastriate cortex demonstrates agreement in the localization of cortical areas mediating face and location perception and dissociations between these areas and those mediating the perception of color and motion.

Objectives: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls., Design: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism., Patients: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/- SD) of the patients and controls were 60 +/- 10 years and 64 +/- 16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls., Results: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism., Conclusions: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections.

Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability > 0.70). The results suggest that this statistical approach may be useful for the early detection of AD.

Correlations between normalized regional cerebral metabolic rates for glucose, determined by positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose, were used to investigate functional associations between pairs of brain regions in 18 adult patients with primary obsessive-compulsive disorder (OCD) of childhood-onset, as compared with 18 age- and sex-matched control subjects. The number of correlations that differed significantly between the two groups exceeded chance, although as many of these correlations were larger in the OCD group relative to controls as were smaller. The two regions that had the largest number of correlations that differed significantly between groups were a left hemisphere superior parietal region and the left hemisphere anterior medial temporal area (which includes principally the amygdala). Correlations involving the caudate nuclei did not differ between the two groups for the most part. Anterior limbic/paralimbic regions had correlations in the OCD group that were significantly larger with frontal areas than in controls, and correlations that were significantly smaller with posterior brain regions. This pattern was especially pronounced for the left hemisphere anterior medial temporal region. These results suggest that the correlation pattern in OCD is not characterized by an overall loss of functional integration but, rather, by functional reorganization.

The rapid progress in PET technology has created the dilemma of how to compare data from old and new tomographs. We examined cerebral metabolic data from two scanners, with different spatial resolutions and methods of attenuation correction, to see if metabolic values from the lower-resolution tomograph (ECAT II) could be adjusted to make them comparable to data from the higher-resolution scanner (Scanditronix PC1024-7B). Nine subjects were scanned on both tomographs after a single injection of [18F]2-fluoro-2-deoxy-D-glucose. Regional and lobar gray matter metabolic rates for glucose were obtained from comparable images from each scanner. Ratios of lobar to global gray matter metabolism also were calculated. Regression coefficients and percent differences were computed to compare ECAT II and PC1024 data. Two-thirds of the region pairs showed significant regressions, although percent differences were quite variable, with measures of glucose utilization ranging from 30 to 120% higher on the PC1024 compared to those from the ECAT II. Comparisons of lobar glucose rates between the two machines were less variable (50 to 80%), and ratios differed by only +/- 5% (except for the temporal ratios). Since there was no simple and consistent relationship between regional metabolic rates on the two tomographs, an overall adjustment of regional ECAT values for comparison to PC1024 values would be impossible. A region-by-region adjustment would be necessary. Lobar ratios are sufficiently similar that direct comparisons might be possible.

The recent development of noninvasive methods for measuring local rates of energy metabolism or blood flow in the brain has made it possible to investigate functional neuroanatomy in healthy human subjects. The best of these methods, high resolution measurement of regional cerebral blood flow (rCBF) with positron emission tomography (PET), provides a precision of anatomical localization that far exceeds that attainable with human brain lesion studies. Moreover, the study of healthy subjects avoids possible confounding effects of brain lesions, such as compensatory reorganization of brain function. PET-rCBF studies have already identified several cortical areas involved in higher-order visual processing, indicating that functional neuroimaging may yield a map of human visual cortex analogous to maps that have been developed by vision research in nonhuman primates. PET-rCBF studies of imagery and language demonstrate the potential of functional neuroimaging to map regions of human cortex that perform functions that cannot be studied so easily in nonhuman primates or perform functions that humans do not share with other species.

We examined patterns of cerebral glucose metabolism in 33 patients with dementia of the Alzheimer type by applying principal component analysis to identify subgroups. Four subgroups were identified: one with predominant parietotemporal hypometabolism (15 patients); one with paralimbic metabolic deficits (8 patients); one with left hemisphere neocortical abnormality (5 patients); and one with frontal and parietotemporal deficit (5 patients). Differences among the subgroups were found in neuropsychological impairments and prevalence of psychiatric symptoms. These metabolic subgroups could not be explained on the basis of dementia severity, illness duration, or age, but were most likely related to an underlying pathology with a variable regional distribution.

Correlations between regional cerebral metabolic rates for glucose, determined by positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose, have been used to indicate functional associations between pairs of brain regions. This method was applied to data from 14 healthy adult subjects with trisomy 21 Down's syndrome (age less than 34 years) and from 24 age-matched healthy controls. Correlations were obtained between ratios of regional-to-global resting glucose utilization. In comparison to age-matched controls, the Down's syndrome group had many smaller correlations for region-pairs within and between the frontal and parietal lobes; some correlations were large and negative in the Down's syndrome group, but large and positive in the controls. One region so affected was the inferior frontal gyrus that includes Broca's area. This result is consistent with the relatively greater language impairment in Down's syndrome subjects. The thalamus also had smaller correlations with temporal and occipital regions in the Down's syndrome group compared to controls. These results suggest that Down's syndrome is accompanied by a functional disruption of neural circuits associated with directed attention.

Three subjects with dementia of the Alzheimer type (DAT) with frontal lobe features of behavioral disinhibition were studied using positron emission tomography with [18F]2-fluoro-2-deoxy-D-glucose (18 FDG) and standardized neuropsychological tests. The three subjects showed significant decrements (p less than .05) in relative glucose metabolism (regional/mean gray metabolism) in the orbitofrontal, prefrontal and anterior cingulate regions when compared to healthy controls. Severity-matched subjects with DAT without the associated frontal lobe features did not show the relative reductions in glucose metabolism in these regions when compared to controls. However, on neuropsychological testing of frontal lobe cognitive functions the three subjects did not show decrements that were more severe than those shown by severity-matched DAT patients without the behavioral features. These data demonstrate physiologic dysfunction in specific cortical regions in subjects with behavioral aberrations attributed to these regions and an apparent dissociation between behavioral and cognitive functions of the frontal lobe.

A linear histogram method was employed to analyze brain images of glucose uptake obtained by positron emission tomography in patients with dementia of the Alzheimer type and in control subjects. A line was drawn by computer which traversed the image of a brain slice taken at 70 mm above and parallel to the inferior orbitomeatal line, and rCMRglc was plotted as a function of distance along this line in 3 brain areas: frontal, sensorimotor and parietal. Peak rCMRglc values were significantly decreased in moderately-to-severely demented patients relative to healthy age-matched controls, but not in mildly demented patients. Furthermore, both the mildly and the more severely demented patients differed from controls in having reduced ratios of parietal association to sensorimotor peak rCMRglc. The variances of right-left metabolic asymmetries did not differ significantly between Alzheimer patients and controls. Severity of dementia, as evaluated by scores on the Mini-Mental State Examination, correlated with ratios of peak rCMRglc in frontal and parietal cortex to that in sensorimotor cortex. These results indicate that measures of focal peak rCMRglc do not discriminate between mildly demented patients and controls, whereas focal ratios of rCMRglc, where the denominator corresponds to rCMRglc from a relatively spared region, provide useful measures of metabolic dysfunction in the early stages of Alzheimer's disease.

The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings.

The rapid progress in positron emission tomography technology has created the dilemma of how to compare data from old and new tomographs. We examined cerebral metabolic data from two scanners, with different spatial resolutions and methods of attenuation correction, to see if data from the lower resolution tomograph (ECAT II) could be "corrected" and then compared to data from the higher resolution scanner (Scanditronix PC1024-7B). Nine subjects were scanned on both tomographs after a single injection of [18F]2-fluoro-2-deoxy-D-glucose. Regional and lobar gray matter metabolic rates for glucose were obtained from comparable images from each scanner. Ratios of lobar to global gray matter metabolism also were calculated. Regression coefficients and percent differences were computed to compare ECAT II and PC1024 data. Twenty-four of the 36 regions showed significant regression slopes, and PC1024 measures of glucose utilization ranged from 30% to 120% higher than those from the ECAT II. Lobar differences between the two machines were less variable (50% to 80%), and ratios generally differed by only +/- 5%. Since there was no simple and consistent relation between regional metabolic rates on the two tomographs, an overall adjustment of regional ECAT values for comparison to PC1024 values would be impossible. A region-by-region adjustment would be necessary. On the other hand, ratios are sufficiently similar that direct comparisons could be made.

To examine the progression of neuropsychologic and metabolic changes in the early stages of dementia of the Alzheimer type (DAT), we studied 11 midly demented patients longitudinally. Three aspects of neuropsychological function were measured: memory, attention to complex sets and abstract reasoning, and lateralized functions, i.e., language and visuoconstruction. Regional cerebral metabolic rates for glucose were measured in frontal, parietal, and temporal association cortices. Our results show that, in general, memory deficits are the first neuropsychological impairments to occur in DAT, followed by problems with attention to complex cognitive sets and abstract reasoning, which are followed in turn by deficits in language and visuospatial abilities. In addition, neocortical metabolic abnormalities usually precede impairment of neocortically mediated attention and abstract reasoning by 8 to 16 months, and precede impairment of neocortically mediated language and visuospatial function by 12 to 37 months. These findings suggest that the first nonmnestic neuropsychological consequence of neocortical physiological dysfunction in DAT is a loss of attentional capacity. Since neocortical metabolic changes generally precede the appearance of neocortically mediated neuropsychological dysfunction, physiologic dysfunction may exist for some time before cognition is affected.

This paper presents, for the first time, repeated assessments of cerebral metabolism and neuropsychological competence in early Alzheimer's disease. Regional cerebral metabolic rates for glucose were measured with positron emission tomography and 18F-fluoro-2-deoxy-D-glucose on three occasions at 8-month intervals, in a 57-year-old man with Alzheimer's disease of 2 1/2 years' duration and with a family history of neuropathologically confirmed Alzheimer's disease. Data were compared with mean cerebral metabolic rates from 12 healthy men. No differences in regional cerebral metabolic rates for glucose were found on the initial patient scan, whereas metabolism on the second and third scans was reduced significantly in the parietal lobes and bilaterally in some parietal lobe regions. Memory loss was demonstrable at the first scan, but then and at later scans, other aspects of cognitive performance remained within normal limits (Wechsler Adult Intelligence Scale, Boston Naming Test, Two-dimensional Block Construction). The results show that memory loss can precede a measurable reduction of cerebral metabolism in early Alzheimer's disease, but that later reductions in parietal lobe metabolism may not be accompanied by additional measurable neuropsychological deficits.