Slowly progressive aphasia: three cases with language, memory, CT and PET data.

Three cases of slowly progressive speech and language disturbance were studied at various points post onset (three, five and 15 years respectively). Language, neuropsychological and brain imaging (computer tomography and positron emission tomography) evaluations were completed on all three patients. The data suggest that the syndrome of "progressive aphasia": 1) does not involve a uniform symptom complex; 2) does not necessarily develop into a full blown dementia syndrome; 3) varies greatly in rate of progression from case to case; 4) is associated with normal brain structure (on computer tomography); and 5) is associated with abnormal left temporal lobe metabolism as measured by fluorodeoxyglucose (FDG) positron emission tomography (PET). One patient had histological findings consistent with Alzheimer's disease at necropsy.

Increased false alarms in a subset of persons at-risk for Huntington's disease.

The accuracy and decision criterion of 51 persons at-risk (AR) for Huntington's disease (HD) along with 36 age-matched, healthy controls were evaluated using a word recognition memory test. Analyses revealed that the AR group was less accurate than the controls at recognizing a previously learned word list. Within the AR group, 13 AR persons were identified who committed significantly more false alarms than the remaining AR and control people. The 13 AR persons also showed evidence of lower cerebral metabolic ratios in frontal, caudate, and insula regions, as evaluated by positron emission tomography using I8F-Fluoro-deoxyglucose, and were considered to be at high risk for HD. One of these 13 AR persons has become symptomatic since testing, confirming the high risk status. These results suggest that certain tests of cognition and decision-making together with measures of regional brain metabolism might show the subtle cognitive changes taking place in potential HD gene carriers years before the clinical symptoms are observed.

Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset.

No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect.

Memory impairments in alcoholism: effects of age and education.

Memory impairments related to alcoholism and to age (young, middle, and old) were examined as a function of educational level (low, high). Factoring of 14 different memory test scores from 93 alcoholics and 73 controls into four components indicated that alcohol-related impairments in verbal memory were observed in adults with low, but not high levels of education. Similarly, age-related decrements in visual-spatial and verbal memory tasks (Components I and II) affected mainly low-education alcoholics and controls. On these components, age and alcoholism did not interact, but were additive. Effects of education were reflected in verbal but not nonverbal tasks (Auditory and Design Recognition, Components III and IV). Neither years of heavy drinking, lifetime consumption, nor abstinence (80% had < 7 wks abstinence) predicted component scores of alcoholics, while age or education accounted for significant variance in visual-spatial, verbal, and design recognition components.

Subcortical structures in aphasia. An analysis based on (F-18)-fluorodeoxyglucose, positron emission tomography, and computed tomography.

Subcortical structural damage that includes the anterior and posterior internal capsule, caudate, thalamus, lenticular nuclei, and insula has been shown to cause aphasias. A critical question that has not been resolved is whether the role of these structures on behavior is a direct one or whether it is indirect through the cortex. We have used pathway analysis to evaluate computed tomography, glucose metabolic, and language data from 47 aphasic patients to answer this question. For fluency (from the Western Aphasia Battery), subcortical structural damage had direct and indirect (through frontal lobe) effects on the behavior. For a comprehension task (sequential commands), subcortical damage had no direct effect and only a slight indirect effect through the temporal lobe. Thus, both direct and indirect effects of subcortical damage can be demonstrated for specific behavioral measures.

Apparent shift in visual field preference after unilateral stroke.

Patients with either a left- or a right-hemisphere stroke lesion scored higher in tasks of word-picture matching and of nonverbal shape matching when information was presented tachistoscopically (120 msec) to the visual field (VF) projecting to their undamaged hemisphere. Left-hemisphere stroke patients (n = 13) were dissociated from right-hemisphere stroke patients (n = 15) by low word recognition from memory and by low right VF but nearly normal left VF accuracy in word-picture matching or shape matching; the former appeared to rely upon processing of word meaning by the right hemisphere. In contrast, right-stroke patients had higher right than left VF scores in both tasks, and their discrimination of nonverbal shapes via the right VF was not different from that of controls (n = 15). Preferred processing by the VF projecting to the undamaged hemisphere appeared as a shift in perceptual asymmetry but may indicate, in support of a "direct access" model, that each hemisphere responds more or less efficiently to word and to nonverbal shape discriminations.

Disconnection and cerebral metabolism. The case of conduction aphasia.

Ten patients with conduction aphasia were studied with computed tomography and 18-F-fluorodeoxyglucose positron emission tomography to examine glucose metabolism. Computed tomographic results identified a postrolandic structural locus for conduction aphasia. All patients demonstrated resting glucose hypometabolism throughout the parietal and temporal regions, and half of the patients also demonstrated reduced metabolic rates in the posterior, inferior, frontal (Broca's) regions. These data suggest that disconnection between posterior and anterior language areas may not be the best anatomical explanation for conduction aphasia.

Cognitive and brain imaging measures of Alzheimer's disease.

Diagnosis of Alzheimer's disease (AD) during life relies upon clinical and neurobehavioral symptoms but is presumptive without microscopic verification of neuropathology. Studies in this review observed considerable heterogeneity in AD symptoms and did not agree on how to detect the earliest symptoms. Problems exist in diagnosis. Differences in symptoms and diagnosis result from how AD is defined neurobehaviorally and on the model used for description. The studies reviewed have been considered under three basic models: A severity (staging) model; a heterogeneity (subtyping) model; and an information processing model. Differences in model intent have resulted in differences in disease description. Brain imaging measures have not invalidated models but add the neural substrate needed to examine correlation of measures within each model.

Cerebellar glucose metabolism in chronic aphasia.

(18F)-Fluorodeoxyglucose PET was used to compare left/right cerebellar hemispheric glucose metabolism in 37 aphasic patients with left hemisphere lesions and 22 age-matched controls. Sixteen aphasic subjects showed cerebellar symmetry. Twenty-one aphasic subjects were found to have cerebellar metabolic asymmetry, which (1) resulted from an absolute reduction in local cerebral metabolic rates of glucose in the right cerebellar hemisphere; (2) was associated with left less than right glucose metabolic asymmetry in the frontal, parietal, caudate, and thalamic regions; (3) was associated with Broca's region and deep hemisphere structural damage to the internal capsule and basal ganglia; (4) related to reduced functional motor performance, spontaneous speech, naming, reading, and writing; and (5) included all Broca's aphasia subjects.

Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease.

Symptomatic patients with Huntington's disease may have reduced glucose metabolism in the caudate nuclei. We used positron emission tomography and [18F]fluorodeoxyglucose to study cerebral glucose metabolism in 95 subjects: 58 clinically asymptomatic (chorea-free) subjects at risk for Huntington's disease, 10 symptomatic patients with the disease, and 27 controls. All the symptomatic patients had marked reductions in caudate glucose metabolism. Despite a normal structural appearance on computed tomography, caudate glucose metabolism was bilaterally reduced in 31 percent of the subjects at risk (18 of 58). Using each at-risk subject's age and the sex of the affected parent, we averaged individual risk estimates for the development of Huntington's disease for this group and predicted that the probability of having the clinically unexpressed Huntington's disease gene should be 33.9 +/- 6.0 percent for the group. Thus, there was excellent agreement between the predicted percentage of carriers of the Huntington's disease gene (33.9 +/- 6.0 percent) and the percentage with metabolic abnormalities of the caudate nuclei (31 percent). These results indicate that the measurement of glucose metabolism may allow the observation of the pathophysiologic effects of the Huntington's disease gene during the natural development of the disease. It may also provide a direct means to monitor the response to experimental treatments during both the clinically asymptomatic and the symptomatic phases of the disorder.

Specificity of memory deficits in alcoholism.

Inferences of specific impairments in memory from prolonged abuse of alcohol have come from initial studies reporting that visuospatial memory and problem solving were impaired but verbal memory and learning were not. The apparent specificity, however, is demonstrated to be an artifact of the more difficult visual tests. With task complexity increased, impairments are shown also in both learning and recall of words, story, or designs. A common condition for deficits to be detected is the demand for effort in encoding and retrieving of to-be-remembered information. In general, deficits are mild and diffuse and do not seem to be clearly specific to material or modality. Furthermore, deficits are more pronounced in old alcoholics, although these tend to have longer drinking careers. Age and length of abstinence are more significant predictors of impairment than length or rate of alcohol drinking; however, concomitant disease and familial history of alcoholism are recognized to contribute to wide differences in effort-requiring memory processing.

Left hemisphere intracerebral hemorrhages studied by ( (F-18)-fluorodeoxyglucose PET.

We used PET to study patients with intracerebral hemorrhages in the left hemisphere. Three anatomic and physiologic patterns were observed. Patients 1 and 2 had midputamen hemorrhages with diffuse left less than right hemispheric metabolic asymmetry most prominent in temporal and parietal regions. Patients 3 and 4 had posterior putamen-insula-temporal hemorrhages with left less than right metabolic asymmetry in temporoparietal cortex and thalamus. Patients 5, 6, and 7 had smaller posterior hemorrhages. Left cortical metabolism was little affected in these three cases. Persistent aphasia was associated with severe metabolic left less than right asymmetry in posterior middle temporal regions.

Comparison of PET measurement of local brain glucose metabolism and CAT measurement of brain atrophy in chronic schizophrenia and depression.

Using [18F]fluorodeoxyglucose and positron emission tomography (PET), the authors examined the regional brain glucose metabolism of six patients with chronic schizophrenia, six patients with chronic depression, and 12 normal control subjects. Three schizophrenic and four depressive patients had CAT scans that showed enlarged ventricles (ventricle-brain ratios higher than 9.0) and widened sylvian fissures. The PET scans of the schizophrenic and depressed patients did not differ significantly from those of the age-matched controls, and a previously reported metabolic "hypofrontality" was not confirmed. The patients with enlarged ventricles and widened sylvian fissures tended to have lower global metabolism.

Aging and delay effects on recognition of words and designs.

Based on a model of inter- and intraitem processes in recognition, this study examined age differences in word recognition (emphasizing interitem elaborative rehearsal) and in design recognition (emphasizing intraitem perceptual processes) over delays of 2, 20, and 200 min. Because repeated exposures should increase intraitem integration, targets were repeated from first to second test halves. Young and old adults showed equivalent accuracy in design recognition and equivalent increases from first to second test halves; the predicted lack of intraitem age differences was supported. Young adults, however, were more accurate than old adults in word recognition, supporting the prediction of age differences in interitem processing. The decline across delays was different for words and designs but was parallel for both age groups. Young and old adults also had equivalent decision criteria and decision speeds.

Brain glucose metabolism and memory functions: age decrease in factor scores.

The F-18 fluorodeoxyglucose (FDG) scan method with positron emission tomography was used to determine age differences in factors underlying both the performances on 18 multivariate memory tests and the rates of cerebral glucose utilization in nine left and nine right hemispheric regions of 23 healthy adults aged 27 to 78 years. Two of the five derived factors separated persons below age 42 from those above age 48 years, one reflecting secondary memory for material verbally processed together with Broca's metabolic ratio, the other defined by tests requiring sequential or organizational coding of information and metabolic measures of thalamic regions. Education did not override their parallel age decrease. Several regional metabolic measures covaried with distinct memory measures. Persons with high superior frontal and low caudate-thalamic metabolic measures were those who performed well in tests of memory for sentences, story, designs, and complex patterns, suggesting a frontal-subcortical interaction in age-dependent memory processing.

Local cerebral glucose utilization in symptomatic and presymptomatic Huntington's disease.

Patterns of local cerebral glucose utilization were measured with positron emission CT using the 18F-fluorodeoxyglucose method in 13 patients with HD, 15 subjects at risk for HD, and control subjects. These data were compared with CT measures of cerebral atrophy, age, and duration and severity of symptoms. The results indicate that in HD there is a characteristic decrease in glucose utilization in the caudate and putamen and that this local hypometabolism appears early and precedes bulk tissue loss. In contrast to demented patients with Alzheimer's disease or Parkinson's disease, in these HD patients glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite apparent shrinkage of brain tissue. Our results indicate that the caudate is hypometabolic in some asymptomatic persons who are carriers of the autosomal-dominant gene for HD.

Patterns of cerebral glucose utilization in depression, multiple infarct dementia, and Alzheimer's disease.

Patterns of local cerebral glucose utilization were determined in moderately to severely disabled patients with D (N = 7), MID (N = 6), and AD (N = 6), and in normal controls (N = 6), using positron emission tomography with the 18F-fluorodeoxyglucose method. Average global metabolic rate was decreased 30% in patients with AD, but overlap among the other groups reduced the discriminant value of this measure. In depressed patients, the cerebral metabolic pattern was normal, except for evidence of hypometabolic zone in the posterior-inferior frontal cortex which was of marginal statistical significance. In MID, focal metabolic defects were scattered throughout the brain and exceeded the extent of infarction. In AD, metabolism was markedly reduced in cortex, especially parietal cortex, but relatively preserved in caudate, thalamus, anterior cingulate gyrus, pre- and post-central gyrus, and calcarine occipital cortex, a pattern duplicating the degree and location of pathological and neurochemical alterations characteristic of this disorder.

Cerebral metabolic relationships for selected brain regions in Alzheimer's, Huntington's, and Parkinson's diseases.

Local CMRGlc values were determined for 13 regions in each hemisphere from tomographs of patients with Alzheimer's, Huntington's, and Parkinson's diseases who were studied using [18F]fluorodeoxyglucose with positron emission computed tomography. Intercorrelations among the 26 regional measures were calculated for each disease state and for normal controls, and were accepted as reliable at p less than 0.01, uncorrected for the number of comparisons. The number of reliable correlations was found to be decreased in Parkinson's and Huntington's diseases, two primarily subcortical disorders, and increased in Alzheimer's disease, a primarily cortical disorder. The changes suggest that one role of the basal ganglia involves coordinating or pacing the ability of cortical brain regions to function as a unit.