Search

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.

The P300 (P3) wave of the auditory brain event-related potential was investigated in patients with probable Alzheimer's disease to determine whether P300 latency discriminated these patients from controls and whether prolonged P300 latency correlated with rates of brain glucose metabolism as measured by Positron Emission Tomography. P300 latency was prolonged by more than 1.5 standard deviations from age expectancy in 14 of 18 patients, but none of 17 controls. In these subjects P300 latency was shown to be inversely correlated with relative metabolic rates of parietal and, to a lesser extent, temporal and frontal association areas, but not with subcortical areas.

The relationship between age, education, length and amount of heavy drinking, and performance on five memory tasks was investigated in 54 chronic alcoholics and 18 age-matched controls. Alcoholics with less than 12 yr of heavy drinking differed reliably from long-term (13-22 yr) and extended long-term drinkers (greater than 23 yr) in recognition memory for visual patterns when scores were corrected for age. Compared with controls, both groups of long-term drinkers were deficient on the visual, auditory, and Faces recognition tests. Age and education of alcoholics accounted for part of performance differences; length of alcohol abuse, however, predicted reliably the decline in memory scores on all but the tactual test. The profile of memory performances seemed to decrease linearly with increasing age and length of alcohol abuse.

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.

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.

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.

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.

(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.

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% had7 wks abstinence) predicted component scores of alcoholics, while age or education accounted for significant variance in visual-spatial, verbal, and design recognition components.

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.

Positron-computed tomography with [18F]fluorodeoxyglucose to measure glucose metabolism has shown changes in the brain distant to a focal area of infarction, demonstrating that what appears as a focal abnormality represents a more widespread functional process. Several approaches are presented to better understand quantitative metabolic data and focus on caudate and basal ganglia function. Area-to-area correlations in Parkinson's and Huntington's diseases showed decreases in the number of cortical relationships compared with control subjects, suggesting that the basal ganglia are involved with the ability of cortical regions to function together. In aphasia, caudate metabolism correlated with several language measures that suggested a role in some undefined basic process, seemingly related to Broca's area function. The studies presented suggest that the caudate may involve integrating the processing of language and cognition with the execution of the resulting response. Motor and cognitive function seem related to similar and overlapping brain systems. The disruption of such systems may result in loss of both cognitive and motor aspects of a function.