This study investigated cerebral glucose metabolism in very early Alzheimer's disease, before a clinical diagnosis of probable Alzheimer's disease is possible, using [18F]fluorodeoxyglucose positron emission tomography. First, 66 patients with probable Alzheimer's disease with a spectrum of dementia severity (Mini-Mental State Examination score, 0-23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three-dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini-Mental State Examination score, 25 +/- 1) at the time of scanning but whose condition later progressed to probable Alzheimer's disease. Both results were compared to cerebral metabolic activity in 22 age-similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21-22%) in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer's disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer's disease.

The disruptive behavior of persons with dementia is a problem ofconsiderable clinical interest and growing scientific concern. This paper offers a view ofthese behaviors as expressions of unmet needs or goals and provides a comprehensive conceptual framework to guide further research and clinical practice. Empiricalfindings and clinical impressions related to wandering, vocalizations and aggression to support and illustrate the framework are presented.

Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum, correcting for total intracranial volume. For 27% of the patients, HF volume fell outside the 95% confidence intervals for normal subject volume given in the literature. In addition, there were significant and specific correlations between HF volume and scores for verbal paired associate learning, verbal recall, and verbal recall corrected for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association between reduced HF volume, memory dysfunction, and elevated cortisol in patients with CS.

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Among nondemented elderly patients, memory loss alone rarely progresses to dementia in the subsequent 2 years. However, the risk of dementia is significantly increased among patients with clear cognitive impairments beyond memory loss. Further study is needed to determine whether patients with impairments limited to memory loss have a distinctive clinical course or pathophysiology.

Frontal, limbic and temporal regions of the brain important in emotion perception and executive functioning also have been implicated in the etiology and maintenance of depression; yet, the relationships among these topics remain poorly understood. The present study evaluated emotion perception and executive functioning among 21 depressed women and 20 nondepressed women controls. Depressed women performed significantly worse than controls in emotion perception accuracy and in inhibitory control, an aspect of executive functioning, whereas the groups did not differ in other cognitive tests assessing memory, visual-spatial, motor, and attention skills. The findings suggest that emotion perception and executive functioning are disproportionately negatively affected relative to other cognitive functions, even in a high-functioning group of mildly depressed women. Measures of emotion perception and executive functioning may be of assistance in objectively measuring functional capability of the ventral and dorsal neural systems, respectively, as well as in the diagnosis of depression.

The academic achievement scores of 122 children with epilepsy were examined in relation to demographic and clinical seizure variables. As a group, these children were making less academic progress than expected for their age and IQ level. Academic deficiencies were greatest in arithmetic, followed by spelling, reading, comprehension, and word recognition. Results of the multiple regression analyses indicated a modest combined predictive significance of the demographic and clinical seizure variables for academic performance. In addition, the magnitude of these relationships varied by academic area. Among the individual variables examined the strongest correlates of academic performance were age of the child, age of seizure onset, lifetime total seizure frequency, and presence of multiple seizures (absence and tonic-clonic). These results are discussed in relation to developing an understanding of the factors which underlie academic vulnerability in children with epilepsy.

In an extension of previous work, we studied the behavioral correlates of medial frontal lobe glucose hypometabolism in chronically alcohol-dependent patients. Thirty-one male patients who were detoxified, medically stable, and free of other central nervous system risk factors for neuropsychological impairment were examined with (1) anatomic imaging (CT or MR), (2) functional imaging with [18F] fluorodeoxyglucose (18F-FDG) and positron emission tomography (PET), and (3) a battery of neuropsychological tests, including two measures of abstraction known to be generally sensitive to frontal lobe disease or dysfunction [the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test (HCT)]. 18F-FDG PET data from 18 age- and sex-matched normal control subjects were used for comparison. All patients met criteria for severe alcohol dependence and for at least a mild degree of alcoholic-induced cognitive impairment. Although the mean IQ level of the alcoholic patients was in the average range, the concepts attained and the error scores on the WCST and HCT were significantly impaired in comparison with established norms. Local cerebral metabolic rate for glucose (LCMRglc) was significantly decreased in a sagittal strip of the medial frontal cortex in the alcoholic patients as compared with the normal controls. Comparison of data from PET scans and anatomic images indicated that the reduced LCMRglc could not be attributed to reduced amounts of tissue alone. A statistically significant relationship was found between LCMRglc in the medial frontal region of the cerebral cortex and performance on the WCST, but not the HCT. These findings suggest that chronic alcohol intake results in impaired function of cerebral tissue in the medial frontal region.(ABSTRACT TRUNCATED AT 250 WORDS)