J. Blin

The pattern of cortical and subcortical neuropathologic lesions in corticobasal degeneration (CBD) should predict a specific cognitive profile in this disease. To characterize this profile and to determine its specificity by comparison with progressive supranuclear palsy (PSP) and senile dementia of the Alzheimer's type (SDAT), we used an extensive neuropsychological battery assessing global efficiency, executive functions, various tests of encoding and retrieval, dynamic motor organization, and upper limb praxis. We compared the performance of patients with CBD (n = 15) with that of controls (n = 19) matched for age and education, and with that of patients with PSP and SDAT (15 in each group), matched for severity of dementia and depression. Patients with CBD showed: (1) a moderate global deterioration; (2) a dysexecutive syndrome similar to that of patients with PSP and more severe than in SDAT; (3) explicit learning deficits, without retention difficulties and easily compensated by using the same semantic cues at encoding and retrieval as in PSP; this was in contrast with SDAT where cued recall and recognition were also impaired; (4) disorders of dynamic motor execution (temporal organization, bimanual coordination, control, and inhibition) similar to those of patients with PSP and not in SDAT; (5) asymmetric praxis disorders (posture imitation, symbolic gesture execution, and object utilization) that were not observed in PSP or SDAT. Patients with CBD show a specific neuropsychological pattern associating a dysexecutive syndrome, likely due to degeneration of the basal ganglia and prefrontal cortex, and asymmetric praxis disorders, which might be related to premotor and parietal lobe lesions. This neuropsychological profile may help to distinguish this condition clinically from other neurodegenerative diseases.

In 41 patients with progressive supranuclear palsy (PSP) that was diagnosed on the basis of eight clinical criteria (25 patients with all eight criteria [probable PSP] and 16 with six or seven criteria [possible PSP]), we studied cerebral energy metabolism by using positron emission tomography and the fludeoxyglucose F 18 or the oxygen 15 method. Compared with age-matched controls, each of the cortical and subcortical metabolic values was significantly reduced, with a predominance in the frontal cortex, in both groups of patients with probable and possible PSP, without a difference between these two groups, suggesting similar underlying disease. The frontal metabolic value decreased with disease duration, but the relative frontal hypometabolism (expressed as the fronto-occipital metabolic ratio) was apparently already present in the early stages of the disease. The parkinsonian motor score was correlated with the caudate and thalamic metabolic values. The intellectual deterioration index was significantly correlated with both the frontal and the nonfrontal metabolic values. Finally, the frontal neuropsychological score was significantly correlated with only the fronto-occipital metabolic ratio. Hence, in PSP, a degenerative brain disease with subcortical lesions, the prominent frontal lobe-like syndrome essentially depends on the relative hypometabolism of the frontal cortex.

Using 18[18F]setoperone and positron emission tomography (PET), alterations in serotonergic 5-HT2 receptor binding were studied in cerebral cortex of nine unmedicated patients with probable Alzheimer's disease and 37 healthy controls. The kinetics of unchanged radioligand in plasma and 18F-radioactivity in blood and brain were obtained for 90 min following tracer injection. The specific binding of [18F]setoperone to 5-HT2 receptors in the cerebral cortex was quantitated by subtraction using cerebellum as reference. In controls, a significant reduction in specific binding was associated with age and similar linear regression slopes were obtained in all the cortical regions studied. No significant difference was observed between patients with Alzheimer's disease and age-matched controls in the injected mass of setoperone, percentage of unmetabolized18setoperone in plasma, 1818F-radioactivity in blood fractions and cerebellar 18F-radioactivity concentration, indicating similar non-specific brain kinetics and metabolism of the radioligand. In contrast, there was a significant reduction in specific [18setoperone binding in the cerebral cortex in patients with Alzheimer's disease relative to control values (temporal, 69% frontal, 69% parietal, 55% temporo-parietal, 54% occipital cortex, 35%). The results demonstrate that the loss in 5-HT2 receptor binding in the cerebral cortex of patients with Alzheimer's disease, long documented by post-mortem studies, can now be assessed in vivo using PET. Correspondence to: Jé rð me Blin, Nouvelle Pharmacie U289, Hðipital de la Salpêtrière, 75651 Paris Cedex 13, France.