Clinical investigations of Alzheimer's disease (AD) have been limited by diagnostic inaccuracy. We employed explicit clinical inclusion and exclusion criteria to identify subjects with senile dementia of the Alzheimer type (SDAT). In a consecutive series of 26 postmortem examinations from this sample, AD was histologically verified in all subjects and was the primary dementing illness. Seventeen of the 26 SDAT subjects had been diagnosed when only mildly demented. Two control subjects were examined neuropathologically; AD was absent in both. We conclude that research clinical diagnostic criteria for SDAT, even in its mild stage, are valid.

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Cranial magnetic resonance (MR) imaging studies in 117 control patients were reviewed to evaluate for focal signal-intensity variations in the posterior internal capsule. Rounded foci of increased signal intensity were found near the junction of the posterior limb and retrolenticular portion of the internal capsule on axial T2-weighted images in 56% of patients imaged at 1.5 T and in 50% imaged at 0.5 T. Corresponding hypointense foci were found on T1-weighted images in 64% of control patients imaged at 1.5 T and in 69% imaged at 0.5 T. With all sequences, the foci were homogeneous and well defined, without mass effect, and bilaterally symmetric. Comparison was made with MR imaging studies in 32 patients with pathologic involvement of the posterior internal capsule region. Symmetric morphology and signal intensity, sharply defined margins, confinement to a characteristic location, signal intensity approximating that of cortical gray matter on T2-weighted images, and isointensity or hypointensity on spin-density-weighted images appear to characterize normal posterior capsular foci and distinguish them from foci of pathologic lesions. A region that stained less intensely than the surrounding internal capsule was noted in tissue blocks from two normal brain specimens, corresponding in morphology and position to the signal-intensity changes seen on MR images. The properties of this focus suggest that it may represent fibers of the parietopontine tract.

An assay of water content and specific gravity in normal and pathological autopsy brain has been correlated with CCT attenuation values obtained just prior to brain cutting. Formalin fixation does not alter normal values so that fixed brain appears to be suitable for this type of study. Low attenuation values in CCT correlate better with changes in specific gravity, rather than water in infarcts, but they have a close relationship to water content in edema. The high water content in infarcts of the white matter reveals a striking disparity in fluid control between cortex and white matter, which has not been emphasized in experimental studies. Water movement within and around blood clots has been discussed.

Thalamic degenerations or dementias are poorly understood conditions. The familial forms are (1) selective thalamic degenerations and (2) thalamic degenerations associated with multiple system atrophy. Selective thalamic degenerations share clinical and pathologic features with fatal familial insomnia, an autosomal dominant disease linked to a mutation at codon 178 of the prion protein (PrP) gene that causes the substitution of asparagine for aspartic acid (178Asn mutation). We amplified the carboxyl terminal coding region of the PrP gene from subjects with selective thalamic dementia or thalamic dementia associated with multiple system atrophy. Three of the four kindreds with selective thalamic dementia and none of the three kindreds with thalamic dementia associated with multiple system atrophy had the PrP 178Asn mutation. Thus, analysis of the PrP gene may be useful in diagnosing the subtypes of thalamic dementia. Moreover, since selective thalamic dementia with the PrP 178Asn mutation and fatal familial insomnia share clinical and histopathologic features, we propose that they are the same disease.