Publications

Theoretical models of higher cognitive function predict that cortical activity will exhibit families of spatial-temporal patterns of activity whose individual members are related to each other by specific symmetry transformations. In the trion model, it is suggested that these inherent symmetries play a vital role in how we think and reason. We have developed a method of analysis (SYMMETRIC analysis), which detects families of patterns in EEG data, and characterizes the symmetry relationships between members of those pattern families. Using this analysis, significant symmetry families have been found in EEG and single unit spike train data. If symmetry is a crucial aspect of brain function, it is possible that different pathologies are associated with specific types of symmetry relationships in brain activity that could be detected in EEG data by a SYMMETRIC analysis.

OBJECTIVE

To evaluate the clinical and pathological features of a subgroup of patients with Alzheimer disease (AD) who exhibited early and disproportionately severe impairments on tests of frontal lobe functioning. We hypothesized that these patients would exhibit a greater degree of either neurofibrillary tangle (NFT) or senile plaque pathology in the frontal lobes than would patients with typical AD.

DESIGN AND OUTCOME MEASURES

We examined the neuropsychological profiles and senile plaque and NFT accumulation in the frontal, entorhinal, temporal, and parietal cortices in 3 patients with AD who exhibited disproportionate frontal impairments during early stages of dementia (frontal AD) and 3 matched patients with typical AD (typical AD).

RESULTS

Compared with the typical AD group, the frontal AD group performed significantly worse on 2 tests of frontal lobe functioning and on the Wechsler Adult Intelligence Scale-Revised Block Design test. No significant group differences were found on other tests. Analysis of brain tissue samples demonstrated that, despite comparable entorhinal, temporal, and parietal NFT loads, the frontal AD group showed a significantly higher NFT load in the frontal cortex than the typical AD group. Senile plaque pathology in the frontal and entorhinal cortices did not differentiate the 2 groups.

CONCLUSIONS

We identified a subgroup of patients with pathologically confirmed AD who presented in the early stages of dementia with disproportionate impairments on tests of frontal lobe functioning and had a greater-than-expected degree of NFT pathology in the frontal lobes, suggesting the existence of a frontal variant of AD that has distinctive clinical and pathological features.