Clinical and pathological evidence for a frontal variant of Alzheimer disease

Arch Neurol. 1999 Oct;56(10):1233-9. doi: 10.1001/archneur.56.10.1233.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / classification*
  • Alzheimer Disease / pathology*
  • Cognition Disorders / pathology
  • Entorhinal Cortex / pathology
  • Female
  • Frontal Lobe / pathology*
  • Humans
  • Male
  • Middle Aged
  • Neurofibrillary Tangles / pathology
  • Neuropsychological Tests
  • Parietal Lobe / pathology
  • Plaque, Amyloid / pathology
  • Temporal Lobe / pathology