Objective

To define brain activity and behavioral changes in mild cognitive impairment (MCI), an isolated memory deficit in the elderly that is a major risk factor for Alzheimer's disease.

Methods

Brain potentials and reaction time were examined in elderly controls (n=12) and MCI (n=15) using a target detection paradigm. Subjects listened to a sequence of tones and responded to high-pitched target tones (P=0.20) that were randomly mixed with low-pitched tones (P=0.80). Measures were a pre-stimulus readiness potential (RP), post-stimulus potentials (P50, N100, P200, N200, P300), and reaction time.

Results

Accuracy was equivalent between groups, but there was a trend for longer reaction times in MCI (P=0.08). Two potentials differed between groups: (1) P50 amplitude and latency were significantly increased in MCI, and (2) P300 latency was significantly longer in MCI. Results from two MCI subjects that converted to Alzheimer's disease are also discussed.

Conclusions

Brain potentials in MCI subjects during target detection have certain features similar to healthy aging (RP, N100, P200, N200), and other features similar to Alzheimer's disease (delayed P300 latency, slower reaction time). P50 differences in MCI may reflect pathophysiological changes in the modulation of auditory cortex by association cortical regions having neuropathological changes in early Alzheimer's disease.

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.

© 2015 Johnson et al.Background: Older adults are the fastest growing segment of the United States population. There is an immediate need to identify novel, cost-effective community-based approaches that promote health and well-being for older adults, par