Related Experiment Video
Updated: Jul 9, 2026

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease
Published on: October 13, 2016
Patients with MCI and N400 or P600 abnormalities are at very high risk for conversion to dementia
J M Olichney1, J R Taylor, J Gatherwright
1Department of Neurology, University of California, Davis, CA, USA/ jmolichney@ucdavis.edu
Objective:
We sought cognitive event-related potential (ERP) biomarkers of disease progression and subsequent conversion to dementia in mild cognitive impairment (MCI).
Background:
Two ERP components, the P600 and N400, are sensitive to abnormal episodic/declarative memory and semantic processing. When congruous category-exemplars are repeated, smaller P600s (relative to initial presentation) are normally elicited. Repetitions of semantically incongruous words yield smaller N400 amplitude. In mild Alzheimer disease (AD), abnormalities of both the N400 and P600 repetition effects are present, suggesting a widespread failure of synaptic plasticity.
Methods:
Patients with amnestic MCI (n = 32) were longitudinally studied annually with an ERP paradigm in which semantically congruous (50%) and incongruous target words are repeated 10 to 140 seconds after initial presentation. ERP data were analyzed to contrast MCI-to-AD converters (within 3 years) vs nonconverters, using split-plot analyses of variance.
Results:
A statistically significant P600 congruous word repetition effect was found only in the nonconverter group (F = 9.9, p = 0.005 vs MCI converters). This effect correlated with verbal memory measures. Repetition of incongruous words produced a significant N400 amplitude attenuation (across right-hemisphere sites) in nonconverters, but not in converters. Patients with MCI with abnormal/reduced N400 or P600 word repetition effects had an 87 to 88% likelihood of dementia within 3 years while those with normal/spared N400 and P600 repetition effects had only an 11 to 27% likelihood.
Conclusions:
Abnormalities of the P600 or N400 in mild cognitive impairment are associated with an increased risk of subsequent conversion to Alzheimer disease (AD). These event-related potential components may offer useful biomarkers for the detection and staging of very early AD.
Related Concept Videos
Dementia l: Introduction
Alzheimer Disease l: Introduction
Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Hepatic Encephalopathy
Dementia
The progression of dementia is generally gradual.
Cryptococcal Meningitis

