Impaired Visual Inhibition in Amnestic Mild Cognitive Impairment

Abstract

Objective.The pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD) is still a matter of debate. Visual system might be precociously altered, especially for its cholinergic connections. We thus studied patients with aMCI compared to AD with paired-pulse flash-visual evoked potentials (paired-F-VEPs), a putative marker of cholinergic function. Methods. We enrolled 12 adult patients with aMCI and 12 with AD. 14 normal age- and sex-matched subjects acted as controls (HS). Stimuli were single flashes, with interspersed random flash pairs at critical interstimulus intervals (ISIs, 16.5 to 125 ms) with closed eyes. The "single" (unconditioned) F-VEP was split into a "main complex" (50 to 200 ms after the flash) and a "late response" (200 to 400 ms). As for paired stimulation, the "test" F-VEP emerged from electronic subtraction of the "single" F-VEP from the "paired"-F-VEP. Results. In the single F-VEP, P2 latency was prolonged in patients (aMCI and AD) compared to HS (p < .05). As to the paired F-VEPs, in aMCI the "late response" normal inhibition was abolished at ISIs 50-62.5 ms (p ≤ .016), compared to AD and controls. No changes were detected for the "main complex". Conclusions. Paired-F-VEPs demonstrate a defective neural inhibition in the visual system of patients with aMCI at critical intervals. It may represent a compensatory mechanism against neuronal loss, the failure of which may be involved in AD development. Paired-F-VEPs may warrant inclusion in future preclinical/clinical studies, to evaluate its potential role in the pathophysiology and management of aMCI.

Keywords: Alzheimer disease; evoked potentials; flash stimuli; mild cognitive impairment; visual cortex.