Fear acquisition and extinction deficits in amnestic mild cognitive impairment and early Alzheimer's disease

Abstract

Impaired learning and memory functioning are prime markers for Alzheimer's disease (AD). Although initial evidence points to impaired fear acquisition in later AD, no study has investigated fear conditioning in early stages and amnestic mild cognitive impairment (aMCI), a condition often preceding AD. The present study examined if fear conditioning gradually decays from healthy elderly to patients with aMCI, to patients with AD. Patients with AD (n = 43), patients with aMCI (n = 43), and matched healthy controls (n = 40) underwent a classical fear conditioning paradigm. During acquisition, a neutral face (conditioned stimulus, CS+) was paired with an electrical stimulus, whereas another face (unconditioned stimulus, CS-) was unpaired. Conditioned responses were measured by unconditioned stimulus expectancy, valence, and skin conductance. Compared to healthy controls, both patient groups showed less differential (CS+ vs. CS-) fear acquisition across all measures. Patients further displayed slowed extinction indexed by higher unconditioned stimulus expectancy and reduced positive valence for CS+, declining from aMCI to AD. Groups did not differ in responses during a preconditioning habituation phase and in unconditioned responding. Diminished differential fear acquisition and slowed extinction could represent prognostic markers for AD onset.