Impaired fear conditioning in Alzheimer’s disease

Abstract

Classical conditioning of the fear response is a basic form of nondeclarative (nonconscious) memory that mediates both normal and pathological responses to aversive stimuli. Because fear conditioning critically depends on the amygdala, a medial temporal lobe structure that frequently undergoes significant pathological changes early in the course of Alzheimer’s disease (AD), we hypothesized that fear conditioning would be impaired in patients with mild to moderate AD. We examined simple classical fear conditioning in a group of 10 patients with probable AD and 14 demographically matched, neurologically intact elderly controls. During conditioning, one stimulus (e.g. a green rectangle, the conditioned stimulus (CS+)), was paired with an aversive stimulus (a loud noise, the unconditioned stimulus (US)) using a partial reinforcement conditioning schedule. The opponent color (e.g. red rectangle), the CS−, was never paired with the US. The elderly controls acquired robust fear responses as demonstrated by their differential skin-conductance responses to the CS+ and CS−. In contrast, the AD group showed a marked impairment in conditioning, failing to exhibit significant conditioned fear responses. This failure to acquire conditioned responses could not be attributed to diminished responding by patients, relative to controls, to the aversive US. The results indicate that fear conditioning, an amygdala-dependent form of memory, is impaired in AD. These findings complement previous reports of impairments in declarative emotional memory in AD by demonstrating that a basic form of nondeclarative emotional memory is also impaired in AD.