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 rep…
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Context-associated memory deficit is typical in AD patients and manifested as dysfunction of fear conditioning involving neural circuits of the amygdala, hippocampus, and prefrontal cortex.
“Context-associated memory: This deficit is typical in AD patients [128][129][130] and manifested as dysfunction of fear conditioning 82 involving neural circuits of the amygdala, hippocampus, and prefrontal cortex 131,132 .”
From NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer’s disease (2025) · cites this paper as [129]
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NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer’s disease
Fan, F., Joshi, P., Liu, X., Kotturu, S. K., Abiola, M., Liu, Q., & Lou, X. (2025) · doi:10.64898/2025.12.21.695860
- Authors
- Hamann, S., Monarch, E. S., & Goldstein, F. C.
- Affiliations
- Emory University (US)
- Corresponding author
- Hamann, Stephan
- Venue
- Neuropsychologia
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 40
- Issue
- 8
- Pages
- 1187-1195
- ISSN
- 0028-3932 (ISSN-L)
- OpenAlex
- W2052839536
- Cited by
- 129
- References
- 8
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 11 · 2013: 5 · 2012: 11
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P30AG010130, P30 AG10130)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, fear conditioning, classical conditioning, implicit memory, emotional memory, amygdala, skin conductance response, aversive stimuli, memory impairment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amygdala, Arousal, Association Learning, Color Perception, Conditioning, Classical, Fear, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Pattern Recognition, Visual, Mental Recall
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