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Original Investigation
May 24, 2023

Association Between False Memories and Delusions in Alzheimer Disease

Author Affiliations
  • 1Division of Psychiatry, University College London, London, United Kingdom
  • 2Dementia Research Centre, University College London, London, United Kingdom
  • 3UCL Institute of Cognitive Neuroscience and UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
  • 4Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom
JAMA Psychiatry. 2023;80(7):700-709. doi:10.1001/jamapsychiatry.2023.1012
Key Points

Question  Is there an association between false memories and delusions among individuals with current or future Alzheimer disease who undergo behavioral testing or volumetric neuroimaging?

Findings  In this cross-sectional study of 728 participants from the Alzheimer’s Disease Neuroimaging Initiative cohort who were diagnosed with Alzheimer disease during follow-up, false recognition was not associated with the presence of delusions when accounting for confounding variables. On volumetric neuroimaging, there was no overlap in brain regions associated with delusions and those associated with false recognition.

Meaning  These findings suggest that delusions experienced by individuals with Alzheimer disease do not arise as a direct consequence of forgetting or misremembering and further support the existence of a transdiagnostic mechanism for psychosis.


Importance  Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories.

Objective  To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions.

Design, Setting, and Participants  Since the Alzheimer’s Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021.

Exposure  Enrollment in the ADNI.

Main Outcomes and Measures  The main outcomes included false recognition, measured with the 13-item Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions.

Results  Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U = 9398.5; P = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94], P < .001), right hippocampal volume (0.94 [0.92-0.97], P < .001), left entorhinal cortex volume (0.94 [0.91-0.97], P < .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P < .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P < .001). There was no overlap between locations associated with false recognition and those associated with delusions.

Conclusions and Relevance  In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis.

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