Neurobiology of delusions, memory, and insight in Alzheimer disease

David L Sultzer; Lorraine P Leskin; Rebecca J Melrose; Dylan G Harwood; Theresa A Narvaez; Timothy K Ando; Mark A Mandelkern

doi:10.1016/j.jagp.2013.06.005

Neurobiology of delusions, memory, and insight in Alzheimer disease

Am J Geriatr Psychiatry. 2014 Nov;22(11):1346-55. doi: 10.1016/j.jagp.2013.06.005. Epub 2013 Sep 8.

Authors

David L Sultzer¹, Lorraine P Leskin², Rebecca J Melrose³, Dylan G Harwood³, Theresa A Narvaez², Timothy K Ando², Mark A Mandelkern⁴

Affiliations

¹ Brain, Behavior, and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address: dsultzer@ucla.edu.
² Brain, Behavior, and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
³ Brain, Behavior, and Aging Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA.
⁴ Nuclear Medicine Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Physics, University of California, Irvine, CA.

Abstract

Objective: Delusional thoughts are common among patients with Alzheimer disease (AD) and may be conceptually linked to memory deficits (cannot recall accurate information, which leads to inaccurate beliefs) and poor insight (unable to appreciate the illogic of beliefs). This study's goals were to examine the clinical associations among delusions, memory deficits, and poor insight; explore neurobiologic correlates for these symptoms; and identify shared mechanisms.

Methods: In a cross-sectional analysis, 88 outpatients with AD (mean Mini-Mental State Exam score: 19.3) were studied. Delusional thoughts were assessed with the Neuropsychiatric Inventory, level of inaccurate insight was assessed with the Neurobehavioral Rating Scale, and memory was assessed with the Mattis Dementia Rating Scale memory subscale. (18)F-fluorodeoxyglucose positron emission tomography was used to measure regional cortical metabolism. Relationships between clinical ratings and regional cortical metabolic activity (voxel-based) were assessed using SPM2.

Results: Patients with delusions had lower Dementia Rating Scale memory subscale scores. Neurobehavioral Rating Scale inaccurate insight scores were no different in those with and without delusions. Cortical metabolic activity was lower in the right lateral frontal cortex, orbitofrontal cortex, and bilateral temporal cortex in patients with delusions. Low cortical metabolic activity in the right lateral, inferior, and medial temporal cortex was associated with poorer memory. This region partially overlapped the region of hypometabolism associated with delusions. In contrast, low cortical metabolic activity in bilateral medial frontal cortex was associated with poor insight.

Conclusion: Delusions in AD are associated with dysfunction in specific frontal and temporal cortical regions. Delusions are partially clinically and neurobiologically linked to memory deficits but not to poor insight.

Keywords: Alzheimer disease; FDG-PET; cerebral metabolism; delusions; insight; memory.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Alzheimer Disease / complications
Alzheimer Disease / metabolism
Alzheimer Disease / psychology*
Brain / metabolism
Comprehension
Cross-Sectional Studies
Delusions / etiology*
Delusions / metabolism
Delusions / psychology
Female
Humans
Male
Memory Disorders / etiology*
Memory Disorders / metabolism
Memory Disorders / psychology
Neuroimaging
Neuropsychological Tests
Positron-Emission Tomography

Abstract

Publication types

MeSH terms

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