Regional cortical thinning predicts worsening apathy and hallucinations across the Alzheimer disease spectrum
Open accessAbstract
Objectives To examine regions of cortical thinning and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers associated with apathy and hallucinations in a continuum of individuals including clinically normal elderly, mild cognitive impairment, and mild AD dementia.Design Cross-sectional and longitudinal studies.Setting Fifty-seven research sites across North America.Participants Eight-hundred twelve community-dwelling volunteers; 413 participants in the CSF sub-study.Measurements Structural magnetic resonance imaging data and CSF concentrations of amyloid-β 1-42, total tau, and phosphorylated tau derived from the Alzheimer Disease Neuroimaging Initiative database were analyzed. Apathy and hallucinations were measured at baseline and over 3 years using the Neuropsychiatric Inventory-Questionnaire. General linear models and mixed effects models were used to evaluate the relationships among baseline cortical thickness in seven regions, and baseline CSF biomarkers, apathy, and hallucinations at baseline and longitudinally. Covariates included diagnosis, sex, age, apolipoprotein E genotype, premorbid intelligence, memory performance, processing speed, antidepressant use, and AD duration.Results Reduced baseline inferior temporal cortical thickness was predictive of increasing apathy over time, and reduced supramarginal cortical thickness was predictive of increasing hallucinations over time. There was no association with cortical thickness at baseline. CSF biomarkers were not related to severity of apathy or hallucinations in cross-sectional or longitudinal analyses.Conclusions These results suggest that greater baseline temporal and parietal atrophy is associated with worsening apathy and hallucinations in a large AD spectrum cohort, while adjusting for multiple disease-related variables. Localized cortical neurodegeneration may contribute to the pathophysiology of apathy and hallucinations and their adverse consequences in AD.
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Apathy in Alzheimer's disease is associated with decreased inferior temporal cortical thickness.
“Two studies note an association of apathy with decreased inferior temporal cortical (ITC) thickness (Donovan et al., 2014; Guercio et al., 2015).”
From Neuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits? (2015) · cites this paper as Donovan et al., 2014
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- Authors
- Donovan, N. J., Wadsworth, L. P., Lorius, N., Locascio, J. J., Rentz, D. M., Johnson, K. A., Sperling, R. A., & Marshall, G. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Donovan, Nancy J.
- ORCID
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 22
- Issue
- 11
- Pages
- 1168-1179
- ISSN
- 1064-7481 (ISSN-L)
- PMC
- PMC3960369
- OpenAlex
- W2086731062
- Cited by
- 106
- References
- 44
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 11 · 2018: 5 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 6
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH grant (U01 AG024904)
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's disease (R01 AG027435, K23 AG033634, K24 AG035007, D01 HP08794-04-00)
- Massachusetts Alzheimer's Disease Research Center (P50 AG005134)
- Harvard Aging Brain Study (P01 AGO36694)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, cortical thinning, apathy, hallucinations, inferior temporal cortex, supramarginal cortex, cerebrospinal fluid biomarkers, amyloid-beta 42, tau protein, mild cognitive impairment, dementia, neurodegeneration, neuropsychiatric symptoms
- MeSH terms
- Aged, Alzheimer Disease, Cerebral Cortex, Cross-Sectional Studies, Female, Hallucinations, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Apathy, Neuroimaging
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