期刊
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
卷 22, 期 11, 页码 1168-1179出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jagp.2013.03.006
关键词
Apathy; hallucinations; MRI; cortical thinning; CSF biomarkers; Alzheimer disease
资金
- National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering [U01 AG024904]
- Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's disease
- Massachusetts Alzheimer's Disease Research Center [P50 AG005134]
- Harvard Aging Brain Study [P01 AGO36694]
- [R01 AG027435]
- [K23 AG033634]
- [K24 AG035007]
- [D01 HP08794-04-00]
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 substudy. Measurements: Structural magnetic resonance imaging data and CSF concentrations of amyloid-beta 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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