Association of anxiety with subcortical amyloidosis in cognitively normal older adults
Open accessAbstract
Late-life anxiety has been associated with increased progression from normal cognition to amnestic MCI, suggesting that anxiety may be a neuropsychiatric symptom of Alzheimer's disease (AD) pathological changes and a possible marker of anatomical progression in preclinical AD. This study examined whether cortical or subcortical amyloidosis, indicating earlier or later stages of preclinical AD, was associated with greater self-reported anxiety among 118 cognitively normal volunteers, aged 65-90 years, and whether this association was stronger in APOEε4 carriers. Participants underwent Pittsburgh Compound B Positron Emission Tomography (PiB-PET) to assess fibrillar amyloid-β burden in cortical and subcortical regions, and measurement of anxiety using the Hospital Anxiety and Depression Scale-anxiety subscale. Higher PiB-PET measures in the subcortex (striatum, amygdala, and thalamus), but not in the cortex, were associated with greater anxiety, adjusting for demographics, cognition, and depression. Findings were similar using a cortico-striatal staging system and continuous PET measurements. Anxiety was highest in APOEε4 carriers with subcortical amyloidosis. This work supports in vivo staging of amyloid-β deposition in both cortical and subcortical regions as a promising approach to the study of neuropsychiatric symptoms such as anxiety in cognitively normal older individuals. Elevated anxiety symptoms in combination with high-risk biological factors such as APOEε4 and subcortical amyloid-β may identify participants closest to MCI for secondary prevention trials.
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Anxiety is considered a risk factor for cognitive impairment in cognitively normal older adults.
“anxiety is considered a risk factor for cognitive impairment in cognitively normal older adults (8).”
From Is acceptance and commitment therapy helpful in reducing anxiety symptomatology in people aged 65 or over? A systematic review (2022) · cites this paper as [8]
The Discussion says a subset of cognitively normal older adults with late-life anxiety may be at high risk of cognitive impairment, particularly when APOEε4 genotype and amyloid-β stage are considered. It describes anxiety as a potential marker, not an established risk factor for cognitively normal older adults generally. (LLM, conf=0.85)
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- Authors
- Hanseeuw, B. J., Jonas, V., Jackson, J., Betensky, R. A., Rentz, D. M., Johnson, K. A., Sperling, R. A., & Donovan, N. J.
- Affiliations
- Cliniques Universitaires Saint-Luc (BE)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Donovan, Nancy J.
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2018-08-16
- Volume
- 25
- Issue
- 10
- Pages
- 2599-2607
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC6377864
- OpenAlex
- W2885621583
- Cited by
- 61
- References
- 45
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 10 · 2023: 6 · 2022: 10 · 2021: 5 · 2020: 9 · 2019: 9
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-12-11)
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (R21AG054953, K24 AG035007, P01 AGO36694, R01 AG037497)
- Fonds De La Recherche Scientifique - FNRS (SPD28094292)
- 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
- anxiety, amyloid-beta, preclinical Alzheimer's disease, APOE ε4, cognitively normal older adults, striatum, amygdala, thalamus, neuropsychiatric symptoms, mild cognitive impairment, secondary prevention
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Anxiety, Brain, Female, Health, Humans, Male, Amyloid beta-Peptides, Positron-Emission Tomography
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