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Anxiety and Depressive Symptoms and Cortical Amyloid-β Burden in Cognitively Unimpaired Older Adults

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The Journal of Prevention of Alzheimer's Disease Aims and scope Submit manuscript

Abstract

Background

There is evidence of relationships between behavioral symptoms and increased risk for Alzheimer’s Disease and/or Alzheimer’s Disease biomarkers. However, the nature of this relationship is currently unknown.

Objectives

To evaluate the relationship between anxiety and depressive symptoms and amyloid-β deposition in cognitively unimpaired older adults, and to assess mediating effects of either objective or subjective cognitive skills.

Design

Cross-sectional analysis of screening data from participants enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study (ClinicalTrials.gov Identifier: NCT02008357)

Setting

Data analysis

Participants

4492 cognitively unimpaired adults, age 65–85, enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study

Measurements

We used linear regression to estimate the associations between amyloid-β standard uptake value ratio (SUVR) and Geriatric Depression Scale (GDS) and State Trait Anxiety Inventory (STAI) scores while adjusting for potential confounding factors as well as for Cognitive Function Index (CFI) or Preclinical Alzheimer’s Cognitive Composite (PACC) scores as possible mediational variables.

Results

4399 subjects with complete covariates were included (mean age: 71.3, 59% female), GDS ranged 0–13 (mean: 1.0), and STAI ranged 6–24 (mean: 9.9). Amyloid-β SUVR was modestly associated with STAI; mean STAI score was estimated to be 0.275 points higher (95% CI: 0.038, 0.526; p-value = 0.023) for each 0.5-point increase in cortical amyloid-β SUVR. Subjective cognitive decline (CFI) attenuated the relationship between SUVR and STAI, while objective cognitive function (PACC) did not. No statistically significant relationship between SUVR and GDS was observed (p = 0.326).

Conclusions

In cognitively unimpaired adults with low levels of depression and anxiety, cortical amyloid-β deposition is associated with anxiety but not depressive symptoms. Attenuation of this relationship by subjective cognitive difficulties suggests that anxiety may be partly due to such a perception resulting from cortical amyloid-β deposition.

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Acknowledgments

We would like to acknowledge the dedication of all the participants, the site personnel, and all of the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available at: a4study.org/a4-study-team.

Funding

Funding: Catriona Lewis was supported by University of California — Irvine, MIND & University of California — Irvine, School of Medicine Summer Research Mentorship Program. Olivia Bernstein was supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-183928 and the ARCS foundation. Joshua Grill, Daniel Gillen, and David Sultzer are supported by NIA AG066519. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review of approval of the manuscript. The A4 Study is a secondary prevention trial in preclinical Alzheimer’s disease, aiming to slow cognitive decline associated with brain amyloid-β accumulation in clinically normal older individuals. The A4 Study is funded by a public-private-philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging, Eli Lilly and Company, Alzheimer’s Association, Accelerating Medicines Partnership, GHR Foundation, an anonymous foundation and additional private donors, with in-kind support from Avid and Cogstate. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer’s Association and GHR Foundation. The A4 and LEARN Studies are led by Dr. Reisa Sperling at Brigham and Women’s Hospital, Harvard Medical School and Dr. Paul Aisen at the Alzheimer’s Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data in order to advance the quest to find a successful treatment for Alzheimer’s disease.

Author information

Authors and Affiliations

  1. School of Medicine, University of California - Irvine, 1001 Health Sciences Rd, Irvine, CA, 92617, USA

    Catriona K. Lewis

  2. Department of Statistics, University of California - Irvine, Donald Bren School of Information and Computer Sciences, Irvine, USA

    O. M. Bernstein & D. L. Gillen

  3. Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California - Irvine, Irvine, USA

    J. D. Grill, D. L. Gillen & D. L. Sultzer

  4. Department of Neurobiology and Behavior, University of California - Irvine, School of Biological Sciences, Irvine, USA

    J. D. Grill

  5. Department of Psychiatry and Human Behavior, University of California - Irvine, School of Medicine, Irvine, USA

    J. D. Grill & D. L. Sultzer

Authors
  1. Catriona K. Lewis
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  3. J. D. Grill
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  5. D. L. Sultzer
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Contributions

Catriona Lewis, Olivia Bernstein, and David Sultzer conceived of the presented idea and designed the study. Olivia Bernstein and Daniel Gillen designed and executed the statistical analysis. All authors analyzed the data and contributed to the interpretation of the results. Catriona Lewis and Olivia Bernstein wrote the manuscript and designed the figures with significant input and feedback from Joshua Grill, Daniel Gillen, and David Sultzer.

Corresponding author

Correspondence to Catriona K. Lewis.

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Disclosures/Conflict of Interest

Dr. Sultzer has received research support from NIH and Eisai, has participated as a paid member of a DSMB or adjudication committee with Acadia, Avanir, Janssen, and Otsuka, and has received consulting fees from Avanir. Dr. Grill reports research support from NIH and is site Co-Investigator of the ongoing A4 study at University of California — Irvine and has received consulting fees from SiteRx, Cogniciti, and Flint Rehab in the last 36 months. Dr. Gillen reports research support from the Alzheimer’s Disease Research Center, University of California — Irvine and from the NIH. Dr. Gillen has also received consulting fees from Eli Lilly, ChemoCyntrix, FibroGen, GlaxoSmithKline, ProventionBio, and Biom’Up and participated as a paid member of a DSMB or advisory board with Pfizer, Biomarin, Novo Nordisk, Novartis, Amgen, Celgene, CRISPR, AstraZeneca, Merck Serano, Array, Seattle Genetics, Genentech/Roche, UCB, Acerta, Juno Therapeutics, Medivation. Other authors report no potential conflicts with any product mentioned or concept discussed in this article.

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Lewis, C.K., Bernstein, O.M., Grill, J.D. et al. Anxiety and Depressive Symptoms and Cortical Amyloid-β Burden in Cognitively Unimpaired Older Adults. J Prev Alzheimers Dis 9, 286–296 (2022). https://doi.org/10.14283/jpad.2022.13

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  • DOI: https://doi.org/10.14283/jpad.2022.13

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