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Hallucinations, Antipsychotic Use, and Mortality in Older Adults with Dementia: Retrospective Cohort Study of Two Medicare-Linked National Health Surveys

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Abstract

Background

Hallucinations are associated with earlier death in older adults with dementia, but antipsychotic medications are also associated with mortality, and comparisons of their relative harms are lacking.

Objective

To determine the individual and combined association between hallucinations, antipsychotic use, and mortality.

Methods

We performed a retrospective cohort study using Medicare-linked survey data from two nationally representative studies (the National Health and Aging Trends Study and the Health and Retirement Study) containing validated dementia identification algorithms and a screening question for hallucinations. Using Medicare claims, we identified participants with dementia who had no history of antipsychotic use during the year of or prior to entry. We used extended Cox regression with time-varying covariates to analyze the association between hallucinations, antipsychotic use, and mortality adjusting for confounders.

Results

We identified 1703 eligible subjects who contributed 4,819 person-years of follow-up. 555 (32.6%) had hallucinations at baseline, 705 (41.4%) reported hallucinations at least once during follow-up, and 284 (16.7%) received antipsychotics. Hallucinations were associated with an increased risk of death in unadjusted models (hazard ratio (HR) 1.36; 95% confidence interval (CI): 1.18–1.5), but antipsychotic use was not (HR 1.03; 95% CI 0.85–1.2). After adjusting for age, race, gender, dementia severity, and comorbidities, the HR for hallucinations attenuated and was no longer statistically significant (1.15, 95% CI 0.98–1.34). There was no significant interaction between hallucinations and antipsychotic use.

Conclusion

Hallucinations are associated with an increased risk of death that is greater than the risk associated with antipsychotic use, though this is partially confounded by dementia severity and comorbidities.

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Acknowledgements

The National Health and Aging Trends Study (NHATS) is sponsored by the National Institute on Aging (grant number NIA U01AG032947) through a cooperative agreement with the Johns Hopkins Bloomberg School of Public Health. The Health and Retirement Study (HRS) is supported by the National Institute on Aging, supplemented by the Social Security Agency, and operated from the Institute for Social Research (ISR) at the University of Michigan. This analysis uses data or information from the Harmonized HRS dataset and Codebook, Version B as of October 2018 developed by the Gateway to Global Aging Data. The development of the Harmonized HRS was funded by the National Institute on Aging (R01 AG030153, RC2 AG036619, 1R03AG043052). For more information, please refer to www.g2aging.org. The data have not been previously presented orally or by poster at scientific meetings.

Author information

Authors and Affiliations

  1. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Dr., Blockley 829, Philadelphia, PA, 19104, USA

    Ali G. Hamedani, Daniel Weintraub & Allison W. Willis

  2. Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ali G. Hamedani

  3. Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research, University of Pennsylvania, Philadelphia, PA, USA

    Ali G. Hamedani & Allison W. Willis

  4. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA

    Ali G. Hamedani & Allison W. Willis

  5. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Daniel Weintraub

  6. Parkinson’s Disease Research, Education and Clinical Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA

    Daniel Weintraub

  7. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Allison W. Willis

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  1. Ali G. Hamedani
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Corresponding author

Correspondence to Ali G. Hamedani.

Ethics declarations

Funding

This work was supported by the NIH (K23 EY033438-01 to AGH, R01 NS099129-05 to AWW), Parkinson Study Group (Mentored Clinical Research Award to AGH), and Acadia Pharmaceuticals (investigator-initiated award to AWW and DW). The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Conflict of interest

Drs. Hamedani, Weintraub, and Willis declare that they have no conflicts of interest.

Ethics approval

This study was approved by the University of Pennsylvania Institutional Review Board.

Consent to participate

Informed consent was obtained from participants in the National Health and Aging Trends Study and Health and Retirement Study at the time of enrollment.

Consent for publication

Not applicable.

Availability of data and material

The data that support the findings of this study are available from the National Health and Aging Trends Study, Health and Retirement Study, and Centers for Medicare and Medicaid Services, but restrictions apply to the availability of some of these data, which were used under license for the current study, and so are not publicly available.

Code availability

The analytic code used to support the findings in this study are available from the corresponding author upon reasonable request.

Author contributions

Dr. Hamedani conceived of the study, performed the primary statistical analysis, and drafted the manuscript. Drs. Weintraub and Willis provided input in study design, results interpretation, and critical manuscript review. Dr. Hamedani had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have read and approved the final submitted manuscript and agree to be accountable for this work.

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Hamedani, A.G., Weintraub, D. & Willis, A.W. Hallucinations, Antipsychotic Use, and Mortality in Older Adults with Dementia: Retrospective Cohort Study of Two Medicare-Linked National Health Surveys. Drugs Aging 39, 967–974 (2022). https://doi.org/10.1007/s40266-022-00991-6

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