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Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers.

Publication ,  Journal Article
La, AL; Walsh, CM; Neylan, TC; Vossel, KA; Yaffe, K; Krystal, AD; Miller, BL; Karageorgiou, E
Published in: J Alzheimers Dis
2019

BACKGROUND: Recent studies reveal an association between slow-wave sleep (SWS), amyloid-β aggregation, and cognition. OBJECTIVE: This retrospective study examines whether long-term use of trazodone, an SWS enhancer, is associated with delayed cognitive decline. METHODS: We identified 25 regular trazodone users (mean age 75.4±7.5; 9 women, 16 men) who carried a diagnosis of Alzheimer's dementia, mild cognitive impairment, or normal cognition, and 25 propensity-matched trazodone non-users (mean age 74.5±8.0; 13 women, 12 men), accounting for age, sex, education, type of sleep deficit (hypersomnia, insomnia, parasomnia), diagnosis, and baseline Mini-Mental State Examination (MMSE). Longitudinal group differences in cognitive testing were evaluated through repeated measures tests over an average inter-evaluation interval of four years. RESULTS: Trazodone non-users had 2.6-fold faster decline MMSE (primary outcome) compared to trazodone users, 0.27 (95% confidence interval [CI]: 0.07-0.48) versus 0.70 (95% CI: 0.50-0.90) points per year (p = 0.023). The observed effects were especially associated with subjective improvement of sleep complaints in post-hoc analyses (p = 0.0006). Secondary outcomes of other cognitive and functional scores had variable worsening in non-users and varied in significance when accounting for co-administered medications and multiple comparisons. Trazodone effects on MMSE remained significant within participants with AD-predicted pathology, with 2.4-fold faster decline in non-users (p = 0.038). CONCLUSIONS: These results suggest an association between trazodone use and delayed cognitive decline, adding support for a potentially attractive and cost-effective intervention in dementia. Whether the observed relationship of trazodone to cognitive function is causal or an indirect marker of other effects, such as treated sleep disruption, and if such effects are mediated through SWS enhancement requires confirmation through prospective studies.

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Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2019

Volume

67

Issue

3

Start / End Page

911 / 921

Location

Netherlands

Related Subject Headings

  • Trazodone
  • Sleep, Slow-Wave
  • Sleep Initiation and Maintenance Disorders
  • Retrospective Studies
  • Neurology & Neurosurgery
  • Mental Status and Dementia Tests
  • Male
  • Humans
  • Female
  • Cognitive Dysfunction
 

Citation

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MLA
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La, A. L., Walsh, C. M., Neylan, T. C., Vossel, K. A., Yaffe, K., Krystal, A. D., … Karageorgiou, E. (2019). Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers. J Alzheimers Dis, 67(3), 911–921. https://doi.org/10.3233/JAD-181145
La, Alice L., Christine M. Walsh, Thomas C. Neylan, Keith A. Vossel, Kristine Yaffe, Andrew D. Krystal, Bruce L. Miller, and Elissaios Karageorgiou. “Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers.J Alzheimers Dis 67, no. 3 (2019): 911–21. https://doi.org/10.3233/JAD-181145.
La AL, Walsh CM, Neylan TC, Vossel KA, Yaffe K, Krystal AD, et al. Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers. J Alzheimers Dis. 2019;67(3):911–21.
La, Alice L., et al. “Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers.J Alzheimers Dis, vol. 67, no. 3, 2019, pp. 911–21. Pubmed, doi:10.3233/JAD-181145.
La AL, Walsh CM, Neylan TC, Vossel KA, Yaffe K, Krystal AD, Miller BL, Karageorgiou E. Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers. J Alzheimers Dis. 2019;67(3):911–921.

Published In

J Alzheimers Dis

DOI

EISSN

1875-8908

Publication Date

2019

Volume

67

Issue

3

Start / End Page

911 / 921

Location

Netherlands

Related Subject Headings

  • Trazodone
  • Sleep, Slow-Wave
  • Sleep Initiation and Maintenance Disorders
  • Retrospective Studies
  • Neurology & Neurosurgery
  • Mental Status and Dementia Tests
  • Male
  • Humans
  • Female
  • Cognitive Dysfunction