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Publications

Journal Article Ahead of print

PubMed: 42264275 DOI: 10.1016/j.bbi.2026.106864

Insomnia and inflammatory exposure impair spatial memory and cognitive mapping in older adults: a randomized controlled trial.

Brain Behav Immun

Authors: Dominique Piber, Richard Olmstead, Joshua Hyong-Jin Cho, Nina Sadeghi, Daisy Castillo, Haesoo Kim, Michael R Irwin

Affiliations

  • Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (UCLA), Los Angeles, CA, United States; Department of Psychiatry, University of Utah Health, Huntsman Mental Health Institute, Salt Lake City, UT, United States; Department of Psychiatry, Charité - Universitätsmedizin Berlin, Germany.
  • Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
  • Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (UCLA), Los Angeles, CA, United States; Department of Psychology, College of Arts and Sciences, UCLA, Los Angeles, CA, United States.

Abstract

BACKGROUND

Insomnia and inflammation are both risk factors for cognitive aging, especially declines of spatial memory and cognitive mapping. This study aimed to evaluate whether older adults with insomnia show deficits in spatial memory and cognitive mapping, and whether an inflammatory challenge might exacerbate those deficits.

METHODS

We analyzed secondary outcomes of an assessor-blinded, parallel-condition, placebo-controlled randomized clinical trial in 84 non-depressed adults aged 60-80 years (26 with insomnia disorder, 58 without insomnia) who were randomized to low-dose intravenous endotoxin or placebo. Two hours post-injection, participants completed a virtual Morris water maze task assessing spatial memory, followed by a room reconstruction task assessing cognitive mapping under real-world conditions. Circulating levels of inflammatory cytokines were repeatedly measured.

RESULTS

Among 84 randomized participants (66.0 ± 4.6 years; 50.0% female), 39 participants (12 insomnia; 27 control) received endotoxin and 45 (14 insomnia; 31 control) placebo. Older adults with insomnia showed impairments in spatial memory and cognitive mapping as compared to controls (P's < 0.01). Further, a significant group (insomnia vs. control) × condition (endotoxin vs. placebo) interaction emerged (P < 0.05), with post hoc tests revealing deficits in cognitive mapping in older adults with insomnia exposed to endotoxin (P < 0.01), but not in insomnia patients who received placebo or in controls. Cytokine responses were not related to spatial memory or mapping outcomes.

CONCLUSION

Older adults with insomnia, as compared to control, exhibit deficits in spatial memory and cognitive mapping, and the latter appears to be exaggerated following inflammatory exposure. Both insomnia and inflammation are potential mechanistic targets to preserve cognitive aging.

MeSH

Cytokines, Spatial Memory, Aging, Cognitive Aging, Endotoxins, Memory, Sleep Initiation And Maintenance Disorders