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

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 controls, 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.