Forskningsartikler

Summary

Despite evidence suggesting that insomnia is associated with the risk of dementia and cognitive dysfunction, studies have shown mixed results. Dementia has a long prodromal phase, and studies with long follow-up are required to avoid reverse causality. In our 11-year follow-up study, we assessed whether probable insomnia disorder (PID) based on diagnostic criteria, and insomnia symptoms were associated with risk of all-cause dementia, Alzheimer’s disease (AD) and cognition, measured with the Montreal Cognitive Assessment scale. We also examined if Apolipoprotein E genotype modified any associations with dementia through interaction. We analysed data from 7492 participants in the Norwegian Trøndelag Health Study. PID was not associated with all-cause dementia (odds ratio = 1.03, 95% confidence interval = 0.74–1.43), AD (odds ratio = 1.07, 95% confidence interval = 0.71–1.60) or Montreal Cognitive Assessment score (regression coefficient = 0.37, 95% confidence interval = −0.06 to 0.80). The insomnia symptom “difficulties maintaining sleep” was associated with a lower risk of all-cause dementia (odds ratio = 0.81, 95% confidence interval = 0.67–0.98), AD (odds ratio = 0.73, 95% confidence interval = 0.57–0.93), and better Montreal Cognitive Assessment score, mean 0.40 units (95% confidence interval = 0.15–0.64). No interaction with Apolipoprotein E genotype was found. PID and insomnia symptoms did not increase the risk of dementia in our study. More research with longer follow-up is needed, and future studies should explore if the associations to dementia risk vary across insomnia subtypes.

Selma Selbæk-Tungevåg, Geir Selbæk, Bjørn Heine Strand, Christian Myrstad, Gill Livingston, Stian Lydersen, Sverre Bergh, Linda Ernstsen

BACKGROUND: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanisms underlying delirium, particularly in relation to the KP, remain elusive.
METHODS: We undertook a multicenter observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and 1-year mortality.
RESULTS: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA) (OR 2.26 [1.78, 2.87], P < 0.001) to be increased and also found increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL) (β 0.43, P < 0.001) and was a strong predictor of 1-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, P < 0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons.
CONCLUSION: Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP.

Leiv Otto Watne, Christian Thomas Pollmann, Bjørn Erik Neerland, Else Quist-Paulsen, Nathalie Bodd Halaas, Ane-Victoria Idland, Bjørnar Hassel, Kristi Henjum, Anne-Brita Knapskog, Frede Frihagen, Johan Raeder, Aasmund Godø, Per Magne Ueland, Adrian McCann, Wender Figved, Geir Selbæk, Henrik Zetterberg, Evandro F Fang, Marius Myrstad, Lasse M Giil