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Cognitive functioning and multimodal neuroimaging in narcolepsy type 1

Multimodal neuroimaging studies highlight the extent brain-wide structural changes in narcolepsy type 1.

In the context of frequent subjective memory complaints of patients with narcolepsy type 1 in clinical practice a recent study showed significant volume loss of the anterior hippocampus which was not related to objective cognitive performance. These structural changes may affect functional connections between the anterior hippocampus, medial prefrontal cortex and the amygdala and render patients more susceptible to cataplexy. Diffusion tensor imaging revealed reduced structural integrity of widespread connections passing through the ventral diencephalon and hypothalamus. These findings highlight the possibly underestimated effect(s) of hypocreting and microstructural white matter composition and the relationship between hypocretin deficiency and axonal density, myelination and axonal thickness. Based on observations in transgenic mice and conflicting human data, a case-control PET study on a homogenous sample of older (>65 years) patients with narcolepsy type 1 showed a significantly reduced brain amyloid burden. Future and longitudinal studies are mandatory to investigate the role of orexin-receptor-antagonists in the delay of amyloid deposition in the brain and thereby the delay of the onset of Alzheimer’s disease.

Key points:

  • Volume loss of the anterior hippocampus does not impair memory function but may participate in the triggering of cataplexy.
  • Diffusion tensor imaging (DTI) reveals structural changes of brain wide connections passing through the ventral diencephalon and hypothalamus.
  • Older patients with narcolepsy type 1 show reduced brain amyloid burden compared to matched controls.

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