Cerebral glucose metabolic correlates of cognitive and behavioural impairments in amyotrophic lateral sclerosis

J Neurol. 2024 Aug;271(8):5290-5300. doi: 10.1007/s00415-024-12388-z. Epub 2024 Jun 11.

Abstract

Objective: Half of ALS patients are cognitively and/or behaviourally impaired. As cognition/behaviour and cerebral glucose metabolism can be correlated by means of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), we aimed to utilise FDG-PET, first, to replicate group-level differences in glucose metabolism between non-demented ALS patients separated into non-impaired (ALSni), cognitively impaired (ALSci), behaviourally impaired (ALSbi), and cognitively and behaviourally impaired (ALScbi) groups; second, to investigate glucose metabolism and performance in various cognitive domains; and third, to examine the impact of partial volume effects correction (PVEC) of the FDG-PET data on the results.

Methods: We analysed neuropsychological, clinical, and imaging data from 67 ALS patients (30 ALSni, 21 ALSci, 5 ALSbi, and 11 ALScbi). Cognition was assessed with the Edinburgh Cognitive and Behavioural ALS Screen, and two social cognition tests. FDG-PET and structural MRI scans were acquired for each patient. Voxel-based statistical analyses were undertaken on grey matter volume (GMV) and non-corrected vs. PVE-corrected FDG-PET scans.

Results: ALSci and ALScbi had lower cognitive scores than ALSni. In contrast to both ALSni and ALSci, ALScbi showed widespread hypometabolism in the superior- and middle-frontal gyri in addition to the right temporal pole. Correlations were observed between the GMV, the FDG-PET signal, and various cognitive scores. The FDG-PET results were largely unaffected by PVEC.

Interpretation: Our study identified widespread differences in hypometabolism in the ALScbi-ni but not in the ALSci-ni group comparison, raising the possibility that cerebral metabolism may be more closely related to the presence of behavioural changes than to mild cognitive deficits.

Keywords: Amyotrophic lateral sclerosis; Cerebral glucose metabolism; Cognition; FDG-PET; Grey matter volume.

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis* / diagnostic imaging
  • Amyotrophic Lateral Sclerosis* / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Cognition Disorders / diagnostic imaging
  • Cognition Disorders / etiology
  • Cognition Disorders / metabolism
  • Female
  • Fluorodeoxyglucose F18* / metabolism
  • Glucose* / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Disorders / diagnostic imaging
  • Mental Disorders / metabolism
  • Middle Aged
  • Neuropsychological Tests*
  • Positron-Emission Tomography*

Substances

  • Fluorodeoxyglucose F18
  • Glucose