Retinal thickness as a biomarker of cognitive impairment in manifest Huntington's disease

J Neurol. 2023 Aug;270(8):3821-3829. doi: 10.1007/s00415-023-11720-3. Epub 2023 Apr 20.

Abstract

Background: Cognitive decline has been reported in premanifest and manifest Huntington's disease but reliable biomarkers are lacking. Inner retinal layer thickness seems to be a good biomarker of cognition in other neurodegenerative diseases.

Objective: To explore the relationship between optical coherence tomography-derived metrics and global cognition in Huntington's Disease.

Methods: Thirty-six patients with Huntington's disease (16 premanifest and 20 manifest) and 36 controls matched by age, sex, smoking status, and hypertension status underwent macular volumetric and peripapillary optical coherence tomography scans. Disease duration, motor status, global cognition and CAG repeats were recorded in patients. Group differences in imaging parameters and their association with clinical outcomes were analyzed using linear mixed-effect models.

Results: Premanifest and manifest Huntington's disease patients presented thinner retinal external limiting membrane-Bruch's membrane complex, and manifest patients had thinner temporal peripapillary retinal nerve fiber layer compared to controls. In manifest Huntington's disease, macular thickness was significantly associated with MoCA scores, inner nuclear layer showing the largest regression coefficients. This relationship was consistent after adjusting for age, sex, and education and p-value correction with False Discovery Rate. None of the retinal variables were related to Unified Huntington's Disease Rating Scale score, disease duration, or disease burden. Premanifest patients did not show a significant association between OCT-derived parameters and clinical outcomes in corrected models.

Conclusions: In line with other neurodegenerative diseases, OCT is a potential biomarker of cognitive status in manifest HD. Future prospective studies are needed to evaluate OCT as a potential surrogate marker of cognitive decline in HD.

Keywords: Cognition; Huntington’s disease; Optical coherence tomography; Retina.

MeSH terms

  • Biomarkers
  • Cognitive Dysfunction* / complications
  • Cognitive Dysfunction* / etiology
  • Humans
  • Huntington Disease* / complications
  • Huntington Disease* / diagnostic imaging
  • Retina / diagnostic imaging
  • Tomography, Optical Coherence / methods

Substances

  • Biomarkers