Cognitive vulnerability to glucose fluctuations: A digital phenotype of neurodegeneration

Luciana Mascarenhas Fonseca, Zoë W. Hawks, Michal Schnaider Beeri, Lanee Jung, Yogish Kudva, Shafaq Rizvi, Jane Bulger, Elizabeth Grinspoon, Kamille Janess, Martin J. Sliwinski, Richard E. Pratley, Michael R. Rickels, Ruth S. Weinstock, Jasmeer P. Chhatwal, Pia Kivisäkk, Laura Thi Germine, Naomi S. Chaytor

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: Cognition is reduced at low and high glucose, reflecting cognitive vulnerability to glucose (CVG) fluctuations. The impact of glucose fluctuations on the aging brain remains unclear. We examined whether CVG is associated with plasma biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration. METHODS: Participants included N = 114 adults with type 1 diabetes assessed for processing speed and sustained attention using ecological momentary assessment (EMA) combined with continuous glucose monitoring (CGM). We characterized associations between CVG and amyloid beta (Aβ) 42/40, phosphorylated tau (p-tau) 181 and 217, neurofilament light chain, and glial fibrillary acidic protein. RESULTS: CVG was associated with all plasma biomarkers, except Aβ 42/40. CVG for sustained attention exhibited strong associations with p-tau biomarkers that persisted across covariate specifications. DISCUSSION: CVG may be a useful digital phenotype of AD. It remains unclear whether CVG contributes to versus arises from neurodegeneration. We consider possible mechanisms linking cognitive vulnerability and long-term glucose variability to the development of neuropathology. Highlights: Cognitive vulnerability to glucose (CVG) may be a useful digital phenotype of neurodegeneration. We used cognitive ecological momentary assessment and continuous glucose monitoring to investigate CVG's associations with plasma biomarkers. Associations of CVG for sustained attention and phosphorylated tau 181 remained significant across covariates. We discuss possible mechanisms relating glucose variability, cognition, and neurodegeneration.

Original languageEnglish (US)
Article numbere70001
JournalAlzheimer's and Dementia
Volume21
Issue number2
DOIs
StatePublished - Feb 2025

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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