TY - JOUR
T1 - Cognitive vulnerability to glucose fluctuations
T2 - A digital phenotype of neurodegeneration
AU - Fonseca, Luciana Mascarenhas
AU - Hawks, Zoë W.
AU - Beeri, Michal Schnaider
AU - Jung, Lanee
AU - Kudva, Yogish
AU - Rizvi, Shafaq
AU - Bulger, Jane
AU - Grinspoon, Elizabeth
AU - Janess, Kamille
AU - Sliwinski, Martin J.
AU - Pratley, Richard E.
AU - Rickels, Michael R.
AU - Weinstock, Ruth S.
AU - Chhatwal, Jasmeer P.
AU - Kivisäkk, Pia
AU - Germine, Laura Thi
AU - Chaytor, Naomi S.
N1 - Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2025/2
Y1 - 2025/2
N2 - 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.
AB - 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.
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U2 - 10.1002/alz.70001
DO - 10.1002/alz.70001
M3 - Article
C2 - 39991795
AN - SCOPUS:85219381331
SN - 1552-5260
VL - 21
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 2
M1 - e70001
ER -