Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study assessing baseline exposure against brain volume change over 4 years.
PubMed 22946113 · doi:10.1212/WNL.0b013e31826846de
What was done
Researchers analyzed data from 266 cognitively healthy adults aged 60 to 64 years without type 2 diabetes participating in the PATH longitudinal aging study. Baseline fasting plasma glucose was measured at wave 1. Hippocampal and amygdalar volumes were manually traced using 1.5 T MRI scans at baseline and at follow-up 4 years later. General linear models evaluated the relationship between baseline glucose and medial temporal lobe atrophy, adjusting for age, sex, BMI, hypertension, alcohol intake, and smoking status.
What was found
Higher baseline fasting plasma glucose within the normal physiological range (defined as <6.1 mmol/L) was significantly associated with greater atrophy of both the hippocampus and amygdala over 4 years. Plasma glucose levels accounted for 6% to 10% of the variance in volumetric change after adjusting for all measured covariates.
Why it matters
These findings suggest that subclinical blood glucose elevations below the threshold for diabetes may independently accelerate structural brain aging and medial temporal lobe atrophy, potentially warranting earlier metabolic monitoring and intervention.
Limits
The observational design cannot establish direct causality. The cohort was restricted to a narrow age band (60-64 years), limiting generalizability across other age groups. Blood glucose was measured at a single baseline time point, and the abstract does not report functional cognitive decline outcomes or additional metabolic parameters like HbA1c or insulin resistance.
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