Emerging evidence links metabolic dysfunction to neurodegeneration, but the specific impact of hyperglycemia on the trajectory of early Alzheimer's disease (AD) remains unclear. This study investigates the association between chronic hyperglycemia, cognitive decline, hippocampal atrophy, and neuronal apoptosis markers in patients with early AD. In this 3-year longitudinal cohort study, 200 patients with early AD were enrolled and stratified by glycemic status (normoglycemic vs. hyperglycemic based on fasting glucose and HbA1c). Cognitive performance was assessed annually using the Mini-Mental State Examination (MMSE), Logical Memory Test, and Trail Making Test. Hippocampal volumes were quantified with MRI volumetry, and plasma/CSF neuronal apoptosis markers (caspase-3 activity, Bax/Bcl-2 ratio) were measured. Mixed-effects regression models were applied to examine longitudinal associations. Hyperglycemic patients exhibited significantly faster cognitive decline compared with normoglycemic participants (annual MMSE decline: –2.4 vs. –1.1 points; p < 0.001). MRI analysis revealed greater hippocampal volume loss in the hyperglycemia group (–5.7% vs. –2.9% over 3 years; p < 0.01). Apoptosis marker levels were consistently elevated in hyperglycemic patients (mean caspase-3 activity: +38%, p < 0.01), correlating with both hippocampal atrophy and worsening cognition. Chronic hyperglycemia is associated with accelerated cognitive decline, increased hippocampal atrophy, and elevated neuronal apoptosis markers in early AD. These findings suggest that hyperglycemia is not merely a comorbidity but a potential pathophysiological driver of neurodegeneration. Tight glycemic control may represent a modifiable intervention to slow AD progression.
Shaikh et al. (Sun,) studied this question.