Keywords
hyperglycemia
hippocampal atrophy
neuronal apoptosis
cognitive decline
HbA1c
How to Cite
Abstract
Background: Alzheimer’s disease (AD) is a leading cause of dementia worldwide, imposing an immense social and economic burden. Growing evidence suggests that metabolic dysfunction, particularly chronic hyperglycemia, contributes to neurodegeneration. This review synthesized findings from longitudinal cohort studies to examine the effect of hyperglycemia on cognitive decline, hippocampal atrophy, and neuronal apoptosis in early AD.
Methods: A comprehensive literature review of studies published between 2005–2025 was conducted using PubMed, Scopus, and ScienceDirect. Search terms included 'hyperglycemia', 'Alzheimer’s disease', 'hippocampal atrophy', and 'neuronal apoptosis'. Inclusion criteria were longitudinal cohort studies with patients aged 55–75 diagnosed with early AD (NIA-AA criteria). Data extraction included cognitive outcomes (MMSE, MoCA, Logical Memory Test), MRI-based hippocampal volumetry, and biomarkers (caspase-3, Bax/Bcl-2 ratio). Quality assessment was performed using PRISMA guidelines and Newcastle-Ottawa scales.
Results: Across included studies, hyperglycemic patients consistently showed accelerated cognitive decline, greater hippocampal volume loss, and higher apoptotic marker expression compared with normoglycemic patients. Evidence from neuroimaging confirmed progressive hippocampal atrophy in hyperglycemia groups. Biomarker analyses highlighted dysregulation of Bax/Bcl-2 balance and caspase-3 activation, suggesting a direct mechanistic link between glucose dysregulation and neuronal apoptosis. Clinical studies also reported that elevated HbA1c was associated with increased dementia risk and faster progression.
Conclusion: Chronic hyperglycemia may act not only as a comorbidity but as a mechanistic driver of AD pathology. These findings emphasize the importance of strict glycemic monitoring and interventions as preventive and therapeutic strategies in early AD.
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