Glucometabolic Changes Are Associated with Structural Gray Matter Alterations in Prodromal Dementia

Area of Science:

• Neuroscience
• Metabolic Health
• Neurodegenerative Diseases

Background:

• High glycemic load (GL) diets and insulin resistance (IR) are implicated as risk factors for Alzheimer's disease (AD).
• The specific impact of these glucometabolic factors on brain structural changes relevant to AD pathology remains unclear.

Purpose of the Study:

• To investigate the association between GL and IR with gray matter volumes in brain regions associated with prodromal dementia.
• To determine if metabolic factors influence brain structures vulnerable in early stages of cognitive decline.

Main Methods:

• Calculated GL and the Triglyceride-Glucose (TyG) index (a marker for IR) in 497 participants.
• Utilized magnetic resonance imaging (MRI) to assess gray matter volumes.
• Employed a machine learning algorithm to identify brain regions linked to mild cognitive impairment (MCI) over a 7-year follow-up.

Main Results:

• Higher GL was significantly associated with reduced amygdala volume.
• The TyG index showed negative correlations with volumes of the hippocampus, amygdala, and putamen.
• These brain regions are critical for memory and emotion processing, often affected in early dementia.

Conclusions:

• Elevated GL and IR are associated with diminished gray matter volumes in key brain areas relevant to Alzheimer's disease.
• These findings highlight the potential role of metabolic dysregulation in driving structural brain changes preceding dementia.
• Further research is warranted to explore therapeutic strategies targeting GL and IR to preserve brain structure and function.