Known & Contested

What the corpus establishes (the established base a research program builds on) and where it actively disagrees (the contested frontier the questions target).

Known — established claims

• Insulin receptors are widely expressed throughout the central nervous system, including the hippocampus and cortex.
• Peripheral insulin resistance is associated with reduced cerebral insulin signaling.
• Midlife insulin resistance predicts later cognitive decline and an increased risk of Alzheimer's disease.
• Exercise improves peripheral insulin sensitivity.
• Exercise is consistently associated with better cognitive outcomes in aging populations.
• Voluntary wheel running increases hippocampal insulin receptor signaling and enhances long-term potentiation.
• The dominant model of Alzheimer's disease centers on amyloid-beta accumulation and downstream tau pathology.
• Metabolic and vascular dysfunction are implicated as early contributors to Alzheimer's disease.
• Microglia respond to both amyloid and metabolic stress.
• Chronic neuroinflammation is consistently observed in postmortem tissue.
• Blood-brain barrier (BBB) dysfunction is recognized in early Alzheimer's disease, often preceding measurable cognitive symptoms.
• Reduced BBB insulin transport has been proposed as a mechanism by which peripheral insulin resistance could initiate neuronal insulin resistance.
• BBB breakdown correlates with synaptic loss, though some studies find synaptic decline occurs earlier than overt barrier failure.
• It remains unresolved whether BBB transport failure is a cause or a consequence of neuronal insulin resistance.
• Animal models show both causal directions between BBB transport failure and neuronal insulin resistance are plausible, while human data are correlational.

Controversial — where scientists disagree

• AMPK activation simultaneously improves cognition via autophagy promotion and suppresses memory formation by inhibiting synaptic translation, indicating opposing downstream outcomes for the same molecular target.
• The temporal hierarchy between the amyloid-tau cascade and metabolic/vascular dysfunction as primary drivers of early Alzheimer's disease remains unresolved, with competing theories suggesting either pathway may initiate or permissively enable the other.
• BBB insulin transport failure may act as either the primary cause or a secondary consequence of neuronal insulin resistance, with animal models supporting bidirectional causality while human data remain strictly correlational.

Contradictions detected