Simply stated the Brain Hypometabolism Hypothesis (BHH) is
‘Brain hypometabolism leads to neuropathology’
This is a very simple but broad statement which is a starting point for elaboration.
In their 2016 paper, Cunnane and colleagues outline several supporting lines of evidence as the basis for their paper
(i) Lower glucose uptake in the frontal cortex of older adults
(ii) Regional deficits in brain glucose uptake in younger adults at risk of Alzheimer’s Type Dementia
(iii) Preservation of ketone uptake in the brain
(iv) Further evidence on consequences of ketone based interventions.
Cannane and colleagues published a paper on brain metabolism and aging based on a database they had compiled using radioactive tracers for glucose and ketone metabolism in the brain.
Figure 2 from Cunnane and colleagues, CC BY
The Rotterdam study looked at insulin resistance in a large prospective cohort. Researchers found a correlation between insulin resistance and incident Alzheimer’s Type Dementia but only within the first three years.
However we know from Kuhn’s work on ‘The Structure of Scientific Revolutions‘ that central paradigms are successful even if there are lines of evidence that do not support the paradigm (as models are approximations to reality).
A Review of ‘The Structure of Scientific Revolutions’
In their 2011 paper, Cunnane and colleagues note that there are three separate isoforms of GLUT1 that facilitate glucose uptake in the brain
(1) One isoform facilitates glucose uptake across the blood-brain barrier
(2) Another isoform facilitates glucose uptake in astrocytes
(3) A third isoform facilitates glucose uptake in neurons
There are however other mechanisms for glucose uptake in the brain.
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