Figure 2.

From migraine to Alzheimer’s Disease (AD): the metabolic physiopathological continuum of the “Neuroenergetic hypothesis”. Brain insulin resistance is the metabolic alteration underlying the common pathophysiological alterations between chronic migraine (CM) and AD, i.e., impaired brain glucose metabolism and altered brain mitochondrial bioenergetics - leading to an overproduction of mitochondrial reactive oxygen species - which generate a reduction in the brain energy metabolism, leading to neuronal stress and subsequent neuronal degeneration, detectable as a reduction in grey matter volume, a disrupted default mode network connectivity and the increased theta and delta activity observed at EEG, shared by CM and AD. In the long run, brain insulin resistance and the related energy deficiency might favour the pathological changes involved in AD, promoting a shift towards the amyloidogenic cascade and increasing tau hyperphosphorylation. The shaded green arrow to the right of the figure illustrates that increased brain insulin resistance sustains the altered metabolic pathway and the progression from CM to AD.