Alzheimer's and Dementia

Alzheimer's disease and related dementias are fundamentally disorders of defective energy metabolism, driven by the accumulation of polyunsaturated fatty acids (PUFAs) and the systemic dysregulation of hormones. 2 Peat argued that the brain's greatly reduced ability to use glucose is a central feature, a condition exacerbated by estrogen's effect of shifting metabolism away from glucose oxidation and decreasing carbon dioxide production. 1 This metabolic suppression creates a state of physiological hibernation, where serotonin reduces energy expenditure, eliminating all brain functions except those needed for simple survival. 3 The structural hallmarks of the disease—amyloid plaques and fibrillary tangles—are downstream consequences of this energetic failure, with the "beta pleated sheet" structure of amyloids being directly related to binding bacterial endotoxin (LPS), linking the pathology to an out-of-control innate immune response. 2

The hormonal profile of Alzheimer's is characterized by a deficiency of protective steroids and an excess of catabolic ones. Peat consistently identified that when pregnenolone is inadequate, cortisol is over-produced, and when progesterone is deficient, estrogen's neurotoxic effects are largely unopposed. 2 This imbalance is compounded by hypothyroidism, which itself promotes estrogen synthesis even in fat cells. 4 The enzyme beta-glucuronidase is activated in inflamed tissue, releasing estrogen within cells and activating further neurotoxic processes. 2 Estrogen exposure exacerbates all the changes leading to dementia, including increased vascular leakiness and the production of acute phase proteins, which Peat cited as the reason for the much higher incidence of Alzheimer's disease in women. 1 Observational data showed that demented women had a much higher incidence of hysterectomy and a lower rate of progestogen use, while former estrogen users had 155% the rate of dementia compared to controls. 2

The accumulation of specific toxins and the loss of protective factors drive the physical degeneration. Peat pointed to the accumulation of iron and calcium with aging, both of which promote excitatory damage and mitochondrial calcification. 10 Roddy noted that neuroprostanes and isoprostanes—breakdown products from omega-3 fats—and acrolein are found in higher levels in Alzheimer's brains, alongside iron accumulation. 6 The structural protein transthyretin, which normally carries vitamin A and thyroid hormone, becomes glycosylated and forms amyloid deposits when there is a deficiency of protective carbon dioxide. 10 This glycosylation is a spontaneous process that occurs when the protein's amino groups are not protected by carbamino groups formed from carbon dioxide, directly linking the respiratory defect to the formation of plaques. 10 The variant form of apolipoprotein E (epsilon 4 allele), associated with Alzheimer's risk, is involved in cholesterol delivery for pregnenolone synthesis, a process regulated by thyroid. 2

Therapeutic intervention, in Peat's framework, centers on restoring oxidative energy metabolism and blocking inflammatory cascades. He suggested that improving energy production, for example by providing ketones as an alternative fuel, while reducing stress hormones, could replace defensive reactions with restorative nerve processes. 3 Substances like aspirin, by blocking prostaglandin production, help retard or prevent neurodegenerative diseases. 2 Methylene blue and thyroid were described as working similarly to help cells function properly by restoring their metabolic capacity. 2 A comprehensive protective program would include the supplementation of pregnenolone and progesterone to oppose cortisol and estrogen, the use of vitamin E and magnesium for their protective effects, and the provision of short and medium-chain saturated fatty acids as a safe energy source that also has hormone-like effects. 9 Since the innate immune system should be able to inactivate the prion-like proteins if the conditions amplifying inflammation are removed, Peat held that these conditions can be avoided and even reversed by systematically reversing the processes that amplify inflammation. 1