St. Louis, MO — September 21, 2026 · World Alzheimer’s Day
Alzheimer’s research has centered on amyloid plaque for thirty years, but Dr. Padda argues cognitive decline is a fuel and inflammation problem that starts decades before the plaque, with measurable, modifiable variables most patients have never had checked.
Dr. Gurpreet Singh Padda, MD, MBA, MHP, a board-certified physician and author of The Starved Brain, is using World Alzheimer’s Day to make an argument the field has circled for a decade without adopting: the difficulty in Alzheimer’s disease may be diagnostic rather than pharmacological. For three decades the dominant model has centered on amyloid plaques, and for three decades therapies aimed at clearing them have produced results modest relative to the investment.
“We have spent thirty years clearing debris from a house that lost power,” Padda said. “The debris is real. It is not why the lights are off.”
Does Alzheimer’s start with the brain’s fuel supply?
The adult brain is roughly two percent of body weight and consumes close to twenty percent of resting energy expenditure. It is the least metabolically forgiving organ in the body, with almost no capacity to store its own fuel. Whatever it needs has to arrive continuously.
Reduced cerebral glucose metabolism appears remarkably early. Reiman and colleagues documented FDG-PET reductions in asymptomatic APOE4 carriers in their twenties and thirties, decades before the age at which Alzheimer’s pathology is expected and before measurable amyloid deposition. Later work found that apolipoprotein E, not fibrillar amyloid, accounted for reduced glucose metabolism in normal aging (Journal of Neuroscience, 2012;32(50):18227). The metabolic signal is not a late consequence of the disease. It arrives first, by a margin measured in decades.
The decisive observation comes from the Sherbrooke group led by Stephen Cunnane. Using PET tracers for both fuels, they showed that while brain glucose uptake is roughly 20 to 25 percent lower in Alzheimer’s disease, brain ketone uptake is essentially preserved. The neurons in hypometabolic regions are not dead. They are starving, and they retain the machinery to burn an alternative substrate.
A parallel finding sharpens the point. Thiamine diphosphate reduction correlates strongly with brain glucose hypometabolism in Alzheimer’s disease, whereas amyloid deposition does not. The cofactor required to metabolize glucose tracks the metabolic failure better than the protein the field has spent thirty years targeting.
“Glucose uptake collapses, and ketone uptake does not,” Padda said. “That is not a dead neuron. That is a neuron cut off from the fuel it was using, waiting for another one.”
How does insulin affect amyloid plaque in the brain?
There is a mechanistic bridge between the metabolic and amyloid stories that is rarely reported, and it is elegant. Insulin-degrading enzyme clears insulin, and it also clears amyloid-beta. The two are competing substrates for the same enzyme.
In chronic hyperinsulinemia, the enzyme is occupied. Amyloid clearance slows, not because the brain has begun producing more of it, but because the machinery that removes it is saturated by a metabolic signal originating in the periphery. On that reading, the plaque is a downstream consequence of systemic metabolic dysfunction rather than a primary event, which would explain why removing plaque late has helped less than the model predicted.
Dr. Padda is careful about how far that argument reaches. The enzymatic competition is well established at the bench; its clinical weight remains debated, and the book presents it as hypothesis-generating rather than settled. What is not in dispute is the direction of the arrow: peripheral metabolic state reaches the brain, and it reaches it early.
Can B vitamins slow brain shrinkage?
The Oxford VITACOG trial randomized 271 people over 70 with mild cognitive impairment to high-dose folic acid, B6 and B12 or placebo for two years. Among the 168 who completed serial MRI, whole-brain atrophy was 0.76 percent per year on treatment versus 1.08 percent on placebo, a 29.6 percent reduction (p = 0.001). In participants whose baseline homocysteine exceeded 13 micromoles per liter, atrophy was 53 percent lower on treatment (Smith AD et al., PLOS ONE 2010;5(9):e12244).
Follow-up found cognitive and clinical benefit as well, and found that the effect depended on omega-3 status. B vitamins helped those with adequate long-chain omega-3 levels and not those without (de Jager et al., 2012). Two modifiable inputs, interacting, neither sufficient alone. That interaction itself argues for measuring rather than supplementing unthinkingly.
B12 deficiency is prevalent in older adults and in long-term users of metformin and proton pump inhibitors, two of the most widely prescribed drug classes in the population most at risk. Unlike most Alzheimer’s risk factors, it shows up on a standard panel and can be corrected.
“A 53 percent reduction in brain atrophy came from three vitamins and a blood test nobody ordered,” Padda said. “We are not short of interventions. We are short of the will to measure.”
What should be measured before plaque ever shows up?
The framing does not promise reversal, and the book does not claim it. Nothing in The Starved Brain asserts that any intervention prevents, treats or reverses Alzheimer’s disease, and Dr. Padda is explicit that the honest version of this argument stops well short of that.
Instead, it argues a question of sequence. Glycemic control, insulin sensitivity, B-vitamin status, inflammatory load, and sleep deserve to be treated as first-line clinical variables rather than as lifestyle advice appended to a pharmacological plan. Each is measurable on tests already available in any primary care office. Each is modifiable. And each, on the evidence above, is moving years or decades before a diagnosis is available to be made.
The Starved Brain runs ten chapters on that argument and is published in Kindle and paperback editions. Each chapter ends with a code that opens a free Deep Dive for readers to hand to their own physician, published at thestarvedbrain.com one chapter at a time. The book’s launch was announced in July: New Book The Starved Brain Reframes Dementia as a Metabolic Disease of Overnutrition.
Frequently asked questions
What causes amyloid plaques?
Dr. Padda points to a clearance problem, not only a production problem. The enzyme that clears insulin, insulin-degrading enzyme, also clears amyloid-beta. When insulin stays high for years, that enzyme stays busy and amyloid clearance slows. On that reading, plaque is a downstream result of whole-body metabolic dysfunction. The Starved Brain presents this link as a hypothesis worth testing. What is not in dispute is that metabolic health reaches the brain early.
What is the role of amyloid plaques in Alzheimer’s disease?
Plaque is real, but in Dr. Padda’s view it is not the first event. Reduced glucose use in the brain shows up in APOE4 carriers in their twenties and thirties, decades before measurable amyloid. As he puts it, thirty years of research have gone into clearing debris from a house that lost power. The debris is there. It is not why the lights are off.
Can amyloid plaques be reversed?
Dr. Padda makes no reversal promise. The Starved Brain does not claim that any intervention prevents, treats or reverses Alzheimer’s disease. What the book argues is a question of sequence: removing plaque late has helped less than the model predicted, so the variables that move years or decades earlier, such as blood sugar control, insulin sensitivity and B-vitamin status, deserve attention first.
How do you get rid of amyloid plaque naturally?
Dr. Padda shifts the target from the plaque to the fuel supply behind it. He names five first-line variables: blood sugar control, insulin sensitivity, B-vitamin status, inflammatory load and sleep. Each is measurable on tests already available in any primary care office, and each is modifiable. In the Oxford VITACOG trial, B vitamins slowed brain shrinkage in people over 70 with mild cognitive impairment.
About The Starved Brain and its author
The Starved Brain examines cognitive decline through brain energy metabolism, nutrient status, and systemic inflammation. Its author, Dr. Gurpreet Singh Padda, MD, MBA, MHP, is a board-certified physician and founder of Regen.MD in St. Louis, board-certified in anesthesiology, pain medicine, interventional pain management, addiction medicine, and obesity medicine, and a certified Metabolic Health Practitioner. The Starved Brain is the first volume in his series The Brain.
For media: This release was distributed nationally via EIN Presswire on September 21, 2026 and carried by AP News, The National Law Review, KTVI FOX 2 St. Louis and the Akron Beacon Journal.
View on EIN Presswire ›View on AP News ›View on The National Law Review ›