Before Memory Fades: Why Metabolic Health Matters

Conversations about Alzheimer’s disease often center on plaques, tangles, and inflammation. Dr. David Perlmutter, a leading neurologist, bestselling author, and a fellow of the American College of Nutrition, urges people to look further upstream: at how the body produces and uses energy.

On an episode of “Vital Signs,” Perlmutter described metabolic dysfunction as an important contributor to the processes that can leave the brain vulnerable years before memory problems emerge.

“The brain’s ability to use fuel appropriately is compromised decades before we become forgetful,” he said. “And that’s all about our metabolism.”

Alzheimer’s involves multiple interacting factors, including aging and genetics. Perlmutter’s emphasis is on an opportunity within that complexity: addressing metabolic health while people still feel well.

“We need to intervene in people your age and make them recognize that the lifestyle choices you are making right now are going to play out when you’re my age,” said Perlmutter, who is in his 70s.

For people hoping to remain mentally sharp later in life, his message is to begin building that foundation in their 30s and 40s.

Alzheimer’s and the Brain’s Energy Crisis

Long before someone struggles to find a word or repeatedly forgets appointments, changes may be developing in the brain’s use of glucose, its principal fuel under ordinary conditions.

Brain-imaging research has found reduced glucose metabolism in regions vulnerable to Alzheimer’s, including in some people who have no symptoms but are at elevated risk. A review in the Journal of Alzheimer’s Disease describes how these changes can precede clinical decline, making energy metabolism an important window into the disease’s early stages.

Perlmutter views this as a reason to take familiar metabolic problems more seriously: insulin resistance, poor blood sugar control, high blood pressure, excess body weight, and abnormal cholesterol or triglyceride levels.

The scale of the problem is substantial. CDC estimates released in 2026 indicate that 40.1 million Americans have diabetes, including all types, and 115.2 million adults have prediabetes. About eight in 10 adults with prediabetes do not know they have it.

Research also suggests that timing matters. A 2021 JAMA study followed more than 10,000 British adults for nearly 32 years. Among participants assessed at age 70, those who had developed type 2 diabetes more than a decade earlier had roughly twice the subsequent dementia risk of those without diabetes. Earlier diabetes onset was associated with greater risk.

The implication extends beyond one blood sugar reading: years of metabolic illness may influence how the brain ages.

When the Brain’s Defenders Become Destroyers

The connection between metabolism and brain health also reaches the immune system.

Microglia, the brain’s primary resident immune cells, normally help protect neurons, clear debris, and respond to injury. Under persistent stress, some of their responses can instead sustain inflammation and contribute to damage.

“The same cells that are your friends can become your foes,” Perlmutter said.

A 2025 study in the Proceedings of the National Academy of Sciences explored this connection. In cell experiments, microglia lacking insulin receptors were less able to take up amyloid-beta. Removing those receptors in an Alzheimer’s mouse model increased amyloid accumulation and neuroinflammation.

Microglial dysfunction is also studied in Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis, making these cells an important focus across neurological research.

For Perlmutter, protecting brain health includes supporting the conditions these cells work in—particularly through exercise, sleep, and blood sugar management.

Sleep research reinforces the long-term perspective. A 2021 study of nearly 8,000 adults found that sleeping six hours or less at ages 50 and 60 was associated with greater later dementia risk than sleeping seven hours.

Fasting Insulin: The Early Warning Signal

Metabolic problems can develop quietly.

Most people rely on an annual fasting blood sugar test to assess metabolic health. Perlmutter considers that approach deeply insufficient. “You can train for that test,” he said. “Eat well for a week and impress the doctor.”

What really matters is fasting insulin.

Insulin levels reveal how hard the pancreas is working to keep blood sugar normal. Even when blood sugar still looks fine, rising insulin signals that insulin resistance is already underway —sometimes decades before diabetes is diagnosed.

“If your fasting insulin is climbing, you have work to do.” Ideally, fasting insulin should be low—roughly 2 to 5 µIU/mL. Higher values indicate that metabolic dysfunction is already underway, increasing Alzheimer’s risk.

Continuous glucose monitors can also offer valuable real-time insight into how food, sleep, stress, and exercise affect blood sugar—not necessarily forever, but long enough to understand your patterns, Perlmutter said.

Beyond insulin, he recommends monitoring key lab markers to protect brain and metabolic health:

HbA1c: for average blood glucose and diabetes risk
Vitamin D: supports brain function and reduces inflammation
B12: essential for nerve health and cognition
Homocysteine: elevated levels signal vascular and cognitive risk and can be improved with methylated B vitamins
Inflammation Markers: such as C-reactive protein.

Emerging brain-specific tests, such as p-tau217, also add precision.

Your Gut Is Your Brain’s Silent Partner

Metabolism fuels the brain, and the gut regulates that fuel. Disruptions to the microbiome—from antibiotics, artificial sweeteners, or poor diet—can increase diabetes risk, promote obesity, and fuel neurodegeneration.

“High-dose antibiotics are like weapons of mass microbial destruction,” Perlmutter said. “They wipe out beneficial bacteria, disturb balance, and compromise metabolism.” The consequences range from life-threatening infections such as Clostridium difficile to subtler metabolic disruptions that increase long-term Alzheimer’s risk.

Permutter’s advice is to ask whether antibiotics are truly necessary, whether a targeted option is available, and whether the course can be shorter. And when they are required, support the microbiome before, during, and after with probiotics, prebiotics, and fiber-rich food—though avoid taking probiotics at the same time as antibiotics.

Artificial sweeteners offer another example of the gut’s metabolic influence. A 2022 randomized trial in Cell studied 120 healthy adults over two weeks. Sweeteners produced differing microbiome changes, and the saccharin and sucralose groups showed impaired glucose tolerance.

For Perlmutter, this underscores the importance of considering food quality and physiological effects beyond a “sugar-free” label.

Which Diet Is Right

Is the Mediterranean diet best? Keto? Paleo? “I don’t care,” Perlmutter said. “I care about what that diet is doing to your physiology.”

Different people respond differently to the same diet. Genetics, nutrient requirements, and variations in the gut microbiome all play a role. What matters is whether your diet controls blood sugar and insulin, reduces inflammation, supports the microbiome, and delivers adequate micronutrients.

One near-universal concern, he said, is fiber deficiency. “We’re not getting enough dietary fiber—and it should be considered a macronutrient.”

Even ketogenic or other metabolically beneficial diets can backfire if they eliminate fiber and starve gut bacteria, he said.

Be the Architect of Your Brain’s Destiny

Research increasingly examines lifestyle habits together. In the 2025 U.S. POINTER trial, 2,111 adults ages 60 to 79 at increased risk of cognitive decline followed either a structured lifestyle program or a self-guided approach. Both addressed exercise, diet, cognitive and social engagement, and cardiovascular health. Over two years, the structured program produced modestly greater improvement in cognitive testing.

The findings support consistent habits with practical guidance and follow-up—and offer encouragement beyond midlife.

“We need to be the stewards of our health destiny. Modern medicine won’t fix everything. But if we make the right choices now—how we eat, sleep, move, and manage our metabolism—we become the architects of our brain’s destiny,” Perlmutter said.

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