The Ketogenic Diet, Perimenopause and Alzheimer’s Risk: Can Ketones Fuel the Midlife Female Brain?

I have always been fascinated by the brain. Ever since I first experimented with the ketogenic diet, I have been hooked on understanding how the brain works and what influences its ability to perform at its best. Whether through exercise, nutrition, learning, or lifestyle, I am constantly looking for ways to challenge myself cognitively and support long-term brain health. As I move through perimenopause myself, I have come to appreciate that this hormonal transition is not something that simply happens to us. We have far more influence over the process than we are often led to believe. We can create an environment where the brain is supplied with both glucose and ketones, where mitochondria are supported, and where the next chapter of life becomes one of strength rather than decline.

One of the most fascinating papers I have read in recent years was published by Lisa Mosconi and colleagues in 2017. The study examined healthy women transitioning through perimenopause and postmenopause and found something remarkable. Compared with premenopausal women, both perimenopausal and postmenopausal women showed reductions in glucose metabolism within key regions of the brain. These were not random areas. They were the same regions that researchers commonly identify as vulnerable in the earliest stages of Alzheimer’s disease. The women in the study did not have dementia, nor were they cognitively impaired, yet measurable changes in brain energy metabolism were already taking place. The researchers described this as the emergence of an Alzheimer’s-like bioenergetic phenotype, suggesting that the seeds of cognitive decline may begin decades before symptoms ever appear.

For decades, we have been told that women are at greater risk of Alzheimer’s disease simply because we live longer. While longevity certainly plays a role, this explanation feels incomplete. The research suggests that the menopausal transition itself may represent a critical turning point in brain health. During perimenopause, fluctuating and declining estrogen levels affect the brain’s ability to efficiently utilize glucose, its primary fuel source. At the same time, mitochondrial function begins to decline. The combination creates what researchers describe as a bioenergetic deficit, essentially a state where the brain is not producing energy as efficiently as it once did. This may explain why so many women report symptoms such as brain fog, forgetfulness, difficulty concentrating, changes in mood, and reduced mental clarity during this phase of life. What is particularly interesting is that these changes are occurring at a time when women are often at the peak of their careers, raising families, caring for aging parents, and managing countless responsibilities.

What I find particularly fascinating is that the brain does not simply stop functioning when glucose metabolism begins to decline. The female brain is remarkably adaptable. Research from Dr. Roberta Brinton’s laboratory has demonstrated that as estrogen declines and the brain becomes less efficient at utilizing glucose, it begins searching for an alternative fuel source. This alternative fuel is ketones. In both animal and human studies, researchers have observed a shift away from glucose metabolism and towards fatty acid and ketone utilization. Rather than viewing this as a problem, I see it as the body’s attempt to adapt and survive.

For decades, the ketogenic diet was viewed primarily as a tool for weight loss or epilepsy management. Today, we understand that ketosis represents a completely different metabolic state, one in which the brain can utilize ketones as a highly efficient fuel source when glucose metabolism becomes impaired. This is particularly relevant during perimenopause because the very changes observed in Mosconi’s research are changes in brain energy metabolism. If the brain is becoming less efficient at using glucose, then supporting the brain’s ability to utilize ketones becomes an incredibly important conversation. Ketones provide energy to neurons, but they also act as signaling molecules throughout the body and brain. Beta-hydroxybutyrate (ketones in the blood) has been shown to reduce inflammation, improve mitochondrial function, support neuronal resilience, increase brain-derived neurotrophic factor, and activate pathways involved in mitochondrial biogenesis such as PGC-1 alpha. Ketones may also improve insulin sensitivity and provide a more stable energy source for neurons struggling to meet their metabolic demands.

When I work with women and men through hormonal transitions, I am not simply focused on weight loss. I am focused on metabolic flexibility. I want the brain to have access to both glucose and ketones. I want mitochondria to remain healthy and adaptable. I want insulin sensitivity preserved. I want individuals to understand that every meal, every walk, every strength training session, every night’s sleep, and every period of nutritional ketosis is sending signals that influence how the brain will function not only today, but twenty or thirty years from now. The ketogenic diet is not a magic solution, but it represents one of the most exciting tools we currently have for supporting brain energy metabolism during a period of significant hormonal change.

This is why I believe the conversation around hormonal shifts needs to evolve. We have spent decades talking exclusively about hormones while overlooking metabolism. Hormones matter tremendously, but hormones and metabolism are inseparable. The decline in estrogen and testosterone influences how the brain produces energy, and the ketogenic diet offers one potential strategy to support that transition. As women, we may spend nearly half of our lives in the postmenopausal state. That means the decisions we make in our forties and fifties have the potential to influence the health of our brains for decades to come. Rather than viewing perimenopause as the beginning of cognitive decline, I believe it is an opportunity to build a metabolically resilient brain capable of thriving for the next fifty years of life.