Why Are Most Alzheimer’s Patients Women?

The discussion of why women are far more likely to get Alzheimer’s disease compared to men is important, and in my opinion, very much neglected. That said, there are a variety of factors that are being explored to help understand this disparity. And this discussion takes multi-pronged approach, with factors spanning from biological to lifestyle.

The role of estrogen, particularly estradiol, and the critical impact of menopause on a woman’s cognitive health offers significant insights into the prevalence of Alzheimer’s disease among women. In her fascinating book, The XX Brain, Dr. Lisa Mosconi presents research further underscoring this hormonal component and other genetic factors.

Let’s first explore the biological aspect of this disparity. Women and men differ greatly in their biological makeup and hormonal composition. Estrogen, plays an integral part in brain health. Estradiol, the most potent estrogen, is known for its neuroprotective qualities and its capacity to promote synaptic plasticity, thereby maintaining memory function and cognition. It modulates the production and accumulation of beta-amyloid, a protein somewhat linked to Alzheimer’s disease (but certainly not required for the disease to manifest). Therefore, adequate levels of estradiol in the body are necessary to counter cognitive decline.

However, during menopause, women experience a dramatic reduction in estradiol production, resulting in a decrease in its neuroprotective effects. This hormonal shift alters the brain’s metabolic processes and increases the risk of Alzheimer’s disease. Lower estradiol levels lead to increased amyloid-beta accumulation, which can trigger neurodegeneration and facilitate the onset of Alzheimer’s. But it may well be the metabolic consequences that are more pivotal as it relates to brain health and disease resistance.

Dr. Lisa Mosconi’s The XX Brain delves into this topic, providing a detailed exploration of the female brain’s unique vulnerabilities to Alzheimer’s disease. Mosconi argues that women’s brains age distinctly differently from men’s, largely due to the effects of menopause on cognitive health. She emphasizes that the decrease in estradiol production during menopause is a significant risk factor for Alzheimer’s disease in women.

The book also explores the ‘X factor,’ or the genetic predisposition women have to Alzheimer’s due to carrying two X chromosomes. Women with a specific variant of the APOE gene (APOE-ε4) on one of their X chromosomes are more likely to develop Alzheimer’s. This variant is known to increase beta-amyloid accumulation in the brain, and women are at a disadvantage due to the ‘dosage’ effect of carrying two X chromosomes.

However, Mosconi stresses that while genetics and hormonal changes play a role, they do not determine one’s destiny. Lifestyle factors such as diet, exercise, sleep, stress management, and social engagement also significantly impact a person’s risk of Alzheimer’s, and I cannot emphasize this enough.  Women often shoulder multiple roles in society – as professionals, caregivers, mothers – that can lead to high stress levels and inadequate sleep, further exacerbating the risk.

The book also offers hope in terms of prevention or at least risk reduction. Mosconi encourages a proactive approach to brain health, emphasizing the importance of timely hormonal therapies, adopting a brain-healthy diet, physical exercise, and cognitive stimulation to counter the risks associated with menopause and genetic predispositions.

The increased risk for this devastating disease in women compared to men can be attributed to a combination of hormonal changes, particularly the reduction of estradiol after menopause, and genetic factors as outlined in The XX Brain. However, understanding these factors allows for targeted preventive measures and lifestyle modifications to reduce the risk of Alzheimer’s disease in women. As our understanding of this complex disease deepens, so does our capacity to make significant strides towards its prevention and cure. And to be sure, as it relates to the offerings of the pharmaceutical industry, even as we read headlines proclaiming the dramatic effects of new drugs, we have a long way to go. That said, recommendations like Dr. Mosconi makes can, and should be implemented today!