Gender and Alzheimer’s Risk

Alzheimer’s disease is the most common form of dementia worldwide and is primarily attributed to increasing longevity, especially in Western countries. While Alzheimer’s affects both men and women, it is far more common in the latter.

At present, women over the age of 65 have a 1 in 6 chance of this condition compared to 1 in 10 for men. However, not all large-scale studies have shown this significant difference in the prevalence and risk of Alzheimer’s between men and women.

This disparity was primarily attributed to differences in the age of death between the sexes for a long time, in that women live longer on average than men. However, the incidence of Alzheimer’s is higher in women between the ages of 60-80 years compared to men, which cannot be linked to corresponding differences in the mortality rates. Therefore, there must be some genetic and physiological basis for the increased prevalence of Alzheimer’s in women.

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Heart Disease Risk Factors

The basis of sex differences between males and females is due to sex chromosomal differences, with the genotype being XY for males and XX for females. This produces the profound morphological and physiological differences between males and females, and inevitably has consequences on every aspect of development, including that of blood vessel and brain function.

One of the biggest risk factors for Alzheimer’s is the presence of vascular and metabolic diseases such as heart disease and type 2 diabetes. While occlusive coronary arterial disease is more prevalent in men, small vessel disease is responsible for more heart disease in women. Furthermore, complications of diabetes are more prevalent in women than in men, and are linked to depression and coronary heart disease.

Therefore, both men and women with high blood pressure and cholesterol levels may have an equal risk of developing vascular disease, but women may be more susceptible to complications as a result leading to earlier or more severe onset of Alzheimer’s compared to men.

However, this relationship is poorly understood and often neglected in large-scale studies, and warrants a more in-depth focus in order to assess whether risk factors affect women more than men.

Hormonal and Sex Differences

Depression is often a symptom of Alzheimer’s; however, it has also been shown that a history of depression early in life can increase the risk of developing Alzheimer’s significantly. Women are generally twice as likely as men to have depression – especially towards midlife menopause. The basis of why women are more likely to suffer from depression than men (aside from all of the social reasons) can be attributed to hormonal changes during puberty.

Anatomically, it has been reported that women have a lower threshold of Alzheimer’s progression attributed to a faster hippocampal shrinkage compared to that of men. In terms of symptomatic differences, the mortality in men as a result of Alzheimer’s is higher and at an earlier age, compared to that of women, coupled with enhanced aggressive traits which are less common in women. Furthermore, women also tend to exhibit more emotional disturbances compared to that of men, again suggesting brain anatomical differences may be in part responsible for these symptomatic and survival differences.

Mitochondrial Differences

Mitochondria are living batteries present in every cell, and provide energy by utilising glucose and oxygen, Over the course of natural aging, reactive oxygen species (ROS) begin to accumulate which are detrimental to cell health and cause cells to either stress, or die.

It has been shown that women tend to have a greater protective effect from mitochondria at a young age, preventing the toxic effects of brain products such as beta-amyloid. Furthermore, compared to men, women’s mitochondria seem to produce less ROS at a younger age too. However, after menopause, due to hormonal changes, primarily changing estrogen levels, the protective abilities of the mitochondria suddenly deteriorate, leaving the cell more susceptible to the toxic effects of beta-amyloid compared to men.

Socioeconomic Differences

Traditionally, women have had fewer educational and employment opportunities compared to men in the past. Higher educational attainment and intellect is often associated with a delayed onset of dementia. This may explain why in some countries where women were not permitted to take higher education in the past century, the dementia rates are higher. Recently, women have been enjoying similar levels of education and employment as men, and in the US for example, the rates of dementia among women are slowly beginning to match that of men.

In summary, there are many hormonal, genetic and anatomical differences between men and women, which often have different susceptibilities to particular pathologies, especially with age. Women seem to be biologically more susceptible to Alzheimer’s disease compared to men. However, this is not a law of nature, and indeed higher cognition skills and education do seem to stave off some effects of dementia in both women and men.

Further Reading

• All Alzheimer's Disease Content
• Alzheimer’s Disease | Definition, Causes, Diagnosis & Treatment
• Alzheimer’s Disease Causes
• Alzheimer’s Disease Symptoms
• Alzheimer’s Disease Diagnosis

Written by

Osman Shabir

Osman is a Neuroscience PhD Research Student at the University of Sheffield studying the impact of cardiovascular disease and Alzheimer's disease on neurovascular coupling using pre-clinical models and neuroimaging techniques.