Sex Differences Evident in Brain Imaging

by Women's Brain Health Initiative:Men's and women's brains are different. They differ in size. They differ in amounts of white and grey matter. And they appear to differ in how they age, with differences becoming most pronounced in older age. These differences can be seen using brain imaging technology."New computerized methods allow precise measurement of the brain's structure, opening up new understanding of how the brain changes with age and how dementia affects women and men differently," explains Sandra Black, a neurology researcher affiliated with Sunnybrook Health Sciences Centre and University of Toronto.What's Different Between Women's & Men's Brains?Black shares some of what we know about differences between men's and women's brains, thanks to brain imaging:

• Premenopausal women have higher blood flow in their brains than men, thanks to high estrogen levels. After menopause, women's blood flow in the brain shifts to be similar to men's.
• Women appear to have more serotonin receptors, which are associated with mood.
• Packing cell density is higher in women in the language area, meaning they have more cells in a given amount of brain volume and the connectivity between the cells is more efficiently organized, perhaps explaining why, though the language area is smaller, women still tend to perform better on language tasks than men.
• Since men tend to be larger in overall size than women, and have larger heads, it's not surprising that brain volume is bigger in men. When you control for head size, though, women actually have proportionately more grey matter (i.e., cerebral cortex).

That last point about variations in head size is an important one. For analysis of brain imaging to be accurate when comparing across sexes, it is essential to make corrections for head size. To date, a lot of brain imaging work hasn't done that as carefully as it should.Brains Shrink Rapidly with Alzheimer'sA healthy brain fills the space inside the skull. Over time, the brain shrinks, much more rapidly when Alzheimer's disease is present. Brain imaging allows scientists to measure the amount of brain shrinkage by considering the volume of the brain itself as a percentage of the amount of space available inside the skull (the total intracranial vault volume); the resulting calculation is called the brain parenchymal fraction (BPF). BPF takes into account head size and makes it possible to compare across men and women. Women tend to have larger BPFs than men.Further evidence of brain shrinkage is the enlarging of ventricles. Ventricles are spaces in the centre of the brain where ventricular cerebrospinal fluid is produced. As the brain shrinks, these enlarge - they are much bigger in Alzheimer's patients. Black points out that, "older men tend to show more generalized shrinkage of the brain as indicated by larger ventricles, relative to head size."Current methods of brain imaging allow the brain to be segmented so that scientists can examine a particular part of the brain in isolation. The hippocampus is an interesting part to examine because of its importance for learning new information and forming short-term memories, and the fact that it is the first part of the brain to show signs of shrinking in Alzheimer's patients. If you look at hippocampal volume in men and women, and don't adjust for head size, it looks like men with Alzheimer's disease have significantly larger hippocampal volume than women with Alzheimer's. However, once you adjust for head size, this difference disappears. There is not much difference in hippocampus shrinkage between men and women with Alzheimer's disease. So, in this area, we actually see a similarity between men and women.Small Vessel Disease More Common in WomenBrain imaging can also reveal different types of small vessel disease that may affect cognition. There are different ways small vessel disease can show up. One is blockages in small arteries in the brain, especially common in people with hypertension and diabetes. "With this type of blockage, there is a kind of remodeling taking place in the brain and you get twisted arteries," explains Black.The tiny arteries can end up completely blocked because they don't have any blood supply and you end up with a hole. That is called a silent stroke. Silent strokes are present in about 28 percent of the population over 65 and even though people are not aware they've had one, they are not benign. Silent strokes are associated with higher risk of experiencing dementia and having an overt stroke."The other way small vessel disease manifests in the body is through what we call White Matter Hyperintensities (WMH)," says Black. WMH shows up as tiny spots or patches that represent an area of circulatory failure that hasn't developed into a hole. "You get this hyperintense appearance on a particular type of MRI scan," explains Black. WMH are much more prevalent than silent strokes. US data from brain imaging of 3500 people over 65 years old showed that WMH was present in 95% of the sample."The presence of WMH tells us that the vessels are aging and parts of the brain are being hurt," says Black. "Just because WMH are so common doesn't mean they are benign. If you just have little bit of WMH, it probably doesn't matter so much. But when you start to have large areas of them, it's becoming a more diffuse disease, which is more of a concern. And it looks like there is a tendency for women to have this more than men."Small vessel disease in the brain is related to overall vascular health. To keep your brain healthy, you need to keep your heart and circulatory system healthy. So, that means eating well, exercising and managing things that impact heart health such as high blood pressure, obesity and diabetes. "So that means hypertension must be recognized even at age 20 or 30, and treated vigorously. We have good medicine now that can do that," urges Black.A lot is known about how the brain works and how women's and men's brains differ, thanks to brain imaging. More research is needed to help us understand why these differences exist and how recommended treatments might be different for each sex. This is a complex topic with much more learning still ahead.