Dementia is a condition that changes the way the brain works, and over time, it causes clear changes in the structure of the brain. These changes do not happen overnight. Instead, they build up slowly, often starting years before any noticeable symptoms appear. The brain is made up of two main types of tissue gray matter and white matter. Gray matter is where the brain’s nerve cells live, and it is responsible for processing information, memory, and thinking. White matter is made up of nerve fibers that connect different parts of the brain, allowing them to communicate with each other. In dementia, especially in Alzheimer’s disease, both gray and white matter are affected, but the changes happen in a specific order and pattern as the disease progresses [1].
In the earliest phase, which scientists call the preclinical phase, there are no obvious symptoms. A person may feel completely normal, but inside the brain, changes are already taking place. The first area to show signs of damage is the medial temporal lobe, which includes the entorhinal cortex and the hippocampus. These regions are very important for memory and learning. Studies using MRI scans have found that the volume of these areas begins to shrink, or atrophy, as much as 5 to 10 years before any memory problems become noticeable [1]. At the same time, the white matter in certain pathways, like the parahippocampal cingulum and the corpus callosum, also starts to change. These changes can be seen as a reduction in the integrity of the nerve fibers, which means the brain’s communication lines are not working as well as they should [1].
As the disease moves into the next phase, called mild cognitive impairment, the atrophy spreads beyond the medial temporal lobe. The hippocampus continues to shrink, and now other areas, such as the parietal and lateral temporal regions, also start to lose volume. These regions are involved in attention, language, and spatial awareness. The white matter damage also becomes more widespread, affecting major association fibers like the superior longitudinal fasciculus. This means that the connections between different parts of the brain are breaking down, making it harder for the brain to coordinate complex tasks [1].
When dementia fully develops, the changes in brain structure become even more severe. The atrophy is no longer limited to a few regions. Instead, there is widespread thinning of the cortex, which is the outer layer of the brain. This thinning affects many areas, including those responsible for memory, language, and executive function. The white matter damage also becomes more extensive, with major tracts like the cingulum bundle and the uncinate fasciculus showing signs of disintegration. This means that the brain’s ability to send signals from one region to another is greatly reduced, which contributes to the worsening of symptoms [1].
The process of brain atrophy in dementia is not random. It follows a specific pattern that reflects the underlying pathology of the disease. In Alzheimer’s disease, for example, the atrophy starts in the medial temporal lobe and then spreads to other regions in a predictable sequence. This pattern is thought to be related to the way that abnormal proteins, such as amyloid and tau, accumulate in the brain. These proteins form plaques and tangles that disrupt the normal functioning of nerve cells and eventually lead to their death [1].
The changes in brain structure are not the only thing that happens in dementia. The way the brain networks are organized also changes. In healthy brains, there is a balance between integration, which is the ability of different regions to work together, and segregation, which is the ability of regions to function independently. In dementia, this balance is disrupted. The brain becomes less efficient at integrating information, and the connections between regions become weaker. This is reflected in changes in network topology, such as a decrease in small-worldness and an increase in the clustering coefficient. These changes mean that the brain is less able to coordinate complex tasks and is more prone to errors [2].
The changes in brain structure and network organization are not limited to Alzheimer’s disease. Other forms of dementia, such as vascular dementia, also cause changes in brain structure, but the pattern may be different. For example, vascular dementia is often associated with damage to the white matter due to small strokes or reduced blood flow. This can lead to a different pattern of atrophy and network disruption compared to Alzheimer’s disease [4].
The process of brain aging itself also plays a role in dementia. As people get older, the brain naturally undergoes changes, such as a gradual loss of volume and a decline in connectivity. However, in people who develop dementia, these changes happen faster and are more severe. Studies have shown that the relationship between age and brain volume is different in people with preclinical Alzheimer’s disease compared to those without. In particular, the entorhinal cortex and amygdala show more rapid shrinkage in people with preclinical Alzheimer’s, even before any symptoms appear [4].
The changes in brain structure that occur in dementia are not just a result of the disease itself. They are also influenced by other factors, such as vascular health. For example, people with high blood pressure or other vascular risk factors are more likely to have changes in brain structure that increase their risk of dementia. These changes can include damage to the white matter and a reduction in the volume of certain brain regions [4].
The process of brain aging and dementia is not the same for everyone. There are turning points in brain development and aging that mark significant shifts in brain structure and function. For example, research has identified four major turning points in brain development at ages 9, 32, 66, and 83. At each of these points, the brain undergoes a reorganization that can affect its structure and function. The turning point at age 32 is particularly important, as it marks the end of adolescence and the beginning of adulthood. At this point, the brain’s wiring undergoes the most directional changes, and the overall trajectory of brain development shifts. The turning point at age 66 is related to aging, with a gradual reorganization of brain networks and a decline in connectivity. The final turning point at age 83 marks the entry into the last phase of brain structure, where there is a shift from global to local connectivity and an increased reliance on certain regions [3].
The changes in brain structure that occur in dementia are not just a result of the disease itself. They are also influenced by other factors, such as hearing loss. Studies have shown that midlife hearing loss is associated with changes in brain structure, cognitive function, and an increased risk of dementia. This suggests that hearing loss may contribute to the process of brain aging and increase the risk of developing dementia [7].
The changes in brain structure that occur in dementia are not just a result of the disease itself. They are also influenced by other factors, such as blood flow. Research has shown that age and biological sex can affect blood flow control in the brain, and differences in blood flow may contribute to the process of brain aging and increase the risk of dementia [8].
The changes in brain structure that occur in dementia are not just a result of the disease itself. They are also influenced by other factors, such as well-being and daily cognitive functioning. Despite self-reported well-being and normal daily cognitive functioning, brain structural changes are
