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NEUROLOGY

The brain and the ravages of time

Even when there are no changes due to disease, aging leads to changes in the brain’s organization and function

Physical exercise, along with an intellectually stimulating life, help keep the brain young

Léo RamosPhysical exercise, along with an intellectually stimulating life, help keep the brain youngLéo Ramos

In the same way that the skin wrinkles and the hair turns white, the brain changes as a person ages. Changes in structure and function occur in how the brain’s different regions communicate and relate. Findings published in the journal Cerebral Cortex help to characterize these changes. “In our observations, the brain goes through a process of reorganization,” explains Geraldo Busatto Filho, from the University of São Paulo Medical School (FM-USP), one of the article’s authors. “Important brain functions require integration and synchronicity between the different areas.”

Luiz Kobuti Ferreira, principal author of the study who is also at FM-USP, says that the study evaluated pairings among 278 regions of the brain as a whole. Among the three most important findings of the study, which was conducted using functional magnetic resonance imaging, is an increase among the elderly in the association between different functional areas that do not in theory need to communicate to complete their respective tasks. The test, which shows the brain at work, demonstrated that the area responsible for vision, for example, has a weak connection with the area related to logical thought in young people and adults. However, as aging occurs, these areas began to function more together.

“According to one of the theories on this phenomenon, some regions of the brain are not able to carry out their functions as well as they used to, and they recruit other areas of the brain to compensate, which leads to a loss of specialization,” says Ferreira. This type of functioning can leave the brain more susceptible to noise, making it more difficult to execute tasks that require attention be paid to the outside world. Since the senior citizens in the study were healthy and did not demonstrate cognitive difficulties, it is also possible that a stronger connection between brain areas is related to more life experience and higher levels of learning.

Another difference between the brains of young people and the elderly is a loss of synchronicity between regions. During early childhood and adolescence, some brain networks begin to communicate more with each other and become activated simultaneously, while regions with different functions can do the opposite: if one is active, the other is not. This is exemplified in the regions responsible for attention, activated under threat, and the Default Mode Network, a set of regions that are active when someone is not connected to the outside world. The synchronicity between these regions, marked in young people and adults, was less marked in some of the study’s senior citizens.

Regional pairs that are strongly associated with each other can also become less connected in the elderly. This was observed mainly in the Default Mode Network and corroborated previous studies on specific brain regions.

These findings are in keeping with previous studies conducted by Busatto’s group, which analyzed how aging effects the brain’s structure. “The brain of a senior citizen is reduced in volume, which can by explained by different changes, including decreased density of synaptic connections, lower neurotransmitter levels, and a loss of neural extensions,” says Busatto.

But this is not reason enough to concede defeat. The effect of the aging process on the brain can be minimized by engaging in physical exercise, maintaining a healthy diet, not smoking in addition to staying psychologically healthy, and participating in activities that are intellectually stimulating.

Other groups are focusing on understanding how unhealthy aging of the brain occurs, like the work being done by Carlos Alberto Buchpiguel and Daniele Farias at the Center for Nuclear Medicine at USP, in collaboration with Busatto’s group.  “They are analyzing patients with minor cognitive impairment and early-stage Alzheimer’s disease, which is responsible for more than half of all dementia cases,” says Busatto.  “PET scanning is being used to produce images of the accumulation of beta amyloid peptide fragments in the brain, which, along with functional magnetic resonance imaging, can be used to analyze whether these accumulations are related to changes in levels of brain connectivity,” he explained, referring to a type of tomography that makes it possible to monitor specific chemical substances in the body.

Studying what happens in the brains of people with Alzheimer’s disease is also the goal of Marcio Balthazar, at the Unicamp School of Medical Sciences (FCM-Unicamp).  He is studying both the structural and functional changes in the brain as well as the similarities and differences between healthy aging and aging with disease.

Balthazar has observed that people with Alzheimer’s disease, compared with healthy senior citizens, have less deactivation in the Default Mode Network when they are doing tasks focused on the outside world, which results in less ability to focus their attention and concentrate.  He also detected a greater number of connections between areas of the brain that carry out different functions. As the disease progresses, the brains of people with Alzheimer’s disease shrink much more when compared to healthy brains, and they stop recruiting other regions of the brain to compensate for diminished capacity.

Prevent and treat
One of Balthazar’s main challenges is to identify early detection methods for Alzheimer’s disease.  One approach is to put together brain connectivity patterns with what is already known about the beta amyloid protein deposits, the main culprit in the loss of connectivity and cognitive problems that characterize the disease. “Our most recent findings indicate that it is possible to use beta amyloid levels to predict the degree of brain connectivity,” he explains. He stresses that the idea of using proteins and brain imaging as biomarkers has potential, but it still has to be refined if it is to have successful clinical applications.

Another goal is to discover an effective treatment for Alzheimer’s disease, which still has no cure.  Balthazar’s group is currently studying whether physical exercise – which helps with prevention – can also be an effective treatment. “Preliminary results indicate that physical exercise has the potential to delay not only the disease’s onset but also its progression.”

Projects
1. Retrieval of autobiographical memory and the aging brain: a study using functional magnetic resonance (nº 2011/00475-3); Grant Mechanism Regular Research Grant; Principal Investigator Geraldo Busatto Filho (FM-USP); Investment R$69,463.87.
2. Translational neuroscience of Alzheimer’s disease: preclinical and clinical studies of b-amyloid peptide and other biomarkers (nº 2012/50329-6); Grant Mechanism Thematic Project; Principal Investigator Geraldo Busatto Filho (FM-USP); Investment R$ 3,082,570.79.
3. Biomarkers in Alzheimer’s disease and mild cognitive impairment: evaluation of functional magnetic resonance imaging methods, plasmatic and cerebrospinal fluid markers (nº 2011/17092-0); Grant Mechanism Young Investigators Project; Principal Investigator Márcio Balthazar (FCM-Unicamp); Investment R$226,940.05.

Scientific Articles
FERREIRA, L. K. et al. Aging effects on whole-brain functional connectivity in adults free of cognitive and psychiatric disorders. Cerebral Cortex. On-line. 26 Aug. 2015.

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