From the Mouth to the Brain
The mouth is the primary gateway into the body. Emerging evidence in neuroscience suggests that dental health problems may be linked to memory or cognitive impairments.
A 2012 study linked clean teeth to staving off dementia. Researchers at the University of California followed close to 5,500 elderly people over an 18-year-period and found those who brushed their teeth less than once a day were up to 65 per cent more likely to develop dementia than those who brushed three times a day.
Other studies have highlighted a link between Alzheimer’s disease (AD), the most common form of dementia, and gum disease-related bacteria. When the bacteria from your mouth enter into the bloodstream, they are transported throughout the body. Some are even able to pass the blood-brain-barrier to enter and populate the brain.
When we’re careless about brushing or flossing, plaque accumulates in and around the gums and may lead to periodontal disease, tooth loss and even impaired nutrition. Harmful bacteria called porphyromonas gingivalis are then released into the bloodstream. When they reach the brain, the immune system responds by kicking inflammation into gear and killing brain cells in the process. Brain cells, once dead, are more or less gone forever leaving us vulnerable to developing memory-related health problems, like dementia.
Brain Invading Bacteria
Periodontitis is a chronic oral biofilm-mediated infection. It is caused by bacteria that lead to local inflammation of the gums and supporting structures of the teeth.
Links between gum disease and dementia were first described in epidemiological studies that found higher rates of periodontitis among cognitively impaired populations. Initially, the reasons for this connection were unclear.
Since then, neuroscientists have been hard at work trying to identify the driving mechanisms that associate these two unlikely accomplices.
A recent paper published in Science Advancestook a look inside the brains of AD patients using a molecular biology technique called polymerase chain reaction (or PCR). Researchers analyzed brain tissue, spinal fluid, and saliva from patients—both living and dead—and found evidence of porphyromonas gingivalis. These bacteria are the keystone pathogen in chronic periodontitis. Moreover, gingipains (the toxic enzyme secreted by P. gingivalis) were found in 96 percent of the 53 brain tissue samples examined, with higher levels detected in those with the pathology and symptoms of AD.
Additionally, researchers including co-author Mark I. Ryder DMD, Professor of Periodontology at the University of California, San Francisco, noted that the presence of P. gingivalis increased the production of a protein called amyloid beta, a principal resident in AD brains.
The study confirmed via animal testing that P. gingivalis can travel from the mouth directly to the brain and that the related gingipains can destroy brain cells. These findings reveal at least one biological mechanism underlying the connection between periodontal disease bacteria and dementia.
What is Alzheimer’s Disease?
Dementia is the name for a set of symptoms that include memory loss and difficulties with thinking or language. Dementia develops when the brain is damaged by disease, including AD. According to the Alzheimer’s Association, AD accounts for 60 to 80 per cent of dementia cases. Most people with the disease get a diagnosis after age 65. If it’s diagnosed before then, it’s generally referred to as early onset AD.
AD was discovered and named by Dr. Alois Alzheimer in 1906, after he noticed changes in the brain tissue of a woman who had died after living with an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now known as amyloid plaques) and tangled bundles of fibers (now neurofibrillary tau tangles).
These plaques and tangles in the brain are still considered some of the main features of AD. Another feature is the loss of connections between nerve cells (neurons) in the brain.
The brain is made up of billions of nerve cells that connect to each other through a complex network. These neurons transmit messages between different parts of the brain, and from the brain to muscles and organs in the body. In AD, the connections between these cells are lost. It’s thought that the build-up of plaques and tangles cause the neurons to die, meaning that brain tissue is irrevocably lost.
The brain also contains important chemicals that help to send signals between cells. People with AD have less of some of these ‘chemical messengers’ in their brain, so the signals are often obscured or lost altogether.
AD is progressive. This means that gradually, over time, more parts of the brain are damaged. As this happens, more symptoms develop, and they also get worse as the memories fade away one by one.
The Memory Network: From Synapses to Neurons
Memories, and the way we interact with those memories, rely upon strong connections between networks of neurons throughout the brain. Recording a new memory requires adjustment to those connections.
Each memory makes a home for itself by altering the connection between subsets of brain cells, thereby changing the way that they communicate. Neurons talk to each other by sending messages across tiny bridges called synapses. A synapse is like a bustling port, complete with machinery for sending and receiving cargo. The cargo of the brain is called a neurotransmitter, which is a specialized chemical that conveys signals between neurons. All of this machinery is built from proteins, the basic building blocks of cells.
One of the leading scientists in this field of neuroscience is Eric Kandel, from Columbia University in New York City. Kandel demonstrated how short-term memories—lasting a few minutes—involve relatively quick and simple chemical changes to the synapse that make it work more efficiently. He discovered that building a memory that lasts hours, days or years, neurons must manufacture new proteins and expand the ‘docks’ to make the neurotransmitter traffic run more efficiently. Long-term memories are built into the brain’s synapses. Once a memory is constructed, it is relatively stable and can’t easily be undone. This process is termed memory consolidation.
This means that gum disease may impact learning and memory even if AD or other forms of dementia do not develop, in much the same way that smoking harms the lungs even in the absence of lung cancer. Damage to the neurons and their synapses means cleaving off large portions of our long-term memory banks.
If metabolites of periodontitis are able to kill brain cells, they are likely to inhibit our brain’s ability to form, consolidate and store memories.
Brain on Fire
Periodontitis is thought to exert its pathological effects on brain cells through a range of complex mechanisms, but largely through local and global inflammation.
Chronic inflammation eventually leads to memory and thinking problems, as described in a recent Neurology paper. Unlike acute inflammation, which arises in response to injury, chronic inflammation persists over months or years.
Inflammation isn’t always a bad thing. It is the body’s natural response against any number of incursions on your health. When bacteria invade your body, the immune system is triggered to create antibodies and other immune compounds to defeat the invaders. But poor dental hygiene will poise the body in a perpetual state of inflammation, as it tries to defend itself from the periodontal bacteria circulating without reprieve.
Researchers at John Hopkins performed blood tests on 12,000 men and women, assigning them an “inflammation composite score” based on white blood cell count, clotting factors and other tests. Alongside this, the participants were assessed for cognitive and memory function over a 20-year period.
They found that the greater the number of inflammatory factors, the steeper the cognitive decline over the 20 years of testing. This is because inflammation mechanically damages brain cells, but also confuses them chemically. Inflammatory markers inhibit a neurons ability to perform its chosen tasks by masking the chemical signals it is designed to transmit and receive.
In a Nature paper published this year, researchers describe how tau protein (one of the proteins associated with AD mentioned earlier) transforms under the influence of inflammation processes from the brain’s immune system.
In healthy brains, tau proteins help to stabilize the skeleton of the nerve cell or neuron. However, in AD, these proteins undergo chemical changes that make them dissociate from the neuron and stick to each other instead. Without mechanical stability, the neuron eventually perishes.
This tau “hyper-phosphorylation” can occur as a result of the sustained inflammation that happens in the brain in the presence of periodontal bacteria.
Losing Teeth Means Losing Your Mind
Tooth loss reflects the end stage of a several oral diseases, including periodontitis. In a prospective study of community dwelling elderly residents in Kwangju, South Korea, people who had experienced tooth loss were most likely to develop dementia.
The irony of tooth loss is that poor nutrition is both a cause and an effect. This is partially because less teeth means lower masticatory efficiency, leading people to adapt to diets low in fiber and essential micronutrients, and high in saturated fats and cholesterol, due to ease of chewing these foods.
Such dietary changes could potentially increase the risk for stroke and dementia by making difficult adherence to diets thought to be protective against AD such as the Mediterranean diet. Micronutrient deficiencies, such as vitamin B12 and thiamine deficiency, may also develop as a result of tooth loss and may contribute to cognitive impairment as these nutrients maintain neuronal health.
But even if you manage to maintain your nutrition following tooth loss, your memory could still be impaired.
European Journal of Oral Sciences published an article in 2007 documenting a relationship between tooth loss and memory function. The study involved 273 participants, with an average 22 teeth each (10 fewer than the full dentition of 32). Participants then faced a series of memory tests. The researchers found that the number of natural teeth was positively associated with performance on episodic memory, recall as well as recognition.
The reasons for this relationship were unclear, but subsequent animal studies revealed some potential underlying mechanisms for this odd phenomenon.
Animal Models Relating Poor Oral Health and Cognitive Impairment
To date, several animal models have started to explore these associations in both experimental tooth loss and periodontitis.
A pioneering study published in Behavioral Brain Researchdemonstrated the effects of tooth loss by surgically removing the teeth of young rats and comparing them to rats with healthy teeth. Both groups were fed nutritionally identical powder, but the toothless rats were significantly more likely than dentate rats to have poor spatial memory and decreased stimulated acetylcholine release in the cortex.
They suggested that natural chewing increases blood flow in the brain and increases activity in numerous brain areas. Without it, blood flow and memory functions are reduced.
Similar findings were reported in a subsequent rat model, where they found that tooth loss led to loss of brain cells specifically in the hippocampus – the structure in the brain that houses memory functions.
These researchers proposed that decreased mastication-induced sensory stimulation led to synapse loss. Sensory impulses created by the movement of our jaw and teeth are fed to the area of the brain that forms and retrieves memories. This reduction in sensory input leads to degeneration of the unused neurons, which operate on a ‘use-it-or-lose-it’ system.
Poor oral health, including tooth loss, caries, and periodontal disease, appear to be risk factors contributing to the development of cognitive impairment through dietary changes, malnutrition, and a systemic inflammatory response.
Science is beginning to reveal the complex mechanisms that connect poor dental health with memory decline, with further studies expanding this understanding every year. This growing body of evidence dignifies the importance of keeping a health mouth through brushing, flossing and regular trips to the dental hygienist.