Early diagnosis will slow dementia

March 29, 2012 - 06:08
Article from University of Oslo

The prevalence of dementia will increase dramatically in the coming decades. But early diagnosis can provide a basis for effective treatment.

More and more people are affected by dementia. Scientists are now laying a foundation for early intervention. (Photo: Colourbox)

We are facing the much-heralded and infamous wave of baby boomers reaching pensionable age. As a result, dementia-related illnesses will become increasingly common.

About 70,000 people in Norway have a dementia disease at present, and at least 250,000 families are affected. In just three decades, patients with dementia will treble.

Age is the most important risk factor for dementia.

"Normal ageing processes interact with the processes involved in the development of dementia diseases,” explains Professor Tormod Fladby, who is researching diagnostics and causes of diseases that lead to cognitive impairment and dementia.

This means that the risk of developing dementia increases significantly with age, which in itself is enough to tell us that the number of dementia cases will triple in the next 30 years.

Will intervene early

Together with colleagues in and outside Norway, Fladby wants to identify the disease mechanisms leading to dementia as early in the process as possible, and to standardise the way diagnoses are made.

When we have sufficient knowledge about how dementia develops from the start, it will hopefully be possible to begin treatment early.

"Some of the disease mechanisms that are probably involved in dementia are in principle possible to mitigate by treatment," explains Fladby.

He said there have been many attempts at treating these categories of patients over the years, and none of them have worked so far.

Fladby therefore believes that the key factor is to identify disease processes at a significantly earlier stage than today, when the processes are more isolated, and then attempt intervention treatment.

The goal of this treatment will be to influence both immunological processes and the metabolism of peptides (chains of amino acids in the cells). This can be done pharmacologically, with the patient taking drugs. It may also be possible to treat the conditions through specific medical nutrition.

Fladby and his group want to establish testing of these two types of treatment.

To get there, scientists have a lot of work to do to develop early diagnostic criteria. They need to compare data from a number of different studies, and then verify that these findings are specific to the development of dementia.

They do this by following patients over time. But the development of dementia is a slow process, and scientists have little time. They must therefore follow a wide range of patients at once to amass many patient observation years in just a few real years.

Unstoppable processes

The reason treating dementia is so difficult today is that the processes in the brain that cause the disease are unstoppable, and that the diagnosis is made too late.

"The problem is that when a dementia diagnosis can be made, much of the brain is already damaged," says Fladby.

According to him different types of disease mechanisms may have been turned on already - it could be inflammation of the brain, or excretion of toxins that can interfere with metabolism or affect the cell walls.

Tormod Fladby at the Institute of Clinical Medicine and Akershus University Hospital, researcher of pre-dementia and early diagnosis of dementia diseases. (Photo: Siv Tonje Håkensen)

Many forms of nerve cell damage may have occurred simultaneously, causing extensive nerve cell death and destruction. Scar tissue may also have formed in crucial parts of the brain, such as the inner parts of the temporal lobe, which are essential for memory and your ability to take care of yourself.

“It is obvious that the condition cannot be reversed at that point."

A range of conditions

A dementia disease is a neurodegenerative condition, caused by dead or damaged nerve cells.

Alzheimer's disease leads to the most common and most well-known form of dementia - Alzheimer's dementia, which accounts for about 60 percent of all dementia cases. That is why Fladby's group mainly concentrates on this disease.

Alzheimer's is caused by the loss of neurons and synapses in the brain. The nerve cells are damaged or die as a result of the accumulation of amyloid beta protein deposits (plaques) between the cells.

The reasons why the deposition starts in the first place is not yet known. The loss of nerve cells in the brain eventually leads to cognitive impairment and personality changes.

The second most common form is vascular dementia, which is thought to come from diminished blood flow to certain areas of the brain. When the blood flow stops, it causes deposits of plaque, including amyloid beta.

Fladby's group is also studying vascular dementia. As they strive for the earliest possible diagnosis, the scientists are mainly focused on pre-dementia states. This condition is characterised by mild cognitive impairment.

Memory fails

The patient group that Fladby's group is researching consists of people who feel they have cognitive impairment, and come to the hospital for answers. They may have found that they constantly forget what month it is, or suddenly lose control of their spending.

Some patients are stroke patients provided they have cognitive impairment.

Of patients who experience cognitive impairment, about 10 to 15 percent will annually develop a dementia disease. This usually takes many years.

The causes of cognitive impairment may also be other conditions, such as depression or stroke without the development of a dementia condition.

Circulates around the brain

A patient evaluated for cognitive impairment is given different neuropsychological tests. For example, the patient may answer a questionnaire with simple tasks that test the patient's memory and orientation ability.

However, questionnaires and other tests are not enough to make a definite diagnosis.

The spinal fluid, on the other hand, may provide some important signals. It circulates around the brain and is in equilibrium with the fluid found outside cells in the brain.

The composition of the spinal fluid consequently reflects the metabolic and potential pathological processes in the brain tissue in a precise manner. For this reason, markers in the cerebrospinal fluid can provide early signals of Alzheimer's.

In analysing the cerebrospinal fluid, the scientists look for the proteins that form plaque in the brain in dementia cases.

Facts

Tormod Fladby heads the Neuro Clinic at the University of Oslo and Akershus University Hospital (Ahus). His research group, the Clinical Neuro-scientific Research Group (CNG), is participating in a new EU project, which is the first project under the EU Joint Programme - Neurodegenerative Disease Research (JPND).

"We are very familiar with a number of markers in the spinal fluid, and these can give us indications of early, incipient dementia. Other markers are in the testing stage," says Fladby.

Some of the markers that may be used in future diagnostics are in the blood.

Advanced images

Last but not least, advanced imaging of the brain must be done. The researchers at Akershus University Hospital (Ahus) use MRI (magnetic resonance imaging), PET (positron emission tomography) and SPECT (single photon emission computed tomography) scans.

MRI examination can tell us a lot about what goes on in the tissue, changes in the axons that conduct impulses away from a nerve cell, and changes in the nerve cells.

"We also want to start using a new type of PET technology: PiB PET. This is a molecular imaging technology where you can look at the molecular and biochemical processes that occur in the brain during amyloid beta deposition,” says Fladby.

The Oslo PET centre is in the process of installing PiB PET technology, but they still lack funds for scientific use of the technology in the project.

Other conditions must be excluded

But if the disease still cannot be treated today, what is the benefit of early detection to the patient?

"First of all, experiencing cognitive impairment may be a symptom of a variety of conditions," says Fladby.

Some of the conditions can be treated and even reversed, while there is no treatment for others as yet. For example normal pressure hydrocephalus, also called adult hydrocephalus.

This is a disease in which fluid accumulation in the brain creates dementia symptoms that can be treated by draining the cerebrospinal fluid from the brain into the abdominal cavity.

“We must therefore first examine whether the cognitive decline is caused by one of these conditions."

Mental preparation

If the patient turns out to have a dementia disease, an early diagnosis can provide the person with an opportunity to prepare for the changes to come.

"The patients included in our research − not to mention their families − want naturally enough to find out what's wrong," says Fladby. "They notice that something is not right with their brain, and want to find out why."

If the patient is diagnosed with dementia, it may make it easier to cope with the symptoms.

"I find that many patients are simply grateful to be able to get the facts about their condition," says Fladby.

"The knowledge allows them to adjust their lives to deal with the diagnosis. A dementia-related diagnosis often entails new priorities and lifestyle changes such as moving closer to one's family."

 
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