What happens to the brain in Dementia?


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To inderstand what happens to the brain in dementia we need to look at the brain structure in someone who clearly suffered from this illness. This is possible only after death of the person. That is the method that helped medicine to discover all the secrets behind illnesses and how they affect the body. From the early rise of modern medicine, dissection of the deceased has provided a wealth of knowledge that helped to devise treatments for the diseased. This is the science of Pathology, the study of the causes of disease and how illness affect the body organs.

Pathology examine the tissues and organs by the naked eye or through the microscope. The diseased tissue is examined under the microscope to see the unhealthy cells. As the tissue of the brain is usually white or semitransparent, various stains are applied to the brain tissue to destiguish its various elements. The brain substance is sliced, by a tool called microtome, into very thin layers to examine under the microscope after staining them with a specific dye.

Neurofibrillary tangles

Neurofibrillary Tangles The key features seen in dementia brain under the microscope is the presence of deposits of a strange protein outside the cells (amyloid) in the form of what is known as neuritic plaques. The second feature is the jumbling together of filaments inside the brain cells into lumps called neurofibriallary tangles. The density of plaques correspond to the severity of the Alzheimer's disease.

Plaques accumulate in frontal, temporal and parietal lobes: the areas of cognitive executive functions. With the accumulation of plaques there is reduction of the number of brain cells and their connections.

Amyloid Changes in Alzheimer's Disease

An amyloid is a deposit of fragments found in many organs. It is derived from breakdown of a larger precursor protein. When the amyloid deposition causes disease, this is often due to a genetic changes. The abnormal protein (tau protein) is broken down causing abnormal deposits. This is seen in familial Alzheimer's disease. Change in the tau protein occurs without a hereditary influence occaisonally in a number of cases of Alzheimer Disease.

Neurofibillary tangles are also formed of amyloid, however, the term amyloid is retained for deposits in plaques outside the cells and in blood vessels. Neurofibillary tangles describe the protein deposits inside the neurons which are, nevertheless, an amyloid. Amyloid deposits are also found in normal old age, and some other neurological conditions. In Down's syndrome, they are found in the brain of persons showing this form of learning disability, which ends in dementia by the age of 35.

A similar kind of plaques are found in diseases of the brain caused by a specific infectious agent. This is not a living organism, it is a simple protein. The prion protein may be transferred by eating the brains of a diseased animal. It causes plaque like deposits in the nervous system that damage the nerve cells. These are Scrapie-type plaques that may be slightly different from Alzheimer Disease senile plaques. They are found in what is known as spongiform encephalopathies or prion diseases.

One of those prion diseases is Creuttfeldt-Jakob disease (CJD) and Kuru. Kuru was found among aboriginal tribes in Papua New Guinea. Those tribes had a traditional funeral ceremony of eating the brains of their deceased ancestors to ingest their souls. An epidemic of Mad Cow Disease spread in Britain during 1900s in cattle fed meat-and-bone meal of other animals. It is known as Bovine spongiform encephalopathy (BSE) and the brains of cattle infected by the prion protein did show scrapie-like plaque and sponge-like picture under the microscope.

Pathology of Alzheimer's Disease

How the brain appears by the naked eye

There is often, but not always, a low brain weight. The loss of brain weight is more prominent in the brain hemispheres rather than the brainstem and cerebellum. The fissures between brain lobes are wider than usual and the area between them are narrower. both sides are affected equally, though the inside of the hemisphreres are more shrunk. There are two big cavities inside the two hemispheres which are known as ventricles; they are larger than normal.

Under the microscope, there are deposits inside and outside the brain cells. Outside the cells, neuritic plaques of amyloid are widely spread around, surrounded by special defense brain cells, which usually try to remove dead or damaged tissues and clean the area.

Inside the diseased cells, the fine filaments which make the cell structure are lumped and twisted together into neurofibrillary tangles. These are more often seen on the inside of the temporal lobe of the brain hemispheres: an area of the brain important for long-term memory formation and integration of hearing and visual information.

In the hippocampus, an area which control the consolidation of new memories, shows abnormal needle shaped bodies and vesicles inside their cells.

These changes cause the brain cells to die. Under the microscope, fewer nerve cells are seen, in particular in the outer layers of the brain hemispheres. Amyloid deposits are also seen in the walls of nlood vessels of the brain and its coverings.

In the normal ageing process of the brain we may see similar picture, although it is by far much less in extent and degree.

How the Alzheimer's Brain appears in the Brain Scan

Computerised scan (CT) or Magnetic Resonance Imaging (MRI) are a routine examination for the evaluation of suspected cases of dementia.

Another scanning method of the brain is Positron emission tomography or (PET) scans. These machines detect glucose use in the brain. The brain's sole source of nutrition is glucose in normal circumstances (in starvation the brain uses ketone bodies from fat cells as source of energy. The pattern of glucose use by a patient's brain seen in a PET scan differentiates Alzheimer's type dementia from other dementias , even before the diagnosis can be confirmed clinically. This scan is very expensive and is used in research not as a routine test.

In a PET scan, deficits of psychological functions are seen as areas of low energy consumption, in particular in the parietal and temporal regions of the brain. It may be more prominent on one side of the brain than the other. For example, Language functions are mainly focused in the left half of the brain (Broca's area), and a dementia patient with more damage on the right side than the left may show little difficulty in use of language. On the other hand, the left brain does all the functions related to analysis, logical, mathematical thinking, cause-effect relations and scientific thinking.

The right side of the brain control soft functions such as appreciation of music, art, recoginition of spatial relations, memory patterns of visual, tactile or spatial. Damage to these areas makes the person unable to recognize the face of other people, or to appreciate music.

PET scanning, when required, may be used for early detection of Alzhiemer's disease.

Another scanning technique is SPECT (single photon emission computed tomography) a scan which measures cerebral blood flow. It show the rate of blood diffusion into the brain areas in Alzheimer's disease, but it has poor outcome compared with PET.

PET (positron emission tomography) study of glucose metabolism in Alzheimer's disease illustrated the characteristic metabolic deficits of Alzheimer's in the parietal and temporal lobes. Over time, the metabolic deficit spreads throughout areas of the cortex, sparing the subcortical structures, as well as the primary sensory areas, such as visual and motor areas. At the late stage of disease, metabolic function of the brain in Alzheimer's disease is similar to that of the newborn baby, which corresponds to the similar behavior and functional capacity of those two individuals.