Dementia "Dementia – a chronic or persistent disorder of the mental processes marked by memory disorders, personality changes, impaired reasoning, etc. due to brain disease or injury" - Oxford Concise Dictionary Nearly 18 million people in the world suffer from dementia, the majority resulting from general brain deterioration with old age and thus affecting one in twenty of people over sixty five and one in five people over eighty1. However dementia can also be obtained congenitally or through severe injury allowing it to prevail in those of young age as well. The human brain, which many scientists believe to be the most complex organ in the universe, is composed of an incredibly intricate design with separate regions of the brain accounting for different characteristics. The cerebellum has been associated with coordination and movement, the olfactory bulb with smell, the hippocampus with memory processing etc. For this reason the list of brain diseases is vast and always growing. In diagnosing dementia a neurologist looks for features which would affect an individual's lifestyle such as memory difficulties and impaired reasoning. Straightforward tests such as instructing a patient to remember a set of cards can be used to discover whether he/she is a sufferer. More recently, Dr. Andrew Blackwell, Professor Sahakian and several colleagues of Cambridge University devised two simple tests which have been shown to be completely accurate in detecting dementia2. By combining the patient's age with two simple tests, physicians can now diagnose dementia earlier allowing ready treatment which can slow down the onset of neuro-degeneration. The causes of dementia are huge in number, spanning from the most common Alzheimer's disease to alcohol dementia. Since such a complex set of several systems is required to maintain the functions which are affected by dementia (e.g. memory and personality) an error in a single junction can result in massive adjustments to a person's abilities. One of the most commonly affected features of a person in dementia is memory. Although continuing evidence is helping us to understand the mechanisms of memory in the brain, there still remains much to be discovered. Memory's influence in shaping ones personality is enormous giving us our childhood memories as well as enhancing our chances of survival in a threatening situation. The arrangement of the brain in respect to memory is highly convoluted in that memory can be defined as so many different concepts. There is the notion of reminiscence of one's youth, ability to navigate around a familiar area, and even those memories which appeal to our senses; Smells can remind us of a place, sounds can help up recognise a voice, and even taste can cause to recall an occasion. To understand how causes of dementia affect our memory, one must first understand how memory is processed and stored in the brain. Biological foundation of memory Still today neurological researchers are trying to understand the details of memory however many studies, some rather tragic, have demonstrated the significance of certain regions of the brain in forming our memories, both in processing and storage. One such case involved a patient, H.M.3 (remains anonymous), who suffered from epileptic seizures regularly. Neurosurgeons removed his medial temporal lobes which included the amygdala and hippocampus. The fact that H.M. could no longer form memories implied that the hippocampus was vital in developing memories. H.M.'s long term memories were still intact and could be recalled by him clearly suggesting that although memories may be processed by the hippocampus, they are stored in a different area. The role of the hippocampus has since been confirmed by positron emission topography (PET) and functional magnetic resonance imaging (fMRI). These brain images measure increases in the rate of blood flow to an area. When performing an action which involves a certain region of the brain, the rate at which neurons fire in that area increases which consequently increases blood flow. Thus the imaging techniques have confirmed that when people are memorising new information, the hippocampus is active. However where are memories stored? The fact that memory can take many different forms e.g. recognition of a human, finding one's way round or nostalgic reminiscence suggests that several areas of the brain would be involved in memory retrieval. Actually this is in some ways true. In a rare disease known as Capgras syndrome the individual can see perfectly but when approached by his parents, he immediately claims they are impostors. Analysis of the patient's brain shows no problem with the hippocampus but instead damage to the neurons connecting the fusiform gyrus and amygdala. The fusiform gyrus is concerned with the process of identification of the object/person being looked at. Once recognised the impulse is sent to the amygdala which informs you emotionally of what you are looking at. Thus one recognises ones parents but feels no emotions towards them causing them to think that these could only possibly be frauds. Capgras syndrome reveals how important a role emotion can play in memory.3 A similar connection has recently been studied by Kim Dalton4 who was analysing the fusiform gyrus as the source of autism's characteristic eye avoidance. She was surprised to find that in fact the amygdala, being overactive in autistics, may be at the root of the disorder suggesting that an abundance of emotions is causing this avoidance. There is also evidence that the areas of the hippocampus are involved in memory retrieval, particularly the aspect of navigation. Studies in rats have shown that when placed in area of familiarity certain neurons in the hippocampus, called place cells, begin to fire. On examining epileptics, these same place cells have been found in the hippocampus of humans leading neurologists to believe that the hippocampus constitutes our ability to find new shortcuts as well as steer ourselves on a return course5. However the notion of memories and learning has primarily been attributed to the synapses, gaps between nerve cells where chemicals known as neurotransmitters diffuse across to maintain a nerve impulse. The nerve cell which sends the impulse is known as the presynaptic cell and the receiving cell, the postsynaptic cell. During the transfer of an impulse, calcium channels in the presynaptic cell cause an influx of calcium ions. These ions encourage vesicles containing neurotransmitters to fuse with the synaptic membrane thus releasing the chemicals into the synapse. When the neurotransmitters reach the postsynaptic cell, receptors bind to the chemicals stimulating a release or uptake of ions.6 This causes a change in the potential across the membrane which can be short term or long term. In 1949 Donald Hebb, a Canadian psychologist, published The Organisation of the Brain in which he proposed the idea of synaptic plasticity. This theory states: "Let us assume that the persistence or repetition of a reverberatory activity (or "trace") tends to induce lasting cellular changes that add to its stability.… When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased."7 Evidence since Hebb has shown support of his theory and contributed to its understanding. However the mechanism of a neuron increasing its efficient involves complex chemistry. Eric Kandel, distinguished neurologist and Nobel laureate, performed brain studies on marine snails which shed light on the formation of both short-term and long-term memory. In short term memory the stimulus is weak generating a short term change in trans-membrane potential and thus causing little change in synaptic function. In long term memory the strong stimulus generates a long term change in the potential across the membrane. These long term changes cause second messenger neurotransmitter to be released into the nerve cell's nucleus instigating protein synthesis. This production of messenger RNA induces changes in the structure of the neuron which make it more efficient hence synaptic plasticity and the storage of long-term memories. Kandel's research on memory also showed that the presence of phosphate groups facilitated the passing of calcium and other ions through the synapse in a process known as phosphorylation.8 Common Forms of Dementia Alzheimer's disease Around 55% of all people with dementia can be accounted as having Alzheimer's disease. First described by German psychiatrist Alois Alzheimer in 1906, the disease was initially thought to have affected only younger people and was often titled presenile dementia. This perhaps resulted from the belief that memory loss in the older patients was just a result of senility however we now know that early-onset Alzheimer's is very rare affecting less than 10% of Alzheimer's sufferers in the United States.9 The warning signs of Alzheimer's begin with mild difficulties in remembering new and straightforward information such as where one left one's glasses. Gradually the symptoms begin to worsen as the sufferer can no longer recall recent events or even what day of the week or month it is. The disease culminates into the patient becoming severely debilitated, no longer able to perform simple tasks such as eating. In the early studies of the disease it was found that all patients suffered from a deficiency in several neurotransmitters – serotonin, norepinephrine somatostatin and especially acetylcholine. Acetylcholine is an essential neurotransmitter which operates principally in the central nervous system and parasympathetic nervous system. This theory of acetylcholine insufficiency is known as the "cholinergic hypothesis" and gained strong popularity as the disease was initially studied.