Brought to neurological evaluation by her brother


"A 58-year-old woman was brought to neurological evaluation by her brother because of a 3 year history of memory impairment. The brother had begun to notice gradually worsening memory impairment and difficulty finding words, but the patient became angry at the suggestion that she may have a progressive impairment. Others had noted decline in housekeeping and financial affairs, but she had no complaints. Elevated arterial blood pressure was documented on several occasions, but she never took medication. She was a well-groomed woman who was alert and friendly. General and elemental neurological exams were normal. Her speech was highly anomic and paraphasic, with a tendency to use vague referents such as "things" and "stuff". She was able to provide her name, but when asked about her current age, she said: "I don't know . . ., about 8 I think." She incorrectly stated her birth month, but then became aware of this. Given three choices, she was able to give the correct month. She was unable to give the year of her birth, the current year, or the name of the current U.S. President. On formal testing, she scored well below average in all cognitive domains. These tests included the Wechsler Memory scale, the Wechsler Adult Intelligence Scale, digit span and similarities subtests, the Boston Naming Test, the CERAD Word List Memory Test, the CERAD Visuo-spatial Construction, the Cross Circle Tests, the California Proverb Test, and the Graphomotor Alternation Test. She tended to perseverate both verbal and motor responses. The conclusion of the evaluation was that she met research criteria for "probable" Alzheimer's disease, that she required complete supervision around the clock to insure her safety, and that she would probably benefit from social stimulation provided by a group living situation." (1)

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Alzheimer's disease is a degenerative disease in which the brain's ability to function slowly and progressively deteriorates. It is defined by dementia, a gradual loss of memory and judgement. Alzheimer's disease was first recognized by a German neuropathologist and psychiatrist in 1906. Even though there are excessive amounts of ongoing research regarding the disease, a cure is still yet to be found.

There are two types of Alzheimer's disease. The more predominant form of the disease is late-onset, which normally occurs in those 65-years of age or above. The less common is early-onset, which occurs in those younger than the age of 65. The incurable, terminal disease affects 26.6 million people worldwide and is predicted to affect 1 in 85 people by the year 2050. (2)

With Alzheimer's disease being a multifactorial disease, it has become difficult to depict it with any one, main individual cause. Reseach indicates that the disease is associated with plaques and tangles in the brain. Genetic-based Alzheimer's is said to be caused by certain gene mutations that are passed down from one generation to the next. The particular genes associated with Alzheimer's are APP, PSE1, and PSE2. When any one of these genes undergo a mutation, large amounts of a toxic protein fragment called amyloid beta peptide ar produced in the brain. When this hormone accumulates in the brain it begins to form clumps known as amyloid plaques. Since the accumulation is accompanied by a reduction of neuronal nicotinic receptors in the brain, nerve cells that are crucial to memory function begin to lyse, leading to the progressive decrease in memory, or eventual dementia. (3)

Further research associates high concentrations of a plasma protein, clusterin, with an increased prevalence of Alzheimer's disease. This genetically linked information is most common in early-onset of Alzheimer's. (3)

This week however, Nature Genetics printed two scientific studies that linked five new genes (MS4A, CD2AP, CD33, BIN1 and ABCA7 (6)) that are now known to be involved in causing late-onset Alzheimer's. Even though each gene only merely increases the risk by 10-15%, it is through all the combined genes together that studies linking high cholesterol, brain inflammation, and cell transport systems with Alzheimer's disease are now being confirmed. These findings present new initiatives for targeting the mysterious disease pertaining to a pharmacological approach, behavioral and environmental adaptations needed, and other potential treatment factors. (4) The discovery of these genes is not as significant as was the discovery made in 1995, uncovering the APOE-e4 allele, which increases the chance of developing Alzheimer's by 400-1000% depending on who you inherit the gene from, both parents or a single parent. This gene leads to an increase in cholesterol and the accumulation of plaques previously mentioned. Publishers of the two studies include two different groups that are working together to uncover further research- one group from America and one from Europe, with professors, graduates, and scientists coming from reknowned universities as Harvard, Yale, and the University of Pennsylvania. With five new genes contributing to Alzheimer's uncovered in the past three years and announced this week, they both hope to combine their efforts to uncover further research in hopes of maybe even leading to prevention. (5)

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Early-onset Alzheimer's disease follows an autosomal dominant pattern, meaning the contribution of one gene or allele is sufficient to inherit the disease. As we know, aggregation of beta amyloid peptides, amyloid fibrils (the protein's toxic form), leads to a disruption in the cell's calcium ion homeostasis, causing apoptosis. This buildup occurs in mitochondria of Alzheimer'saffected brains, also leading to the inhibition of certain enzyme regulations and the utilization and reuptake of glucose by neurons, which may be the predetermining factor for why diabetes patients are at an increased chance for Alzheimer's disease. Other health factors, such as strokes and serveral more neurologically evoked cardiovascular have been identified to be precursors for Alzheimer's as well. It is also said to be caused be decreased firing of the neurotransmitter, acetylcholine. The amyloid hypothesis is linked with the gene for the amyloid beta precursor protein (APP) on chromosome 21, which makes a direct correlation between people with Trisomy 21 (Down's Syndrome) and their inheritance of early-onset Alzheimer's by the approximal age of 40. Another study associates age-related myein breakdown in the brain with the disease. Demyelination leads to a disruption in the number of axons being relayed, leading to a loss of neurons. The amount of iron released during the myelin breakdown is hypothesized to cause further damage to the brain.

Alzheimer's disease is characterized by four separate stages that a patient may present symptoms of- ranging from the mildest, beginning phase, Pre-dementia, and progressively worsening to the Early and Moderate stages, then eventually ending with the most severe of them all, the Advanced stage. Pre-dementia is largely characterized by beginning stages of memory loss, which in most cases means remembering recently learned information or acquiring new information. Symptoms are depicted in areas or attentiveness, flexibility, planning, abstract thinking, or semantic memory, which is the memory of certain meanings and concept relationships. The Early phase of Alzheimer's is more characterized with difficulties with language, executive functions, perception, execution of physical movements, and further memory problems. Older memories tend to stay intact during this period, while newly formed memories are the ones at risk. Language is characterized by less vocabulary, redundant phrases or questions. The typical Alzheimer's patient at this stage is still able to communicate their basic necessities, however, may find it difficult to remember many things and stay on topic during conversations. During the Moderate phase, the Alzheimer's patient slowly becomes reluctant and more dependant on others, as they may be unable to perform the most common activities of daily living. These people have a hard time with vocabulary, as they may forget the meaning of words and use them incorrectly when speaking; they portray a loss in reading and writing skills, and showcase much less coordination, increasing the loss of balance. People from this phase may be easily irritated, angered, aggressive, and very emotional. They may start to become delusional and with even long-term memory lapses. Patients may present with memory so off that they think their son is their brother, since their memory is deteriorating from the most recent activities performed and gradually decreasing day by day. The inevitable, final stage of Alzheimer's is the most dangerous period for the individual, as they slowly lose complete sight and direction of who they are or what meaning their life has. These patients may not be able to stand on their own because the part of their brain that controls balance is no longer intact with communicating neuronal growth, Muscle mass and mobility deteriorate to the point where they are bedridden, and they lose the ability to feed themselves. These patients speak in single words, ultimately losing their entire speech. Random outbursts of emotion, such as unexplained laughter or crying may occur, not necessarily relating to the surounding environment. Their ability to think, speak, move, or comprehend slowly amounts to nothing and they become 100% dependent on a caregiver. (8)

Although there isn't definitive testing for Alzheimer's disease, and especially because it may be confused for other, minor dementia-related health problems, the diagnosis of someone with Alzheimer's may not be concluded until later periods of the disease. This is seen particularly in patients depicting early-onset, as there may be numerous factors as to why they begin to portray a memory deficit. When diagnosing it is very important to obtain a family history to search for certain genes or health factors that may be present in the patient's lineage, from whom they may have inherited from. A physical exam and a Mini-Mental State Exam should also be performed. The latter tests the patient''s basic problem-solving skills, attention span, counting skills, and memory. Furthermore, a chest X-ray, laboratory blood work, a Computed Toomography, or CT scan, and a Magnetic Resonance Imaging, or MRI, should also be ordered. A CT scan will pick up cases where there is a reduction in the size of the brain, otherwise known as atrophy. A MRI is beneficial in ruling out other causes of dementia, such as tumors or strokes. An Electroencephalography, or EEG, may also be done to measure brain function by analyzing the elctrical activity generated by the brain. An electrocardiogram, or ECG, will also be read to record the heart's electrical activity, rate and rhythm. It also can show decreased blood flow, enlargement of the heart, or the presence of damage due to current or past heart attack. One of the main forms of testing that may not so much rule out but instead, help diagnose one with Alzheimer's disease is specific Neurological Testing. This form of test is used when te patient is having serious problems with memory, concentration, remembering words and names, understanding language, perception, and a variety of other symptoms. The tests that may show the most amount of evidence leading to the appearance of Alzheimer's disease in the patient is the Positrom Emission Tomography, or PET Scan and the Magnetic Resonance Spectroscopy Imaging, or MRSI. PET scanning is a three-dmensional imaging technique that allows a physician to examine the heart, brain, or other internal organ. Unline X-rays, CT scans, and MRIs, PET scans can depict how the organs are actually functioning, as opposed to just their body structure. This testing is the primary test for differentiating Alzheimer's with other disease-causing dementias. MRSI is a test that allows the doctor to observe particular substances throughout the brain without the use of radioactive materials. This test concentrates on the changes caused in the brain by the disease- showcasing the areas most affected, leading to determining the next areas of loss in the individuals themselves. Periodic testing using these mechanisms may show the progression of brain matter deterioration as the patient's health worsens overtime. (7)

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While there is no cure for Alzheimer's disease, nor a mechanism to follow which halts it's progression, there are medicines available, as well as other means of providing treatment. If Alzheimer's disease is diagnosed earlier, treatment may enable people to carry out their daily life routines and live independantly for a prolonged period of time. The pharmocological aspect of treating Alzheimer's helps with the disease's symptoms and other troublesome characteristics of the disease, such as, depression, sleeplessness, and behavioral problems like agitation and aggression. Medicinal drugs used to aid patients in coping with Alzheimer's are: cholinesterase inhibitors- Aricept, Cognex, Exelon, and Razadyne. Aricept is the only treatment approved by the FDA for all stages of Alzheimer's disease: mild, moderate, and severe. Namenda is another drug that varies in it's mechanism of action. It targets the neurotransmitter, glutamate, which is responsible for memory and learning. By increasing the chances of it firing, Namenda's goal is to delay the loss of these neurons. (9)

Future planning, therapy, and medical/social involvement can ease the burden on both, patients and family members. Exercise, good nutrition, activities, social interaction, and a calm, structured environment are very important for the beneficial effects that they bring to the patient and family members. A strong support system, comprising of family and friends, while working closely with a specialized physician is the key to aiding patients through the course of this horrific, brain degenerating disease. (10)