On 25 November 1901, German psychiatrist Alois Alzheimer first examine a patient, Auguste D., aged 51, admitted to ‘Hospital for mentally ill and epileptic “in Frankfurt for progressive cognitive impairment, hallucinations, delusions and degradation social personality. Alzheimer notes first a vague diagnosis “forgotten disease” (often Krankheit Vergessens). Disease progression is monitored for five years after the death of patients following an infection, the brain obtained from autopsy of Alzheimer’s is thoroughly examined, revealing previously unknown characteristic changes. The case is presented on November 3, 1906 at the 37th Conference of the South-West German Psychiatrists held in Tübingen and published in professional journals “Allgemeine Zeitschrift für Psychiatrie und Medizin Psychisch-Gerichtliche” (1907, vol 64, pp. 146 -48) under the title Eine der eigenartige Erkrankung Hirnrinde (“A particular bark disease brain”).

Incidence and onset

Alzheimer disease is the most common form of dementia in older people and accounts for half of all cases of dementia. European countries is estimated that in people aged 65 years is that the frequency of Alzheimer’s disease. 2-3% at the age of 70 years 3% 6% 75 years and 25-40% over 85 years. In a recent study called “PAQUID” made in France, it was found that 17.8% of people over 75 years are affected by Alzheimer’s or related form of dementia. According to statistics from Romania, the incidence of mental disorders increased from 605.2 persons per 100,000 inhabitants in 1975 to 883.3 persons / 100,000 inhabitants in 1993, without data on cases of dementia.In case of early onset before age 65 – as in Alzheimer’s princeps – using the term “dementia presenilă” cases occurring late in people aged over 70 years, corresponding to the older notion ”senile dementia”.

Clinical

Most characteristic manifestation of the disease is progressive dementia with character.Memory loss is often the first sign of Alzheimer’s worrying.

Cognitive symptoms

* Memory impairment: difficulty remembering previously learned information and inability to gain new information. First to be lost are recent, while old memories can be preserved.
* Speech disorders: patient no longer find the words, even simple concepts.
* Inability to perform various motor activities coordinated: the patient “not know” how to dress appropriately, as the key to unlock the door, etc..
* Failure to recognize, identify and name common objects.
* Organization of impaired daily activities, inability to make decisions.
* Problems with abstract thinking, impaired calculation, temporal and spatial disorientation, loss of initiative.
* False recognition: the first difficulty in recognizing familiar fizionimiilor followed by misidentification, which can cause anxiety.These symptoms are characterized by a gradual onset, the patient developed some strategies to conceal difficulties for some time remains a “facade” misleading, but decline progressively worsen.

Non-cognitive symptoms

* Agitation and physical or verbal aggression.
* Psychotic disorders: hallucinations, usually visual delusions (of persecution, jealousy, abandonment, etc.)..
* Affective mood disorders: mainly depression and anxiety, euphoria rarely exaggerated.
* Disorders of eating behavior: reduction or increase in appetite exaggerated, unkempt food, ingestion of non-food substances.
* Sexual disinhibition: comments on sexual themes, obscene gestures, sexual aggression less often.
* Urinary incontinence and faecal physiological needs in inappropriate places or in the presence of others.The brain of a patient with Alzheimer’s disease: severe cortical atrophy, more pronounced in frontal regions, parietal and temporal

Morphological changes in the brain (pathological anatomy)

The macroscopic examination (naked eye) shows a sharp decline in brain volume due to atrophy of the cortex (cortical atrophy) with decreasing circumvoluţiilor brain (brain folds), predominantly in frontal regions, parietal and temporal broadening of the convolution ditches, tanks brain and brain ventricles (external and internal hydrocephalus).Histopathology (microscopic) highlights, in particular by using a special technique for silver impregnation staining, lesions characteristic of Alzheimer’s seen already described:* Plates visible tracks among nerve cells (neurons) in the brain. Track plates contain an accumulation of beta-amyloid, which is a fragment of a protein that the body normally produces (the amyloid precursor protein – beta-APP). If a healthy person, these protein fragments are degraded and removed, they accumulate in Alzheimer’s disease in presynaptic terminals of neurons especially to form insoluble plaques and thus preventing nerve transmission from one neuron to another.Neurofibrillary degeneration is * formation within neurons of dense bundles of fibers arranged like balls, consisting essentially of a protein called you, which normally is included in an intracellular structure called microfuge. Microtubules play an important role in transporting nutrient substances within the neuron. In Alzheimer’s disease, abnormal tau proteins and microtubules are affected, and neurons can not function normally.These changes cause the death of a progressively increasing number of large neurons, particularly in structures important for cognitive activities: bark front, hippocampus, basal nucleus of Meynert’s, etc., so the brain can no longer perform normal functions .Causes and mechanisms of production (etiology and pathogenesis)
EtiologyIt is not known for sure because that causes Alzheimer’s disease, but there may be several causes contributing to the disease.

* Risk factors- Advanced age is the most important risk factor, but there is no evidence that Alzheimer’s disease would be caused by biological aging process.
- Harmful factors for cardiovascular system: diabetes, hypertension, high cholesterol level, smoking (the assumption that nicotine may be protective against Alzheimer’s disease proved unfounded) [Nicotine is one of the causes of disease].
- High level of homocysteine ​​in the blood, associated with low vitamin B12 and folic acid.
- Exposure to light metals (eg. Deodorants with aluminum) assumption is not universally accepted. Aluminium, with neurotoxic effects, often found in large quantities in the brains of deceased patients with Alzheimer’s dementia, but can not prove a causal relationship.
- Repeated severe head trauma.
- Some bacteria (chlamydia) and some viruses (slow-virus) would favor the formation of plate tracks.*

Genetic factors-

There are rare inherited cases caused by the presence of a dominant gene in some families. It is estimated that people with a first degree relative suffering from Alzheimer’s disease is absolutely theoretical risk of 26% to 45%. Mutations in presenilin 1 (PS1) on chromosome 14 and presenilin 2 (PS2) on chromosome 1 leads to a very aggressive form of disease in familial cases. Presenilinele were identified as essential components in the proteolytic process by which beta-amyloid is produced by fragmentation of APP (amyloid precursor protein) linked to chromosome 21.
- Alzheimer’s disease is linked to chromosomes 1, 14 and 21 (trisomy 21 is due to Down syndrome, also known as Mongolian idiocy), but there may be other links chromosome.APOE genotype ipsilon 4, linked to chromosome 19, protein involved in cholesterol transport and is involved in neuronal repair processes, is considered predisposing factor for sporadic cases of Alzheimer’s disease.
- Thomas Arendt et al. Institute “Paul-Flechsig für Hirnforschung” recently found Leipzig (2010) that already exist in childhood changes in brain, which would indicate the likelihood of Alzheimer’s disease later. Brains of these individuals contains an increased number of cells hiperploide (cells with multiple pairs of chromosomes in different combinations), which would contribute to brain cell death in patients with Alzheimer’s Born to.

PathogenesisMolecular Biology

There are three major hypotheses to explain the mechanism of developing Alzheimer’s disease.

* Cholinergic hypothesis. In terms of biochemical disorder was a brain neurotransmitter cholinergic system, namely a decrease in the synthesis of the neurotransmitter acetylcholine by decreasing the enzyme choline-acetilază, indispensable in this process of synthesis. This deficiency is found in bands just interested in brain cognitive functions such as Meynert’s basal nucleus. Based on this hypothesis was introduced cholinesterase inhibitor therapy (enzyme that cleaves acetylcholine) to maintain such an increased activity of cholinergic neurotransmitter inter-deficient neural regions.
* Alteration and accumulation of protein hypothesis “your”. Neurofibrillary pathology balls inside neurons are composed of protein aggregates “your” due process of hiperfosforilare. It is not clear whether this process has a causal role in the disease or secondary in nature.
* Accumulation of beta-amyloid hypothesis. Beta-amyloid is a peptide resulting from a precursor protein, amyloid-precursor-protein (APP), inserted on the cell membrane. Beta-amyloid oligomer in insoluble form, is cytotoxic and alters the homeostasis of calcium ions and thereby induces the apoptosis (programmed cell death). It should be noted that ApoE4, genetic risk factor for developing Alzheimer’s major family promotes excess production of beta-amyloid, before the first symptoms of disease. Blocking production of beta-amyloid is an objective of the research on pathogenic disease therapy.The main objection brought hypothesis storage protein ß-amyloid fibrils (SSA) results from the fact that it could not find a correlation between the extent of loading with “plates” of amyloid and dementia severity. Recent observations have shown a progressive deterioration of synapses in the regions affected by the primary disease. Current research results suggest that the mechanism would be based apoptoic loss of storage connection between SST and the phenomenon of proteolysis of the substance “your” process still highlighted in the early stages of the disease.
[Edit] Means of investigationThe only sure diagnosis is Alzheimer’s disease pathology post-mortem examination of brain lesions characteristic of the disease highlighting. A thorough history, followed by an exploration neuroradiologice neuropsychological tests correlated with outcome, all of which may establish the diagnosis with a probability of 85-90%. Essentially, the diagnosis of Alzheimer’s disease is a diagnosis of exclusion, to an elderly person presenting with signs of progressive dementia, after other possible causes have been eliminated.
[Edit] neuro-psychological examinationsIs indicated as being present during the examination and a family member or someone close to the examination, which may give details of the daily behavior of the patient, his memory and the personality changes. If a suspected dementia, it is recommended that a standardized examination, such as the “Mini Mental State Examination” – MMSE (there is a Romanian version), which is relatively simple questions, which examines memory, attention, thinking abstract, the ability to name objects, spatial orientation and other functions vizuo-cognitive. Maximum score is 30 points. Already in the case of performance under 28 points because of low difficulty of the questionnaire, may be suspected dementia. This test allows determining the degree of mental deterioration. It uses the “clock test” examined person is asked to draw a clock dial with the numbers 1 to 12, asking him to put the schedule and the minute hand at a specific time. Pacineţii with Alzheimer’s disease have difficulty in performing this test immense, even in an early stage of disease.

Laboratory

There is no laboratory test that indicates the event of Alzheimer’s disease. Laboratory tests are performed to exclude other possible causes of dementia. Like symptoms may occur in diseases accompanied by mineral imbalances (sodium, potassium, calcium), liver disease, abnormal thyroid hormone levels, nutritional deficiency disorders of folate or vitamin B12. Treating these deficiencies can cause a slowdown or even decline mentally reversibility. The laboratory tests can detect some infectious causes of progressive dementia (test for syphilis, tests to detect “human immunodeficiency virus” – HIV).Exams neuroradiologice

* Computed tomography of the brain

This examination may reveal a reduction in the volume of the brain, especially the cerebral cortex (cortical atrophy), with a specific topographic distribution. The result is not specific.

* Magnetic Resonance Imaging

Nuclear magnetic resonance has a higher resolving power. There is manifest cortical atrophy and enlargement of fluid space (ventricle and cisterns).

* Photon emission computed tomography – SPECT

This examination, which highlights regional differences in blood perfusion of the brain, may allows the differentiation between vascular dementia (dementia with multiple infarcts mini-strokes) and a degenerative (Alzheimer type).

* Positron emission tomography – PETBy performing a positron emission tomography (PET) using glucose molecules labeled with Fluorine-18 (radioactive isotope), there is a reduction in glucose use (the only nutrient of the brain), a so-called “glucose hipometabolism” particularly in the frontal and parietal regions compared with normal individuals.Evolution and prognosisAlzheimer’s disease progresses over time, but rapid progression varies from person to person. Some people may have minimal symptoms until late stages of the disease, others lose the ability to perform daily activities already in an early stage of the disease. There is so far the possibility of healing. A person affected by Alzheimer’s disease live on average 8-10 years at the first symptoms occur unless other intercurrent causes of death.The disease is conventionally divided into three phases:The initial phase
- Loss of orientation
- Loss of ability to initiate certain activities
- New and unfamiliar situations mismatch
- Delayed reactions and slowed storage capacity
- Disorders of law, wrong decisions
- Difficulties in the use of money
- Affective mood disorders, irritability, restlessness
Intermediate phase
- Problems in recognizing familiar people
- Difficulty in reading, writing and calculation
- Difficulties in dressing yourself
- Problems of thinking logically
- Enhanced mood, hostility towards persons close
- Loss of time orientation
- Unjustified suspicion, ideas of persecution, jealousy, stalking
- The need for constant supervision and care
Advanced stage (late)
- Patients do not remember that you must wash, dress, go to the toilet
- Lose the ability to chew food, to swallow, forget that they have already eaten and pretend to be serving meals again
- Difficulties in maintaining echlibrului, difficulty walking
- Headedness, sometimes agitated, especially at night
- Loss of ability to communicate in words
- Loss of bowel or bladder control (incontinence for urine and faeces)Prevention and treatment
Means of prevention (prophylaxis)So far no reliable means of preventing Alzheimer’s type dementia. They are considering some measures to reduce the risk of disease or delay its development.* It seems that maintaining a continuous intellectual activity would reduce the risk of disease, but there is no proof in this regard. However, certain activities like reading a book’s regular newspaper and magazines or, solving crosswords, going to the theater or concerts, participation in social activities are recommended for people after retirement.Eyes long, passive television broadcasts would be rather detrimental effect.
* We recommend sufficient movement, rational nutrition with high amounts of vegetables and fruits rich in vitamin C in combination with high doses of vitamin E (antioxidant effect), fat with high percentage of unsaturated fatty acids, smoking cessation etc.
* Certain medications such as nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen, naproxen, aspirin) and drugs used to lower serum cholesterol levels (statins) may decrease the risk of Alzheimer’s disease, but still no randomized studies demonstrating peremptory in these observations. But must take into account the possibility of adverse effects of these drugs.
* To date (2006), only maintaining normal blood pressure to demonstrate value – following strict scientific criteria studies – a significant decrease (up to 50%) risk of disease (SYST-EUR study).TreatmentAlthough there is still an effective treatment to cure Alzheimer’s, some means must be used to improve the quality of life for patients and keep them as far as possible work in the family and society.Symptomatic treatments
We recommend changing behavior and emotional mood (depression) of patients with psychotropic medications to relieve anxiety, aggression or agitation. Strong acting drugs (neuroleptics, long acting benzodiazepines) are to be avoided but, because of adverse effects or paradoxical.
Agents inhibiting acetilcholinesterazei
In the first phase of the disease, it is recommended acetilcholinesterază enzyme inhibitor drugs. They inhibit the degradation acetilcholinei, neurotransmitter at the synapses of certain neurons in the brain (See: Pathogenesis). Currently using the following preparations (trade name in brackets):* Donepezil hydrochloride (Aricept)
* Rivastigmine (Exelon)
* Galantamine (Reminyl, Nivalin, Razadyne)Although acetilcholinesterazei inhibitors may diminish the intensity of the symptoms temporarily, they do not influence the evolution of disease progression. These preparations are very expensive and have a range of adverse effects without jeopardized.Preparations of the NMDA antagonist
Existence of glutamatergic neuronal excitotoxicity system in patients with Alzheimer’s disease led to the introduction of treatment with the neuronal NMDA receptor antagonists (N-methyl-D-aspartate), as Memantine (Axura, Ebixa). However, treatment results are contradictory.
Therapeutic vaccine
Using a vaccine (active immunotherapy) is expected to treat patients already diagnosed and not prophylactically. We started with the idea of ​​involvement of the immune system to recognize and combat, by stimulating production of specific antibodies, deposits of beta-amyloid with antigenic properties. First results are promising, some patients (6%) developed severe encephalitis but a process. It is currently under study with a vaccine type less toxic Aβ.
Other developing treatments
-Xaliproden – in studies in experimental models in mice reduces the neurodegeneration.
-Tramiprosat (3APS or Alzhemed) is a GAG-mimetic beta-amyloid that maintains solubility to prevent toxic buildup of plaque.
-R-flurbiprofen (MPC-7869) is a gamma-secretase enzyme modulator, induces reduction of toxic beta-amyloid production in favor of shorter polypeptides.Alternative Treatments
Under the generic name assigned Antidementiva pharmacopoeia prepared a series of extracts from plants (eg extract of Ginkgo-biloba funze of) or chemical synthesis (antagonist of calcium ion, Piracetam, Pyritinol-hydrochloric Nicergolin etc.) . Their effectiveness, however, could not be proven.Social problemsAlzheimer’s disease has become a central public health issue, especially in industrialized countries, where life expectancy has increased considerably.
Caring for patients with Alzheimer’s diseaseMost patients with Alzheimer’s disease are cared family at home, which is often a debilitating situation both physically and emotionally. Caring for a sick person can be but a positive experience, in order to maintain the patient’s remaining capacity and safety. Even in the early stages of the disease is necessary to establish a trusteeship under the law, to solve relationship official order or financial.Indication placed in a home
Not always possible home care. As the disease progresses, develops behavioral problems and other health problems occur that can not be solved at home. Unfortunately, in Romania there are not enough institutions in number and, in particular, the technical equipment and qualified personnel to take over the social task properly. And from this point of view, a decision on admission into a home is a difficult and a great moral responsibility with Alzheimer’s disease.