Question

• Describe alzheimer's disorder as well as associated alterations. Explain the pathophysiology of the alterations, including changes that occur in at least two body systems.
• Explain how genetics, gender, ethnicity, age, and behavior might impact the pathophysiology of the alterations you identified, as well as diagnosis and treatment of your selected disorder.
• Construct a mind map for alzheimer's disorder. Include the epidemiology, pathophysiology of alterations, risk factors, and clinical presentation, as well as the diagnosis and treatment of the disorder.

Answer 1

ALZHEIMER'S DISORDER

Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate) and die. Alzheimer's disease is the most common cause of dementia, a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently

The early signs of the disease may be forgetting recent events or conversations. As the disease progresses, a person with Alzheimer's disease will develop severe memory impairment and lose the ability to carry out everyday tasks.

Current Alzheimer's disease medications may temporarily improve symptoms or slow the rate of decline. These treatments can sometimes help people with Alzheimer's disease maximize function and maintain independence for a time. Different programs and services can help support people with Alzheimer's disease and their caregivers

PATHOPHYSIOLOGY :

AD's core neuropathologic findings include extracellular amyloid plaques, intracellular NFTs, synaptic deterioration, and neuronal death.1 Granulovacuolar degeneration in the hippocampus and amyloid deposition in blood vessels (congophilic angiopathy) may also be seen on tissue examination. The "amyloid cascade" hypothesis posits that amyloid plaques interfere with synaptic activity and initiate a series of downstream effects that cause increasing inter- and intraneuronal dysfunction and, ultimately, cell death

AMYLOID PLAQUES :

Although amyloid plaques may be subclassified according to their composition, all contain forms of β-amyloid protein (Aβ). Aβ is an amino acid peptide formed by proteolytic cleavage of APP by β- and γ-secretase. The main products of this cleavage are Aβ1–40 and Aβ1–42. A relative surplus of Aβ1–42 predisposes toward amyloid, aggregation into oligomers and fibrils, which assemble into amyloid plaques.4,5 An important role for amyloid in AD pathophysiology is implied by the fact that the proteins encoded by APP, PS1, PS2, SorL1, and ApoE are all associated with amyloid generation, processing, and/or trafficking. However, several lines of evidence indicate that amyloid plaques are not the primary cause of AD. Amyloid plaque burden

NEUROFIBRILLARY TANGLES :

Tau, a protein involved in microtubule assembly, is essential for normal axonal growth and neuronal development. However, hyperphosphorylated tau protein aggregates into helical filamentous NFT that are deposited preferentially within neurons of the mesial temporal lobe (especially hippocampus), lateral parietotemporal region, and the frontal association cortices. The critical role of NFT in AD pathophysiology is suggested by the correlation between location and density of tau NFT and the symptoms and severity of AD dementia.4 Moreover, some studies have demonstrated that Aβ oligomers are not toxic unless tau is also present

NEURON AND SYNAPSE LOSS :

The distribution of neuronal cell death and synapse loss is similar to that of NFT.4 In typical AD, the death of neurons in the nucleus basalis of Meynert leads to a deficit in acetylcholine (Ach), a neurotransmitter involved in memory. This cholinergic deficit is the target of most current treatments. In the brainstem, loss of median raphe and locus ceruleus neurons leads to deficits in serotonin and norepinephrine, respectively. Abnormal cerebral serotonergic and adrenergic activity likely contribute to dysphoria and insomnia

CHANGES THAT OCCUR IN BODY SYSTEMS

Alzheimer's disease typically destroys neurons and their connections in parts of the brain involved in memory, including the entorhinal cortex and hippocampus. It later affects areas in the cerebral cortex responsible for language, reasoning, and social behavior

Epidemiology and Risk Factors

Alzheimer's disease Women are more affected than men at a ratio of almost 2:1, partly because of the larger population of women who are older than 70 years; however, the prevalence is higher in women even after statistical correction for longevity.2 Other reported risk factors include lower levels of intelligence and primary education, small head size, and a family history of the disease.2 Potentially preventable risk factors include diabetes, hypertension, sedentary lifestyle, smoking, and obesity.3 Head injury is also implicated as a risk factor for in men

Genetics

About 70% of Alzheimer's disease risk at any given age is attributable to genetics. The most common genetic risk factor for Alzheimer's disease is the e4 allele of the gene for apolipoprotein E (ApoE), which is present in approximately 50% of individuals with Alzheimer's disease. e4 heterozygosity triples the risk of AD compared with non-carriers; homozygotes have a sevenfold risk. Other less prevalent risk genes and familial tendencies have also been identified.

Mutations in the genes for amyloid precursor protein (APP, on chromosome 21), presenilin 1 (PS1, chromosome 14), and presenilin 2 (PS2, chromosome 1) cause autosomal dominant early-onset AD. These mutations account for the majority of familial midlife-onset AD, but represent less than 5% of all AD cases. Sortilin 1 (SorL1) mutations cause late-onset Alzheimer's disease

SIGNS AND SYMPTOMS

AD causes progressive dementia in which difficulty forming new memories is typically the earliest and most prominent manifestation. Initially, there is only loss of recent memories (sometimes referred to as "short term"), but remote memory is increasingly affected over the course of the disease.

Other signs and symptoms of parietal and temporal lobe dysfunction usually increase in number and severity over the course of the disease. Language dysfunction (e.g., searching for words) may occur as an early feature in AD dementia, and can interfere considerably with communication as the patient's vocabulary and comprehension become impoverished. Spatial disorientation leads to lost objects and difficulty navigating. Acalculia may manifest as inability to maintain a checkbook or household accounts. Apraxia is an inability to carry out practiced motor tasks, such as brushing teeth or using a remote control. Although these classic AD symptoms are attributable to posterior cerebral dysfunction

The vast majority of AD dementia patients exhibit behavioral problems during their disease course.8 Depression, sleep disturbance, and/or apathy may be present early. Psychotic symptoms, psychomotor agitation, verbal and physical aggression, and inappropriate sexual behavior tend to appear during later

stages of dementia.9 In advanced stages of AD, some patients also develop motor signs such as tremor, gait disturbance, urinary incontinence, and myoclonus. Seizures are also more prevalent in patients with AD than in age-matched controls. AD's terminal stage is a vegetative state in which purposeful brain activity is not evident the maximum specificity of AD diagnoses under this framework is less than 90%, and definitive diagnosis (demonstration of amyloid plaques and tau tangles) has been possible only with biopsy or autopsy.

Diagnosis

Clinical Diagnosis

Alzheimer's disease the maximum specificity Alzheimer's disease of diagnoses under this framework is less than 90%, and definitive diagnosis (demonstration of amyloid plaques and tau tangles) has been possible only with biopsy or autopsy

Although their nomenclature and precise definitions remain unsettled, there are three distinguishable clinical phases in individuals with AD pathology asymptomatic (normal cognition), prodromal or mild cognitive impairment (MCI) due to AD (symptoms present but not severe enough to cause dementia), and AD dementia (symptoms sufficiently severe to interfere with daily activities). It is increasingly evident that AD's asymptomatic phase may last for several years. Progression through these clinical stages is nonlinear, and appears to be influenced by density and distribution of plaques and tangles and numerous other factors

Physical and neurological exam

Your doctor will perform a physical exam and likely assess overall neurological health by testing the following:

Reflexes

Muscle tone and strength

Ability to get up from a chair and walk across the room

Sense of sight and hearing

Coordination

Balance

Lab tests

Blood tests may help your doctor rule out other potential causes of memory loss and confusion, such as a thyroid disorder or vitamin deficiencies.

Mental status and neuropsychological testing

Your doctor may conduct a brief mental status test or a more extensive set of tests to assess memory and other thinking skills. Longer forms of neuropsychological testing may provide additional details about mental function compared with people of a similar age and education level. These tests are also important for establishing a starting point to track the progression of symptoms in the future.

Brain imaging

Images of the brain are now used chiefly to pinpoint visible abnormalities related to conditions other than Alzheimer's disease — such as strokes, trauma or tumors — that may cause cognitive change. New imaging applications — currently used primarily in major medical centers or in clinical trials — may enable doctors to detect specific brain changes caused by Alzheimer's.

IMAGING OF BRAIN STRUCTURES INCLUDE THE FOLLOWING:

Magnetic resonance imaging (MRI). MRI uses radio waves and a strong magnetic field to produce detailed images of the brain. MRI scans are used primarily to rule out other conditions. While they may show brain shrinkage, the information doesn't currently add significant value to making a diagnosis.

Computerized tomography (CT). A CT scan, a specialized X-ray technology, produces cross-sectional images (slices) of your brain. It's currently used chiefly to rule out tumors, strokes and head injuries.

TREATMENTS:

There are no medications proven to slow progression of AD, although symptomatic decline can be slowed by the drugs

Approved Medications for Symptoms of Alzheimer Disease

	Mechanism of Action	Daily Dose Range and Formulations	Common side effects
Donepezil	Acetylcholinesterase Inhibitor	Dose: 2.5 mg-23 mg 5/10/23 mg daily tab 5/10 mg oral dissolvable daily tab 23 mg extended-release daily tab	Nausea Loose stool Anorexia Drowsiness Insomnia Vivid dreams
Galantamine		Dose: 4 mg-24 mg 4/8/12 mg BID tab 4 mg/mL oral solution 8/16/24 mg extended-release daily tab
Rivastigmine		Dose: 1.5 mg-12 mg 1.5/3/4.5/6 mg BID tab 2 mg/mL oral solution
		4.6/9.5/13.3 mg daily patch	As above, plus skin irritation
Memantine	NMDA glutamate receptor antagonist	Dose: 5 mg-28 mg Titration pack of 5 and 10 mg 5/10 mg BID tab 10 mg/5 mL oral solution 7/14/21/28 mg extended-release daily tab

CREATING A SAFE AND SUPPORTIVE ENVIRONMENT

Adapting the living situation to the needs of a person with Alzheimer's disease is an important part of any treatment plan. For someone with Alzheimer's, establishing and strengthening routine habits and minimizing memory-demanding tasks can make life much easier.

You can take these steps to support a person's sense of well-being and continued ability to function:

Always keep keys, wallets, mobile phones and other valuables in the same place at home, so they don't become lost.

Keep medications in a secure location. Use a daily checklist to keep track of dosages.

Arrange for finances to be on automatic payment and automatic deposit.

Carry a mobile phone with location capability so that a caregiver can track its location. Program important phone numbers into the phone.

Make sure regular appointments are on the same day at the same time as much as possible.

Use a calendar or whiteboard in the home to track daily schedules. Build the habit of checking off completed items.

Remove excess furniture, clutter and throw rugs.

Install sturdy handrails on stairways and in bathrooms.

Ensure that shoes and slippers are comfortable and provide good traction.

Reduce the number of mirrors. People with Alzheimer's may find images in mirrors confusing or frightening.

Make sure that the person with Alzheimer's carries identification or wears a medical alert bracelet.

Keep photographs and other meaningful objects around the house.