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Alzheimer’s Disease

Overview

Alzheimer’s disease is the most common form of dementia (memory loss). Every year almost 6 million people in the United States are diagnosed with Alzheimer’s, and it is one of the leading causes of death in the United States. The disease was first discovered in the brain of a dead German woman by Dr. Alois Alzheimer in 1906, hence called Alzheimer’s disease.
It is a progressive neurodegenerative disorder in which, due to unknown causes specific part of the brain called the hippocampus is affected. The disease causes cognitive and behavioral functions to decline, affecting the quality of life. Alzheimer’s has a long and progressive clinical course. The symptoms first appear at old age.

Causes

The exact mechanism by which Alzheimer’s affects the brain is unknown, but the studies suggest plaque formation in the hippocampus. The hippocampus is the part of the brain concerned with encoding memories and affecting the individual’s ability to make decisions. Hippocampus is affected due to the excessive deposition of proteins like beta-amyloid and tau proteins that are usually trapped by the neural cells. The involvement of the hippocampus causes symptoms and signs of Alzheimer’s that appear later in life.

Types

Depending upon the clinical signs and symptoms, Alzheimer’s can be classified into:

  • Preclinical Alzheimer’s: no clinical signs and symptoms can be noted at this time. However, the parts of the brain are affected, and the progression of the disease starts.
  • Mild Alzheimer’s: mild signs and symptoms such as memory impairment with mood changes and ability to function daily tasks are affected.
  • Moderate Alzheimer’s: there is increasing memory loss with involvement of the motor system with symptoms such as gait and balance disturbances and loss of impulse control that causes patients to exhibit inappropriate behaviors such as undressing in public.
  • Severe Alzheimer’s: patients with severe Alzheimer’s cannot take care of themselves. They cannot recognize family members or friends with extreme memory loss and communicate effectively. They also lose control of bowel and bladder movements. Severe Alzheimer’s can result in death eventually.

Risk Factors And Epidemiology

Alzheimer’s disease occurs worldwide. It most commonly occurs in the age group 60-69 years, and the prevalence increases multifold with advancing age. According to some research, it is more common in women than in men.
Following are the risk factors for Alzheimer’s:

  • Advancing age
  • Family history
  • Obesity
  • Depression
  • Insulin resistance
  • Vascular factors
  • Dyslipidemia
  • Hypertension
  • Inflammatory markers
  • Down syndrome
  • Traumatic brain injury
  • Genetic mutation in specific genes such as APP is also a risk factor for Alzheimer’s

Signs And Symptoms

Clinical signs and symptoms of the disease include:

  • Memory loss of varying degrees
  • Loss of orientation of space and time
  • Personality changes of varying degrees
  • Loss of judgment
  • Short attention span
  • Confusion
  • Restlessness
  • Motor problems and muscle twitches
  • Weight loss
  • Difficulty swallowing
  • Seizures
  • Loss of bowel and bladder control

Diagnosis

The only way to definitive diagnosis against Alzheimer’s is an autopsy or brain biopsy. The diagnosis of Alzheimer’s and its type is made on clinical presentation. Following labs and radiological tests are carried out to aid the diagnosis of Alzheimer’s:

  • Blood studies include complete blood count, vitamin B12 levels, liver enzymes, thyroid stimulating hormone, and HIV serology.
  • Lumbar puncture to carry out CSF analysis to see the levels of specific proteins called the Tau proteins and beta-amyloids, usually elevated in Alzheimer’s.
  • Imaging studies are usually done to rule out other causes of memory disturbances that can be treatable such as hydrocephalus or subdural hematoma. Hippocampus is analyzed using PET scans usually.
  • Genotyping for APOE alleles in an at-risk population

Differential Diagnosis

Differential diagnoses of Alzheimer’s include:

  • Age-associated memory impairment
  • Alcohol or drug abuse
  • Vitamin b12 deficiency
  • Depression
  • Parkinson’s disease
  • Cerebrovascular disease and vascular dementia
  • Hypoglycemia
  • Wernicke-Korsakoff syndrome
  • Huntington disease
  • Wilson disease

Complications of Alzheimer’s disease include:

  • Malnutrition due to inability to chew or swallow properly
  • Pneumonia due to increased risk of aspirating food into lungs. Death in most severe Alzheimer’s disease cases is caused by aspiration pneumonia.
  • Coma and death

Treatment

Treatment of Alzheimer’s aims to manage the symptoms and maintain the quality of life. The disease itself is incurable, and nothing can be done to prevent it.

  •  Standard treatment is based on cholinesterase inhibitors and NMDA antagonists, whereas secondary symptoms such as depression, agitation, and sleep disorders are managed using psychotropic drugs.
  • Anti-inflammatory therapy to prevent brain inflammation is shown to slow down the rate of progression for Alzheimer’s.
  • Various experimental therapies include anti-amyloid therapy, estrogen therapy, vitamin E therapy, free radical scavenger therapy, and therapy for reversing excess tau phosphorylation.

Medications

Medications used against Alzheimer’s include:

  • Antidepressants
  • Anxiolytics
  • Anti-Parkinsonism drugs 
  • Beta-blockers
  • Anti-epileptics
  • Neuroleptics
  • Amyloid directed antibody

Prognosis

The prognosis of Alzheimer’s depends upon the time of diagnosis and the type of symptoms. It progresses gradually and can cause death anywhere between 3 to 10 years of diagnosis. The cause of death in most cases is aspiration pneumonia.

Prevention

Alzheimer’s disease is incurable, and no substantial evidence is available against any strategy to prevent the disease. However, certain lifestyle changes can help decrease or slow down the disease progression. These include:

  • An active lifestyle with increased physical activity and regular exercise
  • A low-fat diet with supplementation with vitamin E, vitamin D, vitamin B6, and B12 is thought to decrease the risk of dementia.
  • Cardiovascular fitness
  • Quitting smoking

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