What is Alzheimer’s disease?

Dementia and Alzheimer’s disease are often used interchangeably, but they are different.

Dementia is a loss over time of memory or other mental functions or a change in mood or behavior that is severe enough to interfere with a person’s ability to function at home, socially, or at work. This umbrella term covers a range of cognitive problems, such as memory loss, problem-solving difficulty, and other impairments in thinking skills. Alzheimer’s disease is one type of dementia and the most common. In fact, Alzheimer’s disease accounts for 60% to 80% of all dementia cases. 

Alzheimer’s causes a decline in cognition and memory loss accompanied by changes in mood and behavior. The disease is caused by the accumulation of two types of protein in the brain: tangles (tau) and plaques (amyloid-beta). These tangles and plaques make it difficult for brain cells (neurons) to communicate with one another, impeding memory and other mental functions. Eventually, Alzheimer’s destroys enough brain cells that people die.

After an Alzheimer’s diagnosis, people have an average life expectancy of eight to 10 years in an increasingly dependent state as the disease progresses. There is no cure for Alzheimer’s disease, though some treatments temporarily improve symptoms.

It’s impossible to predict exactly how Alzheimer’s will affect each individual because the symptoms and rate of progression vary. Some develop severe mood and behavior problems; others do not. A symptom can show up early or not appear until much later. For some people, the decline is slow and gradual over a decade or longer; others experience a rapid downhill course that ends in death within a few years. 

1. Understanding the Causes and Mechanisms

Alzheimer’s disease results from complex changes in the brain over time. The primary hallmark features include:

• Beta-Amyloid Plaques: These are abnormal clumps of protein fragments that build up between nerve cells (neurons) in the brain. Amyloid plaques interfere with neuron-to-neuron communication, leading to the breakdown of cell functions and ultimately the death of the neuron.
• Tau Tangles: Inside neurons, another protein called tau accumulates into twisted tangles. Tau tangles disrupt the transport system that carries nutrients and other essential substances within neurons. This disruption further damages cells and contributes to cell death.

The combined effect of plaques and tangles damages brain cells and triggers inflammation, which accelerates the deterioration of brain tissue. This process leads to the symptoms commonly seen in Alzheimer’s patients.

2. Risk Factors for Alzheimer’s Disease

Several risk factors influence the likelihood of developing Alzheimer’s:

• Age: The greatest known risk factor is increasing age. After 65, the risk doubles every five years.
• Family History: If a first-degree relative (parent, sibling) has Alzheimer’s, the risk of developing the disease is higher.
• Genetic Mutations: A small number of people with Alzheimer’s (1%) inherit rare genetic mutations that cause early-onset Alzheimer’s, typically before age 60. Mutations in genes like APP, PSEN1, and PSEN2 lead to the accumulation of beta-amyloid plaques. Another gene, APOE4, is associated with a higher risk of late-onset Alzheimer’s, the most common form of the disease.
• Lifestyle and Health Factors: Conditions that affect cardiovascular health, such as high blood pressure, high cholesterol, obesity, diabetes, and smoking, increase the risk of Alzheimer’s. Physical inactivity, poor diet, and lack of mental and social engagement are also risk factors.
• Head Trauma: A history of traumatic brain injury, especially repeated head injuries, is associated with an increased risk of Alzheimer’s.

3. Symptoms and Progression of Alzheimer’s Disease

Alzheimer’s symptoms worsen progressively over time, categorized into several stages:

• Early Symptoms:
  • Mild memory loss, especially for recent events.
  • Difficulty organizing thoughts, making decisions, or solving problems.
  • Trouble finding the right words in conversation.
  • Becoming disoriented in familiar environments.
  • Apathy, mild depression, or withdrawal from social activities.
• Moderate Symptoms (middle stages):
  • Increasing difficulty with memory and confusion.
  • Inability to recognize familiar people or places.
  • Difficulty performing daily tasks like dressing or preparing food.
  • Sleep disturbances, mood swings, or inappropriate behaviors such as paranoia or aggression.
  • The person may start to wander or become lost in familiar surroundings.
• Severe Symptoms (late stages):
  • Loss of the ability to communicate coherently.
  • Profound memory loss, not recognizing close family members.
  • Dependence on others for all personal care, such as eating and bathing.
  • Loss of motor skills, including the ability to walk or control bladder and bowel functions.
  • In the final stages, the person may be bedridden, and complications like infections or pneumonia are common causes of death.

4. Diagnosis of Alzheimer’s Disease

Alzheimer’s is diagnosed through a combination of tests and evaluations, as there is no single test that can definitively diagnose the disease:

• Clinical Examination: This includes a detailed medical history, symptom assessment, and neurological exams to check reflexes, muscle tone, coordination, and balance.
• Cognitive Testing: Mental status tests, such as the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), measure memory, problem-solving skills, and ability to follow instructions.
• Brain Imaging: CT scans or MRIs are used to rule out other causes of dementia-like symptoms, such as strokes, tumors, or fluid buildup in the brain. More advanced imaging techniques, such as PET scans, can detect amyloid plaques or measure brain activity.
• Biomarkers: New research has led to the development of biomarkers that can detect Alzheimer’s earlier and more accurately. These biomarkers include:
  • Amyloid and tau protein levels: Measured through cerebrospinal fluid or PET scans.
  • Blood tests: Some new tests can detect abnormal levels of amyloid and tau proteins in the bloodstream.
• Genetic Testing: Testing for the APOE4 gene or mutations linked to early-onset Alzheimer’s can be performed, though it’s not commonly recommended unless there’s a strong family history of the disease.

5. Treatment Options

While there is no cure, treatments are aimed at managing symptoms and slowing progression:

• Cholinesterase Inhibitors: These drugs help improve levels of neurotransmitters in the brain. Examples include donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). These medications are often prescribed for early to moderate stages of Alzheimer’s.
• Memantine (Namenda): This medication works by regulating glutamate, a neurotransmitter involved in learning and memory. Memantine is used in moderate to severe stages.
• Amyloid-Targeting Drugs: Newer treatments, like aducanumab (Aduhelm) and lecanemab (Leqembi), target beta-amyloid plaques in the brain. However, their effectiveness and cost are still under debate.
• Symptomatic Medications: These include antidepressants, antipsychotics, and mood stabilizers to manage behavioral symptoms like anxiety, aggression, depression, and sleep disturbances.

6. Non-Pharmacological Interventions

In addition to medications, lifestyle changes and supportive care can improve the quality of life for Alzheimer’s patients:

• Cognitive Stimulation Therapy: Engaging in activities that stimulate thinking, memory, and language can help slow cognitive decline.
• Physical Activity: Regular exercise has been shown to slow the progression of Alzheimer’s and improve overall well-being.
• Nutritional Support: A healthy diet, such as the Mediterranean diet, which is rich in vegetables, fruits, whole grains, fish, and olive oil, may have a protective effect against cognitive decline.
• Caregiver Support: Caregivers play a vital role in managing the day-to-day challenges of Alzheimer’s. Respite care, support groups, and educational resources are essential for caregiver well-being.

7. Ongoing Research

There’s considerable research aimed at understanding and eventually curing Alzheimer’s. Some key areas of focus include:

• Immunotherapy: Ongoing studies are exploring how the immune system might be harnessed to clear amyloid plaques and tau tangles more effectively.
• Gene Therapy: Genetic therapies that target the genes responsible for early-onset Alzheimer’s or those that increase susceptibility (like APOE4) are in early stages of research.
• Neuroinflammation: Researchers are investigating the role of inflammation in Alzheimer’s and exploring anti-inflammatory treatments to prevent or slow brain degeneration.
• Early Detection: Biomarkers and advanced imaging techniques are being developed to identify Alzheimer’s long before symptoms appear, allowing for earlier intervention.