Alzheimer Disease

Pathology & Symptoms

The pathology of Alzheimer disease (AD) involves several key structural and molecular changes in the brain. These pathological features are essential for understanding the progression of the disease: 

1. Amyloid Plaques: 

1. Amyloid plaques are one of the most characteristic features of AD. They are primarily composed of amyloid-beta (Aβ) peptides, which accumulate in the brain due to abnormal cleavage of the amyloid precursor protein (APP). 

2. These plaques are found primarily in the extracellular space and can disrupt cellular communication, provoke inflammatory responses, and induce oxidative stress, contributing to neuronal damage and death. 

2. Neurofibrillary Tangles: 

1. These tangles consist of hyperphosphorylated tau proteins, which normally stabilize microtubules in neurons. In AD, tau becomes abnormally modified and detaches from microtubules, causing them to collapse and disrupt cellular transport. 

2. The accumulation of tau tangles leads to a breakdown in the integrity of the cytoskeleton, further impairing neuronal function and promoting neurodegeneration. 

3. Neuronal Loss and Atrophy: 

1. Over time, the brain undergoes significant shrinkage (atrophy), particularly in regions involved in memory and cognition, such as the hippocampus and cerebral cortex. 

2. This neuronal loss leads to a decrease in synaptic connections and disrupts the brain’s ability to process and store information. 

4. Chronic Inflammation: 

1. Microglial cells, the brain’s resident immune cells, become activated by the presence of amyloid plaques. This inflammatory response can contribute to neuronal injury and exacerbate the disease. 

5. Vascular Changes: 

1. Many individuals with AD exhibit changes in blood vessels in the brain, including reduced blood flow and blood-brain barrier dysfunction. These changes may impair nutrient and oxygen delivery to neurons, further contributing to cognitive decline. 

The symptoms of Alzheimer disease develop gradually and worsen over time. They are primarily related to cognitive and behavioural dysfunction: 

1. Memory Loss: 

1. One of the earliest and most prominent symptoms of AD is short-term memory loss. Patients often forget recent conversations, appointments, or events and may repeat themselves frequently. 

2. Cognitive Decline: 

1. As the disease progresses, individuals experience difficulty with higher cognitive functions, including problem-solving, decision-making, and planning. Complex tasks become harder to execute. 

3. Disorientation and Confusion: 

1. Individuals with AD may become disoriented regarding time and place. They might forget where they are, how they got there, or even the names of family members and friends. 

4. Language Problems: 

1. Individuals may struggle to find the right words or follow conversations. This difficulty in communication often becomes more pronounced as the disease advances. 

5. Changes in Personality and Behaviour: 

1. People with AD may exhibit mood swings, irritability, anxiety, and depression. They may also experience personality changes, becoming more withdrawn or aggressive. 

6. Impaired Judgment: 

1. As AD progresses, individuals may demonstrate poor judgment in everyday situations, such as managing finances or recognizing dangers, leading to safety concerns. 

7. Impaired Motor Function: 

1. In the later stages, motor dysfunction may occur, leading to difficulty walking, swallowing, and maintaining balance. 

Outcome

The outcome of Alzheimer disease is generally progressive and terminal. As the disease advances, cognitive decline becomes more severe, and individuals lose the ability to perform basic activities of daily living. This progression can lead to: 

1. Severe Cognitive and Physical Impairment: 

1. Eventually, individuals with AD may lose the ability to recognize loved ones, communicate, or care for themselves. They may require 24-hour assistance and support. 

2. Loss of Independent Functioning: 

1. People with advanced AD become entirely dependent on caregivers for daily activities such as eating, dressing, and bathing. Their capacity to live independently diminishes significantly. 

3. End-Stage Disease: 

1. In the final stages, individuals with AD experience severe cognitive and physical debilitation. Motor skills may be completely lost, and individuals may be bedridden. At this point, the disease is often associated with complications such as infections (e.g., pneumonia), which are common causes of death. 

4. Life Expectancy: 

1. The life expectancy following an Alzheimer’s diagnosis varies, but individuals typically live between 4 to 8 years after symptoms become noticeable. Some may live longer, but the disease’s progression leads to an eventual decline in physical health. 

Risk Factors