10.3 Introduction to Alzheimer’s Disease

Alzheimer's disease wreaks havoc on the brain, causing protein buildup and neuronal damage. This leads to memory loss, cognitive decline, and eventually, complete dependence on caregivers. Understanding its mechanisms is crucial for developing effective treatments.

Diagnosis involves a mix of cognitive tests, brain scans, and biomarker analysis. While age and genetics play a role, lifestyle factors can influence risk. Early detection is key, as symptoms progress from mild forgetfulness to severe cognitive impairment.

Overview of Alzheimer's Disease

Mechanisms of Alzheimer's disease

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• Abnormal accumulation of proteins in the brain disrupts neuronal function
  • Beta-amyloid plaques form sticky clusters between neurons interfering with cell communication and triggering inflammation
  • Neurofibrillary tangles composed of twisted tau protein fibers accumulate inside neurons causing instability of microtubules and impairing transport of nutrients
• Neuronal dysfunction and loss leads to cognitive decline
  • Synaptic dysfunction impairs communication between neurons due to beta-amyloid plaques and neurofibrillary tangles reducing neurotransmitter release and signaling
  • Neuronal death causes progressive loss of neurons in affected brain regions resulting in brain atrophy and cognitive impairment
• Affected brain regions include the hippocampus and cerebral cortex
  • Hippocampus plays a crucial role in learning and memory formation and is an early site of damage (short-term memory loss)
  • Cerebral cortex responsible for higher cognitive functions such as reasoning and language is gradually affected as the disease progresses (difficulty with complex tasks, language, and decision-making)

Neurobiological factors in Alzheimer's disease

• Neurodegeneration: Progressive loss of structure or function of neurons, including death of neurons
• Cholinergic system: Impairment of this system, which uses acetylcholine as a neurotransmitter, contributes to memory and cognitive deficits
• Neurotransmitters: Imbalances in various neurotransmitter systems affect brain function and cognition
• Neuroplasticity: Reduced ability of the brain to form new neural connections and adapt to changes
• Blood-brain barrier: Alterations in this protective barrier may contribute to disease progression
• Neuroinflammation: Chronic inflammation in the brain exacerbates neuronal damage
• Oxidative stress: Increased cellular damage due to an imbalance between free radicals and antioxidants

Symptoms of Alzheimer's progression

• Early stage characterized by memory loss and mild cognitive impairment
  • Difficulty remembering recent events or newly learned information often repeating questions or statements (forgetting appointments, misplacing items)
  • Trouble with complex tasks, planning, and organizing as well as difficulty with problem-solving and decision-making (struggling to manage finances, getting lost in familiar places)
• Middle stage marked by worsening memory loss, language difficulties, and changes in mood and behavior
  • Inability to recall personal history or recognize familiar people along with confusion about time, place, and events (forgetting names of family members, wandering)
  • Struggling to find the right words or follow conversations with reduced vocabulary and impaired comprehension (using incorrect words, difficulty understanding instructions)
  • Apathy, depression, or irritability as well as restlessness, agitation, or wandering (losing interest in hobbies, becoming easily upset, pacing)
• Late stage characterized by severe cognitive decline, physical deterioration, and complete dependence on caregivers
  • Inability to communicate effectively or respond to the environment with loss of awareness of surroundings and recent experiences (unable to recognize loved ones, unresponsive to stimuli)
  • Difficulty with mobility, balance, and coordination as well as incontinence and difficulty swallowing (bedridden, requiring assistance with feeding and personal care)
  • Require assistance with all daily activities and increased susceptibility to infections and complications (pneumonia, pressure ulcers)

Causes and diagnosis of Alzheimer's

• Potential causes include age, genetic factors, and environmental and lifestyle factors
  • Age is the greatest risk factor with prevalence increasing significantly after age 65
  • Genetic factors include rare familial Alzheimer's disease caused by specific gene mutations inherited from a parent typically developing earlier in life (30s to 50s) and more common genetic risk factors such as APOE-e4 increasing likelihood of developing Alzheimer's without guaranteeing disease development
  • Environmental and lifestyle factors such as head trauma, cardiovascular disease, and low education levels may increase risk while maintaining a healthy lifestyle (exercise, balanced diet) may reduce risk
• Diagnostic methods involve medical history, cognitive assessments, neuroimaging techniques, and biomarker analysis
  1. Evaluation of symptoms, family history, and overall health along with cognitive tests to assess memory, language, and problem-solving skills (Mini-Mental State Exam, Montreal Cognitive Assessment)
  2. Neuroimaging techniques such as Magnetic Resonance Imaging (MRI) to detect brain atrophy and structural changes helping rule out other conditions and Positron Emission Tomography (PET) using radioactive tracers to visualize abnormal protein accumulation (beta-amyloid and tau) and assess brain metabolism and function
  3. Biomarker analysis including cerebrospinal fluid (CSF) tests measuring levels of beta-amyloid and tau proteins (lower beta-amyloid and higher tau levels suggest Alzheimer's) and emerging blood tests potentially detecting Alzheimer's-related changes in blood biomarkers currently used in research settings with ongoing efforts to develop reliable clinical tests