Alzheimer's Disease: The Most Common Neurodegenerative Disorder Today
What is Alzheimer's Disease ?
Alzheimer’s disease (AD) is a neurodegenerative condition marked by gradual cognitive decline, memory impairment, and functional deterioration. As the leading cause of dementia, AD poses a significant public health challenge, particularly among ageing populations.
This article offers a comprehensive overview of Alzheimer’s disease, covering its types and stages, causes, biochemical changes, pathophysiology, symptoms, diagnosis, and clinical care.
Globally, over 55 million people are affected by dementia, with more than 60% living in low- and middle-income countries. Each year, nearly 10 million new cases are diagnosed. In India, over 4 million individuals suffer from some form of dementia. Alzheimer’s disease (AD), the most prevalent type, accounts for approximately 60 to 70% of all dementia cases.
Types of Alzheimer's Disease
- Early-onset Alzheimer’s Disease
- Occurs in individuals younger than 65 and accounts for less than 5% of all Alzheimer’s cases.
- It is often linked to APP, PSEN1, and PSEN2 genetic mutations.
- Late-onset Alzheimer’s Disease
- The more common form typically develops after age 65.
- Its aetiology involves a complex interaction of genetic and environmental factors.
Causes and Risk Factors of Alzheimer's Disease
The etiology of Alzheimer’s disease involves a combination of genetic, environmental, and lifestyle factors:
- Genetic Factors:
- Mutations in the APP, PSEN1, and PSEN2 genes are linked to early-onset AD.
- Numerous studies highlight the APOE e4 allele as a major genetic risk factor. Possessing just one APOE e4 gene can double or even triple the risk of developing Alzheimer’s.
- Environmental Factors: Head injuries, cardiovascular disease, and exposure to toxins may increase the risk of Alzheimer’s.
- Lifestyle Factors: Diet, physical activity, cognitive engagement, and social interactions all play a role in influencing the likelihood of developing AD.
Biochemical Changes and Pathophysiology of Alzheimer's Disease
Alzheimer’s disease is marked by the abnormal accumulation of proteins in the brain, leading to devastating effects on memory and cognitive function. The progression of the disease involves two key pathological processes:
- Beta-Amyloid Pathology:
- Beta-amyloid proteins accumulate between nerve cells, forming plaques.
- These plaques disrupt neuronal communication and induce neuroinflammation, which further damages brain tissue.
- Tau Pathology:
- Tau proteins become abnormally hyperphosphorylated, leading to the formation of neurofibrillary tangles within neurons.
- These tangles impair the stability of microtubules and disrupt axonal transport, which is essential for neuron function.
As these toxic protein buildups increase, neurons begin to die, and chronic inflammation sets in, causing even more damage. Additionally, reduced blood supply deprives brain cells of essential oxygen and nutrients, leading to further harm. This complex cascade of events results in widespread neuron loss throughout the brain, causing brain shrinkage, also known as atrophy.
Initially, the plaques and tangles primarily damage areas of the brain responsible for memory, such as the hippocampus and cortical regions. However, as the disease progresses with age, other regions of the brain are increasingly affected, leading to more widespread cognitive decline.
Stages of Alzheimer's Disease
Alzheimer’s disease (AD) progresses through several stages, each marked by distinct clinical features and varying degrees of cognitive and functional impairment. Understanding these stages is essential for early diagnosis, effective management, and providing appropriate care. The stages can be broadly categorized into three main phases:
- Preclinical Alzheimer’s disease
- Mild cognitive impairment (MCI) due to Alzheimer’s
- Alzheimer’s dementia, which is further subdivided into
- Mild
- Moderate
- Severe stage
1. Preclinical Alzheimer's Disease
Preclinical Alzheimer’s disease refers to the stage where pathological changes in the brain, such as the accumulation of amyloid-beta plaques and tau tangles, begin long before any clinical symptoms appear.
- During this phase, individuals are asymptomatic but may exhibit detectable biomarkers through advanced imaging techniques or cerebrospinal fluid (CSF) analysis.
- Early identification of this stage is primarily valuable for research and potential early intervention strategies.
2. Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease
Mild cognitive impairment (MCI) is the intermediate stage between normal cognitive ageing and the more severe decline seen in Alzheimer’s dementia.
- MCI due to Alzheimer’s is marked by noticeable cognitive decline that exceeds what is expected for a person’s age but does not yet significantly interfere with daily life and activities.
- Common symptoms include:
- Memory problems, particularly with recalling recent events or conversations.
- Difficulty with complex tasks and problem-solving.
- Mild language difficulties, such as finding the right words.
- Slight challenges with spatial awareness and navigation.
Individuals with MCI are at an increased risk of developing Alzheimer’s dementia, though not all who experience MCI will progress to dementia.
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3. Alzheimer's Dementia
a. Mild Alzheimer's Dementia
Mild Alzheimer’s dementia is the stage where cognitive decline begins to more significantly interfere with daily activities and the ability to live independently. Key symptoms at this stage include:
- Increased memory loss, especially of recent events and information.
- Difficulty planning and organizing activities, such as managing finances or following recipes.
- Orientation dysfunction, such as becoming disoriented in familiar places.
- Changes in mood and personality, including depression, anxiety, and irritability.
- Challenges in performing tasks that require multiple steps.
Despite these impairments, individuals in the mild stage of Alzheimer’s can often still perform many basic activities of daily living with some assistance.
b. Moderate Alzheimer's Dementia
Moderate Alzheimer’s dementia is characterized by more pronounced cognitive and functional deficits, significantly impacting the individual’s ability to live independently. Symptoms during this stage include:
- Severe memory loss, including forgetting personal history and difficulty recognizing familiar people.
- Increased confusion and disorientation regarding time, place, and events.
- Greater difficulty with language, such as repeating phrases or struggling to communicate thoughts.
- Behavioral and psychological changes, including agitation, wandering, and sleep disturbances.
- Challenges with basic daily activities, such as dressing, bathing, and eating.
Caregiver support becomes increasingly necessary at this stage to ensure the safety and well-being of the affected individual.
c. Severe Alzheimer's Dementia
Severe Alzheimer’s dementia is the final stage of the disease, marked by profound cognitive and functional decline. Key symptoms include:
- Complete dependence on others for personal care and daily activities.
- Loss of ability to respond to the environment or communicate coherently.
- Severe memory loss and cognitive deficits, including the inability to recognize close family members.
- Physical deterioration, such as difficulty walking, swallowing, and controlling bladder and bowel functions.
- Increased susceptibility to infections and other health problems.
At this stage, palliative care and hospice services may be appropriate to focus on the patient’s comfort and quality of life, as well as support for caregivers.
Symptoms of Alzheimer's Disease
The range of symptoms experienced at different stages of Alzheimer’s disease, from early signs to more advanced impairments are detailed as follows
Early Symptoms of Alzheimer's Disease
- Memory loss, particularly of recent events
- Difficulty with planning and problem-solving
- Challenges in completing familiar tasks
- Confusion with time or place
- Trouble processing visual and spatial relationships
Moderate to Severe Symptoms of Alzheimer's Disease
- Increased memory loss and confusion
- Difficulty recognizing family and friends
- Impaired communication, reading, and writing skills
- Behavioural and personality changes, such as aggression or agitation
- Difficulty with movement and coordination
- Inability to perform everyday activities independently
Diagnosis of Alzheimer's Disease
Diagnostic Criteria:
- Clinical Evaluation: Comprehensive history and physical examination, focusing on cognitive and functional assessment.
- Neuropsychological Testing: Standardized tests to evaluate memory, executive function, language, and visuospatial abilities.
- Biomarkers: Analysis of cerebrospinal fluid for Aβ and tau proteins, along with advanced imaging techniques (PET, MRI) to detect amyloid plaques and neurofibrillary tangles.
- Genetic Testing: Screening for known genetic mutations in early-onset cases and the APOE ε4 allele in late-onset cases.
Management of Alzheimer's Disease
The various treatment approaches focus on alleviating symptoms and enhancing the quality of life for individuals living with Alzheimer’s disease.
Pharmacological Treatment
- Cholinesterase Inhibitors:
- Donepezil, rivastigmine, and galantamine enhance cholinergic function by inhibiting the enzyme that breaks down acetylcholine, a neurotransmitter important for memory and learning.
- They are commonly prescribed for mild to moderate Alzheimer’s disease.
- NMDA Receptor Antagonists:
- Memantine works by regulating glutamatergic activity in the brain.
- It is used for moderate to severe Alzheimer’s disease to help manage symptoms by protecting against excessive glutamate activity, which can be toxic to neurons.
- Adjunctive Therapies:
- Antidepressants, antipsychotics, and anxiolytics may be prescribed to manage behavioural and psychological symptoms associated with Alzheimer’s disease, such as depression, anxiety, and agitation.
Non-Pharmacological Interventions
- Cognitive Stimulation: Activities that engage thinking, memory, and social interaction, which can help slow cognitive decline.
- Physical Exercise: Regular physical activity to promote overall health, improve mood, and support cognitive function.
- Nutritional Support: A balanced diet rich in antioxidants, omega-3 fatty acids, and other essential nutrients to support brain health.
- Environmental Modifications: Creating a safe and supportive living environment to reduce confusion and enhance independence as the disease progresses.
Supportive Care
- Caregiver Support: Education and support groups for caregivers to manage stress and enhance care quality.
- Palliative Care: Focused on comfort and quality of life in advanced stages, addressing physical, emotional, and spiritual needs.
Tips to Reduce the Risk/Prevent Alzheimer’s Disease
- Maintain a healthy diet rich in antioxidants and omega-3 fatty acids.
- Keep your mind engaged by learning new skills and doing activities like crossword puzzles.
- Prioritize good sleep, manage stress, and stay socially and physically active.
- Refrain from smoking and limit alcohol consumption.
- Support cardiovascular health by managing high blood pressure, diabetes, and cholesterol levels.
Conclusion
Alzheimer’s disease remains a significant challenge in neurology and geriatrics, with profound implications for patients, families, and healthcare systems. Advances in understanding its pathophysiology, early diagnosis, and comprehensive care strategies are essential for improving outcomes and quality of life for those affected by this debilitating disorder. Ongoing research into disease mechanisms and therapeutic interventions offers hope for future breakthroughs in the prevention and treatment of the most common form of dementia.
- Alzheimer’s stages: How the disease progresses (mayoclinic.org)
- Alzheimer Disease -StatPearls – NCBI Bookshelf (nih.gov)
- Alzheimer’s disease: Causes and Treatment- A review (academia.edu)
- Biochemical Markers in Alzheimer’s disease (International Journal of Molecular Sciences, Molecular Neurobiology, Vol.21, Issue 6)
- Alzheimer’s A review from pathophysiology to diagnosis, new perspectives for pharmacological treatment (researchgate.net)
Laiba Khan
3rd-year Medical Student | Reviewed by Dr Aarti Nehra
