Neurodegenerative disease

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Obesity, Sleep & Internal medicine
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Neurodegenerative disease
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Cognitive decline, memory loss, motor dysfunction, behavioral changes
Complications	Dementia, paralysis, death
Onset	Varies by specific disease, often middle age or late adulthood
Duration	Progressive, often chronic
Types	Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis
Causes	Genetic factors, environmental factors, protein misfolding
Risks	Age, family history, genetic mutations, exposure to toxins
Diagnosis	Clinical evaluation, neuroimaging, genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Symptomatic treatment, supportive care, physical therapy, medications
Medication	N/A
Prognosis	Generally poor, varies by specific condition
Frequency	Increasing with ageing population
Deaths	N/A

Neurodegenerative disease

Neurodegenerative disease

Neurodegenerative disease refers to a group of progressive disorders characterized by the gradual loss of function and structure of neurons, leading to cognitive decline, motor dysfunction, and other neurological impairments. These diseases are typically chronic and incurable, with increasing prevalence due to aging populations.

Pathophysiology

Neurodegenerative diseases involve progressive neuronal death caused by multiple pathological mechanisms, including:

• Protein misfolding and aggregation – Accumulation of misfolded proteins such as:
• Beta-amyloid and tau protein in Alzheimer‚Äôs disease.
• Alpha-synuclein in Parkinson‚Äôs disease.
• Huntingtin protein in Huntington‚Äôs disease.
• Mitochondrial dysfunction – Impairment in cellular respiration leading to oxidative stress.
• Excitotoxicity – Overactivation of glutamate receptors causing neuronal damage.
• Neuroinflammation – Chronic activation of microglia and astrocytes contributing to cell damage.
• Genetic mutations – Inherited mutations in genes such as APP, PSEN1, PSEN2 (Alzheimer‚Äôs) or HTT (Huntington‚Äôs disease).

Types of Neurodegenerative Diseases

Neurodegenerative diseases are classified based on the primary affected neuronal system:

Alzheimer’s and Related Dementias

• Alzheimer‚Äôs disease – Characterized by memory loss, cognitive decline, and beta-amyloid plaques.
• Frontotemporal dementia (FTD) – Affects behavior, personality, and language skills.
• Lewy body dementia – Involves alpha-synuclein deposits and symptoms of both dementia and Parkinson‚Äôs disease.
• Vascular dementia – Caused by impaired blood flow to the brain, leading to cognitive decline.

Movement Disorders

• Parkinson‚Äôs disease – Affects dopaminergic neurons, leading to tremors, rigidity, and bradykinesia.
• Multiple system atrophy (MSA) – A progressive disorder with autonomic dysfunction and movement impairment.
• Huntington‚Äôs disease – A genetic disorder causing involuntary movements and cognitive decline.
• Progressive supranuclear palsy (PSP) – Characterized by difficulty in eye movement, balance, and speech problems.

Motor Neuron Diseases

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig‚Äôs disease) – Affects the motor neurons, leading to progressive paralysis.
• Spinal muscular atrophy (SMA) – A genetic disorder affecting lower motor neurons.
• Primary lateral sclerosis (PLS) – A rare form of motor neuron disease affecting the upper motor neurons.

Prion Diseases

• Creutzfeldt-Jakob disease (CJD) – A rapidly progressive neurodegenerative disease caused by abnormal prion proteins.
• Kuru – A prion disease historically found in the Fore people of Papua New Guinea.
• Fatal familial insomnia (FFI) – A rare, genetic prion disease causing insomnia and neurodegeneration.

Risk Factors

Several factors contribute to neurodegenerative disease development:

• Aging – The biggest risk factor, as neuronal function declines with age.
• Genetics – Family history increases risk for diseases like Huntington‚Äôs disease and ALS.
• Environmental exposure – Toxins, heavy metals, pesticides, and air pollution may contribute.
• Lifestyle factors – Poor diet, lack of exercise, and chronic stress may increase risk.
• Traumatic brain injury – Linked to chronic traumatic encephalopathy (CTE) in athletes.

Symptoms

Symptoms vary depending on the specific disease but often include:

• Cognitive impairment – Memory loss, confusion, and difficulty with decision-making.
• Motor dysfunction – Tremors, muscle weakness, rigidity, or loss of coordination.
• Behavioral changes – Mood swings, personality changes, and emotional instability.
• Speech and swallowing difficulties – Common in ALS, Parkinson‚Äôs disease, and FTD.
• Autonomic dysfunction – Blood pressure fluctuations and bladder control issues in diseases like MSA.

Diagnosis

Diagnosing neurodegenerative diseases involves:

• Neurological examination – Assessing cognitive and motor functions.
• Neuroimaging:
• Magnetic resonance imaging (MRI) – Identifies brain atrophy and structural changes.
• Positron emission tomography (PET) – Detects protein aggregates and metabolic activity.
• Genetic testing – Identifies mutations in inherited neurodegenerative diseases.
• Cerebrospinal fluid analysis – Used in Alzheimer‚Äôs disease to detect beta-amyloid and tau protein levels.
• Electromyography (EMG) – Assesses motor neuron function in ALS.

Treatment and Management

There are no cures for neurodegenerative diseases, but treatments can slow progression and alleviate symptoms.

Pharmacological Treatments

• Cholinesterase inhibitors (Donepezil, Rivastigmine) – Used for Alzheimer‚Äôs disease.
• Dopamine agonists (Levodopa) – Improve Parkinson‚Äôs disease symptoms.
• Glutamate antagonists (Riluzole) – Prolong survival in ALS.
• Antipsychotics – Used cautiously in Lewy body dementia and frontotemporal dementia.

Non-Pharmacological Approaches

• Physical therapy – Improves mobility and balance in Parkinson‚Äôs disease and ALS.
• Speech therapy – Helps manage communication difficulties.
• Dietary and lifestyle modifications – Antioxidant-rich diets, exercise, and social engagement may reduce risk.
• Deep brain stimulation (DBS) – A surgical treatment for Parkinson‚Äôs disease and essential tremor.

Future Research and Experimental Therapies

Emerging treatments include:

• Gene therapy – Targeting specific genetic mutations in SMA and Huntington‚Äôs disease.
• Stem cell therapy – Investigating neuronal regeneration.
• Immunotherapy – Targeting abnormal protein aggregates with monoclonal antibodies.
• CRISPR gene editing – Potential future treatments for inherited neurodegenerative disorders.

Prognosis

The prognosis varies depending on the specific disease:

• Alzheimer‚Äôs disease – Progressive cognitive decline over 5–20 years.
• Parkinson‚Äôs disease – Slowly progressive but manageable with treatment.
• ALS – Life expectancy of 2–5 years after diagnosis.
• Prion diseases – Rapidly fatal within months to a few years.

Prevention

While no definitive prevention exists, strategies to reduce risk include:

• Regular exercise – Supports brain plasticity and vascular health.
• Cognitive engagement – Activities like reading, puzzles, and social interactions may slow cognitive decline.
• Healthy diet – Diets like the Mediterranean diet may have protective effects.
• Avoidance of toxins – Limiting exposure to pesticides and heavy metals.
• Managing chronic conditions – Controlling diabetes, hypertension, and obesity reduces risk.

See also

• Alzheimer‚Äôs disease
• Parkinson‚Äôs disease
• Amyotrophic lateral sclerosis
• Neurodegeneration
• Huntington‚Äôs disease
• Dementia