NEURO DEGENERATIVE DISORDERS

definition of NDD

Occur when nerve cells in the brain (with/without peripheral nervous system involvement) lose function over time and ultimately die

what happened in NDD

1. irreversible loss of neurons with age

2. protein deposition & aggregation in the neurons

3. altered physicochemical properties in the brain and in peripheral organs

Common conditions under NDD

1. Alzheimer’s disease

2. Lewy Body Dementia

3. Amyotrophic lateral sclerosis

4. Prion disease

5. Huntington disease

6. Spinocerebellar ataxia

7. Parkinson disease

8. Frontotemporal Dementia

Neuronal loss in general in NDD

1. Abnormal protein aggregatioan and inflamation in the brain

2. cause cell death

3. due to Oxidative stress, Mitochondria dysfunction, Excitotoxicity, Neurotransmitter depletion, Abnormal ubiquitination, BBB pathology

Classification of NDD

1. PATHOGENESIS - Protein-based classification – protein processing pathways

2. CLINICAL FEATURES- Predominant signs and symptoms

clinical feature of NDD

1. dementia

2. movement disorders

what is the Pathogenesis of AD

1. Extracellular beta-amyloid deposits- senile plaques

2. Intracellular neurofibrillary tangles (NFT)- tau-containing NFTs

Non modifiable risk factor of AD

1. genetics

   • APP, ApoE4, Presenilin 1&2

2. aging - >75 years old

3. gander- male > female

Modifiable risk factor of AD

1. Lifestyle and mental health

   • diet, personal trait, education, depression, sleep disturbance, physical activity

2. comorbidities and life events

   • Cerebrovascular disease, Type 2 diabetes, Hypertension, Hypercholestrolemia

clinical hallmark of AD

Cognitive impairment

list sign & symptoms or clinical feature AD

1. Withdrawal from society activities

2. confusion with time and location

3. difficulty completing familiar tasks

4. misplacing items

5. difficulty solving problems

6. memory loss (short term memory)

7. difficulty in words

physical feature of AD

• Loss of balance or coordination

• Stiff muscles

• Shuffling gait

• Trouble standing or sitting up in a chair

• Weak muscles and fatigue

• Sleep disturbances

• Trouble controlling bladder or bowels.

• Seizures and uncontrollable movements

What to expect in the late-stage dementia

1. loss of facial expression

2. Problem with everyday activities like bathing, dressing, eating

3. bedround, requires around the clock care

4. unable to speak

5. unable to walk or sit up without assistance

6. loss long term memory

Lewy Body Dementia (LBD) vs Frontotemporal Dementia (FTD)

treatment of Lewy Body Dementia (LBD) vs Frontotemporal Dementia (FTD)

acethyl colinesterase inhibitors

Amyotrophic Lateral Sclerosis

upper and lower motor weaknesses

1. Asymmetrical weakness at first, then affecting all limbs and trunk,

2. Presence of significant wasting with hyperreflexia

3. Pseudobulbar palsy and difficulty breathing Incurable (cant breath, swallow, speak) mesti ada ventillation

4. life expectancy less than 2 years with riluzole

Huntington’s Disease vs Spinocerebellar Ataxia

prion disease / Creutzfeldt-Jakob disease (CJD)

1. Transmissible spongiform encephalopathies or TSEs

2. A group of rare, fatal brain diseases that affect animals and humans.

3. They are caused by an infectious agent known as a prion

4. Prions – misfolded proteins with ability to transmit misfolded shape onto normal variants of the same protein.

5. spread to humans by infected meat products

6. Rapid deterioration of symptoms – death within 4 months to 2 years

Clinical features of prion disease

• loss of intellect and memory.

• changes in personality.

• loss of balance and coordination.

• slurred speech.

• vision problems and blindness.

• abnormal jerking movements.

• progressive loss of brain function and mobility