Neurological disorders and sensory eye disorders

Alzheimer’s Disease

Progressive Neurodegenerative disorder, causing memory, thinking, behavior and functional decline —→ major causes of dementia 60% to 70%

Sporadic A.D.

accounts for 95% Alzheimer’s cases

• Late/Onset 80-90 years

Family/ Genetics

1-5% Alzheimer’s cases

• Early (~45 years)

Dementia

Umbrella term for cognitive decline; Alzheimer’s leading cause.

Amyloid Beta (AB) Hypothesis

Aβ precursor protein (APP): Cell membrane protein in neurons, normally involved in synapse formation & neuroplasticity ( brain rewiring self)

• APP is abnormally proceed by “B” and “Y” secretes enzymes producing Oligomers & Plaque

AB Oligomers

• Contribute to synaptic dysfunction, Tau pathology, and Neuronal DEATH (due to calcium influx)

• mild AB plaque can accumulate in older adults without Alzheimer’s

Tau Protein Hypothesisca

Tau: Microtubule- associated protein in Neurons, stabilizing, microtubules, and supporting axonal transport

• in Alzheimer’s Tau becomes abnormally hyperphosphorylated, detaching from microtibules and misfolding into Neurofrillary Tangles (neurons lose structure and die)

Tau Protein cont.

Tau protein abnormalities, potentially trigger or accelerated by amyloid beta plaque formation I thought to drive neurodegeneration

Cholinergic Hypothesis (Older theory)

Cause: Loss of Cholinergic neurons producing acetylcholine (ACh) leads to an ACh deficit

Acetylcholine

neurotransmitter involved in attention, learning and memory

Post- Mortem Studies

Show a reduction in Cholinergic neurons in AD patients

Drug exist that block the enzyme degrading ACh

What happens to the brain during Alzheimer’s

• progressive loss of neurons leading to widespread brain atrophy

Brain Atrophy impacts

• Hippocampus: Shrinkage ( early hallmark )

• Temporal lobes: Language / Memory

• Parietal lobes: Spatial awareness

• Frontal lobes: Judgement and Planning

Dominantly Inherited Alzheimer’s ( Early Onset)

• Onset ~40 years earlier than Sporadic

late-onset AD

• caused by inherited mutations in specific genes

Specific Genes

• APP = Amyloid Precursor Protein

• PSEN 1 = presenilin 1 protein

• PSEN 2 = presenilin 2 protein

-PSEN 1 & 2 are core components of gamma-secretease

Alzheimer’s Clinical Progression (Early to Mild)

Prodromal (preclinical): Pathology developing, no noticeable symptoms, maybe mild memory loss

• Mild cognitive impairment (MCI): Memory problems greater than expected for age, but not severe enough to impair daily function.

Example: Difficulty recalling recent conversations, Misplacing items often , Mild word finding problems, Repetitive questions,

Alzheimer’s Clinical Progression (Moderate)

• Longest stage, can last years.

• Significant memory loss (including personal history).

• Disorientation to time/place.

• Difficulty recognizing familiar people.

• Increasingly impaired judgment and problem-solving.

• Requires assistance with ADLs (dressing, bathing).

• Behavioral symptoms: Agitation, sleep disturbance, wandering, paranoia or delusions.

• Safety becomes a major concern (falls, medication errors, wandering).

Alzheimer’s Clinical Progression (Severe)

• Profound cognitive and functional decline.


• Limited or no verbal communication.

• Inability to recognize close family members.


• Requires complete assistance for all ADLs.


• Motor impairment (gait loss).


• Incontinence (urinary and fecal).

• Dysphagia → aspiration risk.

• Weight loss and frailty.


• Eventually bedridden

Clinical Diagnosis of Alzheimer’s

• Based on patient family concerns about cognitive decline

• MoCA

• MMSE

• AB-PET (detect AB plaque deposition)

FGD-PET (measure cerebral glucose metabolism glucose) *glucose hypometabolism = neuron loss*

• TAU-PET:(visualizes Tau neurofibrillary tangles)

Imaging

Red FDG = Neuron hypometabolism

Red Tau= More Tau proteins

Cognitive Assessment: MoCA

Tests multiple domains often affected early in neurodegenerative disorders

• Short-term memory recall.

• Visuospatial ability.


• Executive function.


• Sustained attention.


• Language.


• Abstract reasoning.

• Orientation.

Cognitive Assessment Tools: MMSE (Mini-Mental State Examination)

Cognitive screening tool for general cognitive function

• Orientation

• Registration

• Attention and calculation

• Recall

• Language

Dementia pain

Pain does not present normally in patients with dementia.


Patients can have difficulty communicating complaints

PAIND SCALE

Dementia : Eating

• Undernutrition problem in moderate and severe stages.

• Loss of interest in food, decreased ability to self-feed.
•

• Chewing and swallowing difficulties present an aspiration risk.


• Use: pureed food, thickening liquids.


• Possible need for percutaneous endoscopic gastrostomy (PEG) tube.

Dementia Sundowning

• Patient becomes more confused and agitated in late afternoon or evening.


• Cause is unclear.

• Remain calm and avoid confrontation.

Acetylcholinesterase Enzyme Inhibitor (Donepezil)

Mechanism : Inhibits acetylcholinesterase, enzyme breaking down acetylcholine

Goal: Enhance Cholinergic neuron effects by preventing ACh breakdown

Efficacy: Small benefits cognitive & function

N-methyl-D-aspartate (NMDA) Receptor antagonist (Memantine)

Mechanism: Block NDMA receptor, preventing calcium influx

Efficacy: Small improvements in cognition, behavior, and daily living for moderate to severe AD.

Monoclonal Antibody (Lecanemab)

Mechanism : Artificial human antibody designed to detect specific Aβ plaque components (Aβ protofibrils). Once bound, Aβ plaque removed by immune system.

• Efficacy: Reduces brain amyloid burden & slows cognitive decline.

Very Expensive

Bell’s Palsy (Cranial Nerve VII)

Sudden, temporary weakness or paralysis of muscles on one side of the face due to inflammation or dysfunction of the facial nerve (cranial nerve VII).

Bells Palsy Cont.

• Most common cause of facial paralysis.

• Exact cause unknown, associated with HSV-1 viral infection

• Inflammation → swelling → nerve compression → temporary nerve dysfunction.

Bells Palsy Clinical Manifestation

• Rapid onset of symptoms over 24-48 hours.


• Unilateral facial drooping.


• Inability to raise eyebrow, close eye fully, or smile on affected side.


• Drooling.


• Altered taste.


• Decreased or excessive tearing.

Belly’s Palsy Treatment


Corticosteroids.


Sometimes antivirals.


Eye drops.


70-85% of patients recover in weeks to months.


Surgery in extreme cases to decompress the facial nerve.