🧠 Alzheimer’s Disease: Quick PLAB 2 Revision

Alzheimer’s disease is the most common cause of dementia, and understanding its presentation, risk factors, and preventive strategies is essential for your PLAB 2 exams and future clinical practice.

✅ What is Alzheimer’s Disease?

A progressive neurodegenerative disorder characterised by:

• Gradual cognitive decline, starting with short-term memory loss.

• Accumulation of beta-amyloid plaques and neurofibrillary tangles leading to neuronal death.

🔍 Clinical Presentation

Early (Mild) Stage

• Short-term memory impairment (e.g. forgetting recent conversations, misplacing items)

• Word-finding difficulty (anomia)

• Subtle personality changes

• Disorientation to time

Moderate Stage

• Increased disorientation (time, place, person)

• Difficulty with complex tasks (finances, shopping)

• Language problems (following conversations)

• Behavioural changes (agitation, wandering)

• Difficulty recognising familiar faces (prosopagnosia)

Severe Stage

• Severe memory loss, including long-term

• Profound language impairment

• Incontinence

• Motor dysfunction → bedbound

• Swallowing difficulties → aspiration risk

🧬 Genetics and Risk to Offspring

• Family history increases risk but is not a guarantee.

• APOE-e4 allele increases risk:

  • One copy → 2-3x risk.

  • Two copies → up to 8-12x risk.

• Early-onset familial Alzheimer’s (<1%) is autosomal dominant (APP, PSEN1, PSEN2 mutations), with near 100% penetrance if inherited.

✅ Risk Factors

Risk Factor	Mechanism
Age	Doubles every 5 years after age 65.
Genetics	APOE-e4, familial mutations.
Vascular risks	Hypertension, diabetes, obesity, smoking damage cerebral vessels.
Traumatic Brain Injury	History of moderate-severe TBI increases risk.
Low education	Reduced cognitive reserve.
Social isolation / depression	Reduced cognitive engagement.
Physical inactivity	Sedentary lifestyle increases risk.
Untreated hearing loss	Midlife hearing loss is a modifiable risk factor.

✅ Preventive Strategies

Strategy	Benefit
Physical activity	Improves blood flow, reduces vascular risk. Aim: 150 mins/week.
Healthy diet (Mediterranean)	Reduces inflammation and oxidative stress.
Cognitive stimulation	Builds cognitive reserve.
Social engagement	Maintains mental health and cognitive activity.
Good sleep hygiene	Clears beta-amyloid proteins.
Vascular risk control	Manage BP, diabetes, cholesterol.
Avoid smoking and excess alcohol	Reduces neurodegenerative risk.
Treat hearing loss early	May delay cognitive decline.

📝 Key Takeaways for PLAB 2

✅ Alzheimer’s is progressive and irreversible✅ Memory loss, especially short-term, is the hallmark✅ No guarantee of inheritance, but family history increases risk✅ Lifestyle modifications can reduce risk or delay onset✅ Always assess vascular risk factors, social history, and cognitive reserve in elderly patients with memory complaints

💡 Mnemonic for Alzheimer’s Modifiable Risk Factors

“HAVOC DIPS”

• Hearing loss (untreated)

• Activity (physical inactivity)

• Vascular risks (HTN, DM, cholesterol)

• Obesity

• Cognitive inactivity

• Depression

• Isolation (social)

• Poor diet

• Smoking

📚 Revision Tip:When assessing an elderly patient with confusion or memory complaints in PLAB 2, rule out delirium first, then consider dementia causes like Alzheimer’s.

📚 References:

• https://www.ahajournals.org/doi/10.1161/strokeaha.112.651778

• https://www.nice.org.uk/about/what-we-do/into-practice/measuring-the-use-of-nice-guidance/impact-of-our-guidance/niceimpact-dementia/ch1-prevent-or-delay-onset-of-dementia

• https://www.nice.org.uk/guidance/ng97/chapter/recommendations

• https://www.alzheimers.org.uk/about-dementia/managing-the-risk-of-dementia