lecture 8 - memory and disease

What is dementia?

A gradual loss of brain function due to physiological changes in brain structure.

What is the most common form of dementia?

Alzheimer’s disease.

List common symptoms of dementia.

Memory loss, impaired reasoning, reduced language skills, and loss of daily living skills.

Mild symptoms of Alzheimer’s disease include?

Confusion, memory loss, disorientation, problems with routine tasks, personality and judgement changes.

Moderate symptoms of Alzheimer’s disease include?

Difficulty with daily living, anxiety, agitation, wandering, and trouble recognizing family and friends.

Severe symptoms of Alzheimer’s disease include?

Loss of speech, appetite, and bladder/bowel control, with total caregiver dependence.

What is the primary risk factor for Alzheimer’s disease?

Age — risk doubles every 5 years after 65; ~20% of people aged 85+ in NZ have AD.

What does the Phonemic Verbal Fluency (PVF) test assess?

Executive function and language retrieval by generating words starting with a given letter.

What does the Semantic Verbal Fluency (SVF) test assess?

Semantic memory and categorical organization by naming items within a category.

What brain changes are seen in Alzheimer’s disease?

Shrinkage of hippocampus/cortex, enlarged ventricles, amyloid plaques, tau tangles, synaptic loss, and cholinergic neuron degeneration.

Which neurotransmitter system is particularly affected in Alzheimer’s disease?

Cholinergic system — ACh important for memory; treated with AChE inhibitors (e.g., Donepezil).

What are amyloid plaques and how do they form?

Aggregates of beta-amyloid fragments from APP cleavage by secretases; overproduced in AD, disrupting neuron communication.

Name recent drugs showing promise in targeting beta-amyloid.

Donanemab (2023) and trontiemab (2025).

What are neurofibrillary tangles?

Twisted intracellular fibers of hyperphosphorylated tau that disrupt neuron structure and function.

Where do neurofibrillary tangles appear first in Alzheimer’s?

Transentorhinal cortex, spreading to neighboring regions.

What are Braak stages?

A system classifying Alzheimer’s progression by the spread of tau tangles (stages I–VI).

What percentage of Alzheimer’s cases are early-onset and what genes are implicated?

5% (familial); mutations in PSEN1, PSEN2, and APP.

What gene variation increases risk for late-onset Alzheimer’s disease?

APOE4 allele on chromosome 19.

How does APOE4 affect the blood-brain barrier (BBB)?

Disrupts tight junctions via pericyte dysfunction, allowing toxins/inflammation and promoting amyloid buildup.

What did the Nun Study reveal about cognitive reserve?

Early-life language complexity predicted reduced cognitive decline, suggesting cognitive reserve protects against dementia.

List key modifiable risk factors for dementia (early, mid, and late life)

• Early: poor education (5%)

• Midlife: hearing loss (7%), high LDL (7%), depression (3%), TBI (3%), inactivity (2%), diabetes (2%), smoking (2%), hypertension (2%)

• Late: social isolation (5%), air pollution (3%), visual loss (2%)