neuro 5 - azheimers disease

Neurodegeneration

Death of neurons leading to gradual deterioration of bodily functions controlled by the affected part of the NS.

Acute neurodegeneration

E.g. stroke.

Chronic neurodegeneration

E.g. Alzheimer's.

Natural degeneration

E.g. ageing.

Disease induced degeneration

E.g. Alzheimer's.

Dementia

Collection of symptoms affecting memory, language, problem solving, etc.

Most common cause of dementia

Alzheimer's.

Diagnosis of Alzheimer's

Includes bio assessment e.g. MRI/CT and psychological assessment e.g. clinical interview, tests.

Path to diagnosis for Alzheimer's

Includes GP visit, medical history, memory tests, blood tests, and specialist referral e.g. neuropsychologist.

Role of psychologist in Alzheimer's

Diagnosis, therapy, support.

Incidence and first discovery of Alzheimer's

Increases as population ages, over 100 yrs ago

Prevalence of Alzheimer's worldwide

50 million.

Prevalence of Alzheimer's in the UK

1 million.

Risk factor: Age

Most important; over 85 = 32% of population.

Risk factor: Sex

Twice as many women than men over 65, 85-89 yrs - prevalence = 14.2% females, 8.8% males

Risk factor: Genetics - how to tests heritability?

Can get predictive testing.

Modifiable risk factors for Alzheimer's

Lifestyle choices, cardiovascular disease e.g. smoking, diabetes, hypertension.

Preventative recommendations for Alzheimer's

Physical activity, healthy diet, social/cognitive engagement.

Mild cognitive impairment (symptom)

Early stage memory loss, maintain independence, decline in cognitive function beyond ageing.

Early signs of Alzheimer's

Blunt emotional responses, social withdrawal.

Memory impairment in Alzheimer's (symptom)

Progressive memory loss (episodic then declarative).

Changes in personality due to Alzheimer's (symptom)

E.g. apathy, depression.

Stages of Alzheimer's

Early stage: temporary memory lapses; Middle stage: confusion; Later stage: communication difficulty, advanced = total carer dependence etc

Brain dysfunction in Alzheimer's

Accumulation of protein fragment beta-amyloid outside neurons and abnormal tau protein inside neurons.

what biological mechanism causes brain dysfunction in alzheimers

accumulation of protein fragment beta-amyloid outside neurons and abnormal form of tau protein inside neurons

2 Types of Alzheimer's

1) Early-onset: hereditary, diagnosed below 60-65, less 5%; 2) Late-onset: majority, diagnosed after 60-65.

genetic mechanisms behind early onset alzheimers

gene mutations on chromosomes, autosomal dominant inheritance

genetic mechanism behind late onset AD

apolipoprotein E (glycoprotein transports cholesterol in blood, alleles from this protein involve E4 which increases risk of AD), when ApoE attached to B-amyloid = becomes insoluble = more likely deposited in plaques, B-amyloid accumulation can come from infection, excessive drug use etc

pathology of AD: what role does brain atrophy have in AD

AD = degeneration of hippocampus, cerebral cortex and ventricular enlargement

pathology: role of cellular level features in AD? e.g. tau

senile plaques (amyloid)

Neurofibrillary tangles (tau): in non AD tau binds and stabilizes microtubules (nutrient transport) but in AD = detaches and sticks to other tau disrupting transport

pathology: role of synaptic loss in AD?

extensive, depletion of selective neurotransmitter systems (Acetylcholine (Ach), Glutamate, Serotonin, Noradrenaline)

pathology: role of selective loss of neurotransmitter systems in AD? e.g. neurons effected

neurons using ach/glutamate/serotonin and noradrenaline = affected

Cholinergic neurotransmission: Acetylcholine production and destruction.

1) Acetylcholine production: Acetyl CoA + choline -(ChAT) -> Ach and coenzyme A

2) Acetylcholine destruction: Ach -(AchE)-> choline and acetic acid

Cholinergic hypothesis

Neurons used for memory/learning; degeneration effect on this.

psychological treatments for AD

Memory aids e.g. diaries, CBT - reduce depression/anxiety, Music therapy, Structured social interaction, stimulated presence therapy, Caregiving

Pharmacological treatment: Cholinesterase inhibitors - what does it do, what type of AD and effect on symptom presentation

E.g. donepezil; inhibits cholinesterase, boosts cholinergic synapse activity. for mild to moderate, improves symptoms for 6-12 mth

pharmacological treatment: Glutamate receptor antagonists - what do they do, what stage of AD and effect on symptom presentation

E.g. memantine; protects brain cells from toxic levels of glutamate. moderate to severe, slows symptom progression - behavioural

what are some developing AD treatments?

1) Reducing B-amyloid accumulation: Anti-inflammatory agents, Enzyme inhibitors

2) Reduce tau aggregation: anti-inflammatory agents

3) Improve cardiovascular health

Biomarkers for Alzheimer's

Naturally occurring gene/characteristic by which disease can be identified, in blood/organs etc

3 specific AD biomarkers

1) CSF/B-amyloid/tau levels

2) Blood tests of brain derived products

3) Brain imaging