Alzheimer's Disease

62%, but 10% are mixed AD/Vascular Dementia

Early onset AD (i.e under 65) caused by 3 genes: APP, PSEN1 and PSEN2. Accounts only for ~1% of AD

APOE e4 variant. Increases risk 4x for carriers, 10x for homozygous. About 25% of the population are heterozygous but only 2% homozygous.

Age - Risk doubles every 5 years

Gender - Female (not just because they live longer)
Genetics - Family history and Down Syndrome (APP is on Chr.21)

Head injury
Metabolic syndrome features - Cholesterol, hypertension, obesity etc.

Variable. Typically early loss of episodic memory, difficulty with recall, orientation, confusion. Inability to learn new tasks.

These things are severe enough to affect ADLs. If not, it's Mild Cognitive Impairment.

Starts with memory impairment, moves on to language comprehension. After that, variable, includes things like wandering, 'sundowning', hypo/hyperphagia, hallucinations, mood disturbances (depression/aggression), apathy, disturbed sleeping patterns, hallucinations.

- History shows progressive symptoms, affect daily functioning

-Rule out other causes (other dementias, depression, etc)
- Blood tests for Vitamin B12, folate, thyroid hormones (rules out those as a cause)

- MMSE score is poor, multiple areas of cognition affected particularly recall and orientation questions.

- MRI shows atrophy, particularly hippocampal

FDG-PET - AD has loss of glucose metabolism in the parieto-temporal areas, eventually progresses to frontal cortex.

Is highly sensitive for AD, but not very specific. Hypometabolism can develop for many reasons inc. vascular dementia

PET with Pittsburgh compound C, binds to fibrillar amyloid B. AD shows accumulation of AB in prefrontal cortex, striatum, temporal lobes, etc.

Sensitive (90% of AD patients are PIB+), but 30% of normal over 65s are PIB+, so are people with Lewy Body Dementia.

Does distinguish AD from FTLD and Parkinson's though.

AD patients have low ABeta in the CSF and very high total Tau and high phosphorylated tau (p231). CSF ABeta42 and Tau can distinguish AD from other dementias.

Abeta is the product of cleavage of the membrane protein APP by BACE-1 and then gamma secretase. It is a small peptide, between 38-42 amino acids long.

The amyloid hypothesis posits that the deposition of Abeta in the brain is the causative insult that leads the the neuron death seen in AD. Abeta can aggregate into toxic oligomers and large plaques. It is believed that soluble forms of Abeta induce various stresses (ROS generation, synaptic dysfunciton etc) that eventually induce cell death.

Tau is a protein involved in stabilising microtubules. Misfolding of Tau (possibly induced by Abeta) leads to axon damage and formation of neurofibrillary tau tangles.

Abeta pathology appears earlier than Tau, but does not correlate with disease state, severity, duration, anything tbh. Tau on the other hand does, and Braak found tau pathology follows a uniform progression that correlates well with appearance of symptoms.

Acetylcholinesterase inhibitors

An NMDA receptor antagonist

Other symptoms:
SSRIs for depression
Atypical antipsychotics

Donepezil

Rivastigmine
Galantamine

In patients with mild-moderate disease, improvement/stability of cognitive decline for under a year, and improvements to anxiety, ADLs, behavior, memory, concentration.

Most commonly GI disturbance. Also headaches, fatigue. Possibly bradycardia.

Memantine is an NMDA receptor antagonist. NICE has it approved for use in moderate-severe disease and it improves cognition and behaviour, possibly also agitation, aggression, delusions.

Risperidone is the only licenced antipsychotic for dementia, only to be used in the short term. Intramuscular haloperidol and lorazepam are NICE approved for immediate sedation.

Inappropriate antipsychotic use significantly increases risk of stroke and doubles risk of mortality. It also doesn't address the underlying cause of agitation, so should only be used after all other non-pharmalogical approaches have been exhausted. Sedation also increases risk of falls.

Consistent, stable carers.

Retaining a familiar environment
Enviromental adaptation/modification/assitive tech
ADL advice from OT

Minimising relocations

Incontenence advice

Exercise (physiotherapy)

1. Cognitive training - improves memory and cognition

2. Multisensory stimulation - improves behaviour and mood

3. Reality Orientation - Improves cognition and behaviour
4. Reminiscence therapy - Improves cognition and behaviour (and facilitates carer-patient understanding)

5. Validation therapy - Improves behaviour, facilitates behaviour management

6. Improving carer QOL/Carer training - May impact patient, but improves carer QOL.

MCI is a state of mild but noticeable cognitive deficit in areas of Memory, Executive Function, Language and/or Visiospatial ability. MMSE scores may be lower than normal for that age, but MCI does not impair ADLs.

~10% of people with MCI convert to AD every year; 80% of people have AD after 6 years. Up to 20% of over 65s may show MCI.

There is no solid evidence that any one thing can reliably prevent AD or any other sort of dementia. The NuAge study, the framingham study, nun studies show that things like eating a mediterranean diet, engaging in cognitively stimulating activities, not smoking, and regular exercise reduce risk.