Dementia

What is dementia?

• state where an individual has lost the ability to carry out daily life activities independently due to cognitive impairment that is not due to a psychiatric condition

• progressive decline:

  • memory

  • cognition

  • behaviour

  • daily functioning

Types of dementia?

• Alzheimer’s disease

  • abnormal build of beta amyloid proteins and tau protein

  • memory problems

• Vascular dementia

  • impaired blood supply to brain due to stroke, infarction

• dementia with Lewy bodies

  • abnormal protein deposits of Lewy Body

  • affects thinking, memory, movement

  • visual hallucinations

  • sensitive to antipsychotics

• frontotemporal dementia

  • shrinkage of brain’s frontal and temporal lobes due to brain injury, substance misuse, genetics

  • usually younger onset

  • loss of empathy

Cognitive Symptoms of Alzheimer’s?

• memory loss

• impaired orientation

• language disturbance

• agnosia - inability to recognise familiar objects

Functional Symptoms of Alzheimer’s?

• reduced ability to carry out daily life activities

  • personal = washing, dressing, toileting, continence, transferring

  • domestic = cooking, cleaning, shopping, managing finances, taking medication

Neuropsychiatric Symptoms of Alzheimer’s?

• mood disturbances

• agitation

• aggression

• wandering

Symptoms of Lewy Body Dementia?

• visual hallucinations

• delusions

• REM sleep disorder

• fluctuating consciousness

• Parkinson’s like movement:

  • tremors

  • rigidity

  • shuffling gait

• autonomic dysfunction

  • dizziness

  • falls

  • constipation

Signs of Dementia?

• memory loss affecting daily life

• losing conversation threads

• forgetting names of everyday objects

• misplacing items

• difficulty judging distances or colours

• confusion about time, place

• mood changes

• becoming less sociable

How does a timely dementia diagnosis help?

• helps individual plan for future

• aids care planning and reduces crisis

• improves the potential to benefit from medication and slow disease progression

• receiving diagnosis can help alleviate anxiety

• aids families and carers access help and plan

Modifiable Risk Factors?

• exercise

• mental stimulation

• maintaining healthy weight

• blood pressure control

• blood glucose control

What memory screening tests can be used to help diagnose dementia?

• 6-item cognitive impairment

• 10-point cognitive screener

• mini-cog

• general practitioner assessment of cognition

• Montreal cognition assessment

What cognitive domains are assessed in a memory screening test?

• attention and concentration

• recent and remote memory

• language

• praxis

• executive function

• visuospatial function

What alternative causes need to be excluded before making diagnosis?

• depression

• drugs

• deilirium

What imaging test can be done to help with diagnosis?

• MRI scan

• it is more sensitive to picking up vascular damage and atrophy associated with Alzheimer’s disease

What investigations are done to help diagnose?

• full blood count

• ESR

• urea and electrolytes

• bone profile

• HbA1C

• LFTs

• thyroid function test

• serum B12 and folate levels

• mid stream urine if infection

• chest x ray

What is the Addenbrooke’s cognitive examination -III?

• detailed and comprehensive assessment tool for memory impairment which assess 5 domains:

  • attention

  • memory

  • language

  • visuospatial function

  • verbal fluency

How do amyloid plaques form in Alzheimer’s disease and why are they harmful?

• in a healthy brain the amyloid precursor protein (APP) is normally broken down and cleared away

• in Alzheimer’s the APP is cut incorrectly, producing beta-amyloid fragments

• these fragments clump together forming insoluble amyloid plaques outside neurons

  • insoluble = can’t be broken or removed

• plaque builds up and disrupts communication between brain cells = death of neurons that produce acetylcholine

What is acetylcholine responsible for and what effect does it have when acetylcholine producing neurons die?

• it is a neurotransmitter responsible for memory and learning

• loss of cells/neurons that produce acetylcholine leads to decline in memory and cognitive function

How do tau proteins contribute to neuron death in Alzheimer’s?

• in a healthy neuron, tau proteins stabilise microtubules to allow proper communication and transport of nutrients inside brain cells

• in Alzheimer’s tau proteins becomes hyperpolarised (too many phosphate groups added)

• when tau becomes hyperpolarised:

  • detaches from microtubule - nutrient transport stops

  • causes microtubule to collapse

  • clumps together to form tangles

• these leads to loss of neuron function and cell death

• neurons contain acetylcholine so memory and cognitive function declines

What does early Alzheimer’s look like?

• neurons look normal

• few tangles

• amyloid beta clusters start to accumulate outside neuron

  • trigger toxicity

• damage is mild and cell still functions

What does Alzheimer’s look like when it progresses?

• phosphorylated tau levels rise steadily inside neuron

• instability of neuron’s internal structure

• neuron weakness

What does late Alzheimer’s disease look like?

• neuron severely damaged

• high levels of phosphorylated tau fill the cell

• tau clumps into neurofibrially tangles

• amyloid-beta toxicity more widespread around cell

• dendrites and axon shrunken or disrupted

• neuron loses function and dies

How can melatonin help with Alzheimer’s?

• reduce formation of amyloid beta proteins

• prevent excessive tau phosphorylation

• improves sleep quality

What effect does tau tangles have on melatonin?

• tau tangles forms in parts of the hypothalamus

• this reduces melatonin production and disrupts circadian rhythm signals = sundowning

What is sundowning and its symptoms?

• increased confusion, agitation, anxiety or restlessness that occurs in late afternoon, evening or night

• symptoms:

  • irritability, mood swings

  • pacing or wondering

  • difficulty following instructions

  • verbal/physical agitation

What are the current objectives in treating AD?

• reduce memory loss and cognitive dysfunction

• manage secondary symptoms:

  • depression

  • anxiety

  • insomina

  • confusion

  • aggression

MOA of acetylcholinesterase inhibitors?

• block the enzyme acetylcholinesterase which normally breaks down acetylcholine

• more acetylcholine stays active so signal between neurons becomes stronger

• allows for improved mood, attention and cognition

• works of AD but not for vascular dementia

What needs to be done before starting acetylcholinesterase inhibitors?

• ECG as the medication can cause bradycardia or syncope

When are acetylcholinesterase contraindicated?

• first or second degree heart block

• pulse below 50bpm

Examples of acetylcholinesterase inhibitors?

• donepezil

• rivastigmine

• galantamine

What are the side effects of acetylcholinesterase inhibitors?

• GI upset

• nausea

• anorexia

• dizziness

What are the key features, indications, and cautions for Donepezil?

• long half life (70hrs)

• dose = 5mg OD, titrate up to 10mg OD

• used for mild-moderate AD

• GI upset

• start at night but once stable take at any time

• contraindications:

  • bradycardia

  • conduction defects

• cheapest option

What are the key features, indications, and cautions for Rivastigmine?

• taken with food

• used for dementia in PD and mild-moderate AD

• dose = 1.5mg BD

• increase dose at monthly intervals at 6mg BD

• patch available but expensive

What are the key features, indications, and cautions for Galantamine?

• derived from snowdrops

• given in XL formulation for mid-moderate AD

• start at 8mg OD

• increase monthly to 24mg

• better for insomnia

MOA of memantine?

• it is an N-methyl-D-aspartate (NMDA) receptor antagonist

• In AD there is too much glutamate which overstimulate the neurons leading to excitotoxicity (neurons are damaged and die due to overstimulation)

• memantine blocks NMDA receptors to prevent excessive glutamate from binding

• use in severe AD

What are the key features, indications, and cautions for Memantine?

• used in moderate-severe AD when:

  • symptoms worsen

  • daily functioning declines

  • behavioural changes occur

  • acetylcholinesterase inhibitors aren’t enough alone

• safe in people with:

  • bradycardia

  • heart blocks

• need to renal function

• constipation and dizziness can occur

When should treatment with an AChE inhibitor be continued, reviewed, or stopped?

• 3 weeks after starting:

  • check side effects - nausea, GI upset, dizziness, bradycardia

• 3 months after starting:

  • assess cognitive improvement

  • evaluate impact on memory, behaviour and daily functioning

• if no improvement:

  • reassess at 6 months, then consider stopping

  • if still no benefit - discontinue treatment

• switching medication

  • only switch to another acetylcholinesterase inhibitor if side effects occurs

    • don’t switch if there is no response to treatment as they have the same MOA

What are the behavioural and psychological symptoms of dementia (BPSD) ?

• agitation

• aggression

• sleeplessness

• emotional liability

• sexual disinhibition

• poor pain relief and UTI - worsens behaviour

• visual hallucinations

• sundowning

What drugs are prescribed in BPSD?

• sertraline

  • safest antidepressant

  • low anticholinergic burden and low sedation

• citalopram:

  • prolongs QT interval = risk of arrythmias

• trazodone:

  • sedative effects

    • used for = agitation, sleep disturbance, night time restlessness

      • minimal anticholinergic effects

• mirtazapine:

  • sedating at low doses (7.5-15mg)

  • sedation drops at high doses (30-45mg)

  • higher doses can increase agitation or activation

• risperidone

  • short term - 6 weeks

  • for severe agitation or aggression

Can benzodiazepines be used in BPSD?

• avoid long acting - diazepam and nitrazepam

  • confusion

• temazepam and zopiclone increase risk of falls

• short term use only due to tolerance and dependence on benzos

• lorazepam useful in agitation

  • quick acting for PRN use

  • start with 0.5mg dose

  • avoid routine use

Antipsychotics use in dementia?

• used only if no other option

• short periods only - 6 weeks and review regularly

• can be fatal in Lewy Body dementia and dementia of PD

• haloperidol has increased risk of death compared to risperidone

• extrapyramidal symptoms

• sedation

• prolonged QT intervals

• abnormal gait

What are the key features, indications, and cautions for risperidone?

• high risk of severe reactions

  • stroke

• start at 0.5mg once or twice daily

• licenced in AD

• assesss:

  • CVD risk before starting

What are the key features, indications, and cautions for quetiapine?

• least major side effects

• start at low dose 12.5mg OD

Pain management in dementia?

• helps reduce agitation

• paracetamol 3g

What are the risk factors of developing delirium?

• when ill - UTI

• anticholinergic drug burden:

  • oxybutynin

  • tolterodine

  • amitriptyline

  • atropine

  • promethazine

  • nortriptyline

Dementia and alcohol use?

• Memory loss caused by alcohol

• Korsakoff’s syndrome – produced dense amnesia with lack of insight and blunting of behaviour

• teat with high dose thiamine