Clinical Management of Dementia

What is dementia?

When a patient experiences a decline in 2 or more cognitive areas relative to:

- their age

- their level of cognitive function before the condition

Their decline in function cannot be explained by another condition.

The level of cognitive impairment must be enough to significantly interfere with their daily life.

Describe how dementia can be assessed in an individual

1. Take an accurate history - it would be best if a carer or someone who knows the patient well can be present during this assessment.

2. Inquire about when symptoms started (timescale of symptoms)

3. Consider the impact on ADLs (activities of daily life)

4. Conduct a physical examination e.g. neurological scan, blood test

5. Conduct a cognitive test

Give examples of cognitive assessment tools which can be used in the diagnosis of dementia

- 10-point cognitive screener (10-CS)

- the 6-item cognitive impairment test (6CIT)

- the 6-item screener

- the Memory Impairment Screen (MIS)

the Mini-Cog

- Test Your Memory (TYM).

What factors must we consider when conducting a cognitive function test?

- Physical, sensory or learning disabilities or communication difficulties can affect the result of the test

- Their level of cognition before disease (premorbid)

Why do we conduct a physical assessment in patients we suspect have dementia?

To rule out the possibility that decrease in cognitive function is due to a physical condition e.g. an infection.

What is the main difference between dementia and delirium?

Delirium is short onset and is linked to a physiological condition.

Dementia is a long term condition and so has a gradual onset. A point is that dementia is not linked to another physiological condition.

What differential diagnoses for dementia?

1. "Normal-age" related memory changes

2. Mild cognitive impairment (MCI) - can progress into a dementia but doesn't always.

3. Depression

4. Delirium

5. Adverse drug effects - this is something that as pharmacists we can be useful in (e.g. oversedation)

6. Sensory deficits - this can affect how the patient interacts with the world e.g. glasses, hearing aid.

7. Other physical causes e.g. hypothyroidism, hyponatraemia, vitamin deficiencies

What are the different sub-types of dementia?

1. Alzheimer's disease

2. Vascular dementia: physical insult to the brain, causing reduced blood flow resulting in dementia

3. Dementia with Lewy bodies

4. Dementia in Parkinson's disease

5. Frontotemporal lobe dementia (including Pick's disease)

6. Korsakoff's

7. Creutzfeldt-Jakob disease (CJD)

Describe the symptoms and presentation of dementia

1. Cognitive impairment e.g.

- memory loss

- problems with communication and reasoning

- difficulty in making decisions

- disorientation

- dysphasia: condition making it harder to communicate

2. Behavioural and psychological symptoms: can last for 6 months or more e.g.

- psychosis: delusions and/ or hallucinations

- depression and anxiety

- withdrawal

- disturbed sleep cycle

- wandering, restlessness, pacing

- agitation

3. Difficulties with activities of daily living (ADLs) e.g.

- Early dementia: complex household tasks

- Late dementia: bathing, eating, walking (self-care)

What are symptoms specific to Alzheimer's disease?

- First presents with memory loss and dysphasia

- Episodic memory: memory loss of recent events

What are key principles NICE guidelines state for the assessment, management and support of patients with dementia?

- We must consider safety. We should assess whether elderly patient can still drive

- Review polypharmacy and minimise the use of drugs which impair cognition

- Support carers: relatives often looking after vulnerable people in their family. We need to consider how to look after the physical and mental health of carers.

- Use of Mental Capacity act, we always assume someone has capacity for whatever decision we make. Do not assume lack of capacity due to dementia diagnosis. Capacity is decision specific.

- Give dementia patients ability to voice their opinion in their care

What are the aims for pharmacological treatment in dementia?

- Medication is used to temporarily alleviate symptoms or slow disease progression.

- It does not aim to cure dementia - no drugs on the market currently do that.

- The benefits of the medication are small but are offered in combination with a wider care package.

What is the main treatment for dementia?

Cholinesterase inhibitors

Give examples of cholinesterase inhibitors

There are three licensed drugs in the UK:

- donepezil

- rivastigmine

- galantamine

These are licenced for mild-moderate AD

What is the mechanism of action of cholinesterase inhibitors?

In Alzheimer's there is a degeneration of acetylcholine neurons. This therefore decreases the release of Ach. Consequently using a cholinesterase inhibitor, we can increase synaptic levels of Ach.

Describe the efficacy of cholinesterase inhibitors

- Response rates to cholinesterase inhibitors are heterogenous (40-70%)

- Some may experience small improvements in cognitive function in the first 6-12 months of treatment followed by a slow decline

What are some of the adverse effects in cholinesterase inhibitors?

- Leg cramps

- Excess mucous production

- Syncope or bradycardia

They are generally well tolerated

How can adverse effects with cholinesterase inhibitors be managed?

Changing the formulation of the medication can improve tolerability

How can Alzheimer's disease be treated?

First line: Donepezil, galantamine or rivastigmine monotherapy

Memantine monotherapy (under certain conditions)

Combination acetylcholinesterase inhibitors + memantine (under certain conditions)

How can frontotemporal dementia be treated?

It does not use acetylcholinesterase inhibitors or memantine

How can vascular dementia be treated?

It can use AChE inhibitors or memantine if there's a relevant co-morbidity

How can dementia with Lewy bodies be treated?

First line: Donepezil or rivastigmine

Second line: galantamine

Memantine if AChE inhibitors not suitable

How do we decide treatment of dementia?

Medication used for treatment of dementia depends on:

- cost of medication: cheapest is used first line

- side effect profile: if first line option presents with poor side profile for the individual, other options can prescribed

- adverse event profile

- expectations about adherence

medical comorbidity

- possible drug interactions

- dosing profiles

Describe key characteristics of donepezil

- Once daily dosing

- Renally excreted

- CYP450 metabolism

- Lowest acquisition cost

Describe the dosing of rivastigmine

- Twice daily dosing

- Available as patch

- Licensed for use in Parkinson's disease

- Renally excreted

- No hepatic metabolism

Describe the dosing of galantamine

- It enhances response of nicotinic receptors to acetylcholine

- Liquid: twice daily dosing

- Capsules: one daily dosing

What is the mechanism of action of memantine?

It is an NMDA receptor antagonist.

It inhibits Ca2+ influx to neurons.

It prevents excitotoxicity in neurons by stopping excessive effects of glutamate.

What are the side effects of memantine?

Dizziness

Headaches

Tiredness

Raised blood pressure

Constipation

They are generally well tolerated

What is the efficacy in memantine in treating dementia?

It is used as an adjunctive treatment in moderate-severe dementia for those already taking acetylcholinesterase inhibitors.

Offers small but measurable benefits in moderate to severe disease

When do we stop medicines for dementia?

We stop prescribing them when:

- Person cannot take medicines in way prescribed, even with support

-Desired effects (stabilising cognitive and functional status) are not perceived within a reasonable time (e.g., 12 weeks)

- A patient has an apparently negative reaction to the medication.

- A patient's cognitive and functional decline has continued to the degree that they need full time care and/or full assistance with their activities of daily living (i.e., washing, feeding, toileting etc.)

Maintenance of treatment can be continued as long as therapeutic benefit is observed.

We don't stop medication purely on disease severity - reviews should be undertaken so that response to medication can observed.

How do deprescribe medications for dementia?

- If we deprescribe medication, patients often see it as you "giving up on them". Must ensure that you re-assure the patient in the consultation room when you deprescribe.

- Withdraw slowly

- A decision to stop medication should be made after consultation with family and carers who know the person well.

- Undertake a holistic assessment

Whare are some possible complications in dementia?

- Behaviours that challenge

- Psychological symptoms

Give examples of behavioural symptoms of dementia

- Withdrawn, lack of interest

- Aggressive/ physical/ verbal aggression

- Restlessness, pacing, repetitive actions, sleep disturbance

- Hallucinations, delusions

- Sade, tearful, hopeless

When do we consider use of antipsychotics for behavioural symptoms in dementia?

Only offer antipsychotics for people living with dementia who are:

- at risk of harming themselves or others or

- experiencing agitation, hallucinations or delusions that are causing them severe distress.

How do we manage behavioural symptoms pharmacologically in dementia?

First line:

Haloperidol and risperidone (up to 6 weeks)

- we use doses which are much lower than what we use in psychosis.

- we also use behavioural interventions

What dose of risperidone is used for non-cognitive symptoms of dementia?

Initially, 0.25 mg twice daily, adjusted by increments of 0.25 mg twice daily on alternate days according to response

What dose of haloperidol is used for non-cognitive symptoms of dementia?

Initially, 0.5 mg daily, increasing gradually every 1-3 days according to response to a maximum of 5 mg daily if required (in 1-2 divided doses)

What are the risks of antipsychotics in the behavioural symptoms in dementia?

Antipsychotics increase the risk of stroke and other cardiovascular disease three-fold in people with dementia.

Antipsychotics also increase risk of mortality - it can be up to 9-fold risk of stroke in the first four week

Parkinson's and Lewy body dementia can have a severe antipsychotic sensitivity reaction

How often should use of antipsychotics be reviewed?

Every 3 months or according to clinical need

What are other treatments that could used for treatment of challenging behaviours in dementia patients?

Should be started by a specialist.

We need to ensure that these medications are used in a safe way and not to restrict the patient (e.g. by oversedation).

- Antidepressants including trazodone and SSRIs

- Antiepileptics including carbamazepine, lamotrigine and valproate

- Benzodiazepines and z-hypnotics

- Sedating antihistamines

Describe immunological approached to dementia treatment

- The hope is that the immunological medications are interfering with formation of plaques and tangles.

- These are expensive drugs and the data for efficacy are modest/ have a marginal effect.

- There are also significant safety risks and so complex monitoring is required.

- This is therefore a controversial treatment.

NICE made a decision stating that current immunological approaches are not cost-effective; there have been appeals from drug companies (donanemab and lecanemab).

Aducanumab was withdrawn from the market in 2024 (example of an immunological treatment)

How can we demonstrate whole person care when reviewing medication for dementia?

1. Review patient's pill burden

2. Look at analgesia

3. Assess for depression

4. Assess for delirium

5. Is covert administration being used legally?

5. Review care environment

Who are dementia friends?

"A Dementia Friend is somebody that learns more about dementia, how it can affect someone and the small ways they can make a difference in their communities"

The Alzheimer's association encourages this.

What are the 5 NHS England steps in the well pathway for dementia?

1. Preventing well

- provide information for how to reduce risk of getting dementia

2. Diagnosing well

- diagnose in a timely and accurate manner

3. Supporting well

- make sure patients and carers have access to safe high quality health and social care.

4. Living well

- people with dementia can live normally in safe and accepting communities

5. Dying well

- people living with dementia die with dignity in the place of their choosing