Deilium, Dementia (including AD, VaD)

Types of neurological disorders

Delirium, Depression, Dementia (umbrella term)

Other: movement disorder; Parkinson's disease

Delirium

Common presentation of acute illness among older people

15-53% of surgical patients >65

Often occurs with dementia in older hospitalised patients

Cognitive fluctuations over hours/days - often transient

Impaired attention: Deficits in consciousness, attention, orientation

- Restlessness, anxiety, irritability, drowsiness, insomnia

- Distorted perceptions may lead to delusions and violent behaviour

Altered sleep cycles/levels of consciousness

CONSEQUENCES

Long-term cognitive impairment, functional impairment, psychological stress, increased costs, prolonged hospitalization, institutionalization, death

What are the risk factors for delirium?

1) Visual/hearing impairment

2) Cognitive impairment

3) Severe illness

4) Dehydration (increased urea/creatinine ratio), malnutrition

OTHER: >65, male, dementia, delirium history, depression, fall history, low activity, chronic renal/hepatic disease, stroke history, terminal illness, HIV, psychoactive drugs

What are some drug causes of delirium?

Antipsychotics - Chlorpromazine, haloperidol, clozapine

Antidepressants - Tricyclic antidepressants, SSRIs

Antihistamines - Diphenhydramine

Anti-nausea agents - Scopolamine, dimenhydrinate

Antibiotics - Fluoroquinolones

Analgesics - Opioids, NSAIDs

Cardiac agents - Antiarrhythmics, digoxin

Central acting agents - Sedative hypnotics (e.g. BDZ, anticonvulsants)

Corticosteroids

Gastrointestinal agents - Antispasmodics, H2-blockers

management of derilium

Identify and treat underlying causes

Provide environmental and supportive measures

Pharmacological treatment aimed at managing symptoms

- Significant behavioural disturbance -> Antipsychotics

Regular review and follow up

What is dementia?

Progressive impairment of cognition, function, memory and changes in personality & behaviour - sufficient to affect daily life

Not a normal part of ageing - chronic, progressive, and terminal disease

Major symptom: global decline in brain function.

Loss of cognition and ≥1:

• Aphasia (language impairments)

• Apraxia (motor memory impairments)

• Agnosia (sensory memory impairments)

• Abstract thinking (exec. function impairments)

examples: Not recognising family member, Getting lost in own neighbourhood, Forgetting to serve dinner just prepared, Putting phone in fridge

Impairment in social and/or occupational function

NOT EXPLAINABLE by another disorder

What are the warning signs of dementia? (10)

• Challenges understanding visual and spatial info

• Changes in mood and behaviour

• Decreased judgement

• Difficulty performing familiar tasks

• Disorientation to time and place

• Language problems

• Memory loss

• Misplacing things

• Problems with keeping track of things

• Withdrawal from work or social activities

What are the risk factors for dementia?

Physical inactivity, smoking, excessive alcohol consumption, air pollution, head injury, infrequent social contact, less education, obesity, hypertension, diabetes, depression, hearing impairment

subtypes of dementia

Alzheimers dementia

Vascular dementia

Lewy body dementia

Others:

frontotemporal dementia (FTD)

Hard to diagnosed and therefore pt are usually flagged as "mixed dementia" if they have Alzheimer's and vascular pathology

Secondary causes: hypothroidism, alcohol, vitamin B12 deficiency, intracranial lesion, syphillis, normal pressure hydrocephalus, HIV, CJD

What are the management strategies for dementia?

Identify and treat underlying causes, provide environmental and supportive measures, pharmacological treatment aimed at managing symptoms, regular review and follow up.

BPSD SYMPTOM management in dementia

1st line: non-pharm (as meds ineffective)

2nd line: antipsychotics

- modest efficacy in agitation or psychosis

- substantial AE - sedation, gait disturbances, ↑ fall/fracture risk, UTIs, cognitive impairment/confusion, extrapyramidal AE, respiratory complications (pneumonia), cerebrovascular events (stroke), heart rhythm abnormalities, ↑ mortality

- only risperidone is PBS listed for BPSD treatment

- Limited evidence that stopping long-term antipsychotics can be done in older people with dementia and NPS without making their behaviour worse >>> LIMIT ANTIPSYCHOTICS IN DEMENTIA

CHALLENGES: Inappropriate prescribing common in dementia

Use of inappropriate medicines increases by 17% following dementia diagnosis

Is there limited evidence supporting the discontinuation of long-term antipsychotics in older people with dementia and neuropsychiatric symptoms (NPS)?

Yes. limited evidence that stopping wont make their behaviour worse

Role of the Pharmacist in dementia

- Identify patients with mild cognitive impairment

- Identify medication-induced cognitive changes

- Advice on medication selection

- Monitor outcomes of therapy

- Engage with support groups

- Encourage realistic expectations of medication therapy

ALZHEIMER'S DISEASE (AD)

Most common dementia type

Abnormalities in brain structure - disrupts neuron health

- Memory failure, Personality changes, Increasing inability to manage ADL

8-10 year life span after diagnosis

Risk factors for Alzheimer's disease

Age

Family history

Down's syndrome

Head Trauma (esp. late in life)

Female gender - mixed results

Ethnicity - Caucasians have lowest risk

Late-onset depression (>65)

Mild Cognitive Impairment (MCI)

Pathological markers of Alzheimer's disease

THREE consistent neuro-pathological markers:

1. Accumulation of beta-amyloid senile plaques,

2. Neurofibrillary tangles

3. Neuronal degeneration

= Destruction of cholinergic neurones + ↓ ACh conc [years before sx onset] = clinical symptoms

Symptoms of Early-moderate stages of AD

- Memory lapses - i.e. frequent memory difficulties, especially recent events

- Forgetting well-known people or places

- Vagueness in everyday conversation

- Loss of enthusiasm for previously enjoyed activities

- Longer to do routine tasks

- Inability to process questions and instructions

- Deterioration of social skills

- Emotional unpredictability

Symptoms of severe stages of Alzheimer's disease

- Lost in own home

- Unable to recognise family and friends

- Unable to speak (aphasia)

- Judgment extremely impaired

Symptoms of final stages of Alzheimer's disease

Unable to eat, walk, communicate

Management of Alzheimer's disease

NON-DRUG TREATMENT - counselling, social support, occupational therapy, respite care, general nursing, environmental and behavioural therapy

SYMPTOMATIC THERAPY - Behavioural + cognitive symptoms, ADL

DISEASE-MODIFYING AGENTS - alter progression, delay onset

PHARMACOLOGICAL treatments for Alzheimer's disease

None prevent or modify pathology

• Cholinesterases - donepezil, Exelon, reminyl

• Neuropeptide-modifying agent - Memantine

NEW TREATMENTS - Lecanemab (Leqembi)

• Approved for mild AD and mild cognitive impairment due to AD

• mAbs bind to and remove amyloid-β protein from brain

• Slows cognitive decline in early AD, No benefits <65 or women, Delayed disease progression by 27% (about 5 mths)

• IV infusion every 4 weeks

• Significant AE - infusion-related reactions, fever, flu symptoms, N&V, dizziness, changes in heart rate, SOB, brain swelling (rare)

POTENTIAL Tx - Statins: association between high serum cholesterol and ↑ AD susceptibility

What are some new treatments for Alzheimer's disease?

- mAbs bind to and remove a protein called amyloid-β

- Lecanemab (Leqembi) approved for mild Alzheimer's disease and mild cognitive impairment due to AD

A phase 3 clinical trial found that Lecanemab slowed cognitive decline in people with early AD

- Lecanemab is given as an IV infusion every 4 weeks

NOT available in australia

What is the association between high serum cholesterol and AD susceptibility?

High serum cholesterol is associated with increased AD susceptibility.

What are the pharmacological treatments for AD?

Cholinesterase inhibitors (ChEI): Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Reminyl).

Memantine: Neuropeptide-modifying agent.

Cholinesterase inhibitors

MOA: ↓ ACh breakdown, ↓ deficiency of cholinergic neurotransmitter activity

INDICATIONS: mild-mod AD

EFFICACY: Modestly improved cognition

Modestly ↓ rate of cognitive and functional decline

Beneficial effects within 3-6 months

Short term (1-2 years) stabilisation or improved cognitive function - AD pts will eventually regress

All 3 drugs (donepezil, rivastigmine, galantamine) have similar efficacy and AE

- If efficacy/AE are a concern --> switch

AE: Cholinergic stimulation

- Nausea / vomiting

- Diarrhea

- Anorexia (weight loss)

- Dizziness

- Dyspepsia

- Agitation

- Vivid dreams

- Urinary incontinence

- Depression

ChEI DDI

- Anticholinergic drugs - may antagonise ChEI effects, cognitive decline

- Galantamine: Co-prescription with CYP2D6 or CYP3A4 agents may lead to increase in its concentration and possibly increasing cholinergic adverse effects

- Anticholinesterases may cause bradycardia- Monitor for other drugs that slow heart rate

- Anticholinergic burden: use of medicines could increase risk of dementia (antidepressants, antipsychotics, antihistamines, anticholinergic drugs)

Duration of therapy for AD with ChEI

ChEI inhibitors can produce short term ( 1-2years) stabilisation or improvement in cognitive function

- People with AD will eventually regress

- Monitoring progress is essential to inform treatment options- review 3 and 6 months

- Withdraw treatment or switch if significant adverse effects, poor compliance or ongoing decline

- Strict rules on PBS Authority: clear documentation and clear diagnosis of AD

Memantine

MOA: NMDA antagonist

May block glutamine excitotoxicity

May improve function of hippocampal neurons

(AD may be associated with excess glutamate)

indicated for moderate-severe AD

EFFICACY:

Good evidence for AD, limited data for others

Small benefit in thinking, performing daily activities

Mild AD - likely same as placebo

Vascular Dementia - small benefit

Unclear role in severe dementia

Ethical issues - limited data, Cost

AE: Agitation, diarrhoea, incontinence, dizziness, insomnia, fatigue, headache, hallucinations

- Similar withdrawal rates in treatment and control groups

Definition of vascular dementia (VaD)

Occurs when blood supply to brain interrupted by blocked/diseased vascular system

Describes several syndromes characterised by different pathology and mechanisms

types of VaD

1) Mild vascular cognitive impairment

2) Multi-infarct dementia

3) Vascular dementia due to a strategic single infarct

4) Vascular dementia due to lacunar lesions

5) Vascular dementia due to haemorrhagic lesions

6) Sub-cortical (Binswanger disease) dementia

7) Mixed dementia (combination of AD and VaD)

2,6,7 are most common

risk factors of VaD

Age

High blood pressure

Smoking

Diabetes

High cholesterol

Lack of physical activity

History of mild warning strokes

Evidence of disease in arteries elsewhere

Heart rhythm abnormalities

VaD is slightly more common in men than women

Symptoms of VaD

PHYSICAL:

- Memory problems, forgetfulness

- Dizziness

- Leg or arm weakness

- Lack of concentration

- Moving with rapid, shuffling steps

- Loss of bladder or bowel control

Can be used to differentiate with AD

BEHAVIOURAL:

- Depression

- Slurred speech

- Language problems

- Abnormal behaviour

- Wandering/getting lost

- Laughing/crying inappropriately

- Difficulty following instructions

- Problems handling money

VaD Progression

May progress in a 'stepped' manner.

Symptoms may suddenly worsen due to stroke and then remain the same for time.

If another stroke occurs, symptoms may worsen again.

When VaD has been caused by several smaller strokes, a more gradual progression of symptoms is likely to be experienced.

Lifespan for people with VaD is approximately 5 years.

- Death will be caused by a stroke or heart attack

Symptoms at different VaD stages

EARLY-MIDDLE STAGE

• Symptoms similar to other dementia forms

• Confusion and speech problems commonly observed

• Agitation common, may increase over time

LATE STAGE

• Visual disturbance

• Incontinence - complete loss of bladder control

• Motor disability observed in walking

• Speech loss

Management of VaD

NO MEDICATIONS TO TREAT

Disease-modifying agents targeting vascular risk factors - no beneficial effect in VaD

Prevent and reduce severity + slow progression

• Control underlying risk factors for cerebrovascular disease - hypertension, DM

• Healthier lifestyle - stopping smoking, regular exercise, healthy diet, and moderate alcohol intake

• Rehabilitative support - physiotherapy, OT, speech therapy to regain lost functions

POTENTIAL TREATMENTS - Statins

• Significantly decrease stroke risk in vascular patients

• May reduce incidence of post-stroke dementia

• Decrease coronary events in primary and secondary CHD prevention

• Unclear if significant therapeutic effect in dementia

principles of care for dementia

Multi-disciplinary

- Patient

- Family or other carers

- Medical and other formal support services

Dementia is a progressive disease and at each stage need to address:

- Functional, psychiatric and behavioural changes

- Concurrent physical illness

- Carers' needs

Recognise that dementia subtype may impact management

Support & caring approaches for pt living with dementia

1. Support the person to live well at home, for as long as possible

2. Support the person to continue with their hobbies, activities and interests

3. Learn about dementia, so you're better equipped to manage changes

4. Access support services and programs to maintain your health and wellbeing

clinical practice guidelines for dementia care

1. Pt centred care using the 10 principles of dignity and care

2. Improving QOL, maintaining function and maximising comfort throughout disease trajectory. Emphasis on goals changing over time

3. Health and aged care professionals use language that is consistent with the Dementia language guidelines and "Talk to me" communication guide

Living well with dementia and delaying functional declineManaging symptoms: staff training, non-pharmacological approaches Training and supporting families and carers

Strategies for dementia care

1) OCCUPATIONAL THERAPY

• Includes COPE (Care of Persons with Dementia in their Environments)

• OT home visits to optimise home environment and performance in ADLs, caregiver training and info on caring

• Instrumental ADL improvement, less decline in ADLs over 12 months, less caregiver assistance needed in ADLs

2) EXERCISE (aerobic, resistance)

• May attenuate rate of decline but cannot make firm conclusion

• Improved ADL scores, No QOL benefit

• INSUFFICIENT EVIDENCE to suggest increased gait speed, strength, balance

3) MANAGING SYMPTOMS - Pharmacological treatments:

- Acetylcholinesterase inhibitors: Donepezil, Galantamine, Rivastigmine

- Neuropeptide modifying agents: NMDA-R antagonist (Memantine)

+ Practical challenges: admin, monitoring SE, when to stop?

medication management for pt with dementia

Late dementia stages: 90% of carers actively involved in medication management

INCLUDES:

- maintaining supply

- assisting with administration

- communicating with health care providers

- monitoring for medication-related harm

- making decisions about medications

Effective safe medication management is vital:

Improves care -> decrease adverse health outcomes -> decrease caregiver burden in medication management

training and supporting carers for pt with dementia

- Carer training through occupational interventions can maintain/improve pt function

- Carer training is also effective in behaviour management

- Who cares for the carer?

caregiver challenges in pt living with dementia

Carers have a higher rate of:

- Depression: 23-85%

- Anxiety: 16-45%

- Physical illness: ↑ health problems including CV problems

- Doctor visits and use of prescription medications

- Smoking, drinking alcohol, and poor sleep patterns

- Medication use than non-carers

- Unpaid workforce

- Greater burden caring for dementia patient than for patient with physical disability

- Social isolation, restriction of personal interests

- Cultural issues

- Gender issues (personal care)

- Pre-existing relationship can influence behaviours and function, personality and own health all have an impact

-> 55-90% have positive experiences

support services for pt living with dementia

- National Disability Insurance Scheme (NDIS) for younger Australians.

- DVA provides a range of accessible and extensive services.

- MyAgedCare, a single portal for access to aged care services.

- Cultural and linguistic diversity provided.

- Commonwealth Home Support Program (CHSP).

- Home Care Packages (HCP) - Consumer-directed care, Means-tested payment, Case Management.

- Medication review (pharmacist and GP)

SUPPORT FOR LATER STAGES

- Respite care

- Residential care

- End of life care

Delirium vs Dementia

1. Delirium- Acute, dramatic onset, common causes= illness (UTI in old people), toxin, withdrawal, usually reversible. Poor attention and fluctating arousal level.

2. Dementia: Chronic, gradual onset, usually not reversible, attention usually unaffected and normal arousal level.

ACCOMPANYING SYMPTOMS of dementia

BPSD: behavioural & psychological sx of dementia

80-90% of dementia pts

Neuropsychiatric symptoms of disturbed perception, thought content, mood or behaviour

Delusions, hallucinations, agitation, anxiety, aggression, wandering, sleep disturbance, depression, withdrawal, hopelessness

AD Cholinergic Hypothesis

Enhance cholinergic transmission to treat

Cholinergic neuron degeneration occurs early and is most severe

NB: Cholinergic neurons release ACh as their primary neurotransmitter

AChE - enhances ACh hydrolysis 100x106 >>> terminates cholinergic neurotransmission