Dementia

Introduction

Dementia is a life-limiting, progressive syndrome characterized by cognitive and functional decline.

The common causes of dementia are Alzheimer disease (50 to 75% of cases), vascular dementia (20 to 30%), frontotemporal dementias (up to 10%), and dementia with Lewy bodies and Parkinson disease dementia (up to 10%).

  • Many patients have more than one subtype of dementia (mixed dementia); the most common combination is Alzheimer disease and vascular dementia.



Risk Factors

Increasing age is the most significant risk factor.

The "Dementia prevention, intervention, and care: 2020 report of the Lancet Commission" identified 12 potentially modifiable risk factors for dementia - addressing these factors may prevent or delay dementia.



Behavioural and Psychological Symptoms of Dementia (BPSD)

Over 90% of patients with dementia will experience behavioural and psychological symptoms of dementia (BPSD). These symptoms can have a significant effect on the patient and their family, carers or significant others, and precipitate entry into residential aged care.

  • Delusions - distressing beliefs
  • Hallucinations
  • Agitation - easily upset, repeating questions, arguing or complaining, hoarding, pacing, inappropriate screaming, crying out or disruptive sounds, rejection of care (e.g. bathing, dressing, grooming), leaving home
  • Aggression - physical or verbal
  • Depression or dysphoria
  • Anxiety - worrying, shadowing (i.e. following carer)
  • Apathy or indifference
  • Disinhibition - socially or sexually inappropriate behaviour
  • Irritability or lability
  • Motor disturbance - repetitive activities without purpose (e.g. wandering, rummaging)
  • Night-time behaviours - waking and getting up at night



Approach to Managing Dementia

The approach to managing dementia is primarily supportive and nonpharmacological.

  • Ensure the patient understand their dementia diagnosis
  • Reduce the impact of cognitive and functional decline on day-to-day life
    • Determine and address the patient's unmet needs (e.g. organise additional help with personal care or more complex activities of daily living).
    • Encourage the patient to engage in activities that promote functional independence and involve their family, carers or significant others if possible.
    • Assess whether the patient takes their drugs properly and offer them medication aids, if appropriate.
    • Consider whether any drugs could be causing cognitive impairment (e.g. anticholinergics, psychotropics [especially benzodiazepines]) and consider deprescribing them.
    • Review driving ability.
  • Avoid using physical restraint to manage BPSD - it usually adds to the patient's distress and disorientation.
  • Promote general health and wellbeing.
  • Regular review the patient's drug regimen - aim to reduce polypharmacy and administrative burden.
  • Encourage the patient to appoint a substitute decision-maker.



Pharmacologic Therapy

Pharmacological therapy for cognitive impairment is palliative - acetylcholinesterase inhibitors and memantine can temporarily improve or stabilise symptoms of some types of dementia, but are not curative and do not modify disease progression.

  • Acetylcholinesterase inhibitors (i.e. donepezil, galantamine and rivastigmine)
    • All appear to have similar efficacy for Alzheimer dementia.
    • Their modest benefits must be weighed against their significant adverse effects, which include prominent gastrointestinal adverse effects (particularly nausea, vomiting and anorexia), weight loss, vivid dreams, urinary incontinence, tremor, cramps, bradycardia, dizziness and drowsiness.
  • Memantine
    • For people with moderate to severe Alzheimer dementia (monotherapy or in combination with acetylcholinesterase inhibitor).

If the patient tolerates and appears to benefit from an acetylcholinesterase inhibitor or memantine, continue it for as long as quality of life is maintained - that is, until the patient has end-stage dementia (e.g. lost independent mobility, can no longer swallow) and therapy is no longer achieving their goals and preferences.

  • Stopping an acetylcholinesterase inhibitor or memantine can cause an irreversible or more rapid decline in function and cognition, and precipitate severe BPSD.
  • However, this does not preclude stopping treatment at the request of the patient or their substitute decision-maker.
  • It is preferable to avoid abruptly stopping therapy - instead, slowly reduce the dosage (e.g. halve the dosage every 4 weeks until the lowest dose possible is used for 4 weeks, then stop) and regularly assess the patient during the process to:
    • Reduce the risk of severe withdrawal reactions (e.g. agitation, aggression, hallucinations, impaired consciousness).
    • Reduce the impact of cognitive, functional and behavioural or psychological symptoms if they reoccur (these changes can be irreversible).
    • Determine the minimum effective dosage if the drug cannot be stopped.

Aducanumab was granted accelerated FDA approval for treatment of Alzheimer disease in adults in June 2021.

  • However, the approval of this medication has led to significant controversy since the surrogate endpoint of reducing amyloid beta plaques is not yet established as predicting clinical benefit and treatment-related adverse effects (cerebral edema and/or hemorrhage) mandate ongoing monitoring.

Pharmacological management of BPSD is only indicated if either:

  • Nonpharmacological methods have not improved symptoms of agitation, aggression, or psychosis that are distressing for the patient, or the patient is considered a threat to themselves or others.
    • Use the lowest effective dose for the shortest period of time and avoid polypharmacy.
    • Alzheimer disease: Risperidone, olanzapine and to a lesser extent, aripiprazole.
  • The patient develops depression and meets the criteria for antidepressant use.
    • Avoid using an antidepressant with significant anticholinergic effects (e.g. tricyclic antidepressants), which can impair cognition and increase the risk of delirium.



Herbal and Dietary Supplements

Herbal (e.g. ginkgo biloba, ginseng) and dietary supplements (e.g. omega-3 fatty acids, nutritional drinks, vitamin D, vitamin E) do not have a role in the management of dementia. Studies have failed to show clinically significant improvements.

  • Avoid vitamin E - it has been associated with an increase in mortality.



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