Anticholinesterase inhibitors remain the mainstay pharmacological treatment option for Alzheimer’s disease. With an ever ageing population and the prevalence of Alzheimer’s disease and other subtypes of dementia predictably increasing, there is huge pressure on healthcare systems to support the increased workload both in a clinical and cost effective manner. This article gives a brief outline of the treatment options and considerations for the ongoing management of patients with Alzheimer’s disease as well as the estimated and fragmentary cost burden on the healthcare economy in the UK.
Dementia and Alzheimer’s disease
Dementia is the umbrella term used to define the notable characteristics that transpire when the brain is subjected to certain diseases or conditions. Progression of the disease as a result of a degenerative derivation tends to exhibit symptoms of global impairment of intellect, memory and personality, but without impairment of consciousness. Deterioration in emotional control, social conduct and motivation are typically affiliated with disease progression.
There are approximately 850,000 people in the UK living with dementia.1 Alzheimer’s disease is the most common type thought to be affecting about 500,000 people.2 Aetiology of the disease is not fully understood and the cardinal presenting signs include an impaired ability to learn new information or to recall previously learned information, nominal and comprehensive dysphasia, dyspraxia, agnosia and impairment of executive function. Behavioural changes including wandering, agitation and aggression are common and persecutory delusions and depressive symptoms can also challenging.3
The pathophysiology of Alzheimer’s disease is multifactorial in nature. Neurofibrillary tangles and senile neurotic plaques observed principally in the hippocampus damage typical brain function in the early stages affecting day-to-day memory. It is the neurochemical changes and deficits in cholinergic pathways which are of particular interest from a pharmacotherapy perspective. A marked reduction in the neurotransmitter acetylcholine is observed in patients with Alzheimer’s disease4 and this is definitively verified in brain tissue analysis post-mortem.
Financial cost of dementia
Research conducted by the Alzheimer’s Society estimates that the economic impact of dementia in the UK is £26.3 billion, at an average cost of £32,250 per person. As a proportion – £4.3 billion of healthcare costs, £10.3 billion of social care (publically and privately funded) and £11.6 billion of unpaid care (equating to 1.34 billion hours of unpaid carer support).5
With forecasted numbers of patients diagnosed with dementia escalating the economic burden on the health and social care economy is set to increase dramatically. The King’s Fund proposes that the financial burden of dementia will enlarge to £34.8 billion in 2026.6 The Department of Health ‘Dementia Strategy’ evidence suggested that the financial implications of dementia could be significantly reduced by improvement in early diagnosis, treatment and support in order to plan and avoid future hospital admissions through improved clinical management.
The acetylcholinesterase inhibitors donepezil, rivastigmine and galantamine in addition to the NMDA receptor antagonist memantine are the mainstay evidenced based pharmacotherapy options in the treatment of Alzheimer’s disease. The NICE reappraisal in 2011 revaluated their use in the management of the disease and endorsed that donepezil, galantamine and rivastigmine should be considered as an option for managing mild as well as moderate Alzheimer’s disease, and memantine should be considered as an option for managing moderate Alzheimer’s disease for people who cannot take acetylcholinesterase inhibitors, and as an option for managing severe Alzheimer’s disease.7
Prescription data in the UK indicates an upward trend in prescribing practice over a number of years and this is set to continue. Indeed this is hugely beneficial in relation to the broader economic burden. The Department of Health National Dementia Strategy publication made recommendations supporting the early diagnosis and treatment of the disease.
Consequentially the patient and caregivers have the benefit of improvement in cognitive capacity, global functionality, maintaining independence and managing activities of daily living for a longer period than without therapy. Treatment also delays time to institutionalisation and multifactorial analysis indicates this is both clinically effective and cost effective per QALY gained. Regrettably the use of pharmacotherapies has only shown benefit in improving symptom control and not the progression of the disease.7
Given that the pathophysiology of Alzheimer’s disease involves deficits in the neurotransmitter acetylcholine it is vitally important to optimise medications with the objective of reducing the anticholinergic side effect burden. It is reported that approximately half of all patients diagnosed with dementia routinely take medications that exacerbate or contribute to their cognitive deficit, increasing health costs in the process and contribute to an increase in mortality.
The Aging Brain Program of the Indiana University Center for Aging Research developed the Anticholinergic Cognitive Burden (ACB) scale to facilitate clinicians and pharmacists in making decisions on appropriate and safe pharmacotherapies in this group of patients by reducing the risk of harm by classifying medications by the severity of their anticholinergic effects on cognition.
Avoidance of all anticholinergic medications is not always feasible in clinical practice, but improving awareness of the issue is achievable.8 Some common medications with anticholinergic properties which contribute to the risk of harm include tricyclic antidepressants, benzodiazepines, Z-drugs, opioids, antihistamines, oxybutynin, mebeverine, digoxin, warfarin and prednisolone.
Risperidone is the only antipsychotic licensed to manage behavioural and psychological symptoms in dementia for a maximum of six weeks – there has been an increase in its use over the last few years as a percentage of all antipsychotics. The Bannerjee Report9 highlighted the risks of inappropriate prescribing of antipsychotic medications in patients with dementia, which are causally linked to “1800 extra deaths and 820 extra serious adverse events such as stroke per year”.
The benefits of therapy are often short-lived with an estimated 80% of patients having no benefit in symptoms with therapy whatsoever. Nationally, complications occur on transfer between care sectors with hospital discharge letters documenting an antipsychotic rationale and follow up plan in only 29% of cases. Antipsychotics should only be initiated in this group of patients if they pose a serious risk of harm to themselves or other caregivers and should not be considered a mainstay therapy for ‘problematic’ patients.
Delirium is an acute, fluctuating change in a person’s awareness, often characterised by disorientation or confusion, or through difficulties with memory.10 Presentation can be hyperactive, hypoactive or mixed in nature. It is classified as a medical emergency and often triggered by precipitating and/or predisposing factors such as infection, fractured neck of femur, operation, a known diagnosis of dementia or inappropriate pharmacological therapies.
Delirium results in increased length of stay in hospital and evidence demonstrates its link in increasing the risk of developing dementia, accelerating the progression of dementia and the risk of death.11 Focus should be directed on preventing delirium by managing any known risk factors in patients with dementia, including medications.
Preventing delirium in people at risk during their admission to hospital is anticipated to bring cost savings and release resources to the NHS. This is through a reduction in bed stay, a reduction in hospital-acquired complications and by reducing the anticholinergic burden of medications through medicines optimisation. The NICE guideline is based on the best available evidence and will provide doctors, nurses, pharmacists and care assistants with a gold standard for effective treatment.
Over the coming years, healthcare systems need to develop a universal approach to evidence based care planning for the cognitively frail. The best evidence for management to improve outcomes, by way of delirium prevention, derives from the work of Sharon Inouye,12 which shows that a low tech/high touch approach to care using a targeted multi-component interventions in six key areas (including mobility, nutrition and hydration, sleep promotion, cognitive impairment, sensory impairment), can significantly reduce the risk of delirium occurring, reduce length of stay and overall hospital costs.
This approach has been evaluated for cost-effectiveness in the UK13 who concluded that such an approach is cost effective when applied to patients at medium and high risk of developing delirium during their hospital stay, which includes all people with dementia as well as the frail elderly. Multi-component targeted intervention to prevent delirium cost on average £510 less than usual care (£12,690 versus £13,200) for a higher QALY gain (2.22 versus 2.14 for usual care).