Diagnosis and management of dementia

Introduction

Dementia refers to a range of cognitive and behavioural symptoms that can include memory loss, confusion, communication difficulties, change in personality, as well as issues with problem solving and reasoning. It often affects a person’s activities of daily living (ADL), such as undertaking personal care, dressing and cooking. Dementia is a progressive illness, as symptoms gradually get worse over time, and there is currently no cure. The degree of progression will vary from person to person^​1​.

There are various types of dementia — the most common being Alzheimer’s disease and vascular dementia. Dementia typically affects people aged over 65 years but can also affect younger people^​2​.

The Alzheimer’s Society estimates that around 982,000 people currently live with dementia in the UK. In addition, the number of people affected by dementia is expected to rise to 1.4 million by 2040, as the UK population ages^​3​. 

In the UK, the Alzheimer’s Society estimated the economic cost of dementia to be £42bn in 2024 and for this to rise to £90bn by 2040^​3​. The total cost of dementia consists of healthcare, social care and unpaid care contributed by family and friends of the people with dementia^​3​. 

In 2018, dementia was the leading cause of death in the UK, according to the Office for National Statistics^​4​.

Pharmacists are increasingly assuming the role as medicines experts within the multidisciplinary team and are unique in being able to provide structured medication reviews. As patients with dementia may also be living with other long-term conditions, the risk of polypharmacy is likely to be an ongoing issue, which can be partly addressed through regular, comprehensive, holistic medication reviews. Pharmacy professionals may also contribute to patient care by calculating and addressing the anticholinergic burden (ACB) score of medicines. 

A high ACB score can add to or exacerbate cognitive decline in all patients, not just those living with dementia. Medication reviews are necessary in both primary and secondary care settings, and every opportunity should be made to offer this to the patient and their family or carer. Access to medications and effective counselling for patients and/or carers is also necessary to ensure medications are used effectively and safely. 

Types of dementia

There are various types of dementia, although more than 90% of patients will live with one of the four main types of dementia^​5​. Each type has different symptomology; however, the end stage of dementia tends to be similar^​6​.

Alzheimer’s disease

Alzheimer’s disease is the most common sub-type of dementia. It is known as a physical disease, as part of the brain becomes damaged by proteins, such as amyloid, that would otherwise be broken down and removed from the body through natural processes. As a result, nerve cell damage and death occur, which eventually leads to a decline in cognitive function. Owing to these degenerative processes, a loss of brain tissue may also be evident. Several neurotransmitter systems are affected by Alzheimer’s disease. The neurotransmitter acetylcholine is affected by a loss of cells that produce it, affecting the cholinergic system, which is involved in memory, attention, mood, movement and learning. Other neurotransmitter systems affected by Alzheimer’s disease include noradrenaline, dopamine, serotonin, glutamate and gamma-aminobutyric acid^​6​. 

The cause of Alzheimer’s disease is largely unknown; however, there is new evidence to suggest that, as well as age, lifestyle and the environment, genetics can also be a causative factor for developing Alzheimer’s disease^​7​.

Two different types of genes are involved in Alzheimer’s disease: faulty genes and risk genes. Although, faulty genes are rare, they are extremely likely to cause Alzheimer’s disease in those that carry one of the genes, with the onset of symptoms being at a younger age. Risk genes increase or decrease the likelihood of developing Alzheimer’s disease; however, the environment and lifestyle may be associated factors to determine if a person will develop the disease. APO4 is the most significant of all the risk genes. Individuals who carry two APO4 genes may develop symptoms by the age of 65 years. Research published in 2024 has confirmed a link between the presence of amyloid protein in cerebrospinal fluid and in the brain tissue of patients who carry two APO4 genes^​7​.

Vascular dementia

Vascular dementia is the second most common type of dementia, which is associated with common long-term conditions, such as hypertension, stroke and transient ischemic attack (TIA), diabetes mellitus, atrial fibrillation (AF) and smoking.

Other risk factors include family history and male gender^​6​. 

This type of dementia is largely preventable as good control, or the absence of the previously mentioned comorbidities, reduces a person’s risk of developing the condition. Hypertension is the most common cause of vascular dementia^​6​. 

Ongoing efforts within primary care organisations to support patients with hypertension, AF and diabetes in achieving good control of their condition will have the added benefit of reducing the risk of developing vascular dementia.

There is evidence to suggest the use of statins as a primary or secondary prevention may lower the risk of developing vascular dementia. The use of clopidogrel as secondary prevention following a stroke or TIA may also help prevent the development of vascular dementia^​6​.

Vascular dementia has a rapid onset and fast progression, which can often be distressing to patients. Patient’s may experience change in gait, such as a wide shuffling gait. Other symptoms will include cerebral ischemia — presenting as a TIA — and seizures^​6​. 

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is diagnosed solely on symptomology. Two out of three of the following confirms the presence of DLB: 

• Recurrent visual hallucinations;
• Change in cognition;
• Sudden Parkinsonian symptoms. 

Patient’s with DLB are particularly sensitive to antipsychotic medications and experience extra-pyramidal side effects, such as rigidity, pyrexia and collapse, if these are taken. The characteristic cognitive decline is also present in this type of dementia; however, memory and visuospatial abilities may be unaffected. Other symptoms include recurrent falls, syncope and loss of consciousness^​6​.

Mixed dementia

Mixed dementia is when multiple types of dementia manifest in an individual. For instance, a patient with Alzheimer’s disease plus cerebrovascular disease or a patient with vascular dementia and evidence of Alzheimer’s disease^​6​.

Other forms of dementia

Frontotemporal dementia commonly occurs in people under the age of 65 years. It is characterised by a change in personality and behaviour owing to damage to the frontal and temporal areas of the brain. Memory loss may not be evident in the earlier stages of the disease; however, in the latter stages, symptoms may resemble Alzheimer’s disease.

In subcortical dementia syndromes, memory and difficulties with language may not be affected as much as the other types of dementia but changes in personality prevail^​6​.

Symptoms

The symptoms of dementia will differ depending on the type diagnosed, as each patient is unique in terms of the type and severity of symptoms experienced. However, there are some commonly known symptoms of dementia, which include^​8​:

• Memory loss — both short term and long term;
• Forgetting where things were left;
• Easily getting lost in places otherwise known;
• Difficulty remembering the time of day (e.g. not knowing whether its morning or afternoon);
• Difficulty making choices (e.g. when going shopping);
• Being unable to use reasoning and decision-making skills;
• Difficulty communicating (e.g. struggling to remember common words, names and places);
• Difficulty reading and understanding;   
• Mood changes (e.g. becoming increasingly irritable or angrier than usual);
• Changes in personality (e.g. loved ones may no longer ‘recognise’ a person with dementia);
• Incontinence.

Aetiology and risk factors 

Dementia is largely diagnosed in older people; however, it should not be characterised as a natural part of growing old. It is damage to the brain, which causes the symptoms seen in the different types of dementia.

Research has shown that various modifiable lifestyle factors, risk factors and comorbidities can contribute to the development of dementia. Some of these are listed below^​2​:

• Hypertension^​9​; 
• Sedentary lifestyle^​10​;
• Excess alcohol consumption^​11​;
• Smoking^​12​;
• Obesity owing to links to cardiovascular disease (CVD), cerebrovascular disease and type 2 diabetes mellitus^​13​.

Full discussion of the risk factors for dementia is outside the scope of this article. For more information, refer to the National Institute for Health and Care Excellence’s (NICE) clinical knowledge summary of dementia.

Diagnosis and assessment 

As dementia can be slow to progress, identification may be delayed. It can take many years before a patient receives a formal diagnosis.

Diagnosis of dementia involves taking a comprehensive history to rule out any reversible causes of cognitive impairment. The initial history should include the following^​1​:

• Cognitive symptoms;
• Behavioural symptoms;
• Psychological symptoms.

Other important parts of the history include^​14​: 

• Onset of symptoms;
• Their medication history, including medications with anticholinergic side effects, over-the-counter medications, illicit drugs and alcohol use;
• Any comorbidities, such as CVD, cerebrovascular disease, depression and Parkinson’s disease;
• Presence of infection.

Acquiring a comprehensive history from the patient and their family/carer is essential in establishing how these symptoms affect their daily life. 

Physical examinations and assessment of biochemical tests, such as bloods tests and urine samples, are also necessary to rule out any other possible causes of cognitive decline^​1​.

Cognitive testing

There are several validated cognitive tools available to help clinicians evaluate a patient’s cognitive impairment^​1​. 

One of the most commonly used cognitive tests in practice is the ‘Six-item cognitive impairment test’ (6-CIT). It takes just two minutes to conduct and involves asking the patient a series of questions to determine their level of cognition with scores assigned based on the answers given. The 6CIT dementia screening tool is summarised in Table 1^​15​.

A score of 0–7 is considered normal and requires no onward referral. A score of 8–9 is considered mild cognitive impairment and may require a specialist referral. A score of 10–28 indicates significant cognitive impairment, which requires referral to specialist memory services^​15​.

Other score-based cognitive tools (e.g. the ten-point cognitive screener and six-item screener) are also available^​1​. 

Another assessment tool is the Mini-Cog cognitive instrument, which takes just three minutes and asks the patient to recall three words and draw a clock with a given time. It is known to be as effective as other cognitive tests and can differentiate between different types of dementia^​16​. The patient is then scored based on the answers they provide.

If dementia is still suspected in the absence of reversible causes of cognitive decline, referral to a specialist dementia clinic or memory service is advised^​1​. Rapidly progressive dementia may be referred to a neurological service with capacity for advanced testing for other brain disorders with characteristics similar to dementia, such as Creutzfeldt–Jakob disease (CJD)^​1​. 

Specialist dementia diagnostic services or memory clinics can diagnose a dementia subtype using a number of validated criteria, such as^​1​:

• National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease;
• National Institute of Neurological Disorders and Stroke NINDS–Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria for vascular dementia;
• International consensus criteria for DLB;
• Movement disorders society criteria for Parkinson’s disease dementia;
• International criteria for CJD.

Further tests can be offered to the patient if it is required to rule out reversible causes of cognitive decline or if it may support management of their particular type of dementia. Examples may include structural imaging testing (e.g. CT and MRI scans) and examining cerebrospinal fluid to identify the presence of proteins present in different types of dementia^​1​.

Following formal diagnosis of dementia, ongoing care is managed by the specialist dementia clinics or memory services^​1​.

Management

The aim of treatment is to preserve a person’s independence and maintain their cognitive function. A holistic approach is required to effectively manage patients with dementia. Non-pharmacological treatment plays a large role in the treatment of dementia and will involve social support, provision of carers, community dementia teams, day centres, befriending services facilitated by social prescribing teams, primary care and care homes^​17​. Each person’s experience of dementia will be unique, and an individualised, person-centred approach should be adopted. 

In addition, pharmacological treatment of both cognitive and non-cognitive symptoms plays an important role in the management of dementia^​17​.

Acetylcholinesterase (AChE) inhibitors are a class of medications that are most used to treat various types of dementia. Their mechanism of action involves the enzyme, AChE, inhibiting the production of acetylcholine, which is the neurotransmitter responsible for memory, attention, mood, movement and learning. AChE inhibitors prevent the breakdown of acetylcholine, preventing some of the symptoms involved in Alzheimer’s disease^​18​.

Donepezil, galantamine and rivastigmine are AChE inhibitors currently available for the treatment of mild-to-moderate Alzheimer’s disease in the UK. They are oral medications and are the main form of treatment for most types of dementia^​1​.

Selection of AChE inhibitors should be individualised to the patient, depending on personal choice, tolerance, drug interaction, other comorbidities and local formularies. The medication with the lowest acquisition cost should be prioritised in the absence of the above AChE inhibitors^​1​.

Memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, may be used as monotherapy for patients with moderate or severe Alzheimer’s disease. Those who have an intolerance or contra-indication to AChE inhibitors may be prescribed memantine in the case of moderate disease. In Alzheimer’s disease, excessive amounts of glutamate are released, which causes overstimulation of NMDA receptors and, ultimately, results in cell death. Memantine binds to the NMDA receptors to prevent this process^​6​. AChE inhibitors and memantine may also be used together as add-on therapy in cases of moderate or severe Alzheimer’s disease if monotherapy alone is insufficient^​1​. Treatment with these medications is usually long term. 

Currently in the UK, AChE inhibitors and memantine are only licensed for Alzheimer’s disease, although these medications may be used off-label for other types of dementia. For more information on NICE treatment guidelines for varying types of dementia, see Table 2^​1​.

Clinicians both in primary care (i.e. GPs, pharmacists and nurses with a special interest in dementia) and secondary care (i.e. geriatricians, neurologists, psychiatrists and pharmacists) can initiate these medications. Treatment may then be continued by the patient’s GP under a shared care protocol^​1​.

The following information summarises the available formulations, dosage and interactions for donepezil, galantamine, rivastigmine and memantine. For complete information about each medication, see the summary of product characteristics^​19​.

Donepezil

Donepezil is available as a tablet, orodispersible tablet and liquid formulation. Doses start at between 5mg and 10mg daily, usually taken at bedtime. Some of the main side effects experienced by patients may include diarrhoea, aggression and agitation, hallucinations, sleep disorders and fatigue. Common interactions include inhibitors of cytochrome P450 isoenzymes 3A4 (e.g. ketoconazole, ritonovir) and to a lesser extent 2D6 (e.g. fluoxetine, paroxetine^​6​). Donepezil should be avoided in patients who experience bradycardia or who concomitantly take medications that lower the heart rate. Donepezil is also recommended to be used in caution with those affected by gastrointestinal (GI) ulceration^​19​.

Galantamine

Galantamine is available as modified-release tablets and liquid. Doses start from between 8mg and 24mg in 24 hours. Some of the main side effects are similar to donepezil and also include depression, arrythmias and hypertension^​20​. Common interactions are as per the above mentioned for donepezil (i.e. inhibitors of CYP 3A4 and CYP 2D6, which have the potential to increase incidence of cholinergic side effects, such as nausea and vomiting). Galantamine is also to be used with caution for those that suffer from bradycardia or who take medications to lower heart rate, such as digoxin, beta blockers and amiodarone^​20​.

Rivastigmine

Rivastigmine is available as oral capsules, liquid and a transdermal preparation. Doses vary depending on the preparation used. Some of the side effects for this medication are very similar to donepezil and galantamine. There are no significant interactions for rivastigmine, although bradycardia and GI ulceration is a noted caution for use in this medication, as it is for the other AChE inhibitors mention above^​21​.

Memantine

Memantine is available as tablets, orodispersible tablets and liquid preparation. Doses start from between 5mg and 20mg daily. Some of the main side effects include constipation, dizziness, drowsiness and impaired balance^​22​. Significant interactions with barbiturates, anticholinergic medications and baclofen have been reported^​6​. Patients affected by epilepsy or seizures should be offered memantine with caution.

Behavioural and psychological symptoms of dementia

Behavioural and psychological symptoms of dementia (BPSD) are so common that it is estimated that 90% of those living with dementia experience them. The symptoms may include agitation, aggression, hallucinations, as well as other symptoms^​23​. If symptoms are mild to moderate, non-pharmacological approaches to managing BPSD should first be explored. This can include consultation with family members regarding how the patient’s behaviour may be affected and managed, sensory activities, such as massages, smells of cooking, music or having one’s hair brushed, use of positive social interactions and working towards better sleep hygiene^​23​. This may be trialled over a four-week period in a process known as ‘watchful waiting’. 

If watchful waiting is deemed unsuccessful and symptoms appear to be more severe, then more robust, individualised approaches, such as psychosocial interventions, along with a medical review are required. This may include activities tailored to the individuals’ preferences and abilities, such as short social interactions, physical activities and specialist psychosocial activities, guided by those with a clinical psychology background. If non-pharmacological interventions are not providing the desired outcomes for the patient, then consideration should be given to pharmacological interventions for the management of BPSD.

Symptoms of BPSD may be managed with antipsychotics in exceptional circumstances. Antipsychotic medications have a place in therapy for non-cognitive symptoms, such as self-harm or harm to others. Doses of antipsychotics should be started at a low dose and titrated to the lowest effective dose for the shortest duration. Risperidone is the only licensed antipsychotic for dementia and NICE stipulates a limit to the duration of treatment to up to 12 weeks^​23​. A balance between the benefit to the patient and occurrence of adverse effects should be assessed when selecting the most appropriate antipsychotic for the patient, bearing in mind that adverse effects alone (i.e. risk of falls and oversedation) may dictate if a patient should continue antipsychotic therapy. The Alzheimer’s Society have produced detailed guidance on how to safely prescribe antipsychotic therapy for patients experiencing BPSD^​23​. Pharmacists play an important role to ensure inappropriate or overprescribing of antipsychotics is prevented, which may also extend to deprescribing where appropriate.

Monitoring

Response to treatment, compliance and adverse effects should be periodically reviewed once treatment begins. The requirement to step up treatment with the addition of memantine to an AChE inhibitor should also be considered when reviewing response to treatment. This can be done by the primary care prescriber without the need for specialist input.  

Medication reviews play an important role in assessing the above. As most dementia patients are likely to have other comorbidities, drug interactions, polypharmacy and compliance should be addressed when required^​23​.

Patient and carer counselling and support

Counselling patients living with dementia can be challenging owing to the complexity of the condition. Healthcare professionals should use effective consultation skills to support the individual and ensure patient-centred care. 

Pharmacists should actively develop these skills and the Consultation skills for Pharmacy Practice: Practice Standards for England can be a helpful resource for doing so^​24​. The standards were developed to support pharmacy professionals and serve to define the knowledge, skills, behaviours and attitudes that pharmacy professionals should be able to demonstrate when communicating and consulting with patients. To understand some of the standards most relevant to consulting with patients with dementia, see the Box. It should be noted that this is not an exhaustive list and it is recommended that pharmacists read the full document.

Providing a supportive environment during a dementia consultation may sometimes mean consulting in the individual’s usual place of residence to avoid them from feeling distressed or experiencing acute states of confusion or distress owing to the change of environment.

It may also be necessary to react to a range of different emotions that patients may express and modify your communication approach accordingly. A part of every good consultation should also include a summary of the points discussed and review of information provided to the individual and/or their carer, which is no different when counselling a patient living with dementia.   

Quite often, patients with dementia may require a relative or friend to support them in making decisions about their care; however, this should not deter the healthcare professional from fully including the patient in the consultations. Where appropriate, consent is also required from the patient to ascertain if relatives, friends or carers may be present during the consultation process. If the patient is deemed to lack capacity to make decisions for themselves, consultation with carers/relatives is essential to provide the best care. However, establishing mental capacity can be a complex issue, and it is important that pharmacists are aware of relevant local and national policies that support such complex patients, including the Mental Capacity Act 2005. Full discussion of mental capacity and informed consent is outside the scope of this article but further information from the General Pharmaceutical Council on this topic can be found here.

Carers of people living with dementia should be supported so that they can continue to provide care for their loved ones. Providing this care can carry a significant emotional burden, impacting the caregivers’ mental and physical health. NICE has set out a list of recommendations that can support carers in understanding the condition and how to effectively care for the individual, as well as themselves^​1​. Patient’s and families should be signposted to sources of support available in their area. For example, Admiral Nurses, a specialist nurse organisation from Dementia UK, provide a whole host of services and support for both patients and their carers to enable independent living for patients for as long as possible^​25​. Support can take the form of coordinating a patient’s care, psychological support for carers, signposting to useful services and practical help, such as financial support^​25​.