When to suspect dementia

Abstract

Dementia is a syndrome in which there is deterioration in memory, thinking, behaviour and the ability to perform everyday activities. An accurate and timely diagnosis of dementia provides opportunity for early treatment, proactive support and advance care planning. However, there is evidence that GPs lack confidence in diagnosing dementia, in part because patients with dementia present in many different ways. Researchers believe that early detection of Alzheimer’s disease, the most common cause of dementia, is necessary if ways to prevent, slow and stop the disease are to be found. This article highlights the common presenting complaints in dementia and offers how GPs can work towards a diagnosis and refer to specialist services appropriately.

The GP curriculum and dementia

Clinical module 3.05: Care of older adults requires GPs to:

Understand the management of the conditions and problems commonly associated with old age, such as Parkinson’s disease, falls, gait disorders, stroke, confusion, dementia and cancer

Know the epidemiology of older people’s problems presenting in primary care, such as dementia and cancers as well as their risk factors

Understand the special features of psychiatric diseases in old age, including dementia. This incorporates an appreciation of the effects of these conditions on the person, the family and community, and the effects of physical function on the patient's mental state. This understanding should be framed within an understanding of the law relating to mental capacity

Understand the ability of an elderly person to carry out all the activities commensurate with their mental competence (e.g. exercise, travel, sexual activity and independence, etc.)

Recognise the importance of a problem-based approach, taking in the ‘big picture’, rather than a disease-based approach to the care of older people, who often have complex physical, psychological and social problems

Epidemiology and pathophysiology

In 2013, there were 815 827 people with dementia in the UK; 94% of whom were 65 years old or older. This represents 1.3% of the entire UK population and 7% of the population aged 65 years and over. The prevalence is rapidly increasing, and the global burden of dementia is expected to reach 115 000 000 people by 2050 (King’s College London and London School of Economics, 2014).

Alzheimer’s dementia is by far the most common form of dementia, followed by vascular dementia and dementia with Lewy bodies (DLB) (see Fig. 1). Increasingly patients are found to have a mixed dementia, predominantly consisting of Alzheimer’s and vascular types. Researchers are making significant progress with new diagnostic techniques, but presently a true diagnosis of Alzheimer’s disease is only made if pathologically proven through brain biopsy (McKhann et al., 2011). As such the true prevalence of each dementia subtype may be different from the clinically identified numbers. Less commonly occurring dementias are Huntington’s disease and fronto-temporal dementia (also known as Pick’s disease). These more frequently present in younger adults.

Figure 1.

Percentages of patients diagnosed with each type of dementia 2014.

The cause and pathophysiology of dementia is still poorly understood. In Alzheimer’s disease, beta-amyloid (protein) plaques accumulate outside neurons, and tau tangles accumulate within the neurons. These are thought to ultimately lead to memory loss and impaired cognitive functioning through inflammation, impaired synaptic transfer and destruction of neurons. The pathogenesis of DLB has significant overlap with Alzheimer’s disease, both having amyloid plaques and similar risk factors, but in DLB there are Lewy bodies and neurites in the cortex. Lewy bodies comprise of round, eosinophilic, intracytoplasmic neuronal processes that contribute to neuronal and synaptic loss. Vascular dementia is a poorly defined heterogeneous disorder that is contributed to by combinations of large artery infarctions, lacunar infarctions and chronic small vessel ischaemia causing cerebral damage (Kalaria, 2012).

Who is at risk?

See Table 1 for key risk factors for dementia. The greatest risk factor for dementia is age: the incidence dramatically rises in those aged over 65 years. A family history of Alzheimer’s increases risk, particularly in those with the apolipoprotein-e4 gene (APOE-e4). Pre-existing mild-cognitive impairment, cardiovascular disease or cardiovascular risk factors, Down’s syndrome and history of traumatic brain injury all increase an individual’s risk of developing dementia. People with fewer years of formal education are thought to be at higher risk of dementia, according to the cognitive reserve hypothesis. This hypothesis suggests that having more years of education increases cognitive performance and allows the brain to compensate for the early changes in dementia (Tucker-Drob, Johnson, & Jones, 2009). Isolated patients are a group recently identified as being at increased risk. The mechanism for this is unknown, but thought to be related to building cognitive reserve through social and mental stimulus, and reduced levels of stress and depression.

Table 1.

Risk factors for dementia.

Factor	Comment
• Age	• Strongest risk factor for dementia
	• Older than 65 years
• Mild cognitive impairment	• 50–60% subsequently develop dementia
• Learning difficulties	• Affecting up to 75% of patients over 60 years old with Down’s syndrome
• Genetics	• For example, the APOE e4 gene
• Cardiovascular disease risk factors ▪ Diabetes ▪ Smoking ▪ Hypercholesterolaemia ▪ Hypertension	• Up to one-third of Alzheimer’s cases worldwide are thought to be a result of modifiable risk factors
	• Smoking is associated with a 50–80% risk of dementia, and diabetes increases risk by 50%
	• Successful management of vascular risk factors and secondary stroke prevention may reduce the incidence of vascular and mixed dementias
• Parkinson’s disease	• Significant risk factor for DLB
• Stroke	• Risk of developing dementia is approximately doubled in patients following a stroke
• Depression	• Depression is a significant risk factor as well as a differential diagnosis
• Heavy alcohol consumption	• Accounts for around 20% of cases in people younger than 65 years in age and 1% of cases in people older than 65 years in age
• Low educational attainment	• The cognitive reserve hypothesis.
• Low social engagement and support	• Increased likelihood of stress, depression and loneliness

Source: NICE (2016).

Signs and symptoms

Presentation of dementia can be very variable, and brain changes are thought to occur as many as 20 years prior to symptoms developing (Reiman et al., 2012). The most common presenting complaint is difficulty remembering new information. Patients with dementia will demonstrate a measurable cognitive decline that interferes with everyday independence (American Psychiatric Association, 2013).

Common symptoms of Alzheimer’s disease are listed in Box 1. Changes in financial competence can be an early indicator, due to the subtle complexity of managing financial affairs. Problems with personal care and more basic activities of daily living are often later findings, but are more specific (Triebel et al., 2009). In late-stage dementia the patient may require assistance with all activities of daily living, eventually losing the ability to communicate altogether or mobilise, toilet or feed themselves independently (Alzheimer’s Association, 2016).

Box 1.

When to suspect dementia.

Common issues and some specific examples of presenting complaints from patients and relatives:

• Memory loss that disrupts daily life (leaving hob on, leaving doors open, poor medication adherence)

• Difficulty planning or problem-solving (managing bills and shopping)

• Struggling to conduct familiar tasks (cooking, making a cup of tea)

• Disorientation in time or place or to person (not recognising family members)

• Difficulty with visuospatial perception (getting lost, falls/clumsiness)

• Poor judgement (unsafe behaviour, wandering)

• Anomia (word-finding difficulty)

• Misplacing objects and being unable to retrace steps

• Changes in personality (such as withdrawal from social activities)

• Changes in mood (apathy, depression, anxiety, agitation)

• Sleep disturbance (difficulty sleeping at night, ‘sundowning’)

Source: Alzheimer's Association (2017).

Commonly symptoms are noticed by family or friends rather than self-reported, so it is essential to gather a collateral history about a patient’s morbid and premorbid functioning. The variation in signs and symptoms of the main types of dementia are summarised in Table 2.

Table 2.

Presentation, clinical and radiological findings of common types of dementia.

Dementia subtype	Common presentation	Objective cognitive deficit	Neurology
Alzheimer’s	Memory loss, difficulty making decisions	Episodic memory loss	Normal until late stage
Vascular	Stepwise/sudden deterioration in function, apathy, falls, focal weakness, delusions, anxiety	Dependent on regions of brain affected: frontal/executive, cognitive slowing. Memory sometimes spared	Can be normal. Sometimes motor retardation, spasticity
Fronto-temporal	Personality change: apathy/euphoria/depression, disinhibition; impaired judgment and insight; speech/language disturbance; hyperorality	Frontal, executive, language; often spares drawing	Often normal. May have vertical gaze palsy, axial rigidity, dystonia, alien hand, or motor-neuron disease
DLB	Visual hallucinations, rapid eye movement sleep atonia: may often wake partners at night, delirium, Capgras' syndrome (belief that someone they know is an imposter), hallucinations, delusions, depression, parkinsonism (falls, decreased mobility etc.)	Drawing and frontal and executive dysfunction; delirium-prone. Memory often spared	Parkinsonism

Adapted from Seeley and Miller (2013).

Normal cognitive decline, mild cognitive impairment and dementia

Normal age-related cognitive decline includes mild memory deficits and slower information processing, but progression is gradual and daily functioning unaffected. Common complaints may be of difficulty with name recall, losing things, temporarily forgetting things such as words, the day of the week, or monthly payments (Petersen, Smith, Kokmen, Ivnik, & Tangalos, 1992). Self-reported cognitive problems are thought to be an insensitive and nonspecific marker of mild cognitive impairment and dementia, and should be interpreted with care in the absence of objective findings (Mitchell, 2008). However, subjective memory complaints have been shown to predict future cognitive decline in those with measurably normal cognitive function (Geerlings, Jonker, Bouter, Ader, & Schmand, 1999). It may be beneficial to follow-up these patients periodically, but there is limited evidence.

Mild cognitive impairment (MCI) is a noticeable and measureable deterioration in cognitive abilities, for example, memory, speech, language, judgment, reasoning, planning and other thinking abilities. Importantly, the individual’s ability to carry out everyday activities independently is unaffected, in contrast with dementia, where activities of daily living must be affected in order to make a diagnosis. Patients often self-present and can be particularly troubled by their symptoms.

Sixty-percent of people with MCI develop dementia over 10 years. Identifying MCI allows the clinician to establish a cognitive baseline, highlight risk in medical records and monitor if necessary. It may be appropriate to prompt the patient to identify a proxy decision maker or give someone close to them power of attorney, and think about advanced decisions, such as a statement of wishes and preferences or advance directive for refusal of treatment (Robinson, Tang, & Taylor, 2015).

Differential diagnosis

One meta-analysis reported that 9% of people with dementia-like symptoms did not have dementia, but rather had other conditions which were potentially reversible (Clarfield, 2003). The extent to which these are truly reversible is unclear, but early recognition and treatment of reversible causes of dementia will at best lead to an improvement in cognition and at worst lead to a timely diagnosis of dementia.

Box 2 summarises the important differentials in a patient presenting with cognitive disturbance. Delirium can be secondary to infection, constipation, metabolic disturbance and many other systemic insults in the elderly. It tends to follow a more acute and fluctuating course than dementia.

Box 2.

Differential diagnosis of cognitive disturbance.

• Delirium, depression, hypercalcaemia, Wernicke’s encephalopathy, thyroid dysfunction, hepatic encephalopathy, drug toxicity

• Less commonly: Brain tumour, amnestic syndrome, Cushing’s syndrome, hypopituitarism, Wilson’s disease, traumatic brain injury, normal pressure hydrocephalus, neuro-infections (such as Lyme disease, tuberculosis, syphilis, Creutzfeldt–Jakob disease, human immunodeficiency virus), autoimmune disease (sarcoidosis, systemic lupus erythematosus, Sjogren’s disease).

The relationship between depression and cognitive impairment is complicated. Depression can present like dementia and cognitive impairment may be a presenting symptom of depression - so-called pseudo-dementia. Depression may also be an early manifestation of cognitive impairment (Geda et al., 2008). It is important to identify those with mood and behavioural changes, as they may warrant closer follow-up. Typically, those with depression may have subjective memory complaints greater than the objective findings and vice versa for those with dementia. In patients with suspected pseudo-dementia it can be prudent to offer a trial of antidepressants and repeat cognitive testing to elicit any improvement.

Hypercalcaemia can present as a sudden change in cognition, behaviour and function, as can other homeostatic or metabolic disturbances such as acute kidney insult, Wernicke’s encephalopathy, thyroid dysfunction, hepatic encephalopathy and pharmacological toxicity (for example, opiates or tricyclic antidepressants). Table 3 summarises the key investigations to exclude the most common differential diagnoses of cognitive impairment.

Table 3.

Investigations to consider in patients presenting with cognitive impairment.

Investigations		Reason
Haematology and biochemistry	Full blood count, erythrocyte sedimentation rate, and C-reactive protein	• Changes in inflammatory markers: Infection/immunosuppression/autoimmune disease
		• Rule out anaemia/pancytopaenia
	Urea and electrolytes, liver function tests, glucose/glycosylated haemoglobin (HbA1c) and calcium	• Metabolic disturbance/renal failure
		• Hypercalcaemia (primary or secondary, e.g. hyperparathyroidism/malignancy/dehydration)
		• Hepatic disease
		• Hypoglycaemia
	Vitamin B12 and folate	• Vitamin deficiencies associated with cognitive decline
	Thyroid function tests	• Thyroid dysfunction has various effects on cognition in the elderly
Microbiology	Urine for microscopy and culture	• Rule out urinary tract infection
	Human immunodeficiency virus (HIV) and syphilis screening	• If clinically indicated to rule out acquired infection
Radiology	Chest X-ray	• Rule out pneumonia in patients with symptoms or those at high risk, e.g. elderly and immunosuppressed (alcohol excess, HIV infection)
	Computed tomography/magnetic resonance imaging (MRI) of the head	• Rule out acute cerebral insult in the acute setting, such as haemorrhage or infarct, or brain tumour. Characteristic features of each type of dementia are sometimes seen on neuro-imaging. MRI is not always indicated and may be performed by specialist services

Making a diagnosis

The GP’s role in dementia diagnosis is to identify those with symptoms of dementia or cognitive impairment, exclude common reversible causes, and help the patient decide whether they would like further assessment. The diagnostic process is outlined in Box 3. All people identified with suspected dementia should be offered referral to a memory assessment service (National Institute for Health and Care Excellence (NICE), 2016).

Box 3.

The diagnostic process in primary care.

This is likely to comprise an initial appointment, screening tests and investigations and a follow-up appointment.

• The initial appointment:

▪ Often prompted by patient’s, relative’s, or clinician’s concerns

▪ Focused history and examination

▪ Brief cognitive assessment tool (Table 4) if appropriate

• Screening tests and investigations:

▪ These are detailed in Table 3

• The follow-up appointment:

▪ Collateral history from carer or family member

▪ Review of test and investigation results

▪ Treatment of any reversible causes identified

▪ Discuss referral to secondary care, older person's mental health or memory services, as appropriate

When taking the history, effects on activities of daily living and specific cognitive deficits should be explored. It is important to identify relevant risk factors, particularly vascular risk factors. A brief past medical history, family history and psychiatric history should be obtained. Examination should include a neurological examination looking for localising deficits or parkinsonism. Stigmata of liver disease, autoimmune disease and vascular insufficiency should be identified.

A brief objective assessment of cognition is a key part of a dementia assessment in primary care. Assessment of cognitive function should examine attention, concentration, orientation, short- and long-term memory, praxis, language and executive function, ideally using a standardised instrument. The Addenbrookes Cognitive Examination is regarded as the most comprehensive tool, but is not realistic to perform within a standard primary care appointment (Robinson et al., 2015). Table 4 identifies four quick and validated assessment tools that are appropriate to use in primary care. The outcome from these tests gives a useful guide as to whether more detailed assessment from a memory service is indicated. Educational levels, prior level of functioning, language spoken, sensory, physical or neurological impairments and mental health should be taken into account when interpreting scores.

Table 4.

Brief cognitive assessment tools.

Test	Comments	Sensitivity/ specificity
General practitioner assessment of cognition (GP-COG)	• 5-minute test	Sensitivity 82–85%; specificity 83–86%
	• A six-item cognitive assessment with the patient
	• A score under five suggests cognitive impairment. A score between five and eight is equivocal and should prompt the second part of the test, the informant questionnaire
Six-item cognitive impairment test	• 3–4-minute test	Sensitivity 78.5–83%; specificity 77–100%
	• Six questions on orientation and memory
	• Scores less than seven are considered normal and greater than or equal to eight suggest cognitive impairment
Mini-cog assessment instrument	2–4-minute test	Sensitivity 76–99%; specificity 89–96%
	1. Three-item recall
	2. Clock drawing test
	• Inability to recall any of the three items suggests cognitive impairment, or if they recall only one or two items and draw an abnormal clock
Memory impairment screen	• 4-minute test	Sensitivity 74–86%; specificity 96–97%
	• Four-item delayed free-recall and cued-recall memory impairment test
	• A score of less than or equal to four suggests cognitive impairment

Adapted from Yokomizo, Simon, and Bottino (2014).

Referral to specialist memory assessment services is often indicated, particularly in cases where the diagnosis is unclear, or where the dementia subtype needs to be identified in order to inform management. These services should be provided by designated clinics or local mental health teams, and should offer assessment, diagnosis, therapeutic and rehabilitation services for the patient and their families by coordinating services from health, social and voluntary organisations (NICE, 2006).

It is not considered appropriate to screen populations for dementia and there is a lack of consensus on the value of case-finding. Nevertheless, patients with symptoms in-keeping with cognitive impairment should be investigated appropriately. Evidence suggests that despite the distress of the initial diagnosis, most people prefer to know if they have dementia (Robinson et al., 2015).

Management

Challenges to diagnosing dementia in primary care include a lack of clinician confidence and time, and belief by clinicians that there are limited treatments and interventions available (Harmand et al., 2017). However, there are several recommendations for management of the disease, and there has been some success with pharmacological agents which can be initiated under the guidance of a specialist (NICE, 2016).

There are non-pharmacological options available, particularly for behavioural and psychological symptoms of dementia (BPSD), such as aromatherapy, multisensory stimulation, the therapeutic use of music or dancing, animal-assisted therapy and massage. Avoidance or limitation of alcohol should be recommended, due to the exacerbating effects on cognitive impairment, particularly in the evening as it has an adverse effect on sleep.

Cholinesterase inhibitors, such as donepezil, rivastigmine and galantamine, have shown modest symptomatic benefit in Alzheimer’s disease, vascular dementia, mixed dementia, DLB and Parkinson’s disease. These are only recommended for the period in which they provide observable symptomatic relief.

The N-methyl-D-aspartate (NMDA) receptor antagonist memantine is thought to be neuroprotective, and to have modest disease-modifying benefits in those with moderate-to-severe Alzheimer’s disease.

There is evidence that treating vascular risk factors can slow cognitive decline.

Several therapies are still under investigation and in early use, such as vitamin E and other supplements. Antipsychotics should only be considered for severe BPSD, as they increase the risk of cerebrovascular events and cause severe adverse reactions in DLB, such as worsening of extrapyramidal features or acute, severe physical deterioration.

The priorities in primary care are to explore the psychosocial aspects of the disease, including driving, financial capacity, signposting for vulnerable adults such as those who live alone, or those at risk to themselves through wandering or displaying challenging behaviours. Support and practical advice is available through third sector services, such as Age UK and the Alzheimer’s Society. These also provide support for carers, who should be identified and monitored for carer burden and physical health complaints. Advanced care planning is essential while patients still have the capacity to express their wishes about limitations of treatment and end of life plans, with the Gold Standards Framework, an important tool for this purpose (Thomas, Stobbart Rowlands, Foulger , & National GSF Centre in End of Life Care UK, 2017).

KEY POINTS

Dementia is a rapidly growing problem with a prompt diagnosis allowing early intervention, thus empowering the patient to engage in advanced care planning while they still maintain mental capacity

GPs play an important role in identifying those at risk of dementia and those with signs of cognitive impairment

Numerous cognitive screening tools are available to objectively measure cognitive functioning

The diagnosis of dementia should be formed through several interactions over a period of time and include collateral information about their premorbid and morbid functioning

Several simple investigations can be performed in primary care to rule out reversible causes of dementia-like symptoms

GPs, voluntary services and allied professionals can help patients with dementia to live well by effectively managing comorbidities, troubling symptoms, social aspects and BPSD

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