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Next Lesson - Delirium
Contents
Abstract
- Dementia is a common syndrome which presents with cognitive and behavioural symptoms.
- Dementia involves acquired cognitive decline that impairs everyday independence. Assess treatable contributors; symptoms must not be explained solely by delirium.
- There are different types of dementia based on the pathophysiology (how the disease damages the brain) and the brain areas affected.
- Holistic management (care that looks at the whole person) is key to improve the quality of life of patients living with dementia and their carers.
Core
Dementia is an umbrella term for a syndrome that presents with cognitive (to do with thinking and memory) and behavioural symptoms. It involves acquired cognitive decline that interferes with everyday independence. The cognitive deficits must not occur exclusively during delirium (a sudden, short-lived state of confusion) or be better explained by another mental disorder. Dementia and delirium can coexist. Depending on the age at which it first presents, dementia is described as early onset (also called young onset) or late onset. The threshold between the two is 65 years old (source). However, the onset of symptoms can be very subtle and is often insidious (slow and gradual), making it difficult to pinpoint when the symptoms began. The age of onset is usually worked out in hindsight, once a diagnosis is made.
The main cognitive areas that can be affected in dementia include memory, orientation (knowing the time, the place and who people are), learning capacity, judgement, language and planning. Memory is not always affected first: in frontotemporal dementia, for example, memory problems tend to come later. Patients often struggle with short term memory (although long term memory loss also happens much later down the line).
In terms of non-cognitive symptoms, there is a wide array of different ways these can manifest depending on the underlying pathology. These can include behavioural symptoms such as increased agitation, aggression, sexual disinhibition (loss of normal social restraint, for example inappropriate sexual behaviour) or wandering. Patients can show signs of depression and anxiety or sleeping problems such as insomnia and daytime drowsiness. Finally, dementia can also be accompanied by psychotic symptoms (symptoms in which the person loses touch with reality). These include visual and auditory hallucinations (seeing or hearing things that are not there) and persecutory delusions (fixed false beliefs that other people are trying to harm them).
Dementia is a clinical syndrome of acquired cognitive decline that interferes with everyday independence. Diagnosis requires a history of decline, assessment of cognition and function, and investigation of treatable contributors or alternative explanations. Dementia is itself caused by physical (organic) disease of the brain, so the aim is not to exclude every organic cause. The aim is to find and treat reversible causes of cognitive decline. These include delirium, depression, sensory impairment (poor sight or hearing) and medicines with anticholinergic effects (medicines that block the action of acetylcholine).
Some physical conditions can have a similar presentation. Examples are hypothyroidism (underactive thyroid), hypercalcaemia (high blood calcium), vitamin B12 deficiency and normal pressure hydrocephalus (a build-up of cerebrospinal fluid that enlarges the ventricles). Patients in whom dementia is being considered therefore usually need a physical examination and blood and urine tests. They are also offered structural imaging (a CT or MRI head scan), unless dementia is well established and the subtype is clear.
To establish a dementia syndrome, there must be significant decline from the person’s previous cognitive abilities that interferes with independence in daily activities. The deficits must not occur exclusively during delirium or be better explained by another mental disorder. Dementia and delirium can coexist; an acute episode requires assessment and treatment, with the longer-term cognitive history considered separately. Persistent cognitive symptoms alone do not establish dementia without the necessary functional assessment.
There are different types of dementia depending on the pathophysiology (how the disease process damages the brain) underlying the presentation. Some of the most common ones are:
- Alzheimer’s disease
- Vascular dementia
- Lewy body dementia
- Frontotemporal dementia
- Rarer forms of dementia
Alzheimer’s Disease is the most common form of dementia in the UK, making up around 60% of diagnoses (source). It is uncommon under 65 years of age: fewer than 1 in 10 people with the condition are younger than this. Alzheimer’s disease that starts before the age of 65 is called young-onset Alzheimer’s disease. Characteristic changes can be found both macro- and microscopically (with the naked eye and under a microscope).
Macroscopic changes include global atrophy (shrinkage) of the brain, resulting in sulcal widening (widening of the grooves on the brain surface) and enlargement of the ventricles, particularly the lateral ventricles. The shrinkage usually starts in the parts of the brain responsible for memory.
Characteristic microscopic changes include senile plaques (clumps of protein outside neurones) of amyloid-beta (Aβ) protein (a by-product of the breakdown of amyloid precursor protein, APP, a normal protein found in neurones). The second change is neurofibrillary tangles (twisted fibres of protein inside neurones) made of hyperphosphorylated Tau proteins (Tau with too many phosphate groups attached, which makes it clump together). These plaques and tangles ultimately cause increasing neuronal death, so the disease worsens steadily over time.
Vascular dementia is the second most common type of dementia in over 65s (source). It is a result of pathological cerebrovascular events (reduced blood flow to the brain), such as strokes and repeated transient ischaemic attacks (brief episodes of stroke symptoms that settle completely).
Risk factors for vascular dementia include history of stroke, hypertension, hypercholesterolaemia (high blood cholesterol), diabetes and smoking. They all raise the chance of blood vessels in the brain being damaged or blocked.
Vascular dementia classically presents in a stepwise progression, where the patient is stable for a period then undergoes a steep decline following a cerebrovascular event. It can also start suddenly or begin slowly over time. Slowed thinking, difficulty planning and concentrating, and difficulty walking and keeping balance are common. It can also present with focal neurological symptoms, depending on the area of the brain affected by infarction (tissue death from a blocked blood supply). Focal symptoms affect one specific function or part of the body, such as weakness of one arm.
Importantly, vascular dementia can often be found alongside Alzheimer’s disease. When the two occur together, this is known as mixed dementia.
Lewy Body Dementia is a broader term for a condition caused by the deposition of Lewy bodies. These are spherical deposits inside neurones (intracytoplasmic), made of aggregated α-synuclein protein (a protein that clumps together). They are found in the substantia nigra (a dark-pigmented area of the midbrain), temporal lobe, frontal lobe and cingulate gyrus (a fold of cortex on the inner surface of each cerebral hemisphere).
Lewy Body Dementia typically presents with fluctuation in cognition and alertness, vivid visual hallucinations, repeated falls and features of Parkinsonism (slow movement, muscle stiffness and tremor). Sleep can also be disturbed, with violent movements and shouting out as people act out their dreams (rapid eye movement, or REM, sleep behaviour disorder).
Depending on the timing of the cognitive symptoms with regard to Parkinsonian features, patients are classed with Dementia with Lewy Body (DLB) or Parkinson’s Disease Dementia (PDD). In DLB, cognitive decline occurs before or within a year of parkinsonism (tremor, muscle stiffness, etc.), whereas in PDD, cognitive symptoms appear over a year after the onset of parkinsonism. Pathophysiology of both is very similar and they are both classed as Lewy Body dementias.
Finally, it is important to be very cautious with antipsychotics (drugs used to treat psychosis and severe agitation) if Lewy body dementia is suspected. They can worsen movement problems, and there is an increased risk of severe antipsychotic sensitivity reactions (an unusually strong and harmful reaction to these drugs, because people with Lewy body dementia are particularly sensitive to them). Antipsychotics can also cause neuroleptic malignant syndrome. This is a medical emergency characterised by fever, confusion, rigidity (muscle stiffness), raised creatine kinase (an enzyme released when muscle breaks down) and autonomic instability (unstable heart rate, blood pressure and temperature). In any type of dementia, NICE advises offering antipsychotics only if the person is at risk of harming themselves or others, or is severely distressed by agitation, hallucinations or delusions. Non-drug approaches are offered first. Before starting, the benefits and harms are discussed with the person and their family members or carers. The lowest effective dose is used for the shortest possible time, and the person is reassessed at least every 6 weeks to check that they still need it. Any use should be under specialist guidance.
Frontotemporal dementia is uncommon overall (about 2% of dementia in older people), but it makes up around 12% of early-onset dementia. This makes it the third most common cause in that age group, after Alzheimer’s disease and vascular dementia (source). It is caused by degeneration of the frontal and temporal lobes, with abnormal protein deposition inside neurones. In most cases the deposits are tau or TDP-43 protein (TAR DNA-binding protein 43, which clumps together in affected neurones). Pick Bodies (round clumps of tau protein) are found in only one subtype, Pick disease. Symptoms reflect damage to these lobes: loss of inhibition, loss of motivation (without other signs of depression), non-fluent aphasia (slow, hesitant speech with errors in sounds or word order), inappropriate social behaviour, and repetitive behaviours.
HIV-associated neurocognitive disorder (formerly AIDS complex dementia)
HIV-associated dementia (also called AIDS dementia complex) is the most severe of the HIV-associated neurocognitive disorders (HAND), a group that also includes milder problems with thinking. These disorders became less common once effective antiretroviral therapy (ART, medicines that control HIV) was introduced, but milder problems with thinking can still be found in many people whose HIV is treated, and ageing may add to this. The brain damage starts when HIV infected macrophages enter the brain. HIV infects macrophages and microglia (the brain’s own immune cells), but not neurones. The infected cells release toxins that cause indirect damage to neurones. Onset is insidious. Before effective ART it typically progressed rapidly, but the course is now often more protracted (slower and longer). Features include cognitive impairment, psychomotor retardation (slowed thinking and movement), tremor, ataxia (unsteadiness and poor coordination), dysarthria (slurred or poorly formed speech) and incontinence.
Creutzfeldt-Jakob disease (CJD)
CJD is a rare condition caused by an infectious protein called a prion. There are four main types. Sporadic CJD is the most common: a normal brain protein misfolds (changes shape) and becomes a prion, for reasons that are unclear. Variant CJD is likely to be caused by eating meat from a cow with bovine spongiform encephalopathy (BSE, a prion disease of cattle, also called mad cow disease). Inherited (familial) CJD is caused by a mutation in the gene for the prion protein. Iatrogenic CJD is spread accidentally through medical or surgical treatment, for example contaminated brain surgery instruments or human growth hormone taken from infected donors. Iatrogenic CJD is now very rare.
It causes symptoms of memory problems, changes in personality, and problems with balance, vision, mobility, and speech. Most people with CJD die within a year of their symptoms starting. There is currently no cure, so treatment aims to relieve symptoms and make the person as comfortable as possible.
Pugilist dementia (dementia pugilistica, or “punch-drunk” syndrome) is the early name for what is now called chronic traumatic encephalopathy (CTE). It is a serious form of progressive brain damage resulting from repeated head injuries, including concussions (temporary disturbance of brain function after a blow to the head). It is commonly seen in professional athletes (classically boxers, as shown by the name) or military personnel. It can only be confirmed after death, by examining the brain.
There is currently no cure for dementia and management primarily involves symptom management and, in some cases, slowing disease progression (for example, treating high blood pressure and other underlying causes in vascular dementia). Management of dementia requires a holistic approach, encompassing the biological, psychological, and social implications of the disease.
Pharmacologically, acetylcholinesterase inhibitors have been shown to improve cognition for a time in mild to moderate Alzheimer’s disease, and NICE recommends them as options for it. These drugs stop the enzyme acetylcholinesterase breaking down acetylcholine, a chemical messenger between neurones. Examples are donepezil, rivastigmine and galantamine. Donepezil or rivastigmine are also offered in mild to moderate dementia with Lewy bodies. They are not offered in frontotemporal dementia, or in vascular dementia unless Alzheimer’s disease, Parkinson’s disease dementia or dementia with Lewy bodies is also suspected. NMDA antagonists (N-methyl-D-aspartate receptor blockers, such as memantine) reduce overstimulation by glutamate (an excitatory neurotransmitter). Memantine is used in moderate Alzheimer’s disease when acetylcholinesterase inhibitors are not tolerated or are contraindicated, and in severe Alzheimer’s disease. For people with Alzheimer’s disease who already take an acetylcholinesterase inhibitor, memantine can be added: this is considered in moderate disease and offered in severe disease.
Social management needs to be timely and comprehensive: the disease should be explained to the patient in a sensitive way and support provided after appropriate assessment of capacity. Discussions should also cover driving (the person must tell the Driver and Vehicle Licensing Agency, or DVLA, and their car insurer about the diagnosis) and managing money. Clinicians should also be aware that some people have a genetic cause: young-onset Alzheimer’s disease, frontotemporal dementia and young-onset vascular dementia sometimes have one, which matters to relatives. Power of attorney (legally naming someone to make decisions on the person’s behalf if they later lose capacity) should be discussed early on, because the arrangement must be made while the patient is still deemed to have capacity to make such choices. An appropriate care and management plan should be put in place to anticipate care needs and arrange respite care (short-term care that gives carers a break) where required. A single named health or social care professional should coordinate care. Group cognitive stimulation therapy (structured group activities that exercise thinking and memory) should be offered in mild to moderate dementia.
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
Quiz
- 885
