5th June 2023

Dementia

Dementia is an umbrella term encompassing various conditions giving rise to the clinical picture of an acquired progressive deterioration in cognition. Usually, one cognitive domain is affected first, for example:

• Learning and memory
• Language
• Executive function
• Complex attention
• Perceptual motor skills
• Social cognition

The disease progresses to eventually affect multiple or all cognitive domains to the point where it interferes with a person’s ability to perform basic activities of daily living. There are many different disease processes which cause dementia, with the commonest being Alzheimer’s disease and vascular dementia.

Epidemiology

Dementia is common, affecting 1 in 14 people over 65 years old in the UK, and it is the seventh leading cause of death among all diseases globally. The prevalence is likely to increase significantly over the next few decades due to the ageing population, and it is estimated that there will be a million people living with dementia in the UK by 2025 and over two million by 2051.

Clinical features of dementia

Symptoms of dementia include impaired short-term memory, problems with language, impaired visuospatial processing, personality change and hallucinations. The severity of symptoms depends on the stage of dementia and the underlying cause of dementia, and therefore which part of the brain or neurocognitive domain is affected.

Dementia subtypes

Causes of dementia include:

• Alzheimer’s disease
• Vascular dementia
• Frontotemporal dementia
• Lewy Body dementia
• Normal pressure hydrocephalus
• Creutzfeldt-Jakob disease

Alzheimer’s disease is the commonest cause of dementia, accounting for approximately 60% of cases. The pathophysiology is amyloid plaques and tau tangles in the brain leading to death of the cells affected. Short-term memory is affected first, and the onset is usually insidious. Pharmacological treatment is with cholinesterase inhibitors (e.g. donepezil, rivastigmine and galantamine) which increase the availability of acetylcholine. Adverse effects include stimulation of the parasympathetic nervous system, such as bradycardia, diarrhoea, and hypotension.

Vascular dementia is the next commonest cause, accounting for 10-15% of cases and is due to small strokes in the brain. The history is of a stepwise progression in cognition, and vascular risk factors are usually present.

Frontotemporal dementia (or Pick’s disease) is a neurodegenerative condition in which the frontal and temporal lobes are preferentially affected, giving rise to features of frontal lobe dysfunction such as personality change, impulsive behaviour and difficulty with planning and decision making, as well as impaired memory. It is a common cause of early onset dementia and is also associated with motor neuron disease. Around 10% of patients with frontotemporal dementia go on to develop motor neuron disease.

Lewy body dementia is one of the neurodegenerative conditions associated with parkinsonism. Clinical features include parkinsonism, REM sleep behaviour disorder, hallucinations (which are typically visual and of people, faces and animals) and fluctuating cognition. Patients with Lewy body dementia are particularly sensitive to neuroleptic medications, which can precipitate neuroleptic malignant syndrome. It can be differentiated from Parkinson’s disease dementia by the timing of onset of cognitive impairment in relation to parkinsonism. If the cognitive impairment occurs within a year of the onset of parkinsonism, then the diagnosis is generally Lewy body dementia.

Normal pressure hydrocephalus is an uncommon condition which affects people over the age of 60 years. There is a triad of gait apraxia, urinary incontinence, and cognitive impairment. The cerebrospinal fluid opening pressure is normal, and a non-contrast CT brain may show enlarged ventricles. Symptoms improve with a reduction in cerebrospinal fluid pressure through a therapeutic lumbar puncture. This produces a short-lived improvement in symptoms. A more long-term treatment is a ventriculoperitoneal shunt, but the risks of this neurosurgical procedure in an older frail patient cohort mean that it is seldom performed.

Creutzfeldt-Jakob disease is a prion disease and an uncommon cause of rapidly progressive dementia. It is universally fatal, usually within one year. There are four types:

• Sporadic – this is the most common type
• Variant – caused by consuming meat from a cow with bovine spongiform encephalopathy
• Familial – rare
• Iatrogenic – previously caused by growth hormone treatment using human growth hormones from infected individuals. This is very rare now.

Clinical features include rapidly progressive dementia, ataxia, myoclonus, and psychiatric symptoms. Diagnosis is confirmed by electroencephalogram with characteristic periodic sharp waves, demonstrating the abnormal 14-3-3 protein in cerebrospinal fluid, from brain biopsy or at autopsy.

Investigations

Investigations for dementia aim to identify reversible causes and help diagnose the subtype of dementia present, but only if it is likely to change management.

Blood tests include inflammatory markers, thyroid function tests, vitamin B12 and folate. Imaging is usually done with CT or MRI; it is performed to look for conditions such as space-occupying lesions that may mimic dementia or signs such as enlarged ventricles, which may suggest normal pressure hydrocephalus. Structural changes in the temporal lobes may be seen in Alzheimer’s disease, but their absence does not rule it out. The presence of small vessel disease or strokes may also support a diagnosis of vascular dementia.

Diagnosis

Diagnosis of dementia, according to DSM-5, is made based on a history of an acquired progressive cognitive decline affecting at least one cognitive domain and interfering with the ability to perform activities of daily living. This must not occur in the context of delirium, so the history should usually be for at least six months.

The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) are commonly used screening tools for cognitive impairment. The MoCA is more useful for diagnosing cognitive impairment and the MMSE is useful for monitoring.

Management of dementia

Pharmacological management of dementia is dependent on the cause. Acetylcholinesterase inhibitors such as galantamine, rivastigmine and donepezil are licensed for use in Alzheimer’s disease. Memantine, a glutamate receptor antagonist, is also used. Management of vascular dementia involves the treatment of vascular risk factors.

Performing a medication review is essential to avoid drugs with a high anticholinergic burden, which can worsen cognitive impairment.

Other management options depend on the underlying cause of dementia, for example, a ventriculoperitoneal shunt for normal pressure hydrocephalus.