Wilkinson. Essential Neurology 2005

Causes of dementia

The commoner causes of dementia are listed below, followed by brief notes about each of the individual causes.

1.Alzheimer’s disease.

2.Dementia with Lewy bodies.

3.Vascular dementia.

4.Other progressive intracranial pathology:

•brain tumour;

•chronic subdural haematoma;

•chronic hydrocephalus;

•multiple sclerosis;

•Huntington’s disease;

•Pick’s disease;

•motor neurone disease;

•Creutzfeldt–Jakob disease.

5.Alcohol and drugs.

6.Rare infections, deficiencies, etc.:

•HIV–AIDS;

•syphilis;

•B vitamin deficiency;

•hypothyroidism.

Alzheimer’s disease

This is very common, especially with increasing age, and accounts for about 65% of dementia in the UK. Onset and progression are insidious. Memory is usually affected first, followed by language and spatial abilities. Insight and judgement are preserved to begin with. After a few years all aspects of intellectual function are affected and the patient may become frail and unsteady. Epilepsy is uncommon.

The main pathology is in the cerebral cortex, initially in the temporal lobe, with loss of synapses and cells, neurofibrillary tangles and senile plaques. These changes also affect subcortical nuclei, including the ones that provide acetylcholine to the cerebral cortex. This may contribute to the cognitive decline; cholinesterase inhibitors such as rivastigmine and donepezil sometimes provide symptomatic improvement.

People with the apolipoprotein E e4 genotype are at increased risk of developing Alzheimer’s disease, and mutations in the amyloid precursor protein gene and the presenilin genes can cause familial Alzheimer’s disease. Environmental factors are probably also important.

Atrophy of both temporal lobes due to Alzheimer’s disease.

DEMENTIA

Key features of Lewy body dementia

•Dementia

•Parkinsonism

•Visual hallucinations

•Flucuating cognitive impairment

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Dementia with Lewy bodies

Dementia with Lewy bodies accounts for about 15% of dementia in the UK. The intellectual symptoms are similar to those of Alzheimer’s disease but patients are much more likely to develop parkinsonism, visual hallucinations and episodes of confusion.

The distribution of pathology is also similar, but affected neurones form Lewy bodies rather than tangles. The cholinergic deficit is more profound, and the response to cholinesterase therapies usually more marked. Neuroleptic drugs can exacerbate the parkinsonism to a severe, or even fatal, degree.

Vascular dementia (see also p. 31)

This accounts for about 10% of UK dementia. Most cases are caused by widespread small vessel disease within the brain itself, due to hypertension or diabetes, giving rise to extensive and diffuse damage to the subcortical white matter. These patients present with failing judgement and reasoning, followed by impaired memory and language, together with a complex gait disturbance, consisting of small shuffling steps (marche à petits pas). Emotional lability and pseudobulbar palsy are often present, with a brisk jaw-jerk and spastic dysarthria.

A few cases are due to carotid atheroma giving rise to multiple discrete cerebral infarcts, i.e. multi-infarct dementia. These patients have a stepwise evolution with events that can be recognized as distinct strokes and which give rise to focal neurological deficits (such as hemiparesis, dysphasia or visual field defect). Intellectual impairment accrues as these deficits start to summate.

Treatment of vascular risk factors, especially hypertension and hyperlipidaemia, can have a useful preventive effect in both forms of vascular dementia.

Other progressive intracranial pathology

Frontal and temporal tumours occasionally become large enough to cause significant intellectual impairment before producing tell-tale features like epilepsy, focal deficit or raised intracranial pressure.

Patients with chronic subdural haematoma are usually elderly, alcoholic or anticoagulated. They may not recall the causative head injury, but become drowsy, unsteady and intellectually impaired over a few weeks. Because the collection of blood is outside the brain, focal neurological signs appear late.

Any process which causes hydrocephalus slowly may declare itself by failing intellectual ability, slowness, inappropriate behaviour and drowsiness, often with gait disturbance, incontinence of urine and headache.

Neurosurgery may help all these patients.

Severe multiple sclerosis can cause dementia, often with emotional lability.

Dementia that particularly affects frontal lobe functions, with disinhibited and illogical behaviour, is characteristic of Huntington’s disease, the dementia that sometimes accompanies motor neurone disease, and Pick’s disease. This pattern of dementia, where language and spatial abilities are affected late, if at all, is particularly challenging to manage. The patient has no insight into the nature of his problems, often neglects himself and refuses help.

Creutzfeldt–Jakob disease (CJD) classically causes a very rapidly progressive and devastating dementia with ataxia and myoclonic jerks. The patient gets worse day by day and is helpless and bed-bound within weeks or months, dying within a year. It is mercifully very rare.

CT scan demonstrating a frontal meningioma with surrounding cerebral oedema. The tumour enhances after contrast administration (right-side image).

Severe atrophy of the frontal and temporal lobes due to Pick’s disease.

Transmission and CJD

There are two aspects to mention:

1.Whereas most cases of classic CJD are caused by spontaneous deposition of an abnormal form of prion protein within the patient’s brain, a few cases have been caused by iatrogenic, person to person, transmission of this abnormal protein through pituitary extracts, corneal grafts and neurosurgical procedures.

2.The variant form of CJD, which occurs mainly in the UK, takes a slightly slower course and affects younger people. It is thought to be due to transmission of the closely related prion disease in cattle, bovine spongiform encephalopathy, to people by human consumption of contaminated beef.

Frontal toxoplasmosis abscess due to HIV–AIDS.

Alcohol and drugs

In addition to the rather flamboyant syndromes seen in alcoholics who become deficient in vitamin B1, namely Wernicke’s encephalopathy and Korsakoff’s psychosis, it is being increasingly recognized that chronic alcoholism is associated with cerebral atrophy and generalized dementia.

Patients, especially those who are elderly, may become confused and forgetful whilst on medication, especially antidepressants, tranquillizers, hypnotics, analgesics and anticonvulsants.

It is most important to bear in mind alcohol and drugs before embarking upon a detailed investigation of dementia.

Rare infections, deficiencies and metabolic disorders

HIV–AIDS

HIV–AIDS can cause dementia, either through a primary HIV encephalitis or through the CNS complications of immunodeficiency such as opportunistic infection (toxoplasmosis, cryptococcal meningitis) and lymphoma. The risk of all of these is greatly reduced by current highly active retroviral therapy regiments, but tragically these are least available in the countries with the greatest prevalence and need.

Tertiary syphilis

Tertiary syphilis was the AIDS of the nineteenth century but is now rare because of improvements in public health and the widespread use of penicillin, which is lethal to the spirochaete Treponema pallidum. It gives rise to general paralysis of the insane (a dementia with prominent frontal lobe features), tabes dorsalis (with loss of proprioception and reflexes in the lower limbs), taboparesis (a mixture of the two) and meningovascular syphilis (with small vessel strokes, especially of the brainstem) (see p. 248 for further details). Blood tests for syphilis should be a routine part of the investigation of dementia.

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B vitamin deficiency

Vitamin B1 deficiency in Western society occurs in alcoholics whose diet is inadequate, and in people who voluntarily modify their diet to an extreme degree, e.g. patients with anorexia nervosa or extreme vegetarians.

Impairment of short-term memory, confusion, abnormalities of eye movement and pupils, together with ataxia, constitute the features of Wernicke’s encephalopathy. Though associated with demonstrable pathology in the midbrain, this syndrome is often rapidly reversible by urgent intravenous thiamine replacement.

Less reversible is the chronic state of short-term memory impairment and confabulation which characterize Korsakoff’s psychosis, mainly seen in advanced alcoholism.

Whether vitamin B12 deficiency causes dementia remains uncertain. Certainly, peripheral neuropathy and subacute combined degeneration of the spinal cord are more definite neurological consequences of deficiency in this vitamin.

Hypothyroidism

Hypothyroidism is usually rather evident clinically by the time significant impairment of intellectual function is present. It is a cause worth remembering in view of its obvious reversibility.

Investigation of dementia

Usually an accurate history, with collateral information from family and friends, together with a full physical examination, will highlight the most likely cause for an individual patient’s dementia.

It is worth thinking whether the problem has begun in the temporal and parietal lobes (with poor memory, then language and spatial problems, usually indicatingAlzheimer’s disease or dementia with Lewy bodies) or in the frontal lobes (with changes in behaviour, raising the possibility of surgically treatable pathology like tumour or hydrocephalus). It is important to ask about the patient’s past medical history (vascular risk factors) and family history (vascular risk factors again, and genetic dementias such as Huntington’s disease, familial Alzheimer’s disease and Pick’s disease). It is particularly important to ask about the patient’s social circumstances, because of the need to provide support and care during an illness that is usually arduous and prolonged.

The examination must include tests of memory, language, spatial ability and reasoning as already outlined. It must include a search for neurological clues to the cause of the dementia (see table on opposite page), and a careful examination of the

CHAPTER 14

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Management of dementia

Careful explanation is important. Patients vary greatly in the amount of information that they want and can absorb, and establishing this in an individual person requires patience and sensitivity. Family members tend to want more information, especially if there may be genetic implications. The family must be helped to realize that the demented patient will continue to be dependent on them, will thrive better on a familiar routine each day, and may need care to prevent injury from hazards around the home. Additional help and support may be available from disease-specific self-help groups like the Alzheimer Society; voluntary care organizations that provide someone to sit with the patient while the carer pursues activities out of the house; social services facilities like day centres; or old age psychiatry services including community nurses and day hospitals. Ultimately many patients require full-time nursing care.

It may be necessary to encourage the healthy spouse to seek power of attorney, and to obtain advice regarding pensions, investments and wills from a solicitor.

Clearly any treatable underlying condition will be treated. In Alzheimer’s disease, and especially in dementia with Lewy bodies, a careful trial of a cholinesterase inhibitor (such as rivastigmine, donepezil or galantamine) may produce transient symptomatic benefit. Unfortunately many patients do not improve or experience adverse effects, and should not continue the treatment unnecessarily. Coexisting conditions such as anxiety and depression can often be usefully treated.

Most of the drugs that are prescribed for people with dementia are, however, sedatives or neuroleptics directed at modifying undesirable or dangerous behaviours, such as irritability or wandering. There is surprisingly little evidence that such treatments are effective, and increasing evidence that they may be hazardous. In an ideal world they would be used very sparingly, with greater emphasis on non-pharmacological ways of modifying behaviour and supporting carers.

CHAPTER 14

•Explanation

•Practical support

•Careful trials of symptomatic therapy

•Power of attorney

CASE HISTORIES

Case 1

A man of 76, who has suffered from atrial fibrillation for 15 years and takes regular warfarin therapy, starts to cause concern in his wife. He is usually very alert for his age, keeping well abreast of current affairs, and a source of inspiration to his children and grandchildren. She is unable to date the precise onset of his symptoms, but it is all very recent. She has been surprised by her husband forgetting items when shopping, his mistakes over the grandchildren’s names, his lack of concern, and his tendency to sleep more in the daytime.The GP is consulted but cannot really confirm any definite impairment of neurological function, and examination is normal except for his controlled atrial fibrillation.Thyroid function tests are checked and are normal.

Over the next 3 weeks the situation does not improve.All the family can see the change in the patient, who is now mentioning generalized headaches.

a.What are your thoughts about diagnosis?

b.And your management?

Case 2

A 69-year-old woman is brought to the emergency department by her distressed husband. Over the last 2 days she has become increasingly agitated. She has repeatedly seen people around their home, and thinks that he is involved in a conspiracy to house illegal immigrants. She has become aggressive when he tries to persuade her that there is in fact no-one else in the house and no conspiracy. He feels that she has been more forgetful over recent months, and has developed difficulty in navigating around the familiar streets of their town centre. He also describes a recent episode of confusion which settled after 2 days of treatment for a presumed urinary tract infection.

She is highly aroused, shouting angrily for help. She cannot cooperate with a detailed neurological examination but uses all four limbs effectively and has normal eye and facial movements. Her chest is clear and she is afebrile.

a.What are the diagnostic possibilities here, and how would you manage her?

(For answers, see pp. 266–7.)

Poliomyelitis

Herpes zoster, herpes simplex, type 2

Herpes simplex, type 1

Common localized infections

Viral infections

Some viruses have a predilection for particular elements of the nervous system.

Acute poliomyelitis

Acute poliomyelitis is very uncommon in the UK nowadays, because of the effective immunization programme. Rare cases are usually the consequence of inadequate primary or ‘booster’ immunization. It remains a serious problem in some other parts of the world.

After a gastro-enterological infection, the virus takes up residence in the lower motor neurones (in the spinal cord and brainstem). Paralysis ensues, which is often patchy and asymmetrical in the body. Where the infection has been very severe in the neuraxis, lower motor neurones do not recover and the paralysis is permanent. Some of the damage to motor neurones is less complete, and frequently there is recovery of some muscle function after a few weeks. Permanently affected muscles remain wasted and areflexic.

Herpes zoster infections

Herpes zoster infections, or shingles, have been described in Chapters 8 (pp. 123 and 125), 9 (p. 143) and 13 (p. 220). The virus probably enters the dorsal root ganglion cells in childhood at the time of chickenpox infection, and remains there in some sort of dormant condition. Later in life, as a result of some impairment in immunological surveillance (e.g. age, immunosuppressive treatment, lymphoma, leukaemia), the virus becomes activated and causes shingles.

Herpes simplex infections

Cold sores around the mouth and nose are the commonest clinical expressions of herpes simplex virus type 1 infection. A similar dormant state to that in herpes zoster infections occurs here, with the herpes simplex virus resident in the trigeminal nerve ganglion. The altered immunological status that accompanies another viral infection (usually a ‘cold’) allows the herpes simplex virus to become activated in the ganglion, and cause the skin rash in trigeminal territory.

In the case of herpes simplex virus type 2 infections, the site of latent infection is the dorsal root ganglion in the sacral region, and reactivation leads to genital herpes, in which the vesicular ulcerative lesions occur in the urogenital tract and perineal region.