Dementia is a progressive global decline cognitive function, without impairment of consciousness.

There are many causes of dementia, but the two most common are:
  • Alzheimer’s disease (~40-50%)
  • Diffuse vascular disease (aka multi-infarct dementia) ~25%
  • In practice it is often difficult to differentiate the type of dementia present

Epidemiology

  • Very rare <55 years
  • 5-10% prevalence in >65’s
  • 20% in >80 years
  • 80% in >100 years

Aetiology

Alzheimer’s disease
  • Genetic predisposition
    • About 15% of cases are familial. These fall into to two categories:
    • An early on-set autosomal dominant disease
    • A later onset type of disease, whose inheritance is variable
    • The most common gene mutation is apoE4 although mutation of this gene does not necessarily mean you will develop Alzheimer’s.
  • Insulin resistance may be a predisposing factor
  • Female:Male ratio = 2:1
  • The majority of cases are sporadic
  • No environmental factors have yet been proven
    • Cholesterol, atherosclerosis and inflammation are thought to be implicated

Symptoms

General symptoms of Alzheimers and Vascular dementia
  • Memory loss – this is usually the first symptom to appear
    • The damage to brain tissue is not universal, and thus some areas of memory, notably autobiographical and political memory is stored in areas that are less often affected.
    • Short term memory is more readily affected, and confusion may often result. For example, patients may buy many identical items of food on separate occasions, and then wonder why their cupboards are full of these items.
  • Visuo-spatial problems – patients may be easily disorientated by unfamiliar surroundings
  • Emotional disturbance
  • Loss of normal social behaviour
  • Language problems  – Problems both understanding what is being said, and naming objects
  • Concentration issues
  • Short attention span – Also unable to plan, organise, or sequence activities
  • Behavioural changes – Delusions (persecutory), agitiation, aggression, wandering
  • Variable mood
  • Poor sleep
  • Restlessness
  • Hallucinations
  • Apathy
  • Depression / euphoria – Severe depression is rare, due to loss of insight
In later stages of the disease, there may also be:
  • Self-neglect
  • Change in personality – which generally involves loss of inhibition
  • Motor and sensory abnormalities
  • Seizures
In very late stage disease there may be:
  • The patient may become mute
  • They may take little interest in anything
  • Parkinsonianism
  • Wasting
  • Seizures
  • Incontinence
These can be particularly distressing for relatives.
In Alzheimer’s disease the progression of the symptoms is always gradual, but in diffuse vascular disease, the symptoms are more likely to occur acutely. There is often a ‘step-wise progression’, as more small infarcts cause damage.
In cases of vascular dementia you may also find other vascular sings, for example:
  • Raised BP
  • Past strokes
  • Sudden onset / stepwise increase of symptoms

Diagnosis

The main symptom is usually confusion. Diagnosis is usually clinical, and made with the help of the MMSE (Mini-Mental State Exam). Sometimes, IQ tests (Wechsler Adult Intelligence Scale, may also be used). However, as confusion is often apparent, you may have to perform many other tests to rule out other differentials. The later on in life the presentation, the less likely it is to be investigated.
Always assume confusion is due to an acute illness until proven otherwise. This might mean, depending on the history, that you are going to have to do a lot of blood tests:
  • Vitamin deficiencies – ↓folate, ↓B12, ↓thiamine – these could be primary deficiencies, or may be alcohol related.
  • TFT’s – thyroid problems
  • FBC – anaemia
  • U+E’s – renal failure / dehydration
  • LFT’s – carcinoma, cirrhosis, encephalopathy
  • Glucose – diabetes
  • CRP/ESR – acute infection
  • Imaging of the brain – CT/MRI – this may be used to exclude treatable space occupying lesions, such as:
    • Hydrocephalus
    • Tumour
    • Subdural haematoma
    • HOWEVER – the most common abnormality seen on brain scan is general atrophy.

History

This is very important. Dementia is slowly progressive, and the symptoms may have started years ago. It is highly likely you will need to speak to relatives as well as to the patient themselves

Differentials for confusion

Pathogenesis

Alzheimer’s disease

  • The mean survival is 7 years. Most will survive between 2-7.
  • Death usually results from bronchopneumonia
  • There is a general atrophy of brain tissue, and the weight of the brain is usually reduced. The frontal and temporal lobes are particularly affected.
  • There is often compensatory dilatation of the ventricles, resulting in hydrocephalus.
  • The cerebellum and spinal cord are normal
  • There is a build up of amyloid plaques in the brain. These are the breakdown products of amyloid factors.
  • There is also atrophy of cholinergic fibres that run from the hippocampus to the cerebral cortex. Initially there is a reduction on cholinergic transmission, and later a reduction in the synthesis of acetylcholine, particularly in the cerebral cortex itself.
  • The damage is variable, and can occur at different rates in different parts of the brain. Most likely to be affected are the Amygdala, temporal cortex, and a few selected brainstem nuclei.
  • There is no change in the number of muscarinic receptors, but the number of nicotinic receptors is reduced.
  • In very late stage disease there can be variable depletion of other neurotransmitters
  • There may be the excess deposition of beta-amyloid in the brain – leading to the formation of beta-amyloid plaques.

Vascular dementia

This is the result of many small infarcts. Cerebrovascular disease has to be pretty advanced for vascular dementia to become apparent, as large parts of the cortex have to have been affected.
The disease will have a step-wise progression, so for instance, there will be no apparent change in the condition, perhaps for many months, and then there is a sudden drop in function. Infarcts are particularly likely to affect function if they damage the white matter.
As well as dementia, eventually there may be:
  • Pseudobulbar palsy
  • Shuffling gait with small steps – marche a petits pas – sometimes called atherosclerotic Parkinson’s disease.
There is often also a history if TIA’s

Differentiating types of dementia

In the past, as long as B12 and TSH levels were normal, this was not necessary, however, these days, there are specific treatments for Alzheimer’s. The types of dementia can be differentiated by a combination of; history, CT/MRI and neuropsychological testing.

Making a will

If the disease is discovered early enough, then it is possible to make a will, and/or an advanced directive before the patient becomes to ill for one of these to be accepted by law. The patient must be able to:
  • Understand and retain the information involved
  • Believe the information is true
  • Demonstrate they are able to weigh up the pro’s and con’s of an argument and come to a decision based on these

Management

In all types of the disease, the management is only able to reduce the rate of progression of the disease. There is no cure.
 

Alzheimer ’s disease

Anticholinesterase drugs – e.g. donepezil, galantamine, rivastigmine
  • Mechanism – these drugs work by inhibiting cholesterases, and thus increasing cholinergic transmission within the brain.
  • Unwanted effects – anorexia, nausea, vomiting, diarrhoea, abdo pain, insomnia, confusion, agitation, headache
    • Note that some of these effects are similar to the clinical symptoms of Alzheimer’s!
  • Clinical use – will delay the decline of cognitive impairment in 40% of patients – probably only by about 3-6 months.Probably more effective in those without the gene apoE4.
    • Important to assess efficacy, and to stop treatment in those who do not respond.
    • Rapid decline is seen when the drug is stopped in previously responsive individuals
    • Have functional benefits that may improve QOL.
NMDA receptor antagonists – memantine
  • Mechanism – an inhibitor of glutamate NMDA receptors. It binds selectively, depending on the voltage, and thus prevents excitotoxicity, without altering gluatamtes role in normal memory and learning.
  • It can be given WITH anticholinesterases
  • Unwanted effects:
    • Diarrhoea, insomnia, dizziness, headache, hallucinations
    • Again, note that some of these are similar to symptoms of dementia!
  • Clinical use
    • Usually more well tolerated than anticholinesterases, but probably not as effective
    • May provide some benefit in cognitive function, and may slow cognitive decline
  • Not widely used
### Drug treatment should only be initiated in those with a MMSE of >12! ###

This is mild to moderate dementia
NICE guidelines state:

  • Treatment to be reviewed every 6 months
  • Don’t treat if MMSE <12, as side effects of drug likely to outweigh benefits
  • Treatment only to be administered and monitored by specialist centres
  • Don’t rely on MMSE as your only tool for aiding prescribing, e.g. get collateral histories, assess function and behaviour

Drug therapy is controversial

  • Drugs are expensive
  • Some trials have shown no benefit of the drugs over placebos
  • In many cases it is thought that they at least allow a few more months in a home care environment

Vascular Dementia

Prevention
Reduction of vascular risk factors:
  • Aspirin or warfarin therapy – aspirin often quoted anecdotally, but there is actually now evidence that the sort of low dose therapy that many individuals take provides any benefit against vascular dementia. Some at risk patients may be put on warfarin therapy.
  • Controlling BP – use normal system (A-C-D (+B)) for initiating bloop pressure maintenance therapy
  • Anticholinesterases and memantine – may have some benefit in vascular dementia.
The burden of care
The course of the disease is often distressing for both families and patient. Supportive care is necessary to ensure the patient stays in a familiar home environment as long as possible. Often the burden of care falls to relatives.
  • Some recent evidence suggests that engaging in cognitively taxing activities late on in life can protect against dementia!
  • Vitamin E – has shown in some instances to protect against dementia

Other Types of Dementia

Lewy-body dementia (~15-25% of all cases of dementia)
This is characterised by the presence of Lewy bodies in the brainstem and neocortex. It can be differentiated from other types of dementia by:
  • Symptoms fluctuate
  • Permanent memory dysfunction is not apparent in the early stages
  • Associated with Parkinsonianism
  • Associated with depression and sleep disturbance
  • Causes visual hallucinations – often frightening and persecutory
  • There may be transient LOC
The drug rivastigmine may help to improve symptoms
Fronto-temporal dementia
In this condition there is atrophy of the fronto-temporal region, without the histology seen in Alzheimer’s. it may be difficult to differentiate from Alzheimer’s, but behavioural/personality change are more likely to occur early on, and things like memory and spatial awareness may be preserved for longer. There is often massive disinhibition.
Rare causes

Differentials for Dementia

  • Pseudodementia – seen in mood disorders(e.g. depression). Symptoms mimic depression – e.g. a decline in cognitive function, but will resolve when the mood disorder is treated. There is also often a history of depression or other mental illness
  • Delerium
  • Mild/moderate learning difficulties

Related entries