Geriatrics - Dementia

Question 1

What is the definition of dementia?

Answer 1

Dementia is a global loss of cognitive ability in a previously unimpaired person beyond what might be expected in normal ageing.

Question 2

What are the diagnostic criteria needed for a diagnosis of dementia?

Answer 2

DSM IV states that the following criteria are required for a diagnosis of dementia:

1) Evidence of impairment of memory (amnesia) + at least one of
- language impairment
- apraxia
- agnosia
- impairment of executive function

2) Impairment of functioning
3) No other medical or psychiatric explanation
4) Present for at least 6 months

Question 3

What is “mild cognitive impairment”?

Answer 3

Mild cognitive impairment (MCI) is a term that is often used non specifically and as such is not helpful diagnostically. It is applied when there is evidence of memory decline on formal memory tests (e.g. MMSE) WITHOUT any other clinical features of dementia.

Mild memory problems may indicate the early start of dementia but can be associated with other conditions such as depression, anxiety, stress or physical problems.

Question 4

What is the link between MCI and dementia?

Answer 4

Approximately 10-15% of patients with MCI develop dementia every year.

It is important to note that many patients will report subjective memory loss, but unless there is objective evidence of decline in memory the diagnosis of MCI cannot be made.

Question 5

What is the epidemiology of dementia?

Answer 5

The prevalence of dementia is 5% in the over 60s and 20% in the over 90s. The key risk factor for developing dementia is advancing age.

2/3s of patients with dementia are women.

Question 6

How is dementia classified?

Answer 6

There are several classification systems for dementia. These aim to group disorders that have common features, such as which part of the brain is affected:

• Cortical dementia = dementia causing problems with memory, language, thinking and social problems
• Subcortical dementia = dementia causing problems with emotions, movement, and memory problems
• Progressive dementia = dementia that deteriorates over time
• Primary dementia = dementia that is not due to another cause
• Secondary dementia = dementias that occur due to physical injury or disease

Diseases often fit into several classifications -
e.g. Alzheimer’s disease is a primary, progressive cortical dementia.

Sometimes more than one of these can co-exist in the same patient - e.g. a patient with fixed cognitive impairment secondary to brain injury can go on to develop superimposed primary Alzheimer’s disease.

Question 7

Name some degenerative causes of dementia?

Answer 7

Alzheimer's disease
Frontotemporal dementia
Lewy body dementia
Parkinsons disease
Huntington's disease
PSP

Question 8

Give some vascular causes of dementia?

Answer 8

Multi-infarct dementia
Cerebral infarcts
Binswanger's disease
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
Vasculitis (e.g. lupus)

Question 9

What metabolic disorders can cause dementia?

Answer 9

Alcohol related
Heavy metal poisoning
Drug intoxication
HYPOthyroidism 
B12 and folate deficiency
Paraneoplastic
Inherited metabolic disorders (e.g. Wilson's disease)

Question 10

What is the most common type of dementia?

Answer 10

Alzheimer’s disease accounts for 62% of all cases of dementia. The risk of developing AD increases with age. Approx 98% of patients with AD are aged over 65 years.

Question 11

How common is dementia with Parkinson’s disease?

Answer 11

Dementia affects up to 30% of patients with Parkinson’s disease.
The symptoms and signs are similar to those found in dementia with Lewy bodies.
Parkinson’s disease dementia presents in patients who have had a diagnosis of PD for more than 2 years.

Question 12

What is mixed dementia?

Answer 12

This is the 3rd most common type of dementia and refers to a combination of AD and vascular dementia.

A key feature of vascular dementia is that it progresses in a stepwise fashion, as opposed to AD which is a progressive decline.

Question 13

What is Lewy Body dementia?

Answer 13

Lewy body dementia affects 25000 people in the UK. Many symptoms are similar to those found in AD - e.g. memory deterioration, poor attention, communication difficulties. Patients with LBD often show Parkinsonism and hallucinations.

Question 14

What is a key early signs of frontotemporal dementia?

Answer 14

FTD is a rare form of dementia that actually describes a variety of conditions. It includes Picks disease.

It is more common in adults < 65 years old. The early signs are personality and behavioural changes as opposed to memory decline.

Question 15

How does dementia progress?

Answer 15

The progression of dementia can be divided into 3 phases (this is most typical of AD):
1) Early: difficulty embracing change, repetition of questions, short term memory loss

2) Middle: needs prompting, difficulty with daily tasks, failure to recognise people
3) Late: decline in speech, aggression, weight loss, incontinence

Question 16

What is the role of genetics in dementia? How does this affect inheritance of dementia?

Answer 16

The majority of dementias result from a combination of multiple genetic contributions.

Lifestyle and environmental factors are often important and may play a role in how genes are expressed (genotype) and how the patient presents clinically (phenotype).

Whilst the son or daughter of a patient with dementia is at an increased risk of developing the disease, the complex interaction between multiple genes and the environment means that the heritability of dementia is unpredictable.

There are rare forms of dementia where the responsible genes have been identified - e.g. early onset AD.

Question 17

What is early onset AD?

Answer 17

This is a subtype of AD that is rare compared with late onset AD. It is autosomal dominant and has 3 genes associated with it:

i) Amyloid precursor protein
ii) Presenilin gene 1
iii) Presenilin gene 2

If one of these genes is present then the disease is developed aged 30-40 years. If 2 or more close relatives develop AD before the age of 60, a patient should be considered for genetic screening.

Question 18

What is late onset AD?

Answer 18

Late onset AD is the most common form of AD and develops in the over 65s.

Its development is linked to the apolipoprotein E gene (APO-E). There are 3 types: APO-E2, APO-E3, and APO-E4. Everyone has 2 copies of the gene which can be the same or different.

APO-E4 is associated with a higher risk of AD. About 25% of people inherit a single gene and this will increase their risk of AD by 4 times. 2% of the population will inherit 2 copies of the gene which will increase their risk of AD by 10 times.

APO-E3 gene is inherited in a double form by 60% of the population, and of these 50% will develop AD by their late 80s.

APO-E2 is mildly protective against AD.

Question 19

What genes are associated with vascular dementia?

Answer 19

Single gene defects are associated with rare variants of this form of dementia:

• Notch3 gene is linked with CADASIL
• variation of the APP gene causes heritable cerebral haemorrhage with amyloidosis (HCHWA)

High cholesterol, diabetes and hypertension all contribute to the development of vascular dementia and have a genetic component as well.

Question 20

What risk factors are associated with dementia?

Answer 20

Smoking: increases risk of mental decline
Alcohol (M)
Atherosclerosis (M)
Hypercholesterolaemia: raised LDL cholesterol increases risk of vascular dementia (M)
Age
Genetics
MCI

Some of these are modifiable (M).

Question 21

What are the 3 forms of AD?

Answer 21

1) Early onset (rare) - fewer than 10% of AD patients. Associated with the development of myoclonus
2) Late onset (most common) - symptoms begin after 65
3) Familial (rare)

Question 22

What are the features of the late stage of AD?

Answer 22

Remember that AD progresses in 3 stages or phases. The late phase is characterised by:

• increasing dependence on others for care
• inability to recognise familiar objects or even relatives
• increasing frailty
• poor appetite, dysphagia and even weight loss
• incontinence
• restlessness and agitation

Question 23

What are the features of the early phase of AD?

Answer 23

• minor changes in abilities or behaviours, often only realised in hindsight
• loss of recent memory, repetition or questions, slow at grasping ideas
• unwilling to embrace change and difficulty dealing with money

Question 24

How does AD progress clinically?

Answer 24

Symptoms evident during the early stages of AD are short term memory loss with disorientation and errors of judgement.

As the disease progresses:

• sufferers develop difficulty with daily functioning
• language skills decline
• there may be behavioural change with wandering
• often requirement with ADLs

End stages of the illness occur in the last 1-2 years of life:

• patients need intensive levels of care
• communication is severely impaired
• sufferers become incontinent
• swallowing becomes difficult

Most common cause of death is from infections such as pneumonia.

Question 25

What are the macroscopic features of brains affected by AD?

Answer 25

The cortex is atrophic - damaged areas are involved in thinking, planning and remembering.

The hippocampus is severely atrophic - this area plays a key role in memories and is affected early.

The ventricles of the brain are enlarged.

Question 26

What are the microscopic pathological features of AD?

Answer 26

There is an excess of 2 types of abnormal structures found in the brain of people with AD - (i) plaques and (ii) tangles.

Extracellular plaques are thought to block cell to cell signalling or activate immune system responses that trigger inflammation and cell death within the brain. They are made up of deposits of protein fragments called beta amyloid.

Neurofibrillary tangles are thought to destroy the cell transport system which is made from a protein called tau. Tau usually helps the strands of the transport system to link together. Tangles are twisted fibres of tau that are no longer able to link the transport system of the cell which affects intracellular transport.

Question 27

What is the pathogenesis of AD?

Answer 27

Deposition of amyloid beta in the cerebral cortex is believed to be an initiating event in the development of AD leading to tau hyperphosphorylation and tangle formation within neurones (the amyloid cascade hypothesis).

Amyloid beta is produced by proteolytic cleavage of the precursor molecule APP. Processing via the primary (alpha secretase) pathway is dominant and does not lead to amyloid beta release.

Processing via the alternate (beta secretase) pathway releases soluble AB peptide. The ratio of AB40:AB42 (types of amyloid beta released by the alternate pathway) is determined by the gamma secretase complex.

The less soluble AB42 tends to form cortical plaques and is more associated with dementia, whereas AB40 deposition in blood vessels leads to cerebral amyloid angiopathy.

Question 28

What diagnostic criteria are required for AD?

Answer 28

This is outlined in the DSM-IV, and includes:

• memory deficit that can be demonstrated objectively by cognitive tests
• plus at least ONE other cognitive deficit (aphasia, apraxia, agnosia or impairment of executive function)
• reduced ability to perform ADLs
• a gradual onset and progressive course
• a decline from the previous level of functioning
• no evidence of other neurological or medical condition

Question 29

How is vascular dementia subdivided?

Answer 29

1) Post stroke dementia
2) Multi-infarct dementia
3) Subcortical vascular dementia
4) Mixed cortical and subcortical dementia

Question 30

What is post stroke dementia?

Answer 30

This is dementia occurring after a stroke. The prevalence of vascular dementia is 9x higher in patients who have had a stroke.

It is usually associated with large vessel disease. In some cases, a so called “strategic infarct” may lead to a single stroke dementia. This more abrupt decline is caused by damage to an area that is critical for memory such as the hippocampus or anteromedial thalamus.

Question 31

What is multi-infarct dementia?

Answer 31

Vascular dementia typically presents as a step wise decline in cognitive ability (consistent with a series of small strokes) or a gradual decline (in keeping with diffuse white matter or small vessel disease).

Multi infarct dementia is characterised by a step wise decline in cognition caused by multiple strokes in the cerebral cortex (cortical dementia).

Question 32

What is subcortical vascular dementia?

Answer 32

This affects the inner parts of the brain, often in people with a history of high blood pressure.

Ischaemic damage causes demyelination of nerve sheaths. If this is widespread it can be called Binswangers disease.

Question 33

What is the most common pathological feature of vascular dementia?

Answer 33

Small vessel disease (hyaline arteriosclerosis and lipohyalinosis - replacement of smooth muscle with lipid laden foam cells) often in association with arterial hypertension and other vascular risk factors.

Other pathological features include lacunar infarcts, generalised attenuation of the subcortical white matter and enlargement of perivascular spaces.

Question 34

What risk factors are associated with vascular dementia?

Answer 34

History of stroke
Smoking
High blood pressure
Previous heart attack
High cholesterol 
Obesity
Diabetes 
Family history of CVD

Question 35

What are the symptoms of vascular dementia?

Answer 35

The symptoms of vascular dementia may be similar to those of other dementias. However some features favour a diagnosis of vascular dementia:

• memory problems
• stepwise deterioration
• difficulty with concentration
• seizures
• depression
• emotional lability
• incontinence

Question 36

What features distinguish vascular dementia from AD?

Answer 36

Features distinguishing vascular dementia from AD include a fluctuating course and patchy cognitive profile, emotional incontinence and sundowning. There may also be Parkinsonian features or neurological signs consistent with one or more strokes.

Question 37

What is the standard diagnostic criteria for vascular dementia?

Answer 37

The standard criteria used for VaD is the NINDS-AIREN. To make a clinical diagnosis of vascular dementia, there should be:

• dementia defined by cognitive decline, manifesting as memory impairment and impairment of a further cognitive domain (as for AD)
• deficits should be causing limitation with ADLs
• evidence of cerebrovascular disease on examination and imaging

Question 38

What are the core features of DLB?

Answer 38

In addition to cognitive decline, the core features of DLB are visual hallucinations, fluctuation in cognitive performance and Parkinsonism.

The visual hallucinations may be due to reduced cerebral blood flow in the occipital and posterior temporoparietal regions. This is in contrast to other forms of dementia in which the posterior hemisphere tends to be spared.

Question 39

What group of drugs are some patients with DLB sensitive to?

Answer 39

Approximately 50% of patients show neuroleptic sensitivity and there may be autonomic dysfunction or sleep disorders including REM sleep behaviour disorder.

Question 40

What is the main pathological feature of DLB?

Answer 40

DLB is defined by the presence of Lewy bodies. These are intracellular inclusions of the protein alpha synuclein. They are usually bright pink bodies present in the neuronal cytoplasm surrounded by brown neuromelanin pigment.

The pathological features in dementia with Lewy bodies are indistinguishable from Parkinson’s disease dementia.

Areas affected include:

• substantia nigra
• degeneration in the cortex (Lewy bodies here are called cortical Lewy bodies)