Dementias

Question 1

Causes of Dementia

Answer 1

Common causes
Alzheimer’s disease
cerebrovascular disease: multi-infarct dementia (c. 10-20%)
Lewy body dementia (c. 10-20%)

Rarer causes (c. 5% of cases)
Huntington’s
CJD
Pick’s disease (atrophy of frontal and temporal lobes)
HIV (50% of AIDS patients)

Important differentials, potentially treatable
hypothyroidism, Addison’s
B12/folate/thiamine deficiency
syphilis
brain tumour
normal pressure hydrocephalus
subdural haematoma
depression
chronic drug use e.g. Alcohol, barbiturates

Question 2

Diagnosis of Vascular Dementia?

Answer 2

A comprehensive history and physical examination
Formal screen for cognitive impairment
Medical review to exclude medication cause of cognitive decline
MRI scan – may show infarcts and extensive white matter changes

Question 3

Features of Lewy Body dementia?

Answer 3

progressive cognitive impairment
typically occurs before parkinsonism, but usually both features occur within a year of each other. This is in contrast to Parkinson’s disease, where the motor symptoms typically present at least one year before cognitive symptoms
cognition may be fluctuating, in contrast to other forms of dementia
in contrast to Alzheimer’s, early impairments in attention and executive function rather than just memory loss
parkinsonism
visual hallucinations (other features such as delusions and non-visual hallucinations may also be seen)

Question 4

Diagnosis of Lewy Body Dementia

Answer 4

usually clinical
single-photon emission computed tomography (SPECT) is increasingly used. It is currently commercially known as a DaTscan. Dopaminergic iodine-123-radiolabelled 2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123-I FP-CIT) is used as the radioisotope. The sensitivity of SPECT in diagnosing Lewy body dementia is around 90% with a specificity of 100%

Question 5

Treatment of Lewy Body Dementia

Answer 5

both acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine) and memantine can be used as they are in Alzheimer’s. NICE have made detailed recommendations about what drugs to use at what stages. Please see the link for more details
neuroleptics should be avoided in Lewy body dementia as patients are extremely sensitive and may develop irreversible parkinsonism. Questions may give a history of a patient who has deteriorated following the introduction of an antipsychotic agent

Question 6

Alzheimers pathological changes

Answer 6

macroscopic:
widespread cerebral atrophy, particularly involving the cortex and hippocampus
microscopic:
cortical plaques due to deposition of type A-Beta-amyloid protein and intraneuronal neurofibrillary tangles caused by abnormal aggregation of the tau protein
hyperphosphorylation of the tau protein has been linked to AD
biochemical
there is a deficit of acetylcholine from damage to an ascending forebrain projection

Neurofibrillary tangles
paired helical filaments are partly made from a protein called tau
tau is a protein that interacts with tubulin to stabilize microtubules and promote tubulin assembly into microtubules
in AD are tau proteins are excessively phosphorylated, impairing its function

Question 7

Treating Alzheimers

Answer 7

Pharmacological management
NICE updated it’s dementia guidelines in 2018
the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease
memantine (an NMDA receptor antagonist) is in simple terms the ‘second-line’ treatment for Alzheimer’s, NICE recommend it is used in the following situation reserved for patients with
moderate Alzheimer’s who are intolerant of, or have a contraindication to, acetylcholinesterase inhibitors
as an add-on drug to acetylcholinesterase inhibitors for patients with moderate or severe Alzheimer’s
monotherapy in severe Alzheimer’s

Managing non-cognitive symptoms
NICE does not recommend antidepressants for mild to moderate depression in patients with dementia
antipsychotics should only be used for patients at risk of harming themselves or others, or when the agitation, hallucinations or delusions are causing them severe distress

Donepezil
is relatively contraindicated in patients with bradycardia
adverse effects include insomnia