Alzheimer’s disease
D E F I N I T I ON
Primary chronic progressive neurodegenerative dementia1 characterized by
extracellular deposition of b-amyloid protein2 and intracellular neurofibrillary tangles.
Mild cognitive impairment: Impairment in some cognitive domains but insufficient to qualify
for diagnosis of dementia or to affect quality of life.
AET IOLOGY
Unknown cause. Majority of cases are idiopathic with rare monogenic cases.
Risk factors include age, prior intellectual level and family history.
Pathophysiology: Characterised by extracellular deposition of amyloid plaques containing
b-42 peptides and intracellular accumulation of neurofibrillary tangles containing hyperphosphorylated
tau protein (microtubule protein). It remains unclear which is the
causative pathology. Neurone count is reduced particularly in hippocampus, mesial
temporal and precuneate cortex.
E P IDEMI OLOGY
Very common, affecting 5% of those >65 years and accounts for
60–80% of all dementias. Diagnosis before age 60 years is exceptional. The incidence
" exponentially with age.
H ISTORY
Reliable history is best obtained from relative.
Gradual deterioration of cognitive functions:
. Initially, anterograde amnesia, change of personality, apathy, loss of concentration and
disorientation. May be accompanied with psychiatric manifestations (hallucinations and
delusions).
. Language is typically spared until late.
. In late stages, cognitive impairment in all cognitive domains (memory, language, visuospatial),
myoclonus, seizures, behavioural disturbances, incontinence and loss of
independence.
EXAMI N A T ION
Mini-Mental State Exam (MMSE) is a useful screening tool (<27 qualifies
for dementia) but premorbid intellectual function needs to be taken into account.
Typically, in amnestic Alzheimer’s, delayed recall is impaired even with prompting.
I N V E S T IGATIONS
Investigations are aimed at excluding treatable causes of dementia.
Blood: FBC, U&E, LFT, ESR, CRP, TFT (exclude hypothyroidism), folate, ANA, ANCA, vitamin
B12, treponemal serology. Consider HIV serology.
CT/MRI-brain: May show cerebral or hippocampal atrophy. Useful for excluding tumours,
infarction, inflammatory causes, subdural haematoma.
Psychometric testing: Useful for defining domains of impairment. May be helpful for
distinguishing depressive pseudo-dementia.
Electroencephalography: Not diagnostic, but may be useful to exclude non-convulsive status
epilepticus as a cause.
Lumbar puncture: Not usually necessary except if disease is relatively subacute onset or rapid
to exclude other causes (e.g. encephalitis, prion disease). Tau and b-42 peptide levels can
also be measured.
Nuclear imaging: Primarily research tools. 11C-PIB PET can image amyloid distribution in brain
and 99mTc-HMPAO-SPECT shows regional hypoperfusion of affected cerebral regions.
MANAGEMENT
Best provided by multidisciplinary team composing of psychiatrist, social
worker, neuropsychologist.
1 Dementia is the significant impairment of memory and one or more other domain of cognition (language,
visuospatial skills and praxis) in a setting of clear consciousness and interfering with work, social activities or
relationships.
2 b-amyloid deposition can also occur in the cerebral arteries causing cerebral amyloid angiopathy. This is
typified by lobar haemorrhages and can be detected by MRI-gradient echo sequences.
Treatment of intercurrent illness or exarcebating factors: Avoid sedative drugs, antimuscarinic
agents and alcohol, environmental management.
Adaptations: Medicalert bracelet, memory aids (diaries, labels).
Pharmacological: Anticholinesterase inhibitors (e.g. rivastigminem donepezil, galantamine)
are only licensed for mild to moderate disease and provide only modest benefit.
Social: Manage psychological impact of disease on carer and patient. Initiate social support
systems early before advanced disease requires institutional care. Early discussion of endof-
life care may be helpful.
COMPLLI C A T IONS
Poor quality of life, loss of independence, devastating effect on
family.
PROGNOSIS
The average life expectancy from diagnosis is between 3 and 8 years.
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