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Chapter 7: Disorders of conciousness and memory 315

Antidepressantsmayimprovefunctionallevelinthose Neurochemical analysis reveals that patients with

with low mood. Alzheimer’s disease have widespread neurotransmit-
Psychological therapy. terdefects, particularly loss of acetylcholine esterase

For mild to moderate Alzheimer’s dementia, multi- and acetylcholine from the cortex/subcortical struc-

infarct dementia and dementia with Lewy bodies, tures.
cholinesterase inhibitors such as donepezil have been
showntobeofbenefit,indelayingtheneedfornursing Clinical features
home care. The features are those of dementia, but with an insidious
onset and progressive decline in memory and at least one
of:
Alzheimer’s disease
Dysphasia: Loss in language skills, especially with
Definition names and understanding speech.
Aprimary degenerative cortical dementia. Apraxia: Inability to execute a skilled or learned mo-
toract, e.g. inability to brush teeth, write, get dressed
Incidence despite intact muscle function and comprehension.
Most common neurodegenerative disorder and cause of Agnosia: Loss of ability to recognise objects, people,
dementia. sounds, shapes or smells despite normal sensory func-
tions.Usuallyclassifiedbythesenseaffected,e.g.visual
Age agnosia.
The onset can be in middle age, but the incidence rises Disturbance in executive functioning (higher mental
with age. The annual risk of developing Alzheimer’s dis- functions such as planning, abstract thought, organi-
ease (AD) is 1% in people aged 70–74 years, 2% in those sation).
aged 75–79 years and then steeply rises to 8% in those With progression over a number of years patients be-
over 85 years. come immobile and emaciated. Death is commonly due
toacomplication of immobility or other diseases.
Aetiology/pathophysiology
Risk factors include family history, Down’s syndrome Macroscopy

and previous head injury. The brain is small, with shrinkage of the gyri and widen-
Molecular analysis of the amyloid found in the brains ing of the sulci. Temporal lobe atrophy is prominent,

ofpatientswithADshowsthatitisderivedfromafam- particularly in the parahippocampal gyrus but also in
ily of normal cell membrane proteins called amyloid the frontal and parietal lobes.
precursor proteins (APP) encoded on Chr 21. When
APPs are cleaved by specific enzymes called secretases, Microscopy
a highly amyloidogenic protein is produced which is There are several abnormalities.
referred to as β-amyloid protein or Aβ42 protein. It is Senile plaques in the cerebral cortex – spherical de-
thought that these plaques then cause inflammation posits with a central core of amyloid composed of
and hence neurotoxicity and apoptosis. β (A4) protein. Amyloid is also seen deposited in cere-
Mutations on Chr 21 in Down’s syndrome cause over- bral arteries causing amyloid angiopathy.

production of APP. Neurofibrillary tangles – intraneuronal inclusions
Some cases of early onset AD are due to an autosomal comprising bundles of abnormal filaments. The tan-

dominant disorder with mutations on Chr 14 or 21 – gles are composed of a microtubule binding protein
these cause increased activity of the secretases. called Tau protein, and are frequently flame shaped
Apolipoprotein ε4 (apoε4) genotype on Chr 19 is and occupy much of the space within the neuronal

over-represented in AD patients compared with the cytoplasm.
other alleles ε2 and ε3. Heterozygotes have approx- Cortical nerve processes become twisted and dilated
imately twofold relative risk for developing AD and (neuropil threads) due to the accumulation of the
homozygotes have a fourfold or 50% risk. same fibres that cause the tangles.