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a type of dementia that causes problems
with memory, thinking and behavior.
Symptoms usually develop slowly and get
worse over time, becoming severe enough to
interfere with daily tasks.
At later stages, patients will often begin to
have periodic trouble separating the real from
the unreal. They may develop psychotic
symptoms.
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Delusions: are false beliefs caused by the
deterioration of cognitive processes in the brain,
and are often influenced by misunderstandings
or misinterpretations. Patients might think they
are being followed, or might accuse a family
member of stealing from them or plotting
against them.
Hallucinations: involve false perceptions. Patients
can literally “sense” — see, hear, smell, taste, or
feel — something that isn't there. They might see
and talk with old friends who aren't there, or
watch ships floating through the sky outside the
window, or smell foods they enjoyed as a child.
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Alterations in serotonergic neurotransmission
5- hydroxytryptamine (5-HT) and its receptor for
control of behavior – target for antipsychotic
drugs
The principal serotonin centres in the brain are
the caudal and rostral raphe nuclei.
Transmission of serotonin descending from the
rostral raphe nuclei to the temporal lobe (speech,
memory) is decreased in Alzheimer’s disease
compared with normal. The other major
pathways for serotonin transmission, which
project to the cerebellum and frontal lobe and
descend the spinal cord, remain unchanged.
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Genetic component: polymorphism in 5HT2A receptor gene
Single nucleotide polymorph from silent
mutation at position 102: 102T/C
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Patients: 60yrs and older at onset of
diagnosis of probable AD with several
inclusion criteria
Duration: 3 years follow-up
Evaluation: The genotype frequencies of
102T/C polymorph, the presence of psychotic
symptoms and treatment response to
antipsychotic drugs
Clinical assessment, genotyping
NINCDS-ADRDA Alzheimer's Criteria
( National Institute of Neurological and
Communicative Disorders and Stroke and
the Alzheimer's Disease and Related
Disorders Association) : cognitive
impairment, dementia syndrome,
histopathologic picture
 MMSE (neurocognitive test), NPI (behavior),
PSMS( basic activities of daily living)
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Among 80 patients:
27.5% CC genotype
45% TC genotype
27.5% TT genotype
TT genotype- most delusional (highest NPI FxS) –
neuropsychiatric inventory frequency x severity.
TC and TT - showed treatment resistance to
antipsychotics
* NPI- a valid and reliable inventory to assess 12
behavioral dimensions in patients with dementia or
other neurological disorders
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TT genotype seems to be associated with
higher platelet and brain 5-HT2A receptor
density
Thus, greater signal transduction and
enhanced effects from receptor on brain
function including susceptibility to delusions
symptoms
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The presence of T allele is associated with
increased presence of delusion symptoms,
this might also caused treatment resistance
Due to relatively small number of patients
studied, this result should be seen as
preliminary and caution must be applied in
interpretation