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Alzheimer’s Disease

Psychotic Symptoms and Response to Antipsychotic Treatment are asscociated with the 5-HT2A Receptor Polymorphism(102T/C) in Alzheimer’s Disease. Alzheimer’s Disease.

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Alzheimer’s Disease

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  1. Psychotic Symptoms and Response to Antipsychotic Treatment are asscociated with the 5-HT2A Receptor Polymorphism(102T/C) in Alzheimer’s Disease

  2. Alzheimer’s Disease • 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.

  3. Psychotic Symptoms • 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.

  4. Mechanism proposed • 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.

  5. Genetic component: polymorphism in 5-HT2A receptor gene • Single nucleotide polymorph from silent mutation at position 102: 102T/C

  6. Research materials and method • 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

  7. 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)

  8. Discussion • 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

  9. 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

  10. Conclusion • 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

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