A 45 year old male patient with Down syndrome has experienced severe cognitive decline for few years. Now he is completely dependent on others for basic activities of daily living. Cortical neurons in this patient are most likely to show the following histopathologic findings.
Correct Answer: Neurofibrillary tangles
Description: Answer: a) Neurofibrillary tangles (HARRISON 19th ED, P-2599; ROBBINS 9th ED, P-1290)ALZHEIMER'S DISEASEFactors associated with increased risk* Old age (20-40% of the population of age > 85)* Positive family history* Female sex* Low level of education* Diabetes mellitus* ApO E4* Down's syndrome* Increased production of AB peptide* Mutations in the gene encoding Presinilin-1 and Presinilin-2Clinical manifestationsThe cognitive changes follow a characteristic pattern, beginning with memory impairment and spreading to language and visuospatial deficitsPatients will deny that there is anything wrong (anosognosia)Language becomes impaired-first naming, then comprehension, and finally fluencyAphasia is an early and prominent feature.Apraxia emerges, and patients have trouble performing learned sequential motor tasks.Delusions are common and usually simple10% develop Capgras' syndrome, believing that a caregiver has been replaced by an impostorIn DLB, Capgras' syndrome is an early feature, in AD this syndrome emerges laterMost common cause of death - aspiration.Microscopy: silver staining neurofibrillary tangles (abnormally phosphorylated tau protein)Triad for diagnosis:Slowly progressive decline in memory and orientationNormal results on laboratory testsMRI or CT scan showing only distributed or posteriorly predominant cortical and hippocampal atrophyTreatment: donepezil, rivastigmine, galantamine, memantine (NMDA receptor antagonist)
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