اپیدمیولوژی استروژن و زوال عقل در زنان مبتلا به سندرم داون Epidemiology of estrogen and dementia in women with Down syndrome

1. Introduction Alzheimer’s disease (AD) is the most frequent cause of dementia in the elderly. Clinically, AD is characterized by a progressive deterioration of cognitive and functional skills that begins during middle-age (early onset AD) or late in life (late-onset AD). AD is associated with a characteristic pattern of neuropathology, including the deposition of extracellular beta amyloid (Aβ) in neuritic plaques, intracellular accumulation of neurofibrillary tangles, neuronal loss and gross atrophy [1]. Down syndrome (DS), defined cytogenetically by trisomy 21 (in full or in part), is the most common chromosomal disorder associated with intellectual disability, occurring in approximately 1/700 live births [2]. Virtually all individuals with DS develop the characteristic pattern of neuropathology found in neurotypical adults with AD by the time they reach 40 years of age [3], with clear risk for clinical progression to AD beginning in the mid- to late 40s. Triplication and overexpression of the gene for amyloid precursor protein (APP), located on chromosome 21, is believed to play a significant role in the increased risk of dementia in DS which may be mediated by an increased production of Aβ peptides [4]. However, despite the nearly universal occurrence of AD pathology by age 40, there is wide variation in age at onset of dementia and in dementia related phenotypes such as levels of Aβ peptides. The average age at onset of dementia in adults with DS is between 50 and 60 years of age, with an approximate range from the late 30s to 70 years. This together with the fact that not all individuals with DS will develop dementia during their lifetime, suggests that additional genetic, biological and environmental factors may influence the rate and degree of Aβ deposition or clearance and may be important modifiers of risk that accelerate or slow disease progression [5].