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Eur J Neurodegener Dis. 2012 Dec;1(3):353-364.

Alzheimer's Disease in Down Syndrome.

Author information

1
Department of Molecular and Biomedical Pharmacology, University of Kentucky Lexington, KY, 40356 ; Sanders-Brown Center on Aging, University of Kentucky Lexington, KY, 40356.
2
Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky Lexington, KY, 40356 ; Sanders-Brown Center on Aging, University of Kentucky Lexington, KY, 40356.
3
Department of Anatomy and Neurobiology, University of Kentucky Lexington, KY, 40356 ; Sanders-Brown Center on Aging, University of Kentucky Lexington, KY, 40356.
4
Department of Neurology, University of Kentucky Lexington, KY, 40356 ; Sanders-Brown Center on Aging, University of Kentucky Lexington, KY, 40356.

Abstract

A key challenge to adults with Down syndrome (DS) as they age is an increased risk for cognitive decline, dementia, and Alzheimer disease (AD). In DS persons ranging from 40-49 years of age, 5.7-55% may be clinically demented and between 50-59 years, dementia prevalence ranges from 4-55% (reviewed in [1]). Despite the wide ranges reported for dementia prevalence, a consistent feature of aging in DS is the progressive accumulation of AD brain pathologies. By the age of 40 years, virtually all have sufficient senile plaques and neurofibrillary tangles for a neuropathological diagnosis of AD [2]. Thus, there is dissociation between the age of onset of AD neuropathology (40 years) and increasing signs of clinical dementia. We discuss the hypothesis that frontal impairments are a critical factor affecting cognitive function and are associated with white matter (WM) and AD neuropathology. While these may be an early sign of conversion to dementia, we also review several other clinical comorbidities that may also contribute to dementia onset.

KEYWORDS:

Trisomy 21; beta-amyloid; dementia; neurofibrillary tangles; oxidative damage

PMID:
25285303
PMCID:
PMC4184282

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