Segmented Linear Mixed Model Analysis Reveals Association of the APOEɛ4 Allele with Faster Rate of Alzheimer's Disease Dementia Progression.
Abstract
APOEɛ4 allele carriers present with an increased risk for late-onset Alzheimer's disease (AD), show cognitive symptoms at an earlier age, and are more likely to transition from mild cognitive impairment (MCI) to dementia but despite this, it remains unclear whether or not the ɛ4 allele controls the rate of disease progression. To determine the effects of the ɛ4 allele on rates of cognitive decline and brain atrophy during MCI and dementia stages of AD. A segmented linear mixed model was chosen for longitudinal modeling of cognitive and brain volumetric data of 73 ɛ3/ɛ3, 99 ɛ3/ɛ4, and 39 ɛ4/ɛ4 Alzheimer's Disease Neuroimaging Initiative participants who transitioned during the study from MCI to AD dementia. ɛ4 carriers showed faster decline on MMSE, ADAS-11, CDR-SB, and MoCA scales, with the last two measures showing significant ɛ4 allele-dose effects after dementia transition but not during MCI. The ɛ4 effect was more prevalent in younger participants and in females. ɛ4 carriers also demonstrated faster rates of atrophy of the whole brain, the hippocampus, the entorhinal cortex, the middle temporal gyrus, and expansion of the ventricles after transitioning to dementia but not during MCI. Possession of the ɛ4 allele is associate...Continue Reading
References
Individual growth curve analysis of APOE epsilon 4-associated cognitive decline in Alzheimer disease
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