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. 2016 May;41:115-121.
doi: 10.1016/j.neurobiolaging.2016.02.015. Epub 2016 Feb 21.

The Executive Prominent/Memory Prominent Spectrum in Alzheimer's Disease Is Highly Heritable

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Free PMC article

The Executive Prominent/Memory Prominent Spectrum in Alzheimer's Disease Is Highly Heritable

Jesse Mez et al. Neurobiol Aging. .
Free PMC article

Abstract

Late-onset Alzheimer's disease (LOAD) can present heterogeneously, with several subtypes recognized, including dysexecutive AD. One way to identify people with dysexecutive AD is to consider the difference between memory and executive functioning, which we refer to as the executive prominent/memory prominent spectrum. We aimed to determine if this spectrum was heritable. We used neuropsychological and genetic data from people with mild LOAD (Clinical Dementia Rating 0.5 or 1.0) from the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative. We cocalibrated the neuropsychological data to obtain executive functioning and memory scores and used their difference as a continuous phenotype to calculate its heritability overall and by chromosome. Narrow-sense heritability of the difference between memory and executive functioning scores was 0.68 (standard error 0.12). Single nucleotide polymorphisms on chromosomes 1, 2, 4, 11, 12, and 18 explained the largest fraction of phenotypic variance, with signals from each chromosome accounting for 5%-7%. The chromosomal pattern of heritability differed substantially from that of LOAD itself.

Keywords: Atypical Alzheimer's disease; Dysexecutive Alzheimer's disease; Executive function; Genetics; Heritability; Memory.

Conflict of interest statement

Disclosure statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Chromosomal phenotypic variability. Phenotypic variability explained by each chromosome for the continuous LOAD executive functioning–memory difference score (blue) and dichotomous LOAD case-control status (green). The LOAD executive functioning–memory difference score was derived using cocalibrated executive functioning and memory composite scores from the Alzheimer’s Disease Neuroimaging Initiative and the National Alzheimer’s Coordinating Center. The LOAD case-control phenotypic variability was derived previously using data from the Alzheimer’s Disease Genetic Consortium (Ridge et al., 2013).

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