Cross-Sectional and Longitudinal Effects of Genotypes on Individual Differences in Memory and Executive Function: Findings from the BLSA

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2017 Jun 1

PMID 28559842

Citations 7

Authors

Claudia Wolf

Yang An

Toshiko Tanaka

Murat Bilgel

Christopher Gonzalez

Melissa Kitner Triolo

Susan Resnick

Affiliations

Soon will be listed here.

Abstract

Previously, we have shown that the SNP rs10932201 genotype of the cyclic AMP responsive element binding protein 1 gene () contributes to individual differences in executive and memory function at the neural system and behavioral levels in healthy, young adults. However, longitudinal effects of genotypes on cognition have not yet been addressed. Furthermore we were interested in replicating associations between genotypes and human cognition in previous cross-sectional studies and explore whether APOE????4 status might modify these relations. We investigated whether common, independent tag SNPs within (rs2253206, rs10932201, rs6785) influence individual differences in age-related longitudinal change and level of executive function and memory performance independent of baseline age, sex, APOE????4 status, and education. Our analysis included data from cognitively unimpaired older adults participating in the Baltimore Longitudinal Study of Aging. Eleven measures from six cognitive tests (sample sizes range 617-786) were analyzed using linear mixed effects and generalized estimating equations models. Mean baseline age ranged from 50 to 69 years and mean time of follow-up (interval) ranged from 8 to 22 years. We found significant effects of all three SNPs on performance level and/or longitudinal change in performance based on eight measures assessing semantic memory, episodic memory, or both executive function and semantic memory. SNP rs10932201 showed the most significant and largest effect (Cohen's = -0.70, < 0.01) on age-related longitudinal decline of semantic memory. Additionally, we show interactions between all three SNPs and APOE????4 status on age-related longitudinal declines and levels of memory and executive function. Our results suggest that genotypes independently and by interactions with APOE????4 status contribute to individual differences in cognitive aging.

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References

Beydoun M, Boueiz A, Abougergi M, Kitner-Triolo M, Beydoun H, Resnick S . Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline. Neurobiol Aging. 2010; 33(4):720-731.e4. PMC: 2974952. DOI: 10.1016/j.neurobiolaging.2010.05.017. View

Bartolotti N, Bennett D, Lazarov O . Reduced pCREB in Alzheimer's disease prefrontal cortex is reflected in peripheral blood mononuclear cells. Mol Psychiatry. 2016; 21(9):1158-66. PMC: 4995548. DOI: 10.1038/mp.2016.111. View

Caselli R, Reiman E, Osborne D, Hentz J, Baxter L, Hernandez J . Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele. Neurology. 2004; 62(11):1990-5. DOI: 10.1212/01.wnl.0000129533.26544.bf. View

Brightwell J, Gallagher M, Colombo P . Hippocampal CREB1 but not CREB2 is decreased in aged rats with spatial memory impairments. Neurobiol Learn Mem. 2003; 81(1):19-26. DOI: 10.1016/j.nlm.2003.08.001. View

Davies G, Armstrong N, Bis J, Bressler J, Chouraki V, Giddaluru S . Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949). Mol Psychiatry. 2015; 20(2):183-92. PMC: 4356746. DOI: 10.1038/mp.2014.188. View

Wolf C, Linden D . Biological pathways to adaptability--interactions between genome, epigenome, nervous system and environment for adaptive behavior. Genes Brain Behav. 2011; 11(1):3-28. DOI: 10.1111/j.1601-183X.2011.00752.x. View

Zhang X, Odom D, Koo S, Conkright M, Canettieri G, Best J . Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A. 2005; 102(12):4459-64. PMC: 555478. DOI: 10.1073/pnas.0501076102. View

Trivedi M, Greer T . Cognitive dysfunction in unipolar depression: implications for treatment. J Affect Disord. 2013; 152-154:19-27. DOI: 10.1016/j.jad.2013.09.012. View

Payton A, Sindrewicz P, Pessoa V, Platt H, Horan M, Ollier W . A TOMM40 poly-T variant modulates gene expression and is associated with vocabulary ability and decline in nonpathologic aging. Neurobiol Aging. 2016; 39:217.e1-7. DOI: 10.1016/j.neurobiolaging.2015.11.017. View

10.

Price A, Patterson N, Plenge R, Weinblatt M, Shadick N, Reich D . Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006; 38(8):904-9. DOI: 10.1038/ng1847. View

11.

Caselli R, Dueck A, Osborne D, Sabbagh M, Connor D, Ahern G . Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect. N Engl J Med. 2009; 361(3):255-63. PMC: 2928998. DOI: 10.1056/NEJMoa0809437. View

12.

Caselli R, Dueck A, Huentelman M, Lutz M, Saunders A, Reiman E . Longitudinal modeling of cognitive aging and the TOMM40 effect. Alzheimers Dement. 2012; 8(6):490-5. PMC: 3483561. DOI: 10.1016/j.jalz.2011.11.006. View

13.

Jardim de Paula J, de Miranda D, de Moraes E, Malloy-Diniz L . Mapping the clockworks: what does the Clock Drawing Test assess in normal and pathological aging?. Arq Neuropsiquiatr. 2013; 71(10):763-8. DOI: 10.1590/0004-282X20130118. View

14.

Jonsson T, Atwal J, Steinberg S, Snaedal J, Jonsson P, Bjornsson S . A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature. 2012; 488(7409):96-9. DOI: 10.1038/nature11283. View

15.

Yiu A, Rashid A, Josselyn S . Increasing CREB function in the CA1 region of dorsal hippocampus rescues the spatial memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology. 2011; 36(11):2169-86. PMC: 3176558. DOI: 10.1038/npp.2011.107. View

16.

Balthazar M, Cendes F, Damasceno B . Semantic error patterns on the Boston Naming Test in normal aging, amnestic mild cognitive impairment, and mild Alzheimer's disease: is there semantic disruption?. Neuropsychology. 2008; 22(6):703-9. DOI: 10.1037/a0012919. View

17.

Wolf C, Mohr H, Diekhof E, Vieker H, Goya-Maldonado R, Trost S . CREB1 Genotype Modulates Adaptive Reward-Based Decisions in Humans. Cereb Cortex. 2015; 26(7):2970-81. DOI: 10.1093/cercor/bhv104. View

18.

Weintraub S, Wicklund A, Salmon D . The neuropsychological profile of Alzheimer disease. Cold Spring Harb Perspect Med. 2012; 2(4):a006171. PMC: 3312395. DOI: 10.1101/cshperspect.a006171. View

19.

Barral S, Reitz C, Small S, Mayeux R . Genetic variants in a 'cAMP element binding protein' (CREB)-dependent histone acetylation pathway influence memory performance in cognitively healthy elderly individuals. Neurobiol Aging. 2014; 35(12):2881.e7-2881.e10. PMC: 4253058. DOI: 10.1016/j.neurobiolaging.2014.06.024. View

20.

Hixson J, Vernier D . Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990; 31(3):545-8. View