期刊论文详细信息
NEUROBIOLOGY OF AGING 卷:83
Pupillary dilation responses as a midlife indicator of risk for Alzheimer's disease: association with Alzheimer's disease polygenic risk
Article
Kremen, William S.1,2,3  Panizzon, Matthew S.1,2  Elman, Jeremy A.1,2  Granholm, Eric L.1,2,4  Andreassen, Ole A.5,6  Dale, Anders M.2,7,8  Gillespie, Nathan A.9  Gustavson, Daniel E.1,2  Logue, Mark W.10,11,12,13  Lyons, Michael J.14  Neale, Michael C.9  Reynolds, Chandra A.15  Whitsel, Nathan1,2  Franz, Carol E.1,2 
[1] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Ctr Behav Genet Aging, La Jolla, CA 92093 USA
[3] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, La Jolla, CA USA
[4] VA San Diego Healthcare Syst, Psychol Serv, La Jolla, CA USA
[5] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway
[6] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway
[7] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA
[8] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[9] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA
[10] VA Boston Healthcare Syst, Natl Ctr PTSD Behav Sci Div, Boston, MA USA
[11] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA
[12] Boston Univ, Sch Med, Biomed Genet Sect, Boston, MA 02118 USA
[13] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA
[14] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA
[15] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA
关键词: Polygenic risk score;    Risk indicator;    Biomarker;    Early identification;    Locus coeruleus;    Mild cognitive impairment;   
DOI  :  10.1016/j.neurobiolaging.2019.09.001
来源: Elsevier
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【 摘 要 】

Locus coeruleus (LC) tau accumulation begins early. Targeting LC (dys)function might improve early identification for Alzheimer's disease (AD) risk. Pupillary responses during cognitive tasks are driven by the LC and index cognitive effort. Despite equivalent task performance, adults with mild cognitive impairment have greater pupil dilation/effort during digit span than cognitively normal (CN) individuals. We hypothesized that AD polygenic risk scores (AD-PRSs) would be associated with pupillary responses in middle-aged CN adults. Pupillary responses during digit span tasks were heritable (h(2) = 0.30-0.36) in 1119 men aged 56-66 years. In a CN subset-all with comparable span capacities (n = 539)-higher AD-PRSs were associated with greater pupil dilation/effort in a high (9-digit) cognitive load condition (Cohen's d = 0.36 for upper vs. lower quartile of AD-PRS distribution). Results held up after controlling for APOE genotype. Results support pupillary response-and by inference, LC dysfunction-as a genetically mediated biomarker of early mild cognitive impairment/AD risk. In combination with other biomarkers, task-evoked pupillary responses may provide additional information for early screening of genetically at-risk individuals even before cognitive declines. (C) 2019 Elsevier Inc. All rights reserved.

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