Neural correlates of subjective cognitive decline in adults at high risk for Alzheimer’s disease

Frontiers in Aging Neuroscience

Aging Neuroscience

Aleeza Shumacher¹  Reut Raizman¹  Galia Tsarfaty²  Abigail Livny³  Liat Ben-Ami⁴  Anthony Heymann⁵  Michal Schnaider Beeri⁶  Inbal Sharvit-Ginon⁷  Ramit Ravona-Springer⁸  Lior Greenbaum⁹  Eitan Okun^1,10  Barbara B. Bendlin^1,11 

[1] Division of Diagnostic Imaging, Sheba Medical Center, Ramat Gan, Israel;Division of Diagnostic Imaging, Sheba Medical Center, Ramat Gan, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Division of Diagnostic Imaging, Sheba Medical Center, Ramat Gan, Israel;The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;The Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel;Division of Diagnostic Imaging, Sheba Medical Center, Ramat Gan, Israel;The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Maccabi Healthcare Services, Tel Aviv, Israel;The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel;Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States;The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel;Department of Psychology, Bar-Ilan University, Ramat Gan, Israel;The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel;Memory Clinic, Sheba Medical Center, Ramat Gan, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat Gan, Israel;The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, Israel;The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel;The Paul Feder Laboratory on Alzheimer’s Disease Research, Bar-Ilan University, Ramat Gan, Israel;Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI, United States;

关键词: subjective cognitive decline (SCD);    Alzheimer’s dementia (AD);    neuroimaging;    fMRI;    working memory;    diffusion tensor imaging;    family history (FH);    APOE;   

DOI  :  10.3389/fnagi.2023.1067196

 received in 2022-10-11, accepted in 2023-01-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionRecently, interest has emerged in subjective cognitive decline (SCD) as a potential precursor to Alzheimer’s disease (AD) dementia. Whether individuals with SCD harbor brain alterations in midlife, when AD-related pathology begins, is yet to be elucidated. Furthermore, the role of apolipoprotein ε4 (APOE ε4) allele, a robust AD risk factor, in the relationship between SCD and brain alterations is unknown. We examined whether APOE genotype modulates the association of SCD with brain measures in individuals at high AD risk.MethodsMiddle-aged adults with parental history of AD dementia underwent magnetic resonance imaging (MRI) and the Memory Functioning Questionnaire. Regression analysis tested the extent to which SCD was associated with activation during an functional MRI (fMRI) working-memory task, and white-matter microstructure. APOE ε4 genotype was tested as a moderator.ResultsAmong APOE ε4 carriers, but not among non-carriers, SCD was associated with higher activation in the anterior cingulate (p = 0.003), inferior, middle, and superior frontal cortices (p = 0.041, p = 0.048, p = 0.037, respectively); and with lower fractional anisotropy in the uncinate fasciculus (p = 0.002), adjusting for age, sex, and education.ConclusionIn middle aged, cognitively normal individuals at high AD risk, higher SCD was associated with greater brain alterations possibly reflecting incipient AD pathology. When accompanied by a family history of AD and an APOE ε4 allele, SCD may have important clinical value, allowing a window for early intervention and for participants’ stratification in AD prevention clinical trials.

【 授权许可】

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Copyright © 2023 Ben-Ami, Ravona-Springer, Tsarfaty, Raizman, Shumacher, Sharvit-Ginon, Greenbaum, Bendlin, Okun, Heymann, Schnaider Beeri and Livny.