Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline

NEUROBIOLOGY OF AGING

卷:58

Article

Hohman, Timothy J.¹  Tommet, Doug²  Marks, Shawn³  Contreras, Joey⁴  Jones, Rich²  Mungas, Dan⁵ 

[1] Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, 1207 17th Ave S,Suite 204F, Nashville, TN 37212 USA

[2] Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA

[3] Univ Calif Berkeley, Sch Publ Hlth, Dept Neurosci, Berkeley, CA 94720 USA

[4] Indiana Univ, Ctr Neuroimaging, Dept Radiol, Indianapolis, IN USA

[5] Univ Calif Davis, Med Ctr, Dept Neurol, UC Davis Alzheimers Dis Res Ctr, Sacramento, CA 95817 USA

关键词: CSF biomarkers;    Structural imaging;    MRI;    Cognition;    Longitudinal modeling;    Parallel process model;   

DOI  :  10.1016/j.neurobiolaging.2017.06.022

来源: Elsevier

【 摘 要 】

Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

Free