TY - JOUR
T1 - Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline
AU - Alzheimer's Neuroimaging Initiative
AU - Hohman, Timothy J.
AU - Tommet, Doug
AU - Marks, Shawn
AU - Contreras, Joey
AU - Jones, Rich
AU - Mungas, Dan M
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - Cognition
KW - CSF biomarkers
KW - Longitudinal modeling
KW - MRI
KW - Parallel process model
KW - Structural imaging
UR - http://www.scopus.com/inward/record.url?scp=85024381845&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85024381845&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2017.06.022
DO - 10.1016/j.neurobiolaging.2017.06.022
M3 - Article
C2 - 28732249
AN - SCOPUS:85024381845
VL - 58
SP - 120
EP - 128
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -