Altered whole-brain white matter networks in preclinical Alzheimer's disease.
Surrogates of whole-brain white matter (WM) networks reconstructed using diffusion tensor imaging (DTI) are novel markers of structural brain connectivity. Global connectivity of networks has been found impaired in clinical Alzheimer's disease (AD) compared to cognitively healthy aging. We hypothesized that network alterations are detectable already in preclinical AD and investigated major global WM network properties. Other structural markers of neurodegeneration typically affected in prodromal AD but seeming largely unimpaired in preclinical AD were also examined. 12 cognitively healthy elderly with preclinical AD as classified by florbetapir-PET (mean age 73.4 ± 4.9) and 31 age-matched controls without cerebral amyloidosis (mean age 73.1 ± 6.7) from the ADNI were included. WM networks were reconstructed from DTI using tractography and graph theory. Indices of network capacity and the established imaging markers of neurodegeneration hippocampal volume, and cerebral glucose utilization as measured by fludeoxyglucose-PET were compared between the two groups. Additionally, we measured surrogates of global WM integrity (fractional anisotropy, mean diffusivity, volume). We found an increase of shortest path length and a decrease of global efficiency in preclinical AD. These results remained largely unchanged when controlling for WM integrity. In contrast, neither markers of neurodegeneration nor WM integrity were altered in preclinical AD subjects. Our results suggest an impairment of WM networks in preclinical AD that is detectable while other structural imaging markers do not yet indicate incipient neurodegeneration. Moreover, these findings are specific to WM networks and cannot be explained by other surrogates of global WM integrity.
University Medical Center Mainz, Untere Zahlbacher Str. 8, Mainz 55131, Germany.
Florian Udo
FU
Fischer
University Medical Center Mainz, Untere Zahlbacher Str. 8, Mainz 55131, Germany.
Dominik
D
Wolf
University Medical Center Mainz, Untere Zahlbacher Str. 8, Mainz 55131, Germany.
Armin
A
Scheurich
University Medical Center Mainz, Untere Zahlbacher Str. 8, Mainz 55131, Germany.
Andreas
A
Fellgiebel
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D015415:Biomarkers; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005026:Ethylene Glycols; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D066127:White Matter / Q000473:pathology*
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C545186:florbetapir; D005947:Glucose
Brain network; DTI; Preclinical Alzheimer's disease