title: The Alzheimer structural connectome: changes in cortical network topology with increased amyloid plaque burden.
abstract: OBJECTIVE
  To evaluate differences in the structural connectome among patients with normal cognition (NC), mild cognitive impairment (MCI), and Alzheimer disease (AD) and to determine associations between the structural connectome and cortical amyloid deposition.
  
  
  METHODS
  Patients enrolled in a multicenter biomarker study (Alzheimer's Disease Neuroimaging Initiative [ADNI] 2) who had both baseline diffusion-tensor (DT) and florbetapir positron emission tomography (PET) data at the time of data analyses in November 2012 were studied. All institutions received institutional review board approval. There were 102 patients in ADNI 2 who met criteria for analysis. Patients' T1-weighted images were automatically parcellated into cortical regions of interest. Standardized uptake value ratio (SUVr) was calculated from florbetapir PET images for composite cortical regions (frontal, cingulate, parietal, and temporal). Structural connectome graphs were created from DT images, and connectome topology was analyzed in each region by using graph theoretical metrics. Analysis of variance of structural connectome metrics and florbetapir SUVr across diagnostic group was performed. Linear mixed-effects models were fit to analyze the effect of florbetapir SUVr on structural connectome metrics.
  
  
  RESULTS
  Diagnostic group (NC, MCI, or AD) was associated with changes in weighted structural connectome metrics, with decreases from the NC group to the MCI group to the AD group shown for (a) strength in the bilateral frontal, right parietal, and bilateral temporal regions (P < .05); (b) weighted local efficiency in the left temporal region (P < .05); and (c) weighted clustering coefficient in the bilateral frontal and left temporal regions (P < .05). Increased cortical florbetapir SUVr was associated with decreases in weighted structural connectome metrics; namely, strength (P = .00001), weighted local efficiency (P = .00001), and weighted clustering coefficient (P = .0006), independent of brain region. For every 0.1-unit increase in florbetapir SUVr, there was a 14% decrease in strength, an 11% decrease in weighted local efficiency, and a 9% decrease in weighted clustering coefficient, regardless of the analyzed cortical region or, in the case of weighted local efficiency and clustering coefficient, diagnostic group.
  
  
  CONCLUSIONS
  Increased amyloid burden, as measured with florbetapir PET imaging, is related to changes in the topology of the large-scale cortical network architecture of the brain, as measured with graph theoretical metrics of DTI tractography, even in the preclinical stages of AD. Online supplemental material is available for this article.
authors.affiliation: From the Department of Radiology (J.W.P., K.R.C., J.P.), Department of Psychiatry (P.M.D.), Department of Medicine (P.M.D.), and Duke Institute for Brain Sciences (P.M.D.), Duke University Medical Center, Box 3808, Durham, NC 27710; and Brain Image Analysis Center, Duke University, Durham, NC (A.G., C.L.).
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Prescott
authors.forename: Arnaud
authors.initials: A
authors.lastname: Guidon
authors.forename: P Murali
authors.initials: PM
authors.lastname: Doraiswamy
authors.forename: Kingshuk
authors.initials: K
authors.lastname: Roy Choudhury
authors.forename: Chunlei
authors.initials: C
authors.lastname: Liu
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Petrella
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D015415:Biomarkers; D063132:Connectome / Q000379:methods*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D009656:North America; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography
chemical_list: D015415:Biomarkers