title: Mild cognitive impairment: cerebrospinal fluid tau biomarker pathologic levels and longitudinal changes in white matter integrity.
abstract: OBJECTIVE
  To evaluate the relationship between (a) pathologic levels of cerebrospinal fluid (CSF) total tau as an index of the intensity of ongoing neuronal degeneration and (b) longitudinal changes in white matter (WM) integrity in patients with mild cognitive impairment (MCI).
  
  
  METHODS
  Participants gave written informed consent, and the Norwegian committee for medical research ethics approved the study. Thirty patients with MCI and nonpathologic CSF total tau levels, nine patients with MCI and pathologic CSF total tau levels, and 16 age-matched healthy control subjects underwent diffusion-tensor imaging at baseline and after a mean follow-up of 2.6 years ± 0.54 (standard deviation), with range of 1.58-3.98 years. The effect of diagnosis (MCI vs no MCI) at baseline and CSF tau levels at fractional anisotropy (FA), mean diffusivity, radial diffusivity (D(R)), and axial diffusivity were tested with tract-based spatial statistics. Differences in WM integrity at baseline and follow-up and change over time were compared among patients with pathologic CSF total tau levels (MCI high tau), patients with normal CSF total tau levels (MCI low tau), and healthy control subjects. Linear mixed-model between-group within-subject analyses were conducted to examine differences in rate of change over time in FA and D(R).
  
  
  RESULTS
  Longitudinal analysis of regional WM change revealed significant decrease in FA (P = .038) and increase in D(R) (P = .018) in the MCI high-tau group relative to control subjects. For D(R), the changes were regionally specific to the right cingulum and the right superior and inferior longitudinal fasciculi.
  
  
  CONCLUSIONS
  Reduction in WM integrity was greater in patients with MCI who had the most intense neuronal degeneration as indexed by using CSF total tau, suggesting that these patients might represent a subgroup of MCI with more intense WM degeneration who are possibly at greater risk of developing Alzheimer disease.
authors.affiliation: Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Pb. 1094 Blindern, 0317 Oslo, Norway. inge.amlien@psykologi.uio.no
authors.forename: Inge K
authors.initials: IK
authors.lastname: Amlien
authors.forename: Anders M
authors.initials: AM
authors.lastname: Fjell
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Walhovd
authors.forename: Per
authors.initials: P
authors.lastname: Selnes
authors.forename: Vidar
authors.initials: V
authors.lastname: Stenset
authors.forename: Ramune
authors.initials: R
authors.lastname: Grambaite
authors.forename: Atle
authors.initials: A
authors.lastname: Bjørnerud
authors.forename: Paulina
authors.initials: P
authors.lastname: Due-Tønnessen
authors.forename: Anders
authors.initials: A
authors.lastname: Skinningsrud
authors.forename: Leif
authors.initials: L
authors.lastname: Gjerstad
authors.forename: Ivar
authors.initials: I
authors.lastname: Reinvang
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000473:pathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D016875:tau Proteins