MRS shows abnormalities before symptoms in familial Alzheimer disease

A K Godbolt, A D Waldman, D G MacManus, J M Schott, C Frost, L Cipolotti, N C Fox, M N Rossor

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Pathologic change in Alzheimer disease (AD) begins some years before symptoms. MRS has the potential to detect metabolic abnormalities reflecting this early pathologic change. Presenilin 1 (PS1) and amyloid precursor protein (APP) mutation carriers have a nearly 100% risk of developing AD and may be studied prior to symptom onset.

METHODS: Short echo time proton MR spectra were acquired from a midline posterior cingulate voxel in presymptomatic carriers of PS1 or APP mutations ("presymptomatic mutation carriers" [PMCs]; n = 7) and age- and sex-matched control subjects (n = 6). Ratios of N-acetyl aspartate (NAA), myo-inositol (MI), and choline-containing compounds (Cho) to creatine (Cr) were measured and NAA/MI calculated. Regression analyses and t tests were performed after log transformation.

RESULTS: PMC and control subjects were matched for age and sex. PMC subjects were 1.7 to 21.6 years (mean 9.8 years) before expected symptom onset, predicted from family-specific mean age at onset. Age did not significantly affect metabolite ratios. Geometric mean ratios in control subjects were as follows: NAA/Cr = 1.75, MI/Cr = 0.59, and NAA/MI = 2.95. NAA/Cr and NAA/MI were significantly reduced in PMC relative to controls (NAA/Cr mean decrease 10% [95% CI 2 to 18%]; NAA/MI mean decrease 25% [95% CI 3 to 44%]). MI/Cr was increased in PMC, but the differences did not achieve significance (19% increase [95% CI 1% decrease to 41% increase]; p = 0.07)). In PMCs, reduction in NAA/MI (p = 0.001) and MI/Cr (p = 0.002) were related to proximity of expected age at onset.

CONCLUSIONS: Metabolic changes are detectable in presymptomatic mutation carriers years before expected onset of Alzheimer disease. Their magnitude is related to proximity of expected age at onset.

Original languageEnglish
Pages (from-to)718-22
Number of pages5
JournalNeurology
Volume66
Issue number5
DOIs
Publication statusPublished - 14 Mar 2006

Keywords

  • Adolescent
  • Adult
  • Age of Onset
  • Alzheimer Disease
  • Brain
  • Carrier State
  • Child
  • Child, Preschool
  • Family
  • Female
  • Humans
  • Infant
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Reference Values
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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