MRS shows abnormalities before symptoms in familial Alzheimer disease
Abstract
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. 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. 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%...Continue Reading
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