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% 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.
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.
SourceAvailable from: Masaaki WaragaiAlzheimer's and Dementia 07/2014; 10(4):P717-P718. DOI:10.1016/j.jalz.2014.05.1327 · 17.47 Impact Factor
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ABSTRACT: The rapidly increasing prevalence of cognitive impairment and Alzheimer's disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer's disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer's disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer's disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer's disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.Neural Regeneration Research 02/2013; 8(5):435-44. DOI:10.3969/j.issn.1673-5374.2013.05.007 · 0.23 Impact Factor
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ABSTRACT: Reduction of 18F-fluorodeoxyglucose uptake in PET (hypometabolism) and grey matter volume in MRI (atrophy) are found in the cerebral cortex of patients with Parkinson’s disease (PD). This doctoral thesis studied the relationship between hypometabolism and atrophy in successive stages of cognitive decline in PD: cognitively normal, mild cognitive impairment (PD-MCI) and dementia (PDD); as well as the biochemical profile of hypometabolic and atrophic areas. Z-score maps for atrophy and hypometabolism, obtained by comparing individual images to a data set of healthy control subjects, were compared using a direct voxel-based technique (paired Student’s t-test p<0.05 FDR corrected). Additionally, areas with hypometabolism and atrophy were biochemically characterized by proton magnetic resonance spectroscopy (MRS). In PD-MCI patients hypometabolism exceeded atrophy in the angular gyrus, occipital, orbital and anterior frontal lobes. In PDD patients the hypometabolic areas observed in PD-MCI group were replaced by areas of atrophy, which were surrounded by extensive zones of hypometabolism. In both groups, areas where atrophy was more extended than hypometabolism were found in the precentral and supplementary motor areas in the temporal lobe and hippocampus. In the MRS study, the areas of hypometabolism and atrophy showed significant differences in resonance frequencies (1.27, 1.31, 1.62, 2.23 and 3.11 ppm) whose correlate is uncertain. In conclusion, these findings suggest a gradient of severity in cortical changes associated with the development of cognitive impairment in PD, in which hypometabolism and atrophy represent consecutive stages of the same process. MRS technique may provide biochemical markers to be investigated in the near future.09/2013, Degree: MD, PhD, Supervisor: José A. Obeso, María C. Rodríguez-Oroz