An 1H-MRS framework predicts the onset of Alzheimer's disease symptoms in PSEN1 mutation carriers.
Alzheimers Dement
; 10(5): 552-61, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24239247
ABSTRACT
BACKGROUND:
Alzheimer's disease (AD) is the most common cause of dementia; the main risk factors are age and several recently identified genes. A major challenge for AD research is the early detection of subjects at risk. The aim of this study is to develop a predictive model using proton magnetic resonance spectroscopy (1H-MRS), a noninvasive technique that evaluates brain chemistry in vivo, for monitoring the clinical outcome of carriers of a fully penetrant mutation that causes AD.METHODS:
We studied 75 subjects from the largest multigenerational pedigree in the world (â¼5000 people) that segregates a unique form of early-onset Alzheimer's disease (EOAD) caused by a fully penetrant mutation in the Presenilin-1 gene (PSEN1 p.Glu280Ala [E280 A]). Forty-four subjects were carriers of the mutation, and 31 were noncarriers. Seventeen carriers had either mild cognitive impairment (MCI) or early-stage AD (collectively MCI-AD). In right and left parietal white mater and parasagittal parietal gray matter (RPPGM and LPPGM) of the posterior cingulate gyrus and precuneus, we measured levels of the brain metabolites N-acetylaspartate (NAA), inositol (Ins), choline (Cho), and glutamate-glutamine complex (Glx) relative to creatine (Cr) levels (NAA/Cr, Ins/Cr, Cho/Cr, and Glx/Cr, respectively) with two-dimensional 1H-MRS. Using advanced recursive partition analysis and random forest analysis, we built classificatory decision trees for both mutation carrier status and the presence of MCI-AD symptoms, fitting them to 1H-MRS data while controlling for age, educational level, and sex.RESULTS:
We found that (1) the combination of LPPGM Cho/Cr<0.165 and RPPGM Glx/Cr>1.54 fully excluded carriers; (2) LPPGM Cho/Cr>0.165, RPPGM Glx/Cr<1.54, and left parietal white mater NAA/Cr>1.16 identified asymptomatic carriers with sensitivity of 97.7% and specificity of 77.4%; and (3) RPPGM NAA/Cr>1.05 defined asymptomatic subjects (independent of carrier status) with sensitivity of 100% and a specificity of 96.6%.CONCLUSIONS:
Brain metabolites measured by 1H-MRS in the posterior cingulate gyrus and precuneus are optimally sensitive and specific potential noninvasive biomarkers of subclinical emergence of AD caused by the PSEN1 p.Glu280Ala (E280 A) mutation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Presenilina-1
/
Doença de Alzheimer
/
Espectroscopia de Prótons por Ressonância Magnética
/
Heterozigoto
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article