Premium
P1‐110: Comparison of diagnostic power of cerebrospinal fluid Aß and Tau variables for Alzheimer's disease diagnosis: proposition of a simple decision tree
Author(s) -
SchraenMaschke Susanna,
Vercruysse Olivier,
Sergeant Nicolas,
Buée Luc,
Sablonniere Bernard,
Bombois Stephanie,
Pasquier Florence,
Salleron Julia,
Deken Valérie
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.389
Subject(s) - cerebrospinal fluid , medicine , biomarker , disease , memory clinic , dementia , diagnostic accuracy , biochemistry , chemistry
Background: Advanced glycations endproducts (AGE) are known to cause increased oxidant stress, inflammation, and neurotoxicity; serum levels are increased in diabetes and aging. We examined the relationship between levels of serum methylglyoxal (sMG), an AGE precursor, and cognitive decline in elderly. Methods: Subjects were 266 initially non-demented elderly who had complete data including at least two MMSEs. Tobit mixed regression models assessed the association of baseline MG with cognitive decline in the Mini Mental State Exam (MMSE) score over time, controlling for sociodemographic factors (age, sex, and years of education), and cardiovascular risk factors (diabetes and presence of anAPOE4 allele). sMGwas assessed by ELISA. Results: The sample averaged 83.5 years of age, 14.3 years of education, 36 months of follow up, and 0.93 nmol/ml of sMG. Average baseline MMSE of 28.2 reflected this cognitively normal sample. Seventy six percent of the sample was male since a major source of recruitment was the Mount Sinai affiliate James J. Peters Veterans Affairs Medical Center; 18% had diabetes and 20% carried an APOE4 allele. The fully adjusted model showed an annual decline of 0.33 MMSE points per unit increase in baseline sMG (p 1⁄4 0.015). Significance improved as additional risk factors were added to the model. The interactions of sMGwith diabetes, sex, age, and APOE4 genotype were not significant and did not substantially improve the model fit. In a small replication sample of 49 younger elderly (average age 70, education 14.6, 18 months of follow up, sMG1⁄4 0.91 nmol/ml, baselineMMSE 28.8, 53%males, 13% had diabetes, 9% carried an APOE4 allele), who had a broad neuropsychological battery, results were essentially identical: for the fully adjusted model: p 1⁄4 0.01 when using the MMSE as outcome measure and p 1⁄4 0.03 when using an overall cognition outcome measure. Conclusions: Higher levels of circulating MG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, APOE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated circulating MG may be indicative of brain cell injury initiated before clinically evident cognitive compromise. Because levels of MG in blood correlate with those consumed with diet, lowering MG by AGE restricted diet has potential for preventing cognitive compromise.