Development of a Novel Nutrition-Related Multivariate Biomarker for Mild Cognitive Impairment Based on the Plasma Free Amino Acid Profile

Abstract

Nutritional epidemiology has shown the importance of protein intake for maintaining brain function in the elderly population. Mild cognitive impairment (MCI) may be associated with malnutrition, especially protein intake. We explored blood-based biomarkers linking protein nutritional status with MCI in a multicenter study. In total, 219 individuals with MCI (79.5 ± 5.7 y) from 10 institutions and 220 individuals who were cognitively normal (CN, 76.3 ± 6.6 y) in four different cities in Japan were recruited. They were divided into the training (120 MCI and 120 CN) and validation (99 MCI and 100 CN) groups. A model involving concentrations of PFAAs and albumin to discriminate MCI from CN individuals was constructed by multivariate logistic regression analysis in the training dataset, and the performance was evaluated in the validation dataset. The concentrations of some essential amino acids and albumin were significantly lower in MCI group than CN group. An index incorporating albumin and PFAA discriminated MCI from CN participants with the AUC of 0.705 (95% CI: 0.632–0.778), and the sensitivities at specificities of 90% and 60% were 25.3% and 76.8%, respectively. No significant association with BMI or APOE status was observed. This cross-sectional study suggests that the biomarker changes in MCI group may be associated with protein nutrition.

Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment

“…Control participants (CN, N = 220) who received comprehensive health examinations were recruited from community-dwelling adults at four different cities across Japan (Hatoyama Town, Mitsuke City, Ashikaga City, and Kawasaki City) and from CN participants who visited Sunagawa City Medical Center ( 19 ).…”

“…Since this clinical study is a continuation of the previous report, the study is basically proceeding according to the protocol reported in the previous report ( 19 ). Neuropsychological assessments were conducted to evaluate cognitive function of the participants.…”

“…The following are the inclusion and exclusion criteria for the current study as previously described ( 19 ). The common criteria for MCI and CN participants were as follows: (1) aged 50 years or older; (2) not diagnosed as having dementia; (3) living independently; (4) able to undergo neuropsychological tests with an MMSE score of 24 points or higher; and (5) no depression and a GDS-15 score less than six points.…”

“…Precision biomarkers linking nutritional status and cognitive decline have been intensively investigated (14) and several candidate markers based on cerebrospinal fluid (CSF) or blood samples were reported in both rodent model and clinical studies (15)(16)(17)(18). We previously demonstrated the following as the first report of this clinical study (19). We cross-sectionally compared the concentrations of plasma free amino acid (PFAA) and albumin (Alb) in multicenter clinical study with 219 elderly individuals with MCI and 220 cognitively normal (CN) individuals.…”

“…We cross-sectionally compared the concentrations of plasma free amino acid (PFAA) and albumin (Alb) in multicenter clinical study with 219 elderly individuals with MCI and 220 cognitively normal (CN) individuals. We found that the concentrations of essential amino acids (EAAs), such as Lys, His, and Thr, and Alb were lower in the MCI group (19). We are currently following up these individuals with MCI for up to 3 years to assess AD development and are developing a prognostic blood-based biomarker focusing on PFAAs.…”