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

Takeshi Ikeuchi,Tadanori Hamano,Ryoko Koike,Kenjiro Ono,Nobuhiko Miyazawa,Takayoshi Tokutake,Minoru Yamakado,Ryuji Yajima,Yuki Yano,Fumiyoshi Morikawa,Satoshi Yano,Kumiko Utsumi,Wataru Sato,Kensaku Kasuga,Chika Nishimura,Shuta Toru,Yuri Yokoyama,Akihiko Kitamura,Shin Tanaka,Kenji Nagao,Satoshi Naruse,Eiji Kaneko,Yasuko Kuroha

doi:10.3390/nu14030637

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 year) from 10 institutions and 220 individuals who were cognitively normal (CN, 76.3 ± 6.6 year) 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.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative condition that is highly prevalent in old age [1] and has a significant socioeconomic impact [2]
We evaluated the relationship between the PFAA index values and the APOE genotypes in the Mild cognitive impairment (MCI) group and found no significant differences in the PFAA index values between the APOE-positive and APOE-negative groups (Supplementary Figure S1B)
The relationship between the PFAA index and other MCI risk factors, such as diabetes mellitus, hypertension, low-density lipoprotein cholesterol level, and triglyceride level, were analyzed, and no associations were found (Supplementary Figure S2). In this multicenter clinical study, we generated an index with PFAA and albumin concentrations as variables to identify individuals who are at high risk for MCI in the population over the age of 50 years

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative condition that is highly prevalent in old age [1] and has a significant socioeconomic impact [2]. As the care for patients with diseases that affect cognitive function require the support of multiple stakeholders, they impose a substantial socioeconomic burden [2]. Pathological changes, such as the accumulations of amyloid-β (Aβ) and hyperphosphorylated tau in the brain, occur more than two decades before the appearance of cognitive impairment [1]. Even if the onset of cognitive impairments could be delayed by a novel medication that could prevent such accumulation for decades, it is economically challenging to continue a treatment intervention for this long from the preclinical period. In the long-term randomized controlled trial called the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a multidomain lifestyle-based intervention ameliorating vascular and lifestyle-related risk factors was found to preserve cognitive function and reduce the risk of cognitive decline among older adults with increased risk of dementia [5]

Results

Discussion

Conclusion