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

Background: Nutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.
Method: In a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal ("MCI-stable," N = 87) and converted to Alzheimer's disease (AD) ("AD-convert," N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 ( APOE ε4) allele possession was also conducted.
Results: Plasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession ( p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.
Conclusion: The PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.
Clinical Trial Registration: [https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000025322], identifier [UMIN000021965].
Competing Interests: TI, FM, STor, CN, TTa, NM, STan, KU, KO, TH, SN, NK, CK, HT, AK, EK, and MY’s respective institutions or research organizations were paid for joint research or case incorporation by Ajinomoto Co., Inc. MK, HK, YYa, STou, YKa, HJ, and KN are full-time employees of Ajinomoto Co., Inc. Ajinomoto Co., Inc. funded the study and participated in the study design, implementation, analysis, and interpretation of the data. This does not alter the authors’ adherence to all of the journal policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Ikeuchi, Kanda, Kitamura, Morikawa, Toru, Nishimura, Kasuga, Tokutake, Takahashi, Kuroha, Miyazawa, Tanaka, Utsumi, Ono, Yano, Hamano, Naruse, Yajima, Kawashima, Kaneko, Tachibana, Yano, Kato, Toue, Jinzu, Kitamura, Yokoyama, Kaneko, Yamakado and Nagao.)