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

Abstract

BackgroundNutritional 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.MethodIn 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.ResultsPlasma 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.ConclusionThe 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_view.cgi?recptno=R000025322], identifier [UMIN000021965].

A modified Mediterranean-style diet enhances brain function via specific gut-microbiome-brain mechanisms

“… 61 Given its status as an essential AA, dysregulation or impairment in leucine transporters can trigger neurological and neurobehavioral abnormalities, increasing the risk of AD. 59 , 62 Our findings revealed an increased abundance and enhanced function of astrocytes in the hippocampus, suggesting that leucine might more actively convert to neurotransmitters, especially in AD mice. However, the brain’s leucine level was relatively lower in MkD, presumably due to rapid uptake and transamination in astrocytes.…”

Cognition and nutrition: the role of dietary protein and amino acids in cognitive health

“…It was discovered that concentrations of several EAAs and albumin were significantly lower in the MCI group as compared to the cognitively normal group. Intriguingly, in a two-year follow-up comparison of PFAA profiles between MCI individuals who developed Alzheimer's disease and those who did not, it was found that PFAA profiles might predict cognitive function changes [20 ▪ ]. MCI individuals who converted to Alzheimer's disease had lower concentrations of EAAs compared to those who remained with MCI.…”

Enhancing cognitive function in older adults: dietary approaches and implications

“…The plasma free amino acid (PFAA) profile is known to reflect nutritional status ( 67 ) and may have the potential to predict changes in cognitive function. A recent report by Takeshi Ikeuchi et al ( 68 ) presents the results of a two-year interim analysis of a three-year longitudinal study following patients with mild cognitive impairment (MCI). Fasting plasma samples were collected from participants.…”