Keisuke Sakurai

Since daily dietary habits can affect cognitive function, dietary patterns such as the Mediterranean-DASH Intervention for Neurodegenerative Delay diet have been proposed as interventions to slow cognitive decline. However, because dietary habits vary widely among different food cultures, it is necessary to establish dietary pattern intervention methods that are appropriate for each population. Therefore, in this study, the dietary patterns of elderly Japanese individuals were classified using cluster analysis, and their relationship with cognitive function was investigated. We then modeled the dietary patterns and applied them to another cohort of elderly Japanese individuals to determine whether differences in dietary patterns could predict cognitive decline. One hundred and fifty older adults ≥ 65 years of age in the community were recruited. Their daily food intake and cognitive function were measured using the brief-type self-administered diet history questionnaire and Montreal Cognitive Assessment, respectively. K-means cluster analysis identified a high-carbohydrate (HC) dietary pattern with high cereal intake and a protein-balanced (PB) dietary pattern with high intake of legumes, vegetables, seafood, meat, and eggs. Cognitive function was significantly higher in the PB group than in the HC group. Furthermore, to classify the new data into HC and PB patterns, a classification model was created by discriminant analysis using food groups with significantly different intakes among dietary patterns. Next, we recruited 267 new older adults ≥ 65 years of age and measured food intake and cognitive function assessed using the memory performance index score. Individuals with cognitive decline were identified and their detailed cognitive functions were assessed using the neurocognitive index score. Cognitive function was significantly impaired in the HC pattern in both the general elderly and cognitively impaired cohorts. These findings suggest that a dietary pattern of low carbohydrate and high protein intake is associated with good cognitive function in elderly Japanese individuals. Classification by these dietary patterns can predict cognitive reservation in community-dwelling older adults.

The use of probiotics is expected to be an intervention in neurodegenerative conditions that cause dementia owing to their ability to modulate neuroinflammatory responses via the microbiome-gut–brain axis. Therefore, we selected Lactiplantibacillus plantarum OLL2712 (OLL2712), the optimal anti-inflammatory lactic acid bacteria strain with high IL-10-inducing activity in immune cells, and aimed to verify its protective effects on memory function in older adults. A 12-week, randomized, double-blind, placebo-controlled trial was performed with older adults over the age of 65 years with declining memory. The participants consumed either powder containing heat-treated OLL2712 cells or placebo. Memory function was assessed using a computer-assisted cognitive test, Cognitrax. Daily dietary nutrient intake was assessed using the Brief-type Self-administered Diet History Questionnaire (BDHQ). The composition of the gut microbiota was analyzed by fecal DNA extraction and 16S rDNA sequencing. Data from 78 participants who completed the entire procedure were analyzed, and significant improvements in composite memory and visual memory scores were observed in the active group, after accounting for the effect of daily nutritional intake (p = 0.044 and p = 0.021, respectively). In addition, the active group had a lower abundance ratio of Lachnoclostridium, Monoglobus, and Oscillibacter genera, which have been reported to be involved in inflammation. The present study suggests that OLL2712 ingestion has protective effects against memory function decline in older adults.

Neuroinflammation has been recognized as a promising target when considering strategies for treating AD. In particular, it has been shown that neutrophils and MPO-mediated neuroinflammatory responses with the production of HClO play a role in the progression of AD. In this study, we aimed to evaluate the effects of anserine, a scavenger of HClO, on the protection of cognitive declines in persons with MCI. Fifty-eight elderly volunteers were screened, and 36 MCI individuals were assigned either to an active arm, who received 500 mg anserine per day, or a placebo arm, for 12-weeks. To assess cognitive function, we performed MMSE at baseline and after the ingestion. The data of the MMSE for 30 subjects who completed the follow-up tests were analyzed. A significant difference was detected in the change score of MMSE between the active arm (1.9 ± 2.0; n = 15) and the placebo arm (0 ± 2.8; n = 15) (p = 0.036). After the correction with the daily intake of anserine, the significance was elevated (p = 0.0176). Our results suggest that anserine protects elderly persons with MCI from cognitive declines by suppressing MPO-mediated neuroinflammatory responses.

We recruited 154 community-dwelling elderly individuals and conducted a cohort study to find out the nutrient intake that is suitable for maintaining cognitive function in Japanese elders. Cognitive function was evaluated by the two functional tests, the Montreal Cognitive Assessment (MoCA) and Wechsler Memory Scale-Delayed Recall (WMS-DR), and daily nutrient intake was estimated from a Brief-type Self-administered Diet History Questionnaire (BDHQ). By a multiple regression analysis, among the four major nutrients (protein, fat, carbohydrate and ash), we detected a significant correlation between the score of cognitive functions assessed by both MoCA and WMS-DR and daily consumption of fat (p = 0.0317 and p = 0.0111, respectively). Among categories of fatty acid, we found a significant correlation between the score of both MoCA and WMS-DR and consumption of monounsaturated fatty acid (MUFA) (p = 0.0157 and p = 0.0136, respectively). Finally, among MUFAs, we observed a significant correlation between the score of both MoCA and WMS-DR and consumption of oleic acid (p = 0.0405 and p = 0.0165, respectively). From these observations, we can propose that daily consumption of fat, especially in oleic acid, has a beneficial effect against cognitive decline in community-dwelling Japanese elderly individuals.

Impulse control disorders are recognized as one of the behavioral and psychological symptoms of dementia (BPSD). Majority of studies on the treatment of BPSD related to impulsivity have rather focused on the aggression and agitation. In particular, it has not been investigated how cognitive declines are associated with impulsivity in community-dwelling elderly people. Here, we have measured the cognitive and memory functions and impulsivity of 212 elderly community-dwelling people using a psychometric test battery and analyzed the correlation between their level of impulsivity and cognitive functions by multiple regression analysis. We found an elevation of impulsivity, which was evaluated by the Barratt Impulsiveness Scale-11, closely related to decline of cognitive functions, which were evaluated by the Montreal Cognitive Assessment and the Mini-Mental State Examination, and Logical Memory function, which were evaluated by the Wechsler Memory Scale-Delayed Recall. Then we have divided them into groups based on the severity of cognitive decline and conducted an analysis of each group, the result of which showed that as this tendency was particularly noticeable in the suspected dementia group. Therefore, we have concluded that heightened impulsivity is negatively associated with cognitive and memory functions in community-dwelling elderly people.

Matcha Green Tea Powder contains a variety of active ingredients beneficial to health, such as tea catechins, lutein and vitamin K. It is also known that these ingredients confer benefits upon cognitive functions of elderly people. Therefore, we aimed to investigate the relationship between a daily supplementation of Matcha and the change in cognitive functions of community-dwelling elderly people. A randomized, double-blind, placebo-controlled 12-week trial was performed. Sixty-one participants were recruited and randomly assigned to receive test drink containing 3 g powder from fresh Matcha or placebo powder per day. Changes in cognitive function were assessed utilizing a psychometric test battery. Daily food intake was assessed by a Brief-type Self-administered Diet History Questionnaire (BDHQ). In the gender-specific analysis, a significant cognitive enhancement was observed in the Montreal Cognitive Assessment (MoCA) score in the active group of women. In dietary analysis, we found a significant inverse correlation between consumption of vitamin K in daily diet, excluding test drinks, and change in MoCA. The present study suggests that daily supplementation of Matcha Green Tea Powder has protective effects against cognitive decline in community-dwelling elderly women.

Alzheimer’s disease (AD), a neurodegenerative disease, causes behavioural abnormalities such as disinhibition, impulsivity, and hyperphagia. Preclinical studies using AD model mice have investigated these phenotypes by measuring brain activity in awake, behaving mice. In this study, we monitored the behavioural alterations of impulsivity and hyperphagia in middle-aged AD model mice. As a behavioural readout, we trained the mice to accept a water-reward under thirsty conditions. To analyse brain activity, we developed a measure for licking behaviour combined with visualisation of whole brain activity using awake fMRI. In a water-reward learning task, the AD model mice showed significant hyperactivity of the dorsal raphe nucleus in thirsty conditions. In summary, we successfully visualised altered brain activity in AD model mice during reward-oriented behaviour for the first time using awake fMRI. This may help in understanding the causes of behavioural alterations in AD patients.