The incidence of dementia, including AD, continues to increase worldwide [
1]. Aβ is considered to be the major cause of AD and the large aggregates of Aβ, which is called senile plaque, is a major hallmark of AD. However, most Aβ cascade blockers such as β/γ-secretase inhibitors and Aβ immunotherapies have failed to show efficacy in clinical trials. As the development of Aβ abnormalities precedes the onset of cognitive dysfunction in AD by approximately 20 years [
34], it is probably too late to provide these drugs and therapies after the onset of cognitive dysfunction. Therefore, preventive approaches including items in the daily diet are very important practical measures and we focused on BR. Although BR is nutrient-rich, containing many components effective against the development of dementia, it is very difficult for them to be absorbed them into the body because BR is difficult to digest. Thus BR was treated with HP to improve digestibility and absorption without changing its nutrient composition. HP can enhance the nutritional values of BR. For example, GABA in BR increases by HP treatment [
35], and this agrees with our result. BR is difficult to cook because the bran is very hard and has decreased water absorbency. However, HPBR had the same level of high water absorbency as PR (Fig.
1). These results suggest that HPBR contained the high nutritional content of BR along with the good cooking characteristics of PR.
In the present study, we tested the effects of HPBR in vivo using the SAMP8 model. The HPBR-fed mice showed a higher rate of spontaneous alternation in the Y-maze test than the wheat-fed controls and PR-fed mice (Fig.
3a). The amount of Aβ
1–42 in the brain of HPBR-fed mice was also lesser than those in the other groups (Fig.
5a). The results suggest that HPBR ameliorated the cognitive dysfunction of SAMP8 mice via the reduction of the amount of Aβ
1–42. On the other hand, the amounts of Aβ
1–40 among the groups did not differ (Fig.
5b). Aβ
1–42 is more neurotoxic and easy to aggregate compared to Aβ
1–40 [
36,
37]. HPBR might specifically inhibit the production of Aβ
1–42, as some nonsteroidal anti-inflammatory drugs and γ-secretase modulators do [
38], but further research is needed to clarify the detailed mechanism. An increase in the amount of APP has been demonstrated in the brain of SAMP8 mice [
27]. In this study, a trend toward a decrease in the amount of APP in HPBR-fed mice was observed (Fig.
5c). This might be one of the reasons why HPBR reduced the amount of Aβ. The HPBR-fed mice had better motor functions than the control and PR-fed mice. The HPBR-fed mice had a significantly greater grip strength than the control mice (Fig.
4b). Also, in rotarod test, the HPBR-treated mice had a trend toward an increase in fall latency (Fig.
4a). The HPBR-treated mice also had a higher total number of arm entries in the Y-maze than those in the other groups (Fig.
3b). Motor dysfunction may be correlated with cognitive dysfunction in AD or other dementias. Middle-aged adults with a slow walking speed and weak hand grip have a more than 2.5-fold increased risk of developing AD [
33]. Reduced muscle strength or motor activity leads to decreased blood flow in the entire body, including the brain. Decreased cerebral blood flow results in lack of oxygen and nutrition, which is associated the deterioration of neurological function. Improvement in motor function by associated with HPBR may thus contribute to the prevention of AD and other dementias. Previous studies have evaluated the effects of BR on diabetes or obesity [
39,
40]. BR is rich in dietary fiber which blocks the absorption of sugar and fat from the gastrointestinal tract and contributes to its beneficial effects in diabetes or obesity. However, there are few reports on the effects of BR on dementia in animal models or in humans. The nutrients in BR may be difficult to absorb, and HPBR may have ameliorated cognitive dysfunction in SAMP8 mice because HP treatment made BR easier to digest.
The adoption of daily activities that help prevent AD and other dementias is important, and dietary strategies are realistic and practical. We believe that HPBR offers suitable benefits and effects against AD and other dementias in human and that this topic requires further investigation.