Alzheimer's disease (AD) is one of the most common forms of dementia, which cannot be cured at the moment. Therefore, researchers also look for the alternative approaches to its treatment. It is suggested that changes in human gut microbiome mediated by exercise could influence the development and progression of AD and a new term"muscle-gut-brain axis"is introduced. There is much evidence to support this assumption. The gut microbiology is closely related to a wide range of diseases of the nervous system and therefore any negative qualitative and quantitative changes in the composition of the gut microbiota can potentially contribute to the pathophysiology of AD. Research shows that the treatment of intestinal dysbiosis with probiotics/synbiotics/eubiotics can prevent or alleviate the symptoms of these chronic neurological diseases. Studies also point to the positive effects of movement on the health of seniors. A positive correlation can be found between cognitive functions and physical stress, both in the elderly and in AD patients. Even short-term interventions with a relatively low frequency seem to produce positive results, while physical activities can be performed by using relatively simple and cost-effective means. In addition, physical activity can significantly modulate gut microbiome. Thus, it can be concluded that physical activity in humans seems to correlate with gut microbiome, which can prevent the incidence and development of AD.

Evidence suggests that physical exercise can serve as a preventive strategy against Alzheimer's disease (AD). In contrast, much less is known about the impact of exercise when it is introduced after cognitive deficits are established. Using the TgCRND8 mouse model of amyloidosis, we compared the effects of exercise as an intervention strategy aimed at altering disease progression. Voluntary running for 1 month or 2 months was introduced in 3-month-old TgCRND8 mice, which exhibit amyloid-beta (Aβ) plaque pathology and cognitive deficits at this age. Specifically, we examined Aβ plaque load, spatial memory, and neurogenesis in the dentate gyrus in the hippocampus. After 1 month of running, TgCRND8 mice spent more time in the novel arm of the Y-maze compared to the familiar arms, indicating improved memory. The levels of doublecortin (a marker of immature neurons) were increased in TgCRND8 mice running for 1 month, but with no significant difference in the number of new mature neurons or plaque burden. As the disease progressed, running prevented further deficits in the Y-maze performance and hippocampal neurogenesis and it reduced plaque load pathology in TgCRND8 mice running for 2 months, compared to non-running transgenics. Therefore, the impact of running on memory, neurogenesis, and amyloid pathology was of greater significance when sustained through later stages of the disease.

BACKGROUND:Coconut oil has been widely used to improve health because there is much information available by word of mouth, in books, and on the internet. However, researchers still continue to search for the best diets to improve the quality of life, especially for people with cognitive decline.

OBJECTIVES:The aim of this review is to develop a novel dietary approach, the Keto-Mediet, which may help prevent the onset of Alzheimer's disease.

METHODS:Evidence gained through literature review from 1982 to 2015 on gene-by-diet interaction and lipid and glucose metabolism in the brains of Alzheimer's patients is converted into the new Keto-Mediet approach.

DESIGN:The Keto-Mediet approach combines the benefits of a Ketogenic diet and a Mediterranean diet into a pyramidal model that is rich in various types of vitamins and substitutes coconuts for saturated animal fats. Limited glucose intake is intended to delay brain degeneration. A revised adult food pyramid was created to illustrate the principles of the Keto-Mediet approach.

CONCLUSION:The Keto-Mediet approach represents and interprets food groups according to the revised adult food pyramid. This approach also encourages adherence to this healthy diet and lifestyle changes including exercise for people whose age ranges from 40 to 75 years. Those who comply with this approach will significantly enhance their knowledge and adopt a healthier lifestyle, as compared to those whose modern eating patterns are typically less healthy. Therefore, the Keto-Mediet approach can be applied in hopes of preventing and decreasing Alzheimer's disease in different ethnicities and cultural groups.

Ginseng, a perennial plant belonging to the Panax genus of the Araliaceae family, has been used in China, Korea, and Japan as a traditional herbal medicine for thousands of years. Ginseng is recorded to have exhibited a wide variety of beneficial pharmacological effects and has become a popular and worldwide known health supplement and drug. The protective effects of ginseng on central nervous system are discussed in this review. Ginseng species and ginsenosides and their intestinal metabolism and bioavailability are concisely introduced. The molecular mechanisms of the effects of ginseng on central nervous system, mainly focused on the neuroprotection properties of ginseng, memory, and learning enhanced properties, and the effects on neurodegenerative disorders are presented. Thus, ginseng and its constituents are of potential merits in the treatment of cerebral disorders.

Physical activity has long been hypothesized to influence the risk and pathology of Alzheimer's disease. However, the amount of physical activity necessary for these benefits is unclear. We examined the effects of three months of low and high intensity exercise training on soluble Aβ40 and Aβ42 levels in extracellular enriched fractions from the cortex and hippocampus of young Tg2576 mice. Low (LOW) and high (HI) intensity exercise training animals ran at speeds of 15m/min on a level treadmill and 32 m/min at a 10% grade, respectively for 60 min per day, five days per week,from three to six months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. Soleus muscle citrate synthase activity increased by 39% in the LOW group relative to SED, and by 71% in the HI group relative to LOW, indicating an exercise training effect inthese mice. Soluble Aβ40 concentrations decreased significantly in an exercise training dose-dependent manner in the cortex. In the hippocampus, concentrations were decreased significantly in the HI group relative to LOW and SED. Soluble Aβ42 levels also decreased significantly in an exercise training dose-dependent manner in both the cortex and hippocampus. Five proteins involved in Aβ clearance (neprilysin, IDE, MMP9, LRP1 and HSP70) were elevated by exercise training with its intensity playing a role in each case. Our data demonstrate that exercise training reduces extracellular solubleAβ in the brains of Tg2576 mice in a dose-dependent manner through an up-regulation of Aβ clearance.

OBJECTIVE:To identify the acupoint combinations used in the treatment of Alzheimer's disease (AD).

METHODS:The clinical literature regarding acupuncture and moxibustion for AD was searched and collected from databases including Chinese Biomedical Medicine, China National Knowledge Infrastructure, Wanfang Database and PubMed. The database of acupuncture and moxibustion prescriptions for AD was established by using Excel software so as to conduct the descriptive analysis, association analysis on the data.

RESULTS:Baihui (GV 20), Sishencong (EX-HN 1), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6), Fengchi (GB 20), Taixi (KI 3), Dazhui (GV 14), Shenshu (BL 23), Sanyinjiao (SP 6), Shenting (GV 24), Fenglong (ST 40), Xuanzhong (GB 39), Shuigou (GV 26) and Taichong (LR 3) were of higher frequency in the treatment of AD with acupnucture and moxibustion. Most acupoints were selected from the Governor Vessel. The commonly used acupoints were located on the head, face, neck and lower limbs. The combination of the local acupoints with the distal ones was predominated. The crossing points among the specific points presented the advantage in the treatment. The association analysis indicated that the correlation among Fengchi (GB 20)-Baihui (GV 20) was the strongest, followed by combinations of Dazhui (GV 14)-Baihui (GV 20), Shenshu (BL 23)- Baihui (GV 20) and Neiguan (PC 6)- Baihui (GV 20) and indicated the common rules of the clinical acupoint selection and combination for AD.

CONCLUSION:Our findings provide a reference for acupoints selection and combination for AD in clinical acupuncture practice.

BACKGROUND:Alzheimer's disease (AD) is the most common cause of dementia. However, none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present. Acupuncture has attracted more and more attention in recent years due to its efficacy and very few side effects. Lately, a systematic review has thought that the evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough. Therefore, the aim of this study is to explore the efficacy and safety of acupuncture in patients with mild to moderate AD.

METHODS:This was a randomized, controlled, parallel-group, exploratory study with 4-week baseline (T0), 12-week treatment phase (T1) and 12-week follow-up period (T2). Patients with mild to moderate AD meeting the included criteria were randomly allocated into either acupuncture or donepezil hydrochloride groups. The acupuncture group(AG) was given acupuncture treatment three times per week and the donepezil hydrochloride group(DG) group was administered donepezil hydrochloride once daily (5 mg/day for the first 4 weeks and 10 mg/day thereafter). Primary efficacy was measured using Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog) and Clinician's Interview-Based Impression of Change-Plus (CIBIC-Plus). The second outcomes were measured with 23-Item Alzheimer's disease Cooperative Study Activities of Daily Living Scales (ADAS-ADL23) and Neuropsychiatric Index (NPI).

RESULTS:Of 87 participants enrolled in the study, 79 patients finished their treatment and follow-up processes. The ADAS-cog scores for AG group showed obvious decreases at T2 and∆(T2-T0)when compared with DG group, and significant between-group differences were detected (all p < 0.05). The mean CIBIC-Plus values for the AG group at T1 and T2 were much lower than that for the DG group, and there were significant differences between the two groups (푃<0.05). There were no significant between-group differences in the scores of ADAS-ADL23 and NPI during the study period. Treatment discontinuations due to adverse events were 0 (0%) and 4 (9.09%) for the AG and DG groups, respectively.

CONCLUSIONS:Acupuncture is safe, well tolerated and effective in improving the cognitive function, global clinical status of AD.

TRIAL REGISTRATION:ChiCTR-IOR-17010465 (Retroactively registered on 18 JAN 2017).

OBJECTIVE:To investigate the effect of acupuncture plus moxibustion on learning-memory ability and expression of hippocampal Janus kinase-2 (JAK2)/signal transducer and activator of transcription-3 (STAT3)/suppressors of cytokine signaling-3 (SOCS3) signaling in Alzheimer's Disease (AD) rats, so as to reveal their mechanisms underlying improvement of AD.

METHODS:A total of 60 SD rats were randomly divided into four groups：normal control, sham-operation, model and acupuncture-moxibustion (Acu-moxi,＝15 in each group) groups. The AD model was established by microinjection of β-amyloid 1-42(Aβ1-42，5 µL)into the bilateral hippocampus. Seven days after modeling, Acu-moxi intervention was given. After insertion of acupuncture needles into"Baihui"(GV20) and bilateral"Shenshu"(BL23) and manipulating them for a while, the needles were then retained for 15 min, when, the mild moxibustion was performed at the same time. The treatment was conducted once daily, 5 times a week for consecutive 4 weeks. After the treatment, Morris water maze test was used to detect the animals' learning-memory ability. Immunohistochemistry and Western blot were respectively used to detect the number of positive cells and protein expression levels of JAK2, STAT3 and SOCS3 in the hippocampus tissue.

RESULTS:Following modeling and compared with the normal control and sham-operation groups, the average escape latency was significantly prolonged (<0.01), and the number of the original platform crossing and the residence time in the platform quadrant were significantly shortened in the model group (<0.01). The numbers of hippocampal JAK2- and STAT3-positive cells and expression levels of hippocampal JAK2 and STAT3 proteins were significantly increased (<0.01), and the number of hippocampal SOCS3-positive cells as well as the expression of SOCS3 protein significantly decreased in the model group relevant to the normal control and sham-operation groups (<0.01). After the intervention, the average escape latency was significantly shortened (<0.01), and the number of the original platform crossing and the residence time in the platform quadrant were significantly increased in the Acu-moxi group (<0.01), and the expression levels of JAK2 and STAT3 were significantly down-regulated and that of SOCS3 was considerably up-regulated in the Acu-moxi group relevant to the model group (<0.01)．.

CONCLUSION:Acu-moxi intervention can improve the learning-memory ability in AD rats, which is associated with its functions in inhibiting hippocampal JAK2/STAT3 signaling and up-regulating SOCS3 (a negative feedback factor) protein level.

BACKGROUND:There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer's disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD.

METHODS AND FINDINGS:This study was a 26-week randomized controlled trial comparing the effects of 150 minutes per week of aerobic exercise vs. non-aerobic stretching and toning control intervention in individuals with early AD. A total of 76 well-characterized older adults with probable AD (mean age 72.9 [7.7]) were enrolled and 68 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. Neuropsychological tests and surveys were conducted at baseline,13, and 26 weeks to assess memory and executive function composite scores, functional ability (Disability Assessment for Dementia), and depressive symptoms (Cornell Scale for Depression in Dementia). Cardiorespiratory fitness testing and brain MRI was performed at baseline and 26 weeks. Aerobic exercise was associated with a modest gain in functional ability (Disability Assessment for Dementia) compared to individuals in the ST group (X2 = 8.2, p = 0.02). There was no clear effect of intervention on other primary outcome measures of Memory, Executive Function, or depressive symptoms. However, secondary analyses revealed that change in cardiorespiratory fitness was positively correlated with change in memory performance and bilateral hippocampal volume.

CONCLUSIONS:Aerobic exercise in early AD is associated with benefits in functional ability. Exercise-related gains in cardiorespiratory fitness were associated with improved memory performance and reduced hippocampal atrophy, suggesting cardiorespiratory fitness gains may be important in driving brain benefits.

TRIAL REGISTRATION:ClinicalTrials.gov NCT01128361.

BACKGROUND AND PURPOSE:Individuals with Alzheimer disease (AD) experience progressive loss of independence-performing activities of daily living. Identifying interventions to support independence and reduce the economic and psychosocial burden of caregiving for individuals with AD is imperative. The purpose of this analysis was to examine functional disability and caregiver time in individuals with early-stage AD.

METHODS:This was a secondary analysis of a randomized controlled trial of 26 weeks of aerobic exercise (AEx) versus stretching and toning (ST). We measured functional dependence using the Disability Assessment for Dementia, informal caregiver time required using the Resources Utilization in Dementia Lite, and cognition using a standard cognitive battery.

RESULTS:We saw a stable function in the AEx group compared with a significant decline in the ST group (4%; F = 4.2, P = .04). This was especially evident in more complex, instrumental activities of daily living, with individuals in the AEx group increasing 1% compared with an 8% loss in the ST group over 26 weeks (F = 8.3, P = .006). Change in memory was a significant predictor of declining instrumental activities of daily living performance (r = 0.28, 95% confidence interval = 0.08∞, P = .01). Informal caregiver time was not different between the AEx and ST groups.

CONCLUSIONS:Our analysis extends recent work by revealing specific benefits for instrumental activities of daily living for individuals in the early stages of AD and supports the value of exercise for individuals with cognitive impairment.

In a random and prospective study, Alzheimer's disease (AD) patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. Serum 25-OHD level increased by 2.2-fold in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). INTRODUCTION: A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and have osteoporosis. We previously showed that 25-hydroxyvitamin D (25-OHD) deficiency caused by sunlight deprivation with compensatory hyperparathyroidism causes reduced BMD in elderly women with AD. This study was undertaken to address the possibility that sunlight exposure with calcium supplementation may maintain BMD and reduce the incidence of nonvertebral fractures in elderly women with AD. MATERIALS AND METHODS: In a random and prospective study, AD patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. BMD of the second metacarpal bone was measured using a computed X-ray densitometer (CXD). The CXD method measures BMD and cortical thickness at the middle of the second metacarpal bone on a radiogram of the hand and an aluminum step wedge as a standard (20 steps; 1 mm/step). Incidence of nonvertebral fractures in the two patient groups during the 1-year follow-up period was assessed. RESULTS AND CONCLUSION: At baseline, average hospitalization period was 1.7 years in both groups, and activity of daily living (ADL) was decreased. Patients of both groups showed vitamin D deficiency caused by sunlight deprivation and decreased dietary intake of vitamin D with compensatory hyperparathyroidism. The exposed group patients were exposed to sunlight (3615 minutes/year). BMD increased by 2.7% in the sunlight-exposed group and decreased by 5.6% in the sunlight-deprived group (p<0.0001). Serum 25-OHD level increased from 24.0 to 52.2 nM in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). Sunlight exposure can increase the BMD of vitamin D-deficient bone by increasing 25-OHD concentration and lead to the prevention of nonvertebral fractures.

The current absence of a disease-modifying treatment for Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) highlights the necessity for investigating the benefits of non-pharmacological approaches such as physical exercise (PE). Although evidence exists to support an association between regular PE and higher scores on cognitive function tests, and a slower rate of cognitive decline, there is no clear consensus on the underlying molecular mechanisms of the advantages of PE. This review seeks to summarize the positive effects of PE in human and animal studies while highlighting the vascular link between these benefits. Lifestyle factors such as cardiovascular diseases, metabolic syndrome, and sleep apnea will be addressed in relation to the risk they pose in developing AD and VCID, as will molecular factors known to have an impact on either the initiation or the progression of AD and/or VCID. This will include amyloid-beta clearance, oxidative stress, inflammatory responses, neurogenesis, angiogenesis, glucose metabolism, and white matter integrity. Particularly, this review will address how engaging in PE can counter factors that contribute to disease pathogenesis, and how these alterations are linked to endothelial cell function.