Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 3.759
Filter
1.
Alzheimers Res Ther ; 16(1): 147, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961421

ABSTRACT

BACKGROUND: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them. METHOD: A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records. RESULTS: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake. CONCLUSION: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density. TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688, 2017-07-08.


Subject(s)
Alzheimer Disease , Prodromal Symptoms , Humans , Alzheimer Disease/diet therapy , Alzheimer Disease/prevention & control , Male , Female , Aged , Pilot Projects , Life Style , Diet, Mediterranean , Exercise , Diet/methods , Combined Modality Therapy , Middle Aged , Diet, Healthy/methods
2.
Gut Microbes ; 16(1): 2374608, 2024.
Article in English | MEDLINE | ID: mdl-38972055

ABSTRACT

With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aß and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aß and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.


Subject(s)
Brain , Diet, High-Fat , Gastrointestinal Microbiome , Mice, Inbred C57BL , NF-kappa B , Oxidative Stress , Quinic Acid , Signal Transduction , Tryptophan , Animals , Gastrointestinal Microbiome/drug effects , Tryptophan/metabolism , Diet, High-Fat/adverse effects , Mice , NF-kappa B/metabolism , Signal Transduction/drug effects , Male , Oxidative Stress/drug effects , Quinic Acid/analogs & derivatives , Quinic Acid/pharmacology , Quinic Acid/metabolism , Brain/metabolism , Brain/drug effects , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/prevention & control , I-kappa B Kinase/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Indoleacetic Acids/metabolism , Kynurenic Acid/metabolism , Inflammation/metabolism , Inflammation/drug therapy , Inflammation/prevention & control
3.
Int J Mol Sci ; 25(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38892314

ABSTRACT

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.


Subject(s)
Apolipoproteins E , Atherosclerosis , Periodontal Diseases , Porphyromonas gingivalis , Animals , Mice , Apolipoproteins E/deficiency , Periodontal Diseases/microbiology , Periodontal Diseases/prevention & control , Atherosclerosis/metabolism , Atherosclerosis/prevention & control , Atherosclerosis/microbiology , Telomerase/metabolism , Peptide Fragments/pharmacology , Alzheimer Disease/metabolism , Alzheimer Disease/prevention & control , Alzheimer Disease/microbiology , Periodontitis/microbiology , Periodontitis/prevention & control , Bacteroidaceae Infections/microbiology , Bacteroidaceae Infections/complications , Bacteroidaceae Infections/prevention & control , Disease Models, Animal , Mice, Inbred C57BL , Male , Humans
4.
Nutrients ; 16(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38892521

ABSTRACT

The rhizomes of Acorus tatarinowii Schott and Acorus gramineus Solander are widely used for treating amnesia in traditional Chinese medicine. In contrast, their leaves are usually discarded without their medicinal properties being known. Here, we found that the hot water extract of leaves improved cognition and tau pathology in model mice of frontotemporal dementia, similar to or even better than that of rhizomes. To explore the optimal method of processing, we made three preparations from dried leaves: hot water extract, extraction residue, and non-extracted simple crush powder. Among them, the simple crush powder had the strongest effect on tauopathy in mice. The crush powder also ameliorated Aß and α-synuclein pathologies and restored cognition in mouse models of Alzheimer's disease and dementia with Lewy bodies. These findings suggest the potential of Acorus tatarinowii/gramineus leaves as a dietary source for dementia prevention and reveal that simple crushing is a better way to maximize their efficacy.


Subject(s)
Acorus , Dementia , Plant Extracts , Plant Leaves , Animals , Plant Leaves/chemistry , Acorus/chemistry , Mice , Plant Extracts/pharmacology , Dementia/prevention & control , Disease Models, Animal , Cognition/drug effects , Amyloid beta-Peptides/metabolism , Male , Alzheimer Disease/prevention & control , tau Proteins/metabolism
6.
Phytomedicine ; 130: 155753, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38795693

ABSTRACT

BACKGROUND: Meningeal lymphatic vessels (mLVs) have great potential to be the therapeutic target for ß Amyloid protein (Aß) clearing in Alzheimer's disease (AD), but the regulatory methods of the mLVs are limited. The lymphatic valve, marked by FOXC2, is the fundamental structure for maintaining stable lymphatic drainage function. Preliminary evidence suggested that borneol (BO) as the classical phytochemicals could enhance the expression of FOXC2 in the mLVs of healthy mice. PURPOSE: This study aims to explore the regulatory ability of BO on lymphatic valves of mLVs in the AD model mice. STUDY DESIGN: We used the intracerebroventricular injection of Aß42 oligomers to construct the AD-like symptoms model induced by toxic protein deposition. We administered BO nano micelles(BO-Ms) orally before and after to simulate the AD prevention and treatment strategy. METHODS: Herein, this study characterized the efficacy and pathways of BO-Ms for regulating mLVs in AD model by Rt-PCR, WB and confocal microscopy, and determined the effects of BO-Ms on Aß clearance, behavior and safety of AD mice. RESULTS: The AD modeling process severely impaired the expression of lymphatic valves. However, after oral administering BO-Ms for prevention and treatment, an increase in the lymphatic valves of the transverse sinus was observed, which derived from the up-regulation of the transcription factor (FOXC2 and Akt) and the down-regulation of the transcription inhibitors (FOXO1 and PRDM1). Furthermore, the effects of BO-Ms on the lymphatic valves could enhance the lymphatic drainage of the mLVs in AD-like mice, promoting the clearance of toxicity aggregates, protecting neurons, and alleviating AD-like symptoms. Simultaneously, continuous oral BO-Ms for 30 days didn't show any significant organ toxicity. The most important thing was that the preventive effect of BO administration was superior to therapeutic administration in all data. CONCLUSION: In summary, our research indicated that BO is a promoter of lymphatic valve formation in the mLVs, and could prevent or repair damage caused by toxic Aß42. BO was the only bioactive natural product with the ability to regulate mLVs valves. Thus, BO has the potential to become phytochemicals for alleviating AD symptoms by enhancing the drainage function of mLVs.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Camphanes , Disease Models, Animal , Forkhead Transcription Factors , Animals , Amyloid beta-Peptides/metabolism , Alzheimer Disease/prevention & control , Alzheimer Disease/drug therapy , Mice , Camphanes/pharmacology , Forkhead Transcription Factors/metabolism , Male , Lymphatic Vessels/drug effects , Meninges/drug effects , Mice, Inbred C57BL
8.
J Prev Alzheimers Dis ; 11(3): 589-600, 2024.
Article in English | MEDLINE | ID: mdl-38706275

ABSTRACT

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.


Subject(s)
Cognitive Dysfunction , Aged , Female , Humans , Male , Middle Aged , Alzheimer Disease/prevention & control , China/epidemiology , Cognitive Dysfunction/prevention & control , Life Style
9.
J Alzheimers Dis ; 99(3): 1093-1104, 2024.
Article in English | MEDLINE | ID: mdl-38759001

ABSTRACT

Background: There are significant public health benefits to delaying the onset of Alzheimer's disease (AD) in individuals at risk. However, adherence to brain healthy behaviors is low. The Health Belief Model proposes that specific beliefs are mediators of behavior change. Objective: To characterize health belief measures from the Science of Behavior Change Research Network (SBCRN) in an older adult population and associations between health beliefs, AD risk, and current health behaviors. Methods: A total of 172 individuals from the Rhode Island AD Prevention Registry participated. SBCRN health belief measures included assessments of future time perspective, self-efficacy, deferment of gratification, and consideration of future consequences. Outcome measures included individual AD risk index score, dementia risk awareness, and lifestyle behaviors including physical, cognitive, and social activity. Results: Participants who were older had higher scores for AD risk, lower future time perspective, and lower generalized self-efficacy (all at p < 0.001). Higher generalized self-efficacy was related to increased physical activity (p < 0.010). Higher future time perspective (p < 0.001) and generalized self-efficacy (p = 0.48) were associated with lower AD risk score. Subjective cognitive decline (SCD) was associated with lower self-efficacy, ability to delay gratification, and a less expansive future time perspective. Conclusions: Greater self-efficacy and perceived future time remaining were associated with lower AD risk and greater engagement in physical activity. SCD was associated with health beliefs that may negatively affect engagement in positive brain health behaviors. Assessment of and psychoeducation about these intrapersonal health belief constructs may be important targets for behavioral interventions to reduce AD risk.


Subject(s)
Alzheimer Disease , Health Behavior , Self Efficacy , Humans , Alzheimer Disease/psychology , Alzheimer Disease/prevention & control , Male , Female , Aged , Health Knowledge, Attitudes, Practice , Aged, 80 and over , Exercise/psychology , Middle Aged , Risk Factors , Health Belief Model , Registries
10.
Med Sci Monit ; 30: e945091, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38736218

ABSTRACT

Alzheimer's disease is the most common form of dementia and includes cognitive, personality, and behavioral changes. The 2024 report from the Alzheimer's Association estimated that 6.9 million adults >65 years in the US are currently living with Alzheimer's disease. Modeling studies predict that this number will double by 2050, and associated healthcare costs will reach $1 trillion. In June 2021, regulatory approval of aducanumab, a humanized recombinant monoclonal antibody to amyloid ß, initially raised expectations for improved disease-modifying therapy. However, in February 2024, production of aducanumab and a post-marketing clinical trial ceased in the US due to the costs and limitations of aducanumab therapy. In March 2024, biobank data identified significant modifiable risk factors for Alzheimer's disease, including diabetes mellitus, exposure to nitrogen dioxide (a proxy for air pollution), and the frequency of alcohol intake. Therefore, modification of identifiable risk factors, combined with testing for disease-susceptibility genes, could be the most effective approach to reduce the incidence. This article aims to review the current status of disease-modifying therapies and prevention of Alzheimer's disease.


Subject(s)
Alzheimer Disease , Alzheimer Disease/prevention & control , Alzheimer Disease/drug therapy , Humans , Risk Factors , Antibodies, Monoclonal, Humanized/therapeutic use , Amyloid beta-Peptides/metabolism
11.
J Sci Med Sport ; 27(6): 402-407, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38664148

ABSTRACT

OBJECTIVES: To investigate if higher baseline physical activity levels are associated with less ß-amyloid burden and whether the ApoE4 genotype moderates this association cross-sectionally and longitudinally. DESIGN: Prospective cohort study. METHODS: 204 cognitively normal older adults (74.5 ±â€¯6.6 years; 26 % ApoE4-carrier) were analyzed. Baseline physical activity was measured using the Minnesota Physical Activity Questionnaire. Brain ß-amyloid burden was measured with positron emission tomography using 11C-labeled Pittsburgh compound. A subsample of 128 participants underwent longitudinal positron emission tomography (2.0 ±â€¯0.9 scans over 5 ±â€¯3 years). Statistical analysis was run according to physical activity (high/low group) and the ApoE4 genotype (carrier/noncarrier). RESULTS: The ApoE4 genotype moderated the relationship between physical activity and ß-amyloid, such that low physical activity had a greater impact on ß-amyloid deposition in ApoE4-carriers than noncarriers. This ApoE4 × physical activity effect on brain ß-amyloid deposition was also observed when all available ß-amyloid scan timepoints were included in the model. ß-amyloid deposition increased over time (p < 0.001), and ApoE4-carriers had disproportionately greater ß-amyloid accumulation than ApoE4-noncarriers. The lower physical activity group had marginally greater ß-amyloid accumulation than the higher physical activity group (p = 0.099), but there was no significant ApoE4 effect on ß-amyloid accumulation. CONCLUSIONS: Low physical activity in combination with the ApoE4-carrier genotype is associated with increased ß-amyloid burden, suggesting that ApoE4 moderates the effect of physical activity on ß-amyloid load. However, this effect was insufficient for baseline physical activity to modulate the change in ß-amyloid accumulation over time.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Apolipoprotein E4 , Brain , Exercise , Positron-Emission Tomography , Aged , Aged, 80 and over , Female , Humans , Male , Alzheimer Disease/prevention & control , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Apolipoprotein E4/genetics , Brain/metabolism , Brain/diagnostic imaging , Cross-Sectional Studies , Exercise/physiology , Genotype , Longitudinal Studies , Prospective Studies
12.
Zhongguo Zhong Yao Za Zhi ; 49(4): 902-911, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38621897

ABSTRACT

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Amyloid beta-Peptides/metabolism , Medicine, Chinese Traditional , Quality of Life , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/prevention & control
13.
Biosci Rep ; 44(4)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38577975

ABSTRACT

Since 1975, the incidence of obesity has increased to epidemic proportions, and the number of patients with obesity has quadrupled. Obesity is a major risk factor for developing other serious diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Recent epidemiologic studies have defined obesity as a risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and other types of dementia. Despite all these serious comorbidities associated with obesity, there is still a lack of effective antiobesity treatment. Promising candidates for the treatment of obesity are anorexigenic neuropeptides, which are peptides produced by neurons in brain areas implicated in food intake regulation, such as the hypothalamus or the brainstem. These peptides efficiently reduce food intake and body weight. Moreover, because of the proven interconnection between obesity and the risk of developing AD, the potential neuroprotective effects of these two agents in animal models of neurodegeneration have been examined. The objective of this review was to explore anorexigenic neuropeptides produced and acting within the brain, emphasizing their potential not only for the treatment of obesity but also for the treatment of neurodegenerative disorders.


Subject(s)
Anti-Obesity Agents , Neuropeptides , Neuroprotective Agents , Obesity , Humans , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Animals , Obesity/drug therapy , Obesity/metabolism , Neuropeptides/metabolism , Neuropeptides/pharmacology , Neuropeptides/therapeutic use , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/therapeutic use , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/prevention & control , Hypothalamus/drug effects , Hypothalamus/metabolism , Hypothalamus/pathology , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/prevention & control , Brain/drug effects , Brain/metabolism , Brain/pathology , Eating/drug effects
14.
Neurobiol Aging ; 139: 20-29, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38583392

ABSTRACT

Brazilian green propolis (propolis) is a chemically complex resinous substance that is a potentially viable therapeutic agent for Alzheimer's disease. Herein, propolis induced a transient increase in intracellular Ca2+ concentration ([Ca2+]i) in Neuro-2A cells; moreover, propolis-induced [Ca2+]i elevations were suppressed prior to 24-h pretreatment with amyloid-ß. To reveal the effect of [Ca2+]i elevation on impaired cognition, we performed memory-related behavioral tasks in APP-KI mice relative to WT mice at 4 and 12 months of age. Propolis, at 300-1000 mg/kg/d for 8 wk, significantly ameliorated cognitive deficits in APP-KI mice at 4 months, but not at 12 months of age. Consistent with behavioral observations, injured hippocampal long-term potentiation was markedly ameliorated in APP-KI mice at 4 months of age following repeated propolis administration. In addition, repeated administration of propolis significantly activated intracellular calcium signaling pathway in the CA1 region of APP-KI mice. These results suggest a preventive effect of propolis on cognitive decline through the activation of intracellular calcium signaling pathways in CA1 region of AD mice model.


Subject(s)
Alzheimer Disease , Calcium , Cognitive Dysfunction , Disease Models, Animal , Propolis , Animals , Propolis/therapeutic use , Propolis/administration & dosage , Propolis/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Alzheimer Disease/psychology , Alzheimer Disease/etiology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/prevention & control , Cognitive Dysfunction/drug therapy , Calcium/metabolism , Mice, Transgenic , Calcium Signaling/drug effects , Long-Term Potentiation/drug effects , Male , Amyloid beta-Peptides/metabolism , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/drug effects , Mice
15.
Alzheimers Dement ; 20(6): 3864-3875, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38634500

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD. METHODS: Genome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians. We calculated a polygenic risk score (PRS) for each individual and investigated the functional properties of SNPs enriched/depleted in centenarians. RESULTS: Cognitively healthy centenarians were enriched with the protective alleles of the SNPs associated with AD risk. The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5-fold lower PRS in centenarians compared to AD cases (P = 7.69 × 10-71), and 2-fold lower compared to age-matched controls (P = 5.83 × 10-17). DISCUSSION: Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems. HIGHLIGHTS: Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD). The protective effect is concentrated on variants involved in the immune and endolysosomal systems. Combining variants into a polygenic risk score (PRS) translated to > 5-fold lower PRS in centenarians compared to AD cases, and ≈ 2-fold lower compared to middle-aged healthy controls.


Subject(s)
Alzheimer Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Humans , Alzheimer Disease/genetics , Alzheimer Disease/prevention & control , Female , Male , Aged, 80 and over , Genetic Predisposition to Disease , Multifactorial Inheritance/genetics , Alleles , Case-Control Studies
16.
Psychogeriatrics ; 24(3): 701-718, 2024 May.
Article in English | MEDLINE | ID: mdl-38528391

ABSTRACT

Curcumin and omega-3 polyunsaturated fatty acids (ω-3 PUFA) are multifunctional compounds which play an important role in Alzheimer's disease (AD) and little has been addressed about the role of these two compounds together in the progression of the disease. There is evidence of the beneficial effect of combined administration of ω-3 PUFA and other dietary supplements such as vitamins and polyphenols in the prevention of AD, although much remains to be understood about their possible complementary or synergistic activity. Therefore, the objective of this work is to review the research focused on studying the effect and mechanisms of action of curcumin, ω-3 PUFA, and the combination of these nutraceutical compounds, particularly on AD, and to integrate the possible ways in which these compounds can potentiate their effect. The most important pathophysiologies that manifest in AD will be addressed, in order to have a better understanding of the mechanisms of action through which these bioactive compounds exert a neuroprotective effect.


Subject(s)
Alzheimer Disease , Curcumin , Dietary Supplements , Fatty Acids, Omega-3 , Neuroprotective Agents , Curcumin/therapeutic use , Curcumin/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Humans , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Drug Synergism
17.
Aging Clin Exp Res ; 36(1): 77, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519775

ABSTRACT

BACKGROUND: Dementia affects 5-8% of the population aged over 65 years (~50 million worldwide). Several factors are associated with increased risk, including diet. The Mediterranean diet (MedDiet) has shown potential protective effects against several chronic diseases. AIMS: This systematic review with meta-analysis aim was to assess the association between adherence to the MedDiet and the risk of dementia in the elderly. METHODS: PRISMA-2020 guidelines were followed. PubMed/MEDLINE and Scopus were searched on 17 July 2023. The Newcastle-Ottawa Scale tool was used to assess the risk of bias. The protocol was pre-registered in PROSPERO (registration number: CRD 42023444368). Heterogeneity was assessed using the I2 test. Publication bias was assessed by visual inspection of the funnel plot and by Egger's regression asymmetry test. The final effect size was reported as OR or HR, depending on the study design of the included studies. RESULTS: Out of 682 records, 21 were included in the analysis. The pooled OR was 0.89 (95% CI = 0.84-0.94) based on 65,955 participants (I2 = 69.94). When only cohort studies were included, HR was 0.84 (95% CI = 0.76-0.94) based on 55,205 participants (I2 = 89.70). When only Alzheimer Disease was considered OR was 0.73 (95% CI = 0.62-0.85) based on 38,292 participants (I2 = 63.85). DISCUSSION: Despite the relatively low risk reduction associated with higher adherence to MedDiet among elderly, it should be considered that this population is the most affected. CONCLUSIONS: Adherence to MedDiet could be an effective non-pharmacological measure to reduce the burden of dementia, even among elderly.


Subject(s)
Alzheimer Disease , Diet, Mediterranean , Aged , Humans , Alzheimer Disease/prevention & control , Cohort Studies , Risk , Research Design
18.
JAMA Intern Med ; 184(5): 563-572, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38436963

ABSTRACT

Importance: Dementia affects 10% of those 65 years or older and 35% of those 90 years or older, often with profound cognitive, behavioral, and functional consequences. As the baby boomers and subsequent generations age, effective preventive and treatment strategies will assume increasing importance. Observations: Preventive measures are aimed at modifiable risk factors, many of which have been identified. To date, no randomized clinical trial data conclusively confirm that interventions of any kind can prevent dementia. Nevertheless, addressing risk factors may have other health benefits and should be considered. Alzheimer disease can be treated with cholinesterase inhibitors, memantine, and antiamyloid immunomodulators, with the last modestly slowing cognitive and functional decline in people with mild cognitive impairment or mild dementia due to Alzheimer disease. Cholinesterase inhibitors and memantine may benefit persons with other types of dementia, including dementia with Lewy bodies, Parkinson disease dementia, vascular dementia, and dementia due to traumatic brain injury. Behavioral and psychological symptoms of dementia are best treated with nonpharmacologic management, including identifying and mitigating the underlying causes and individually tailored behavioral approaches. Psychotropic medications have minimal evidence of efficacy for treating these symptoms and are associated with increased mortality and clinically meaningful risks of falls and cognitive decline. Several emerging prevention and treatment strategies hold promise to improve dementia care in the future. Conclusions and Relevance: Although current prevention and treatment approaches to dementia have been less than optimally successful, substantial investments in dementia research will undoubtedly provide new answers to reducing the burden of dementia worldwide.


Subject(s)
Dementia , Aged , Humans , Alzheimer Disease/prevention & control , Cholinesterase Inhibitors/therapeutic use , Dementia/prevention & control , Memantine/therapeutic use , Risk Factors , Aged, 80 and over
19.
Food Funct ; 15(8): 3920-3938, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38517682

ABSTRACT

Alzheimer's disease (AD) currently lacks effective treatments, making its prevention a critical focus. While accumulating evidence supports that plant-based fermented foods may contribute to AD prevention, the neuroprotective effect of plant-based fermented foods on AD has not been comprehensively reviewed. In this study, we conducted a systematic review of preclinical studies on the efficacy of plant-based fermented foods in AD. The literature search was based on databases including PubMed, Embase, Web of Science, and Scopus. The PICO approach was employed for report inclusion, and each report was assessed for risk of bias using the SYRCLE's RoB tool. From the analysis of 25 retrieved reports, we extracted essential details, including bibliographic information, animal models and characteristics, sources of plant-based fermented foods, dosages, administration routes, durations, and outcome measures. Our findings indicate that plant-based fermented foods may positively impact acute and long-term cognitive function, as well as beta-amyloid-mediated neurodegeneration. This review sheds light on the potential neuroprotective benefits of plant-based fermented foods for various AD-related aspects, including oxidative stress, synaptotoxicity, neuroinflammation, tau hyperphosphorylation, dysfunctional amyloidogenic pathways, and cognitive deficits, as observed in rodent models of AD. However, the small number of studies obtained from our literature search and the finding that many of them were of moderate methodological quality suggest the need for further investigation to substantiate the beneficial potential of this class of functional food for the management of AD.


Subject(s)
Alzheimer Disease , Fermented Foods , Neuroprotective Agents , Alzheimer Disease/prevention & control , Alzheimer Disease/diet therapy , Animals , Humans , Neuroprotective Agents/therapeutic use , Disease Models, Animal , Oxidative Stress/drug effects , Amyloid beta-Peptides/metabolism
20.
Methods Mol Biol ; 2785: 15-33, 2024.
Article in English | MEDLINE | ID: mdl-38427185

ABSTRACT

The development of effective prevention and treatment strategies for Alzheimer's disease (AD) and dementia is hindered by limited knowledge of the underlying biological and environmental causes. While certain genetic factors have been associated with AD, and various lifestyle and environmental factors have been linked to dementia risk, the interactions between genes and the environment are not yet fully understood. To identify new avenues for dementia prevention, coordinated global efforts are needed to utilize existing cohorts and resources effectively and efficiently. This chapter provides an overview of current research on risk and protective factors for AD and dementia and discusses the opportunities and challenges associated with population-based approaches.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/genetics , Alzheimer Disease/prevention & control
SELECTION OF CITATIONS
SEARCH DETAIL
...