Prevention Of Alzheimer's Disease Research Articles

Sex‐specific effects of genetically predicted BMI and education on risk of AD

AbstractBackgroundExamining sex differences on the impact of modifiable risk factors in Alzheimer’s disease (AD) risk can help us better understand the mechanisms underlying sex differences in the prevalence and incidence of AD. Here, we used polygenic risk scores (PRS) and Mendelian randomization (MR) to investigate sex‐specific effects of sleep duration, insomnia, blood pressure, diabetes, alcohol intake, smoking, body mass index, high cholesterol, and education on AD risk.MethodWe obtained combined and sex‐stratified genome‐wide association study (GWAS) summary statistics for each risk factor from the UK Biobank and used them as the base dataset for constructing PRS and exposure datasets in the MR analysis. Linkage disequilibrium clumping was performed to identify independent genome‐wide significant single nucleotide polymorphisms (SNPs) across the sex‐combined, male‐specific, and female‐specific GWAS. The combined lead SNPs were then weighted by their strata‐specific effect sizes in the stratified PRS and MR analyses. PRS were constructed for each risk factor in participants from the Alzheimer’s Disease Genetics Consortium. Linear regression was used to investigate the association of each PRS with AD risk, adjusting for age, principal components, and cohort. MR was used to estimate sex‐stratified causal effects of each risk factor on AD. Sex differences in PRS associations and MR causal estimates were determined using Fisher’s Z score method.ResultsAssociation testing of the PRS with AD risk in sex stratified cohorts revealed that the BMI PRS was associated with differential effects in men and women (OR [95%CI]: males: 1.05 [1.00, 1.10] vs females: 0.96 [0.93, 0.99], p = 0.003). Furthermore, the university completion PRS was non‐significant in men but was associated with reduced risk in women (OR [95%CI]: males: 0.96 [0.92, 1.01] vs females: 0.92 [0.89, 0.96], p = 0.12). In the follow‐up MR analysis, university completion was also causally associated with reduced risk in women only (OR [95%CI]: males: 1.09 [0.77, 1.53] vs females: 0.55 [0.42, 0.72], p = 0.002) (Figure 1). No other risk factors showed evidence of sex‐differences.ConclusionOur study found sex‐specific effects of genetically predicted BMI and educational attainment on AD risk. These findings suggest the need for sex‐specific approaches to AD prevention and management.

Depressive symptoms in relation to markers of neurodegeneration, cerebrovascular injury and Alzheimer’s Disease (AD) in community‐dwelling older adults: a plasma and multimodal neuroimaging study

AbstractBackgroundDepressive symptoms are common with aging and Alzheimer’s Disease (AD). Both neurodegenerative and cerebrovascular diseases have been postulated as underlying mechanisms, but it’s unclear if they contribute to depressive symptom pathogenesis in preclinical stages of AD. Probing these mechanisms using both central (neuroimaging) and peripheral (plasma) biomarkers is critical to gain insight into the neurobiology of depression and provide opportunities for clinical translation.MethodLongitudinal data were analyzed from 350 Harvard Aging Brain Study participants, an observational cohort study of older adults who are cognitively unimpaired and have no/minimal depressive symptoms at baseline. Depressive symptoms were assessed annually with the 30‐item Geriatric Depression Scale (GDS) (average follow up = 7.2+/‐3.4yrs). At baseline, all participants underwent blood sampling for a plasma marker of general neurodegeneration, neurofilament light (NfL) and 11 cerebrovascular markers in plasma. Participants also underwent baseline amyloid (PiB) PET‐ wherein a cortical amyloid composite was derived‐ and baseline and subsequent MRI scans every three years‐ to derive slopes of regional cortical thickness and global white matter hyperintensities (WMH). Linear mixed effects models examined relationships between longitudinal GDS scores and predictors: (NfL or cerebrovascular markers)*time, and covariates: age, sex, education. Secondary model examined plasma markers and amyloid as interactive predictors of GDS, and repeated analyses using predictors: regional cortical thickness (neurodegeneration) or global WMH (cerebrovascular injury) slopes.ResultHigher baseline levels of NfL and of ICAM1, a marker of cerebrovascular injury, predicted increasing GDS scores over time (NfL: β = 0.03+/‐0.01, t = 2.7, p = 0.007; ICAM1: β = 0.02+/‐0.01, t = 2.2, p = 0.03). Each also interacted with amyloid in predicting GDS scores: (NfL X PiB: β = ‐0.03+/‐0.01, t = ‐2.42, p = 0.02; ICAM1 X PiB: β = 0.023+/‐0.01, t = 2.44, p = 0.02). Regarding neuroimaging correlates, medialorbitofrontal cortical thickness slope (β = ‐0.03+/‐0.01, t = ‐2.94, p = 0.004), but not global WMH slope, predicted increasing GDS over time. None of the other cerebrovascular markers interacted with amyloid in predicting GDS.ConclusionFindings suggest that cerebrovascular injury, and peripheral and central biomarkers of regional neurodegeneration, alone and in synergy with amyloid burden, are associated with depressive symptoms in cognitively unimpaired older adults. Future studies incorporating additional measures of peripheral and central neurodegeneration, tauopathy, and cerebrovascular injury are needed to guide AD prevention efforts targeting depressive symptoms.

Herpes Simplex Virus Infection and in vivo Alzheimer’s Disease Pathologies

AbstractBackgroundInterest in the role of Herpes Simplex Virus (HSV) infection in the pathogenesis of Alzheimer’s disease (AD) has increased in recent years. However, previous studies yielded inconsistent findings and no studies have yet investigated the relationship between HSV infection and in vivo AD pathologies such as beta‐amyloid (Aβ) and tau deposition in brain. We examined whether the level of serum anti‐HSV immunoglobulin G (IgG) antibodies (HSV‐IgG), an index of past infection of HSV, is associated with in vivo Aβ and tau deposition in nondemented individuals. We also investigated the modulating effect of HSV‐IgG titer on the relationship between Aβ and tau deposition.MethodA total of 426 nondemented older individuals (55‐90 years old) were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. All participants underwent comprehensive clinical assessment, [11C]‐Pittsburgh Compound B positron emission tomography (PET), and blood sampling for measurement of serum HSV antibodies. A subset of participants (N = 129) underwent [18F] AV‐1451 PET. Individuals whose HSV‐IgG titer was lower than 25 percentile of the whole group was classified as the HSVlow group, while those with HSV‐IgG titer higher than 25 percentile were classified as the HSVhigh group.ResultThere was no significant difference in age, sex, clinical diagnosis (cognitive normal vs. mild cognitive impairment), and apolipoprotein E e4 positivity (APOE4) between the HSVlow (N = 106) and HSVhigh (N = 320) groups. In terms of AD biomarkers, neither global Aβ nor tau deposition was different between the HSVhigh and HSVlow groups, even after controlling the effect of age, sex, and APOE4. However, there was a significant HSV group x Aβ deposition interaction effect on tau deposition (p = 0.037), suggesting the level of HSV‐IgG modulates the relationship between Aβ and tau deposition. Subsequent subgroup analyses showed a significant positive association between Aβ and tau deposition only in the HSVhigh group (p < 0.001), but not in the HSVlow group.ConclusionOur finding suggests that past HSV infection may aggravate the influence of Aβ on tau deposition. In regard of AD prevention, the result also supports that more attention needed to be paid to controlling HSV infection.

The health economics of an Alzheimer’s prevention therapy

AbstractBackgroundAmyloid reducing antibodies have been shown or suggested to slow decline in early Alzheimer’s disease (AD), and prevention trials in preclinical AD are ongoing. We estimate cost‐effectiveness of AD prevention from a payer perspective, which considers cost offsets and QALYs gains, and a societal perspective, which adds reduction in caregiver burden.MethodWe estimate cost‐effectiveness in the 2023 cohort of 55–79‐year‐olds with a Markov model under the following assumptions: Everyone would undergo an AD blood test (cost $125), which would generate positive or negative results in 80% of cases with sensitivity and specificity of 80% and inconclusive results in 20%. Individuals (80%) testing positive would go directly to treatment, the other 20% to confirmatory testing with PET (50%, cost of $4,000) or CSF (50%, cost of $600), receiving treatment accordingly. Individuals testing negative at any stage would return for another blood test in five years and those with inconclusive results in one. We assume average annual therapy cost of $5,850 per person (the list price of the PCSK9 inhibitors) for duration of 12 years, treatment effect of 50%, and four (baseline and 6, 12 and 18 month) MRIs ($400) for ARIA.ResultThe program would be cost‐effective from a payer perspective with cost of $45,157 and value of $53,721 per person. From a societal perspective, it would generate $24,704 in net value per person (Figure 1). If the treatment delayed progression by 25 percent, the program would no longer be cost‐effective from a payer or societal perspective. The treatment would have to eliminate the progression from preclinical AD to MCI to become cost‐neutral (Figure 2). Higher specificity of the blood test would decrease cost per person with no change in value generation and higher sensitivity would increase cost and decrease valueConclusionA prevention treatment that reduces the progression from preclinical AD to MCI by 50% could be economically viable from a payer perspective. The results are preliminary and need to be adjusted as more data become available, but the findings should stimulate a discussion among stakeholders about the contours and economic viability of such a prevention program.

Traditional Chinese Medicine studies for Alzheimer's disease via network pharmacology based on entropy and random walk.

Alzheimer's disease (AD) is a common neurodegenerative disease having complex pathogenesis, approved drugs can only alleviate symptoms of AD for a period of time. Traditional Chinese medicine (TCM) contains multiple active ingredients that can act on multiple targets simultaneously. In this paper, a novel algorithm based on entropy and random walk with the restart of heterogeneous network (RWRHE) is proposed for predicting active ingredients for AD and screening out the effective TCMs for AD. First, Six TCM compounds containing 20 herbs from the AD drug reviews in the CNKI (China National Knowledge Internet) are collected, their active ingredients and targets are retrieved from different databases. Then, comprehensive similarity networks of active ingredients and targets are constructed based on different aspects and entropy weight, respectively. A comprehensive heterogeneous network is constructed by integrating the known active ingredient-target association information and two comprehensive similarity networks. Subsequently, bi-random walks are applied on the heterogeneous network to predict active ingredient-target associations. AD related targets are selected as the seed nodes, a random walk is carried out on the target similarity network to predict the AD-target associations, and the associations of AD-active ingredients are inferred and scored. The effective herbs and compounds for AD are screened out based on their active ingredients' scores. The results measured by machine learning and bioinformatics show that the RWRHE algorithm achieves better prediction accuracy, the top 15 active ingredients may act as multi-target agents in the prevention and treatment of AD, Danshen, Gouteng and Chaihu are recommended as effective TCMs for AD, Yiqitongyutang is recommended as effective compound for AD.

Topological properties analysis and identification of mild cognitive impairment based on individual morphological brain network connectome.

Mild cognitive impairment is considered the prodromal stage of Alzheimer's disease. Accurate diagnosis and the exploration of the pathological mechanism of mild cognitive impairment are extremely valuable for targeted Alzheimer's disease prevention and early intervention. In all, 100 mild cognitive impairment patients and 86 normal controls were recruited in this study. We innovatively constructed the individual morphological brain networks and derived multiple brain connectome features based on 3D-T1 structural magnetic resonance imaging with the Jensen-Shannon divergence similarity estimation method. Our results showed that the most distinguishing morphological brain connectome features in mild cognitive impairment patients were consensus connections and nodal graph metrics, mainly located in the frontal, occipital, limbic lobes, and subcortical gray matter nuclei, corresponding to the default mode network. Topological properties analysis revealed that mild cognitive impairment patients exhibited compensatory changes in the frontal lobe, while abnormal cortical-subcortical circuits associated with cognition were present. Moreover, the combination of multidimensional brain connectome features using multiple kernel-support vector machine achieved the best classification performance in distinguishing mild cognitive impairment patients and normal controls, with an accuracy of 84.21%. Therefore, our findings are of significant importance for developing potential brain imaging biomarkers for early detection of Alzheimer's disease and understanding the neuroimaging mechanisms of the disease.

Biotransformation of American Ginseng Stems and Leaves by an Endophytic Fungus Umbelopsis sp. and Its Effect on Alzheimer’s Disease Control

Background: Common ginsenosides can be transformed into rare ginsenosides through microbial fermentation, and some rare ginsenosides can prevent Alzheimer’s disease (AD). This study aimed to transform common ginsenosides into rare ginsenosides through solid-state fermentation of American ginseng stems and leaves (AGSL) by an endophytic fungus and to explore whether fermented saponin extracts prevent AD. Methods: The powders of AGSL were fermented in a solid state by endophytic fungus. Total saponins were extracted from fermentation products using the methanol extraction method. The types of saponins were analyzed by liquid chromatography mass spectrometry (LC/MS). The Aβ42 concentration and β-secretase activity were measured by ELISA for the prevention of AD. Results: After AGSL was fermented by an endophytic fungus NSJG, the total saponin concentration of the fermented extract G-SL was higher than the unfermented CK-SL. Rare ginsenoside Rh1 was newly produced and the yield of compound K (561.79%), Rh2 (77.48%), and F2 (40.89%) was increased in G-SL. G-SL had a higher inhibition rate on Aβ42 concentration (42.75%) and β-secretase activity (42.22%) than CK-SL, possibly because the rare ginsenoside Rh1, Rh2, F2, and compound K included in it have a strong inhibitory effect on AD. Conclusion: The fermented saponin extracts of AGSL show more inhibition effects on AD and may be promising therapeutic drugs or nutrients for AD.

Why freshwater hydra does not get Alzheimer’s disease

The history of research into the basic mechanisms of the pathogenesis of Alzheimer’s disease (AD) is briefly considered. Concepts are analyzed in which a decisive role in the development of this disease was attributed to aluminum or free radicals. The lack of reliable data to date to support these concepts is emphasized. The point of view of the author is presented, according to which almost all the results indicating the feasibility of using antioxidants (as well as other potential drugs for AD) for the prevention and treatment of AD were obtained on model animals with certain pathologies (for example, with severe oxidative stress), which contribute to the formation of symptoms similar to those of AD in humans. In this regard, parallels are drawn with experimental gerontological research aimed at studying the effect of a calorie-restricted diet on aging and life span. It is noted that in these studies, animals were used that were either not completely normal or were in unfavorable conditions. According to the author, the lack of significant progress in the development of effective geroprotectors or drugs for the prevention/ treatment of AD is due to the fact that most specialists ignore the principles of classical gerontology, in particular, the definitions of aging and age-related diseases, as well as the correct approaches to the selection of control objects for their studies. It is emphasized that humans, unfortunately, cannot use the freshwater hydra method to combat aging and age-related diseases. Under certain conditions, it continuously renews all cells (including nerve ones) of its body and thereby ensures its “immortality.” In humans, the replacement of “old” neurons can lead to the loss of personality/individuality, and the “repair” of these cells today seems impossible. In this regard, the author considers it expedient to study the aging of postmitotic cells in experiments on stationary cell cultures, which can accelerate, in particular, the deciphering of the mechanisms of accumulation of beta-amyloid and senile pigments such as lipofuscin in neurons. The need for clinical studies of AD is noted as complementary to experimental work, although the first ones are much more expensive and time-consuming. Only confirmation in human studies of the effectiveness of drugs developed in experiments on model animals will allow them to be recommended for use in the clinical practice.

Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer's Disease Neurodegeneration.

Alzheimer's disease (AD) is a leading neurodegenerative condition causing cognitive and memory decline. With small-molecule drugs targeting Aβ proving ineffective, alternative targets are urgently needed. Neuroinflammation, which is central to AD's pathology, results in synaptic and neuronal damage, highlighting the importance of addressing inflammation and conserving neuronal integrity. Cannabidiol (CBD), derived from cannabis, is noted for its neuroprotective and anti-inflammatory properties, having shown efficacy in neuropathic pain management for epilepsy. To investigate the therapeutic efficacy of CBD in AD and to elucidate its underlying mechanisms, we aimed to contribute valuable insights for incorporating AD prevention recommendations into future CBD nutritional guidelines. Aβ1-42 was employed for in vivo or in vitro model establishment, CBD treatment was utilized to assess the therapeutic efficacy of CBD, and RNA-seq analysis was conducted to elucidate the underlying therapeutic mechanism. CBD mitigates Aβ-induced cognitive deficits by modulating microglial activity, promoting neurotrophic factor release, and regulating inflammatory genes. The administration of CBD demonstrated a protective effect against Aβ toxicity both in vitro and in vivo, along with an amelioration of cognitive impairment in mice. These findings support the potential inclusion of CBD in future nutritional guidelines for Alzheimer's disease prevention.

Assessing the Biological Mechanisms Linking Smoking Behavior and Cognitive Function: A Mediation Analysis of Untargeted Metabolomics.

(1) Smoking is the most significant preventable health hazard in the modern world. It increases the risk of vascular problems, which are also risk factors for dementia. In addition, toxins in cigarettes increase oxidative stress and inflammation, which have both been linked to the development of Alzheimer's disease and related dementias (ADRD). This study identified potential mechanisms of the smoking-cognitive function relationship using metabolomics data from the longitudinal Wisconsin Registry for Alzheimer's Prevention (WRAP). (2) 1266 WRAP participants were included to assess the association between smoking status and four cognitive composite scores. Next, untargeted metabolomic data were used to assess the relationships between smoking and metabolites. Metabolites significantly associated with smoking were then tested for association with cognitive composite scores. Total effect models and mediation models were used to explore the role of metabolites in smoking-cognitive function pathways. (3) Plasma N-acetylneuraminate was associated with smoking status Preclinical Alzheimer Cognitive Composite 3 (PACC3) and Immediate Learning (IMM). N-acetylneuraminate mediated 12% of the smoking-PACC3 relationship and 13% of the smoking-IMM relationship. (4) These findings provide links between previous studies that can enhance our understanding of potential biological pathways between smoking and cognitive function.

Aerobic exercise combined with chlorogenic acid exerts neuroprotective effects and reverses cognitive decline in Alzheimer's disease model mice (APP/PS1) via the SIRT1/ /PGC-1α/PPARγ signaling pathway.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease account for 60-80% of the total number of people with dementia, but its treatment and prevention strategies are still in a long process of exploration. It has been reported that a healthy lifestyle may be an effective non-pharmacological intervention for the prevention and treatment of AD, including increased physical activity and the consumption of polyphenol-rich foods. This study, therefore, investigated the effects of 8 weeks of moderate-intensity aerobic exercise (EX), administration of chlorogenic acid administration (GCA), and a combination of both (EX+GCA) on β-amyloid (Aβ) deposition, inflammatory factors, oxidative stress markers, neuronal damage, and cognitive performance in the brains of AD model mice (APP/PS1) and which signaling pathways may be responsible for these effects. The study used Western blot to detect the expression of signaling pathway-related proteins, enzyme-linked immunosorbent assay to detect the expression of inflammatory factors, hematoxylin-eosin staining to detect hippocampal neuronal morphology, immunohistochemistry to detect changes in Aβ deposition in the hippocampus, an oxidative stress marker kit to detect oxidative stress status and the Morris water maze to detect changes in cognitive performance. This study showed that an 8-week intervention (EX/GCA/EX+GCA) activating the SIRT1/PGC-1α signaling pathway improved oxidative stress, neuroinflammation, Aβ deposition, and cognitive performance in mice. However, there was no obvious difference between the EX and GCA groups. In contrast, the combined EX+GCA intervention was significantly better than phase EX or GCA. Our study suggests that although relief of Aβ deposition, neuroinflammation, oxidative stress, neuronal damage, and cognitive decline could also be achieved with EX or GCA, the combined EX+GCA intervention showed better results. These relief effects on AD-related conditions may be obtained by mediating the activation of the SIRT1/PGC-1α signaling pathway. This study is the first to explore the improvement of AD-related conditions with a combined lifestyle of EX+GCA. This healthy lifestyle could be a candidate option for the treatment of AD.

Research Progress on Natural Plant Molecules in Regulating the Blood-Brain Barrier in Alzheimer's Disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder. With the aging population and the continuous development of risk factors associated with AD, it will impose a significant burden on individuals, families, and society. Currently, commonly used therapeutic drugs such as Cholinesterase inhibitors, N-methyl-D-aspartate antagonists, and multiple AD pathology removal drugs have been shown to have beneficial effects on certain pathological conditions of AD. However, their clinical efficacy is minimal and they are associated with certain adverse reactions. Furthermore, the underlying pathological mechanism of AD remains unclear, posing a challenge for drug development. In contrast, natural plant molecules, widely available, offer multiple targeting pathways and demonstrate inherent advantages in modifying the typical pathologic features of AD by influencing the blood-brain barrier (BBB). We provide a comprehensive review of recent in vivo and in vitro studies on natural plant molecules that impact the BBB in the treatment of AD. Additionally, we analyze their specific mechanisms to offer novel insights for the development of safe and effective targeted drugs as well as guidance for experimental research and the clinical application of drugs for the prevention and treatment of AD.

Neuroprotective Effects of Davallia mariesii Roots and Its Active Constituents on Scopolamine-Induced Memory Impairment in In Vivo and In Vitro Studies.

Beta-amyloid (Aβ) proteins, major contributors to Alzheimer's disease (AD), are overproduced and accumulate as oligomers and fibrils. These protein accumulations lead to significant changes in neuronal structure and function, ultimately resulting in the neuronal cell death observed in AD. Consequently, substances that can inhibit Aβ production and/or accumulation are of great interest for AD prevention and treatment. In the course of an ongoing search for natural products, the roots of Davallia mariesii T. Moore ex Baker were selected as a promising candidate with anti-amyloidogenic effects. The ethanol extract of D. mariesii roots, along with its active constituents, not only markedly reduced Aβ production by decreasing β-secretase expression in APP-CHO cells (Chinese hamster ovary cells which stably express amyloid precursor proteins), but also exhibited the ability to diminish Aβ aggregation while enhancing the disaggregation of Aβ aggregates, as determined through the Thioflavin T (Th T) assay. Furthermore, in an in vivo study, the extract of D. mariesii roots showed potential (a tendency) for mitigating scopolamine-induced memory impairment, as evidenced by results from the Morris water maze test and the passive avoidance test, which correlated with reduced Aβ deposition. Additionally, the levels of acetylcholine were significantly elevated, and acetylcholinesterase levels significantly decreased in the brains of mice (whole brains). The treatment with the extract of D. mariesii roots also led to upregulated brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding protein (p-CREB) in the hippocampal region. These findings suggest that the extract of D. mariesii roots, along with its active constituents, may offer neuroprotective effects against AD. Consequently, there is potential for the development of the extract of D. mariesii roots and its active constituents as effective therapeutic or preventative agents for AD.

Amyloid-β mediates intestinal dysfunction and enteric neurons loss in Alzheimer's disease transgenic mouse.

Alzheimer's disease (AD) is traditionally considered as a brain disorder featured by amyloid-β (Aβ) deposition. The current study on whether pathological changes of AD extend to the enteric nervous system (ENS) is still in its infancy. In this study, we found enteric Aβ deposition, intestinal dysfunction, and colonic inflammation in the young APP/PS1 mice. Moreover, these mice exhibited cholinergic and nitrergic signaling pathways damages and enteric neuronal loss. Our data show that Aβ42 treatment remarkably affected the gene expression of cultured myenteric neurons and the spontaneous contraction of intestinal smooth muscles. The intra-colon administration of Aβ42 induced ENS dysfunction, brain gliosis, and β-amyloidosis-like changes in the wild-type mice. Our results suggest that ENS mirrors the neuropathology observed in AD brains, and intestinal pathological changes may represent the prodromal events, which contribute to brain pathology in AD. In summary, our findings provide new opportunities for AD early diagnosis and prevention.

Harnessing cognitive trajectory clusterings to examine subclinical decline risk factors.

Cognitive decline in Alzheimer's disease and other dementias typically begins long before clinical impairment. Identifying people experiencing subclinical decline may facilitate earlier intervention. This study developed cognitive trajectory clusters using longitudinally based random slope and change point parameter estimates from a Preclinical Alzheimer's disease Cognitive Composite and examined how baseline and most recently available clinical/health-related characteristics, cognitive statuses and biomarkers for Alzheimer's disease and vascular disease varied across these cognitive clusters. Data were drawn from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal cohort study of adults from late midlife, enriched for a parental history of Alzheimer's disease and without dementia at baseline. Participants who were cognitively unimpaired at the baseline visit with ≥3 cognitive visits were included in trajectory modelling (n = 1068). The following biomarker data were available for subsets: positron emission tomography amyloid (amyloid: n = 367; [11C]Pittsburgh compound B (PiB): global PiB distribution volume ratio); positron emission tomography tau (tau: n = 321; [18F]MK-6240: primary regions of interest meta-temporal composite); MRI neurodegeneration (neurodegeneration: n = 581; hippocampal volume and global brain atrophy); T2 fluid-attenuated inversion recovery MRI white matter ischaemic lesion volumes (vascular: white matter hyperintensities; n = 419); and plasma pTau217 (n = 165). Posterior median estimate person-level change points, slopes' pre- and post-change point and estimated outcome (intercepts) at change point for cognitive composite were extracted from Bayesian Bent-Line Regression modelling and used to characterize cognitive trajectory groups (K-means clustering). A common method was used to identify amyloid/tau/neurodegeneration/vascular biomarker thresholds. We compared demographics, last visit cognitive status, health-related factors and amyloid/tau/neurodegeneration/vascular biomarkers across the cognitive groups using ANOVA, Kruskal-Wallis, χ2, and Fisher's exact tests. Mean (standard deviation) baseline and last cognitive assessment ages were 58.4 (6.4) and 66.6 (6.6) years, respectively. Cluster analysis identified three cognitive trajectory groups representing steep, n = 77 (7.2%); intermediate, n = 446 (41.8%); and minimal, n = 545 (51.0%) cognitive decline. The steep decline group was older, had more females, APOE e4 carriers and mild cognitive impairment/dementia at last visit; it also showed worse self-reported general health-related and vascular risk factors and higher amyloid, tau, neurodegeneration and white matter hyperintensity positive proportions at last visit. Subtle cognitive decline was consistently evident in the steep decline group and was associated with generally worse health. In addition, cognitive trajectory groups differed on aetiology-informative biomarkers and risk factors, suggesting an intimate link between preclinical cognitive patterns and amyloid/tau/neurodegeneration/vascular biomarker differences in late middle-aged adults. The result explains some of the heterogeneity in cognitive performance within cognitively unimpaired late middle-aged adults.

31 Understanding Health Beliefs and Health Behaviors in Older Adults at Risk for Alzheimer’s Disease

Objective:Given the aging population, there are significant public health benefits to delaying the onset of Alzheimer’s disease (AD) in individuals at risk. However, adherence to health behaviors (e.g., diet, exercise, sleep hygiene) is low in the general population. The Health Belief Model proposes that beliefs such as perceived threat of disease, perceived benefits and barriers to behavior change, and cues to action are mediators of behavior change. The aim of this study was to gain additional information on current health behaviors and beliefs for individuals at risk for developing AD. This information can then be used to inform behavioral interventions and individualized strategies to improve health behaviors that may reduce AD risk or delay symptom onset.Participants and Methods:Surveys were sent to the Rhode Island AD Prevention Registry, which is enriched for at-risk, cognitively normal adults (i.e., majority with a family history and/or an APOE e4 allele). A total of 177 individuals participated in this study. Participants were 68% female; 93% Caucasian and non-Hispanic; mean age of 69.2; 74% with family history of dementia; 40% with subjective memory decline. The survey included measures from the Science of Behavior Change (SoBC) Research Network to measure specific health belief factors, including individual AD risk, perceived future time remaining in one’s life, generalized self-efficacy, deferment of gratification, consideration of future consequences as well as dementia risk awareness and a total risk score for dementia calculated from a combination demographic, health and lifestyle behaviors.Results:Participants who were older had higher scores for dementia risk (r=0.78), lower future time perspective (r=-0.33), and lower generalized self-efficacy (r=-0.31) (all at p<0.001). Higher education correlated with higher consideration of future consequences (r=-.31, p<0.001) and lower overall dementia risk score (r=-0.23, p=0.006). Of all scales examined, only generalized self-efficacy had a significant linear relationship to both frequency (r2=0.06) and duration (r2=0.08) of weekly physical activity (p<0.001). Total dementia risk score also had significant linear relationships (r2=0.19) with future time perspective (p<0.001) and generalized self-efficacy (p=0.48).Conclusions:Overall, individuals who rated themselves higher in self-efficacy were more likely to exercise more frequently and for a longer duration. Individuals who had lower overall risk for dementia due to both demographic and behavioral factors were more likely to endorse higher self-efficacy and more perceived time remaining in their lives. Increasing self-efficacy and targeting perceived future time limitations may be key areas to increase motivation and participation in behavioral strategies to reduce AD risk. Developing individual profiles based on these scales may further allow for individually tailored intervention opportunities.

Multipredictor risk models for predicting individual risk of Alzheimer’s disease

BackgroundEarly prevention of Alzheimer’s disease (AD) is a feasible way to delay AD onset and progression. Information on AD prediction at the individual patient level will be useful in AD prevention. In this study, we aim to develop risk models for predicting AD onset at individual level using optimal set of predictors from multiple features.MethodsA total of 487 cognitively normal (CN) individuals and 796 mild cognitive impairment (MCI) patients were included from Alzheimer's Disease Neuroimaging Initiative. All the participants were assessed for clinical, cognitive, magnetic resonance imaging and cerebrospinal fluid (CSF) markers and followed for mean periods of 5.6 years for CN individuals and 4.6 years for MCI patients to ascertain progression from CN to incident prodromal stage of AD or from MCI to AD dementia. Least Absolute Shrinkage and Selection Operator Cox regression was applied for predictors selection and model construction.ResultsDuring the follow-up periods, 139 CN participants had progressed to prodromal AD (CDR ≥ 0.5) and 321 MCI patients had progressed to AD dementia. In the prediction of individual risk of incident prodromal stage of AD in CN individuals, the AUC of the final CN model was 0.81 within 5 years. The final MCI model predicted individual risk of AD dementia in MCI patients with an AUC of 0.92 within 5 years. The models were also associated with longitudinal change of Mini-Mental State Examination (p < 0.001 for CN and MCI models). An Alzheimer’s continuum model was developed which could predict the Alzheimer’s continuum for individuals with normal AD biomarkers within 3 years with high accuracy (AUC = 0.91).ConclusionsThe risk models were able to provide personalized risk for AD onset at each year after evaluation. The models may be useful for better prevention of AD.

Product Design for Preventing Alzheimers Disease in Aging Society

With the continuous development of society, the population of Alzheimers disease has been rapidly increasing. The prevention of Alzheimers disease should attract everyones attention. In the medical aspect, there are constantly some new treatment methods and breakthroughs for Alzheimers disease, but there are relatively few educational products on the market to prevent and slow down Alzheimers disease. This paper is mainly about brain training products in prevention of Alzheimers disease. In this essay, we will explore the symptom of Alzheimers disease and the prevention of this disease. The paper adopts a variety of research methods, including literature retrieval method, case analysis method, etc. First, we consulted research papers related to Alzheimers disease at home and abroad. At the same time, we conducted a comparative analysis of different types of educational products on shopping websites to find out the advantages and disadvantages of each product. Through these methods to provide the basis for the research and analysis of the elderly and educational products. The number of Alzheimers patients is increasing, and the disease not only affect the life of the patient alone, but their family members also need to spare time to take care of them. Therefore, if the disease can be effectively prevented or delayed, it will be beneficial to the family. The burden will also be relatively reduced.

Gac (Momordica cochinchinensis Spreng.) oil supplementation mitigates cognitive decline in AlCl3-induced rats through the regulation of Alzheimer's disease markers and autophagy via gut-brain communication

Previous studies showed that oleic acid-rich camellia oil (Camellia oleifera Abel., CO) alleviates the cognitive impairment symptoms of Alzheimer's disease (AD). Gac oil (Momordica cochinchinensis Spreng., GO) is rich in β-carotene, lycopene, and oleic acid; no study has explored the effects of GO on AD. Accordingly, this study examined the effects of GO and CO on AD prevention in rats subjected to AlCl3 intragastric gavage. The results exhibited similar effects of GO, CO, and GO/CO supplementation on restraining AlCl3-induced brain RAGE/NF-κB signaling, proinflammatory cytokines, MDA, and AD markers by upregulating anti-inflammatory cytokines, antioxidative enzymes, and autophagy, which subsequently enhanced the clearance of Aβ1-42 and memory capacity. Gut microbiota composition increased the proportions of short-chain fatty acids (SCFAs)-producing [Eubacterium]_coprostanoligenes_group and Lactobacillus_johnsonii in the oil intake groups, which were positively correlated with anti-inflammatory, autophagy, and dementia mitigation. This compelling evidence implies that consuming GO and CO is a strategy for AD prevention.

1,7-diphenyl-4-hepten-3-one mitigates Alzheimer's-like pathology by inhibiting pyroptosis via activating the Nrf2 pathway.

Pyroptosis-mediated neuron death plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). However, the effect of 1,7-diphenyl-4-hepten-3-one (C1), a natural diarylheptanoid, on AD is unclear. Herein, we investigated the therapeutic effect of C1 on APP/PS1 mice and β-amyloid (Aβ)-induced HT22 cells. Our findings showed that C1 attenuated cognitive impairment and mitigated pathological damage in APP/PS1 mice. Furthermore, we found that C1 prevented oxidative stress damage and decreased the levels of pyroptosis-related proteins. In vitro experiments showed that C1 can improve the proliferation of Aβ-induced HT22 cells and decrease the levels of pyroptosis-related proteins in them. When Nrf2 was silenced, the positive effects of C1 in inhibiting pyroptosis were inhibited. Particularly, the production of pyroptosis-associated proteins, including NLRP3, GSDMD, and caspase-1, and the secretion of pro-inflammatory molecules, including IL-1 and IL-18, were increased. Altogether, these findings indicate that C1 can mitigate AD-like pathology via the inhibition of pyroptosis by activating the Nrf2 pathway. We believe that this study can provide alternative strategies for the prevention and treatment of AD.