Prevalence Of Alzheimer's Disease Research Articles

Secular trends in the prevalence of dementia based on a community-based complete enumeration in Japan: the Nakayama Study.

BackgroundThe number of dementia patients is increasing worldwide, especially in Japan, which has the world's highest ageing population. The increase in the number of older people with dementia is a medical and socioeconomic problem that needs to be prevented, but the actual situation is still not fully understood.MethodsFour cross‐sectional studies on dementia were conducted in 1997, 2004, 2012, and 2016 for complete enumeration of all residents aged 65 years and older. We examined the secular trends in the prevalence of all‐cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and other/unclassified dementia.ResultsThe age‐standardised prevalence of all‐cause dementia significantly increased (4.5% in 1997, 5.7% in 2004, 5.3% in 2012, 9.5% in 2016; P for trend <0.05). Similar trends were observed for AD (1.7%, 3.0%, 2.5% and 4.9%, respectively; P for trend <0.05) and other/unclassified dementia (0.8%, 1.0%, 1.0% and 2.2%, respectively; P for trend <0.05), whereas no significant change in VaD was seen (2.1%, 1.8%, 1.8%, 2.4%, respectively; P for trend = 0.77). The crude prevalence of all‐cause dementia and AD increased from 1997 to 2016 among participants aged 75–79 years and ≥85 years (all P for trend <0.05). Similar trends were observed for other/unclassified dementia among participants aged ≥80 years (all P for trend <0.05), but not in VaD.ConclusionsThe prevalence of dementia has increased beyond the ageing of the population, suggesting that factors in addition to ageing are involved in the increase in the number of older people with dementia. To control the increase in the number of older people with dementia, elucidation of secular trends in the incidence, mortality, and prognosis of dementia as well as the factors that promote and protect against dementia, and development of preventive strategies are necessary.

TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study

ObjectivesAnkylosing spondylitis (AS) is a chronic progressive and debilitating form of arthritis with associated extra-articular features including uveitis, intestinal and lung apical inflammation and psoriasis. Putative associations between AS and neurologic disorders has been relatively overlooked. The purpose of this study is to assess the link between AS and major neurologic disorders and whether treatment with Tumor-Necrosis-Factor inhibitors (TNFi) has an impact on that association. MethodsA retrospective cross-sectional study was carried out based on the Clalit Health Services (CHS) computerized database. AS patients were compared to age- and gender-matched controls with respect to the proportion of Alzheimer’s disease (AD), Parkinson's disease (PD), epilepsy, and multiple sclerosis (MS). The impact of AS therapy (biologic vs conventional therapy) was assessed as well. Results4082 AS patients and 20,397 age- and gender-matched controls were identified. AS was associated with a higher prevalence of AD (odds-ratio(OR) 1.46 [95%Confidence-interval(CI) 1.13–1.87], p = 0.003), epilepsy (OR 2.33 [95%CI 1.75–3.09] p < 0.0001) and PD (OR 2.75 [95%CI 2.04–3.72], p < 0.0001), whereas no statistically significant association was found for MS. Association with PD remained significant in the multivariate analysis (OR 1.49 [95%CI 1.05–2.13],p = 0.027). Within AS patients, the use of TNFi (OR 0.10 [95%CI 0.01–0.74], p = 0.024) were associated with a lowered risk of developing AD. ConclusionAS is positively associated with AD, PD, and epilepsy but not MS. AS patients treated with TNFi have lower rates of AD.

Annual Trends in the Incidence and Prevalence of Alzheimer's Disease in South Korea: A Nationwide Cohort Study.

Despite recent studies suggesting a declining incidence and prevalence of dementia on a global scale, epidemiologic results with respect to Alzheimer's disease (AD) are lacking due to the methodological limitations inherent to conducting large-scale cohort investigations of this topic. The aim of the current study was to investigate the incidence and prevalence of AD in Korea. We conducted a secondary analysis within the National Health Insurance System (NHIS) database, a unique resource that reports medical information for the entire Korean population. AD diagnoses as well as evaluations of vascular risks were defined based on International Statistical Classification of Diseases (ICD-10) codes along with prescription records. The cut-off age for diagnosing AD was defined as the age of the patient's highest Youden index. In this study, the incidence and prevalence of AD in the Korean population aged 40 years or older showed an overall increase between 2006 and 2015. Although both older and younger age groups showed an increase in the incidence and prevalence of AD, the highest increase was observed in older age groups. Based on the highest Youden's index value (sensitivity + specificity – 1), the cut-off value for the diagnosis of AD was 69 years with an area under the curve (AUC) of 0.92. We found that the incidence of AD was higher in individuals with underlying vascular risks. However, in recent years, the prevalence of AD was conversely found to be lower in individuals with hypertension or dyslipidemia. Despite efforts toward reducing the number of AD cases through educational, policy, and various public health and preventive medicine interventions, the incidence and prevalence of AD continues to grow in Korea. Efforts aimed at early diagnosis and the modification of underlying risks may be critical to reducing the socioeconomic burden of AD.

Alzheimer's Disease-Related Dysbiosis Might Be Triggered by Certain Classes of Antibiotics with Time-Lapse: New Insights into the Pathogenesis?

Several putative factors are identified in the literature as causative agents or risk factors for the development of Alzheimer's disease (AD). The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades, but recent studies raised the possible role of dysbiosis in the development of AD, which prevents memory loss. Finding possible associations between antibiotic consumption patterns and the prevalence of AD in European countries. Antibiotic consumption (European Centre for Disease Prevention and Control, ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, has been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the years 1997-2007 (r: 0.37, p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-2018, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (r: 0.406, p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (r: 0.344, p: 0.063), but none for the years 1997-2007 (r: 0.256, p: 0.241). Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Gene‐to‐gene damaging variant rate analysis uncovers novel Alzheimer’s disease‐associated genes

Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disease that exacts a heavy toll on our social and health care systems. AD is presumably caused by pathogenic variants in a large number of genes working in concert with environmental factors and personal behaviors. However, despite years of worldwide efforts, only a few dozen AD‐associated genes have been identified to date. Employing the gene‐to‐gene damaging variant rate (g2gDVR) analysis of published datasets containing 181,388 subjects we discovered 2114 potentially AD‐associated genes, of which 711 were linked to the higher AD prevalence among African‐Americans. The DVRs of these genes in AD population (55,460 subjects found in NIAGADS) were at least two‐fold higher than those in the general population (125,748 subjects in gnomAD) with false discovery rate less than 1x10‐12. The advantage of the g2gDVR method for studies of disease is that it focuses on variants expected to impact gene function, in contrast to methods based on SNP analysis, such as GWAS, that are gene‐agnostic. In combination with transcriptome profiling of 21 brain regions from 2728 human AD and control samples (collected from various GEO datasets) we identified three of the 711 genes (GNB5, SNAP91 and AKAP11) that were candidate causative genes based on their reduced expression in both hippocampus and entorhinal cortex regions of AD patient brains. In the context of the APP/PSEN1 mouse model of AD, we further confirmed that Gnb5 heterozygosity exacerbates the formation of both amyloid plaques and neurofibrillary tangles, the hallmarks of AD brain neuropathology. These results suggested that the g2gDVR analysis method is highly effective in identification of AD‐associated genes and is expected to be broadly applicable to other polygenic diseases.

The neuroprotective effects of oxygen therapy in Alzheimer’s disease: a narrative review

Alzheimer’s disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD. Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Multiple cellular processes synergistically promote hypoxia, including aging, hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, and traumatic brain injury. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Treatments targeting hypoxia may delay or mitigate the progression of AD. Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD. Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism, tau phosphorylation, neuroinflammation, neuronal apoptosis, oxidative stress, neurotrophic factors, mitochondrial function, cerebral blood volume, and protein synthesis. In this review, we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations. We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

Dapsone is an anticatalysis for Alzheimer’s disease exacerbation

SummaryBrain inflammation generally accelerates neurodegeneration. Alzheimer’s disease (AD) triggers an innate immune response by activating a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. Our study investigated patients with leprosy and AD. They were treated with dapsone (4,4′-diaminodiphenyl sulfone, DDS) as a neuroinflammasome competitor and cGAS/STING pathway inhibitor. Four groups were defined: Treatment (T) 1: DDS prescribed AD diagnosed, T 2: DDS prescribed AD undiagnosed, T 3 DDS unprescribed AD diagnosed, and T 4: DDS unprescribed AD undiagnosed. Dapsone effects on AD can be clearly distinguished according to dapsone presence or absence. T1:T3 proved that the incidence of AD was significantly reduced by dapsone. T2:T3 proved that the prevalence of AD was significantly high without dapsone. T1:T4 proved that the prevalence decreased when taking dapsone. Our study demonstrates that dapsone can prevent AD exacerbation and may represent a preventive therapeutic option for exacerbated AD.

Animal Models of Neurodegenerative Disease: Recent Advances in Fly Highlight Innovative Approaches to Drug Discovery.

Neurodegenerative diseases represent a formidable challenge to global health. As advances in other areas of medicine grant healthy living into later decades of life, aging diseases such as Alzheimer's disease (AD) and other neurodegenerative disorders can diminish the quality of these additional years, owed largely to the lack of efficacious treatments and the absence of durable cures. Alzheimer's disease prevalence is predicted to more than double in the next 30 years, affecting nearly 15 million Americans, with AD-associated costs exceeding $1 billion by 2050. Delaying onset of AD and other neurodegenerative diseases is critical to improving the quality of life for patients and reducing the burden of disease on caregivers and healthcare systems. Significant progress has been made to model disease pathogenesis and identify points of therapeutic intervention. While some researchers have contributed to our understanding of the proteins and pathways that drive biological dysfunction in disease using in vitro and in vivo models, others have provided mathematical, biophysical, and computational technologies to identify potential therapeutic compounds using in silico modeling. The most exciting phase of the drug discovery process is now: by applying a target-directed approach that leverages the strengths of multiple techniques and validates lead hits using Drosophila as an animal model of disease, we are on the fast-track to identifying novel therapeutics to restore health to those impacted by neurodegenerative disease.

A Concise Overview of Biosensing Technologies for the Detection of Alzheimer's Disease Biomarkers.

Alzheimer's disease (AD) is a brain-linked pathophysiological condition with neuronal degeneration and cognition dysfunctions and other debilitations. Due to the growing prevalence of AD, there is a highly commended trend to accelerate and develop analytical technologies for easy, costeffective, and sensitive detection of AD biomarkers. Biosensors are commanding analytical devices that can conduct biological responses on transducers into measurable signals. This review focuses on up-todate developmets, contests, and tendencies regarding AD biosensing principally, with the emphasis on the exclusive possessions of nanomaterials. In the last decade, remarkable advancements have been achieved to the progression of biosensors, predominantly optical and electrochemical, for the detection of AD biomarkers. These analytical devices can assist the case finding and management of AD.

The war against Alzheimer, the mitochondrion strikes back!

Alzheimer's disease (AD) is a leading neurodegenerative pathology associated with aging worldwide. It is estimated that AD prevalence will increase from 5.8 million people today to 13.8 million by 2050 in the United States alone. AD effects in the brain are well known; however, there is still a lack of knowledge about the cellular mechanisms behind the origin of AD. It is known that AD induces cellular stress affecting the energy metabolism in brain cells. During the pathophysiological advancement of AD, damaged mitochondria enter a vicious cycle, producing reactive oxygen species (ROS), harming mitochondrial DNA and proteins, leading to more ROS and cellular death. Additionally, mitochondria are interconnected with the plaques formed by amyloid-β in AD and have underlying roles in the progression of the disease and severity. For years, the biomedical field struggled to develop new therapeutic options for AD without a significant advancement. However, mitochondria are striking back existing outside cells in a new mechanism of intercellular communication. Extracellular mitochondria are exchanged from healthy to damaged cells to rescue those with a perturbed metabolism in a process that could be applied as a new therapeutic option to repair those brain cells affected by AD. In this review we highlight key aspects of mitochondria’s role in CNS’ physiology and neurodegenerative disorders, focusing on AD. We also suggest how mitochondria strikes back as a therapeutic target and as a potential agent to be transplanted to repair neurons affected by AD.

Transcript levels in plasma contribute substantial predictive value as potential Alzheimer's disease biomarkers in African Americans.

SummaryBackgroundAfrican Americans (AA) remain underrepresented in Alzheimer's disease (AD) research, despite the prevalence of AD being double in AA compared to non-Hispanic whites. To address this disparity, our group has established the Florida Consortium for African American Alzheimer's Disease Studies (FCA3DS), focusing on the identification of genetic risk factors and novel plasma biomarkers.MethodUtilizing FCA3DS whole exome sequence (WES) and plasma RNA samples from AD cases (n=151) and cognitively unimpaired (CU) elderly controls (n=269), we have performed differential gene expression (DGE) and expression quantitative trait locus (eQTL) analyses on 50 transcripts measured with a custom nanoString® panel. We designed this panel to measure, in plasma, cell-free mRNA (cf-mRNA) levels of AD-relevant genes.FindingsAssociation with higher plasma CLU in CU vs. AD remained significant after Bonferroni correction. Study-wide significant eQTL associations were observed with 105 WES variants in cis with 22 genes, including variants in genes previously associated with AD risk in AA such as ABCA7 and AKAP9. Results from this plasma eQTL analysis identified AD-risk variants in ABCA7 and AKAP9 that are significantly associated with lower and higher plasma mRNA levels of these genes, respectively. Receiver operating characteristic analysis of age, sex APOE-ε4 dosage, CLU, APP, CD14, ABCA7, AKAP9 and APOE mRNA levels, and ABCA7 and AKAP9 eQTLs, achieved 77% area under the curve to discriminate AD vs. CU, an 8% improvement over a model that only included age, sex and APOE-ε4 dosage.InterpretationIncorporating plasma mRNA levels could contribute to improved predictive value of AD biomarker panels.FundingThis work was supported by the National Institute on Aging [RF AG051504, U01 AG046139, R01 AG061796 to NET; P30 AG062677 to JAL and NGR]; Florida Health Ed and Ethel Moore Alzheimer's Disease grants [5AZ03 and 7AZ17 to NET; 7AZ07 to MMC; 8AZ08 to JAL].

Sex Differences in the Metabolome of Alzheimer's Disease Progression.

Alzheimer's disease (AD) is the leading cause of dementia; however, men and women face differential AD prevalence, presentation, and progression risks. Characterizing metabolomic profiles during AD progression is fundamental to understand the metabolic disruptions and the biological pathways involved. However, outstanding questions remain of whether peripheral metabolic changes occur equally in men and women with AD. Here, we evaluated differential effects of metabolomic and brain volume associations between sexes. We used three cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI), evaluated 1,368 participants, two metabolomic platforms with 380 metabolites in total, and six brain segment volumes. Using dimension reduction techniques, we took advantage of the correlation structure of the brain volume phenotypes and the metabolite concentration values to reduce the number of tests while aggregating relevant biological structures. Using WGCNA, we aggregated modules of highly co-expressed metabolites. On the other hand, we used partial least squares regression-discriminant analysis (PLS-DA) to extract components of brain volumes that maximally co-vary with AD diagnosis as phenotypes. We tested for differences in effect sizes between sexes in the association between single metabolite and metabolite modules with the brain volume components. We found five metabolite modules and 125 single metabolites with significant differences between sexes. These results highlight a differential lipid disruption in AD progression between sexes. Men showed a greater negative association of phosphatidylcholines and sphingomyelins and a positive association of VLDL and large LDL with AD progression. In contrast, women showed a positive association of triglycerides in VLDL and small and medium LDL with AD progression. Explicitly identifying sex differences in metabolomics during AD progression can highlight particular metabolic disruptions in each sex. Our research study and strategy can lead to better-tailored studies and better-suited treatments that take sex differences into account.

Endogenous and Exogenous Estrogen Exposures: How Women's Reproductive Health Can Drive Brain Aging and Inform Alzheimer's Prevention.

After advanced age, female sex is the major risk factor for late-onset Alzheimer’s disease (AD), the most common cause of dementia affecting over 24 million people worldwide. The prevalence of AD is higher in women than in men, with postmenopausal women accounting for over 60% of all those affected. While most research has focused on gender-combined risk, emerging data indicate sex and gender differences in AD pathophysiology, onset, and progression, which may help account for the higher prevalence in women. Notably, AD-related brain changes develop during a 10–20 year prodromal phase originating in midlife, thus proximate with the hormonal transitions of endocrine aging characteristic of the menopause transition in women. Preclinical evidence for neuroprotective effects of gonadal sex steroid hormones, especially 17β-estradiol, strongly argue for associations between female fertility, reproductive history, and AD risk. The level of gonadal hormones to which the female brain is exposed changes considerably across the lifespan, with relevance to AD risk. However, the neurobiological consequences of hormonal fluctuations, as well as that of hormone therapies, are yet to be fully understood. Epidemiological studies have yielded contrasting results of protective, deleterious and null effects of estrogen exposure on dementia risk. In contrast, brain imaging studies provide encouraging evidence for positive associations between greater cumulative lifetime estrogen exposure and lower AD risk in women, whereas estrogen deprivation is associated with negative consequences on brain structure, function, and biochemistry. Herein, we review the existing literature and evaluate the strength of observed associations between female-specific reproductive health factors and AD risk in women, with a focus on the role of endogenous and exogenous estrogen exposures as a key underlying mechanism. Chief among these variables are reproductive lifespan, menopause status, type of menopause (spontaneous vs. induced), number of pregnancies, and exposure to hormonal therapy, including hormonal contraceptives, hormonal therapy for menopause, and anti-estrogen treatment. As aging is the greatest risk factor for AD followed by female sex, understanding sex-specific biological pathways through which reproductive history modulates brain aging is crucial to inform preventative and therapeutic strategies for AD.

Diabetic Retinopathy Predicts Risk of Alzheimer's Disease: A Danish Registry-Based Nationwide Cohort Study.

Background:Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD).Objective:To investigate diabetes and DR as a risk marker of present and incident AD.Methods:A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes.Results:At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59–0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81–0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08–1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18–1.53).Conclusion:Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR.

Perspective: Estrogen and the Risk of Cognitive Decline: A Missing Choline(rgic) Link?

ABSTRACTFactors that influence the risk of neurocognitive decline and Alzheimer's disease (AD) may provide insight into therapies for both disease treatment and prevention. Although age is the most striking risk factor for AD, it is notable that the prevalence of AD is higher in women, representing two-thirds of cases. To explore potential underlying biological underpinnings of this observation, the intent of this article is to explore the interplay between cognitive aging and sex hormones, the cholinergic system, and novel hypotheses related to the essential nutrient choline. Mechanistic evidence points toward estrogen's neuroprotective effects being strongly dependent on its interactions with the cholinergic system, a modulator of attentional functioning, learning, and memory. Estrogen has been shown to attenuate anticholinergic-induced impairments in verbal memory and normalize patterns of frontal and occipital cortex activation, resulting in a more “young adult” phenotype. However, similar to estrogen replacement's effect in cardiovascular diseases, its putative protective effects may be restricted to early postmenopausal women only, a finding supportive of the “critical window hypothesis.” Estrogen's impact on the cholinergic system may act both locally in the brain but also through peripheral tissues. Estrogen is critical for inducing endogenous choline synthesis via the phosphatidylethanolamine N-methyltransferase (PEMT) gene–mediated pathway of phosphatidylcholine (PC) synthesis. PEMT is dramatically induced in response to estrogen, producing not only a PC molecule and source of choline for the brain but also a key source of the long-chain ω-3 fatty acid, DHA. Herein, we highlight novel hypotheses related to hormone replacement therapy and nutrient metabolism aimed at directing future preclinical and clinical investigation.

Coconut oil as a therapeutic treatment for alzheimer's disease: a review

The coconut tree ( Cocos nucifera ) which is also known as the “Tree of life” has its own values in each part of the tree and coconut oil is more prestigious among them. At present, the consumption of coconut oil is booming all around the world owing to its tremendous health benefits. The unique chemical composition of coconut oil enriched with medium chain fatty acids (MCFAs) has led to the exploration of these nutritional and therapeutic influences. Unlike the long chain fatty acids (LCFAs), the MCFAs generated from the digestion of medium chain triglycerides (MCTs) has a specific pathway for the metabolism, as it bypasses the lymphatic system and enter the liver directly through the portal vein. Due to such distinct attributes in absorption and metabolism, MCTs are readily capable of forming ketone bodies than other triglycerides. These ketone bodies are a competent energy source for the brains, especially those having cognitive impairments like Alzheimer's disease (AD). AD is a neurodegenerative disease characterized clinically by accelerating shortfalls in memory and behavioral changes. The principal biochemical hallmarks behind the pathogenesis of AD are the development of extracellular amyloid β plaques and the accumulation of intracellular neurofibrillary tangles. Occurrence of Cardiovascular diseases (CVD) with elevated LDL levels, hypertension, Type 2 diabetes, obesity, and insulin resistance are some key risk factors that are responsible for the increasing prevalence and incidence of AD. There is sufficient evidence to prove that MCTs in coconut oil are metabolized and absorbed in such a way that retards the severity of these physiological risk factors. Besides, coconut oil is endowed with many polyphenolic compounds that are serving as antioxidants by combating oxidative stress and inflammation, which in turn downregulates the etiology of AD. But depending on the different processing conditions applied in extraction techniques of coconut oil, variations in antioxidant capacity can take place. Even though there are inadequacies in peer-reviewed large cohort clinical data for the long run, this article reviews that coconut oil, its constituents, and metabolism have positive findings on the potentiality to treat AD as a nutritional supplement.

Prevalence of Alzheimer's disease and related dementias among older US Medicare beneficiaries with and without HIV: a successive cross-sectional study

BackgroundNearly 50% of people with HIV have at least mild cognitive impairment, even when they are taking suppressive antiretroviral therapy (ART). There is growing concern among HIV researchers that people with HIV will have a disproportionate burden of dementia as they age; however, there is no nationwide population-based research data on changes in trend over time in Alzheimer's disease and related dementias (ADRD) prevalence among older people with HIV versus people without HIV. MethodsWe used 100% of beneficiaries with HIV diagnosis and a 5% national sample of Medicare enrollees in 2007–19 from all 50 US states and District of Columbia. All individuals who reached age 65 years in the calendar year and had at least 3 years of fees for service coverage were included in the denominator. All ADRD cases were identified by International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) and International Classification of Diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis codes. Prevalence of ADRD was calculated in successive cross-sectional cohorts for each calendar year. Joinpoint regression analysis was performed to compute the average annual percentage change (AAPC) in ADRD prevalence by sex and age groups (65–69, 70–74, 75–79, and ≥80 years) for people with and without HIV, respectively. FindingsWe identified 26 887 and 608 141 ADRD-prevalent cases in all years among 87 216 people with HIV and 2 289 831 people without HIV, respectively. In the overall sample, 55·6% of beneficiaries were female, 84·5% were White, and 8·9% were Black. Mean age at entering the cohort was 73·3 (SD 8·1), More people with HIV were male (65·7%; 34·3% female) compared with people without HIV (43·6%; 56·4%). Mean age was 72·6 (6·7) years for male beneficiaries without HIV, 74·0 (7·8) for female beneficiaries without HIV, 70·0 (5·7) for male beneficiaries with HIV, and 72·8 (7·7) for female beneficiaries with HIV. There were more Black beneficiaries among people with HIV than among people without HIV (7·6%, 8·4%, 30·7%, and 37·1%, respectively). The prevalence of ADRD increased over years among older age groups (≥70 years) especially for people with HIV and female beneficiaries. Among people aged 80 years or older, ADRD prevalence increased from 26·2% to 33·3% for male beneficiaries with HIV and 31·4% to 44·1% for female beneficiaries with HIV, and from 21·0% to 23·5% for male beneficiaries without HIV and 27·4% to 29·9% for female beneficiaries without HIV. The AAPCs for the entire study duration by age groups were highest among female beneficiaries with HIV (range 1·2% [95% CI 0·6 to 1·8] to 3·1% [2·3 to 3·9]), whereas AAPCs estimates among female beneficiaries without HIV ranged from 0% (–0·3 to 0·3) to 0·9% (0·3 to 1·4). InterpretationPeople with HIV had a higher prevalence of ADRD, which increased over time in both male and female beneficiaries, compared with people without HIV. However, the magnitude of the increase was more prominent in female beneficiaries and with increasing age, indicating an increase in the dementia burden over 13 years among people with HIV, especially those who are female and aged 80 years or older. The findings underscore the need to develop clinical practice guidelines that facilitate integration of dementia screening and evaluation into routine primary care of ageing people with HIV, thus targeting resources to the most clinically vulnerable population. Future research is needed to understand factors associated with the increase in dementia among people with HIV. FundingXY and ABB are supported by a research career development award (K12HD052023; primary investigator ABB). XY is also supported by Sustained Training in Aging and HIV Research (R25MH108389; primary investigators Dilip V Jeste and Scott L Letendre. TPG is supported by the MD Anderson Foundation Chair at Baylor College of Medicine and Texas Developmental Center for AIDS Research (P30AI161943; primary investigator TPG).

Relationship between Oral Microbiota and Alzheimer's Disease

Alzheimer's disease (AD) is a common neurodegenerative disease. In an aging society, the high prevalence of AD and the low quality of life of AD patients create serious problems for individuals, families and the society. However, the etiology and pathogenesis of AD are still not fully understood. Age, genetics, environment and other factors are all relevant to AD, and treatment has not achieved satisfactory results. Recent studies have found that oral dysbiosis is closely related to the pathogenesis of AD, and that oral bacterial infection may be one of the causes of AD. Oral cavity is the largest microbial ecosystem of human body, and its homeostasis is critical to health. Bacterial infections caused by oral dysbiosis can directly and indirectly induce the metabolic imbalance of amyloid β-protein (Aβ) in the brain and the hyperphosphorylation of Tau protein. Then, the precipitation forms senile plaques and neurofibrillary tangles (NFTs) that damage neurons. Based on the latest research findings, we herein discussed the correlation between oral microbiota and the pathogenesis of AD and the mechanisms involved, as well as the pathogenic mechanism of main oral bacteria. In addition, we explored the potential application prospects of oral microbiota-targeted therapy.

Genetic Effects of NDUFAF6 rs6982393 and APOE on Alzheimer's Disease in Chinese Rural Elderly: A Cross-Sectional Population-Based Study.

PurposeTo investigate the associations of genotypes of NDUFAF6 rs6982393 and APOE and their combined genotypes with the risk of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) in Chinese rural elderly.MethodsThis cross-sectional population-based study included 5096 older adults (age ≥60 years, 57.1% female). Genotypes of NDUFAF6 rs6982393 and APOE were detected using the multiple-polymerase chain reaction amplification. We diagnosed AD following the criteria of Diagnostic and Statistical Manual of Mental Disorders, the fourth edition and diagnosed MCI following the Petersen’s criteria MCI. Data were analyzed using the logistic regression model.ResultsThe overall prevalence of AD and MCI was 3.57% (95% confidence interval [CI]: 0.040, 0.053) and 22.65% (95% CI: 0.223, 0.247), separately. The TT versus CC/CT genotype of NDUFAF6 rs6982393 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 1.61 (1.02, 2.54) in the total sample, 3.36 (1.48, 7.60) in those aged 60–69, and 1.24 (0.71, 2.17) in those aged 70 years and above. The interaction between genotype of NDUFAF6 rs6982393 with age groups (60–69 versus ≥70 years) was significant on the risk of AD. The presence of APOE ε4 was not significantly associated with the risk of AD. Carrying both NDUFAF6 TT and APOE ε4 was related to a higher risk of AD with the multi-adjusted odds ratio (95% CI) being 2.69 (1.10, 2.56). In addition, there was no significant association between the above genotypes and MCI.ConclusionIn Chinese rural elderly, the TT versus CT/CC genotype of NDUFAF6 rs6982393 was associated with an increased likelihood of AD; such an association only existed among young-old adults. Carrying both NDUFAF6 rs6982393-TT and APOE ε4 was related to a higher risk of AD. This finding highlights the importance of considering age and combined genotype in studying the genetic profiles of AD.

Periodontal Infection Aggravates C1q-Mediated Microglial Activation and Synapse Pruning in Alzheimer's Mice.

Periodontitis is a dysbiotic infectious disease that leads to the destruction of tooth supporting tissues. There is increasing evidence that periodontitis may affect the development and severity of Alzheimer’s disease (AD). However, the mechanism(s) by which periodontal infection impacts the neurodegenerative process in AD remains unclear. In the present study, using an amyloid precursor protein (APP) knock-in (App KI) AD mouse model, we showed that oral infection with Porphyromonas gingivalis (Pg), a keystone pathogen of periodontitis, worsened behavioral and cognitive impairment and accelerated amyloid beta (Aβ) accumulation in AD mice, thus unquestionably and significantly aggravating AD. We also provide new evidence that the neuroinflammatory status established by AD, is greatly complicated by periodontal infection and the consequential entry of Pg into the brain via Aβ-primed microglial activation, and that Pg-induced brain overactivation of complement C1q is critical for periodontitis-associated acceleration of AD progression by amplifying microglial activation, neuroinflammation, and tagging synapses for microglial engulfment. Our study renders support for the importance of periodontal infection in the innate immune regulation of AD and the possibility of targeting microbial etiology and periodontal treatment to ameliorate the clinical manifestation of AD and lower AD prevalence.