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Abstract The Plasmodium is responsible for malaria which poses a major health threat, globally. This study is based on the estimation of the relative abundance of mosquitoes, and finding out the correlations of meteorological parameters (temperature, humidity and rainfall) with the abundance of mosquitoes. In addition, this study also focused on the use of nested PCR (species-specific nucleotide sequences of 18S rRNA genes) to explore the Plasmodium spp. in female Anopheles. In the current study, the percentage relative abundance of Culex mosquitoes was 57.65% and Anopheles 42.34% among the study areas. In addition, the highest number of mosquitoes was found in March in district Mandi Bahauddin at 21 °C (Tmax = 27, Tmin = 15) average temperature, 69% average relative humidity and 131 mm rainfall, and these climatic factors were found to affect the abundance of the mosquitoes, directly or indirectly. Molecular analysis showed that overall, 41.3% of the female Anopheles pools were positive for genus Plasmodium. Among species, the prevalence of Plasmodium (P.) vivax (78.1%) was significantly higher than P. falciparum (21.9%). This study will be helpful in the estimation of future risk of mosquito-borne diseases along with population dynamic of mosquitoes to enhance the effectiveness of vector surveillance and control programs.

Telehealth facility was launched to extend veterinary services throughout Kashmir valley. It was also desired for continuation of veterinary internship during the COVID-19 lock-down period. A total of 714 response forms were received from the participating veterinary faculty of clinical disciplines in six months. The majority (n=504, 70.6%) of the cases pertained to the dairy cattle. Thirty per cent (n=9/30) of the designated specialists participated. The tele-health facility was availed by interns (44.25%), farmers/animal owners (36.51%), field veterinarians (15.28%) and the para-veterinarians (3.97%) in significantly decreasing order. Telephone mobile calls, WhatsApp messages (text, photos and videos), and the SMS text messages were the platforms used. The animals with medical problems (67.66%) were significantly more than those showing gynaecological (18.25%) and surgical (14.09%) ailments. More than half (52.58%) of the cases were reported from the nearby three districts. The remaining (47.42%) animal owners resided in rest of the seven districts. Most of the complaints pertained to skin and appendages (27.18%), alimentary (25.79%) and reproductive tract (18.25%) in the affected cattle respectively. Udder and teat affections, metabolic diseases, and repeat breeding were tentatively diagnosed in majority of the cows. From this preliminary study, it is concluded that the veterinary telehealth service can reach far-off places and education can be continued amidst lockdown period. Short duration and lack of the follow up details are the weakness of this study. Additionally, more veterinary specialists need be persuaded to participate in telehealth modality.

Abstract Introduction People with Down's syndrome (DS) have a high prevalence of early‐onset Alzheimer's disease. Early markers of Alzheimer's disease pathology identifiable before clinical change are needed for the evaluation of preventative treatments. The retina, an extension of the brain, may provide a noninvasive imaging site. Methods Forty‐nine adults with DS and 36 age‐matched controls completed retinal nerve fibre layer (RNFL) assessments using optical coherence tomography. RNFL thickness was analyzed in relation to cognitive status and age and previously acquired cortical thickness and cerebral amyloid β binding data in a subgroup. Results RNFL thickness was greater in the DS group and did not show age‐related thinning. RNFL correlated positively with cognitive scores and cortical thickness and was reduced in participants with positive cerebral amyloid β binding. Discussion Increased RNFL in adults with DS may represent early Alzheimer's disease–related changes. Thinning was present in those with cerebral amyloid β binding, independent of age.

Abstract Introduction Comorbid Alzheimer disease pathologies are frequently found in people with Down syndrome (DS). We report a deep phenotyping study undertaken over 7 years in a participant with DS who was nondemented at baseline but developed dementia after 5 years. Methods Throughout the course of the study, the participant was seen 4 times (2010, 2013, 2015, and 2017). Multimodal neuroimaging, including three serial scans of [11C]‐PiB‐PET, four structural magnetic resonance imagings, as well as a [18F]‐AV1451 scan, was interpreted alongside detailed neuropsychological assessments over the study period. Results Amyloid beta accumulation preceded the onset of dementia and cognitive decline, which in turn corresponded to the predominant deposition of tau in temporoparietal cortices. Discussion Until now, data on the longitudinal trajectories of amyloid accumulation, tau pathology, and brain atrophy over multiple time points remain scarce in DS. This case report highlights the potential for deep phenotyping imaging to elucidate the substrates of cognitive decline in DS, although further longitudinal studies are necessary to clarify the relative contributions of both amyloid and tau.

Background Diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in people with Down syndrome is a major challenge. The Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) has been validated for diagnosing prodromal Alzheimer's disease and Alzheimer's disease dementia, but the diagnostic process lacks guidance. Aims To derive CAMDEX-DS informant interview threshold scores to enable accurate diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in adults with Down syndrome. Method Psychiatrists classified participants with Down syndrome into no dementia, prodromal Alzheimer's disease and Alzheimer's disease dementia groups. Receiver operating characteristic analyses assessed the diagnostic accuracy of CAMDEX-DS informant interview-derived scores. Spearman partial correlations investigated associations between CAMDEX-DS scores, regional Aβ binding (positron emission tomography) and regional cortical thickness (magnetic resonance imaging). Results Diagnostic performance of CAMDEX-DS total scores were high for Alzheimer's disease dementia (area under the curve (AUC), 0.998; 95% CI 0.953–0.999) and prodromal Alzheimer's disease (AUC = 0.954; 95% CI 0.887–0.982) when compared with healthy adults with Down syndrome. When compared with those with mental health conditions but no Alzheimer's disease, CAMDEX-DS Section B scores, denoting memory and orientation ability, accurately diagnosed Alzheimer's disease dementia (AUC = 0.958; 95% CI 0.892–0.984), but were unable to diagnose prodromal Alzheimer's disease. CAMDEX-DS total scores exhibited moderate correlations with cortical Aβ (r ~ 0.4 to 0.6, P ≤ 0.05) and thickness (r ~ −0.4 to −0.44, P ≤ 0.05) in specific regions. Conclusions CAMDEX-DS total score accurately diagnoses Alzheimer's disease dementia and prodromal Alzheimer's disease in healthy adults with Down syndrome.

Flexible/biased cell association in uniform Heterogeneous Cellular Network (HCN) can lead to poor offloading, particularly near to the Macrocell Base Station (MBS). Additionally, in the cell-edge region, a user might offload to an SBS even if unbiased cell association is employed. In this paper, firstly, we consider a Non-uniform HCN (NuHCN) model in which SBSs are not deployed in a circular region around each MBS within a predefined radius, which we call the inner region. Secondly, we define the outer region, which is disjoint to the inner region, as the cell-edge region. In these two regions, based on maximum received power; we propose hard cell association scheme, where users located in the inner region shall only be served by MBS, whereas users located in the outer region shall be served only by SBS. Finally, for the region between the inner and the outer region, called the annular region, we shall use the flexible cell association scheme. Based on the proposed system model, analytical closed forms for the downlink coverage and single user throughput are derived. It is observed that with non-uniform deployment of SBSs and precisely selecting the size of inner, annular, and outer region, both coverage and single user throughput are significantly improved compared to uniform HCN.

The liver-derived hormone hepcidin, a member of the defensin family of antimicrobial peptides, plays an important role in host defense and innate immunity due to its broad antibacterial and antiviral properties. Ferritin, an iron storage protein is often associated with iron deficiency, hypoferritinemia, hypoxia, and immune complications, which are all significant concerns for systemic infection in Alzheimer’s disease (AD) and Down’s syndrome (DS) dementia. Serum and post-mortem brain samples were collected from AD, DS and age-matched control subjects. Serum samples were analyzed with ELISA for ferritin, hepcidin and IL-6. Additionally, post-mortem brain sections were assessed by immunohistochemistry for iron-related and inflammatory proteins. A significant increase in serum hepcidin levels was found in DS, compared to controls and AD subjects (p < 0.0001). Hepcidin protein was visible in the epithelial cells of choroid plexus, meningeal macrophages and in the astrocytes close to the endothelium of blood vessels. Hepcidin co-localized with IL-6, indicating its anti-inflammatory properties. We found significant correlation between hypoferritinemia and elevated levels of serum hepcidin in AD and DS. Hepcidin can be transported via macrophages and the majority of the vesicular hepcidin enters the brain via a compromised blood brain barrier (BBB). Our findings provide further insight into the molecular implications of the altered iron metabolism in acute inflammation, and can aid towards the development of preventive strategies and novel treatments in the fight against neuroinflammation.

Introduction: Adults with Down syndrome (DS) are predisposed to Alzheimer's disease (AD) and reveal early amyloid beta (Aβ) pathology in the brain. Positron emission tomography (PET) provides an in vivo measure of Aβ throughout the AD continuum. Due to the high prevalence of AD in DS, there is need for longitudinal imaging studies of Aβ to better characterize the natural history of Aβ accumulation, which will aid in the staging of this population for clinical trials aimed at AD treatment and prevention. Methods: Adults with DS (N = 79; Mean age (SD) = 42.7 (7.28) years) underwent longitudinal [C-11]Pittsburgh compound B (PiB) PET. Global Aβ burden was quantified using the amyloid load metric (AβL). Modeled PiB images were generated from the longitudinal AβL data to visualize which regions are most susceptible to Aβ accumulation in DS. AβL change was evaluated across Aβ(-), Aβ-converter, and Aβ(+) groups to assess longitudinal Aβ trajectories during different stages of AD-pathology progression. AβL change values were used to identify Aβ-accumulators within the Aβ(-) group prior to reaching the Aβ(+) threshold (previously reported as 20 AβL) which would have resulted in an Aβ-converter classification. With knowledge of trajectories of Aβ(-) accumulators, a new cutoff of Aβ(+) was derived to better identify subthreshold Aβ accumulation in DS. Estimated sample sizes necessary to detect a 25% reduction in annual Aβ change with 80% power (alpha 0.01) were determined for different groups of Aβ-status. Results: Modeled PiB images revealed the striatum, parietal cortex and precuneus as the regions with earliest detected Aβ accumulation in DS. The Aβ(-) group had a mean AβL change of 0.38 (0.58) AβL/year, while the Aβ-converter and Aβ(+) groups had change of 2.26 (0.66) and 3.16 (1.34) AβL/year, respectively. Within the Aβ(-) group, Aβ-accumulators showed no significant difference in AβL change values when compared to Aβ-converter and Aβ(+) groups. An Aβ(+) cutoff for subthreshold Aβ accumulation was derived as 13.3 AβL. The estimated sample size necessary to detect a 25% reduction in Aβ was 79 for Aβ(-) accumulators and 59 for the Aβ-converter/Aβ(+) group in DS. Conclusion: Longitudinal AβL changes were capable of distinguishing Aβ accumulators from non-accumulators in DS. Longitudinal imaging allowed for identification of subthreshold Aβ accumulation in DS during the earliest stages of AD-pathology progression. Detection of active Aβ deposition evidenced by subthreshold accumulation with longitudinal imaging can identify DS individuals at risk for AD development at an earlier stage.

Introduction: Adults with Down syndrome are genetically predisposed to develop Alzheimer’s disease and accumulate beta-amyloid plaques (Aβ) early in life. While Aβ has been heavily studied in Down syndrome, its relationship with neurofibrillary tau is less understood. The aim of this study was to evaluate neurofibrillary tau deposition in individuals with Down syndrome with varying levels of Aβ burden. Methods: A total of 161 adults with Down syndrome (mean age = 39.2 (8.50) years) and 40 healthy, non-Down syndrome sibling controls (43.2 (12.6) years) underwent T1w-MRI, [C-11]PiB and [F-18]AV-1451 PET scans. PET images were converted to units of standardized uptake value ratios (SUVrs). Aβ burden was calculated using the amyloid load metric (AβL); a measure of global Aβ burden that improves quantification from SUVrs by suppressing the nonspecific binding signal component and computing the specific Aβ signal from all Aβ-carrying voxels from the image. Regional tau was assessed using control-standardized AV-1451 SUVr. Control-standardized SUVrs were compared across Down syndrome groups of Aβ-negative (A-) (AβL

Abstract Introduction Adults with Down syndrome (DS) are predisposed to Alzheimer's disease (AD) and the relationship between cognition and glucose metabolism in this population has yet to be evaluated. Methods Adults with DS (N = 90; mean age [standard deviation] = 38.0 [8.30] years) underwent [C‐11]Pittsburgh compound B (PiB) and [F‐18]fluorodeoxyglucose (FDG) positron emission tomography scans. Associations among amyloid beta (Aβ), FDG, and measures of cognition were explored. Interregional FDG metabolic connectivity was assessed to compare cognitively stable DS and mild cognitive impairment/AD (MCI‐DS/AD). Results Negative associations between Aβ and FDG were evident in regions affected in sporadic AD. A positive association was observed in the putamen, which is the brain region showing the earliest increases in Aβ deposition. Both Aβ and FDG were associated with measures of cognition, and metabolic connectivity distinguished cases of MCI‐DS/AD from cognitively stable DS. Discussion Associations among Aβ, FDG, and cognition reveal that neurodegeneration in DS resembles sporadic AD with the exception of the putamen, highlighting the usefulness of FDG in monitoring neurodegeneration in DS.

Abstract Introduction Individuals with Down syndrome (DS) show enhanced amyloid beta (Aβ) deposition in the brain. A new positron emission tomography (PET) index of amyloid load (AβL) was recently developed as an alternative to standardized uptake value ratios (SUVrs) to quantify Aβ burden with high sensitivity for detecting and tracking Aβ change.1 Methods AβL was calculated in a DS cohort (N = 169, mean age ± SD = 39.6 ± 8.7 years) using [C‐11]Pittsburgh compound B (PiB) PET imaging. DS‐specific PiB templates were created for Aβ carrying capacity (K) and non‐specific binding (NS). Results The highest values of Aβ carrying capacity were found in the striatum and precuneus. Longitudinal changes in AβL displayed less variability when compared to SUVrs. Discussion These results highlight the utility of AβL for characterizing Aβ deposition in DS. Rates of Aβ accumulation in DS were found to be similar to that observed in late‐onset Alzheimer's disease (AD; ≈3% to 4% per year), suggesting that AD progression in DS is of earlier onset but not accelerated.

Abstract Introduction Virtually all individuals with Down syndrome (DS) will develop Alzheimer's disease (AD) pathology by age 40. Cerebrospinal fluid (CSF) biomarkers have characterized AD pathology in cohorts of late‐onset AD (LOAD) and autosomal‐dominant AD (ADAD). Few studies have evaluated such biomarkers in adults with DS. Methods CSF concentrations of amyloid beta (Aβ)40, Aβ42, tau, phospho‐tau181 (p‐tau), neurofilament light chain (NfL), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase‐3‐like protein 1 (YKL‐40), alpha synuclein (αSyn), neurogranin (Ng), synaptosomal‐associated protein 25 (SNAP‐25), and visinin‐like protein 1 (VILIP‐1) were assessed in CSF from 44 adults with DS from the Alzheimer's Biomarker Consortium–Down Syndrome study. Biomarker levels were evaluated by cognitive status, age, and apolipoprotein E gene (APOE) ε4 carrier status. Results Biomarker abnormalities indicative of amyloid deposition, tauopathy, neurodegeneration, synaptic dysfunction, and neuroinflammation were associated with increased cognitive impairment. Age and APOE ε4 status influenced some biomarkers. Discussion The profile of many established and emerging CSF biomarkers of AD in a cohort of adults with DS was similar to that reported in LOAD and ADAD, while some differences were observed.

Yanling Jin,1,* Nitika Sanger,2,* Ieta Shams,3,* Candice Luo,4,* Hamnah Shahid,5,* Guowei Li,1,* Meha Bhatt,1 Laura Zielinski,6 Bianca Bantoto,7 Mei Wang,1 Luciana PF Abbade,8 Ikunna Nwosu,4 Alvin Leenus,1 Lawrence Mbuagbaw,1 Muhammad Maaz,1 Yaping Chang,1 Guangwen Sun,1 Mitchell AH Levine,1,9 Jonathan D Adachi1,9 Lehana Thabane,1,9 Zainab Samaan1,10 1Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 2Department of Medical Science, Medical Sciences Graduate Program, McMaster University, Hamilton, ON, Canada; 3Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada; 4Faculty of Health Sciences, Bachelors of Health Sciences, McMaster University, Hamilton, ON, Canada; 5Department of Arts and Science, McMaster University, Hamilton, ON, Canada; 6Department of Neuroscience, McMaster Integrative Neuroscience Discovery and Study, McMaster University, Hamilton, ON, Canada; 7Department of Science, Honours Integrated Sciences Program, McMaster University, Hamilton, ON, Canada; 8Department of Dermatology and Radiotherapy, Botucatu Medical School, Universidade Estadual Paulista, UNESP, São Paulo, Brazil; 9St. Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 10Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada *These authors contributed equally to this work Purpose: Reporting guidelines (eg, Consolidated Standards of Reporting Trials [CONSORT] statement) are intended to improve reporting standards and enhance the transparency and reproducibility of research findings. Despite accessibility of such guidelines, researchers are not required to adhere to them. Our goal was to determine the current status of reporting quality in the medical literature and examine whether adherence of reporting guidelines has improved since the inception of reporting guidelines. Materials and methods: Eight reporting guidelines, such as CONSORT, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), STrengthening the Reporting of OBservational studies in Epidemiology (STROBE), Quality of Reporting of Meta-analysis (QUOROM), STAndards for Reporting of Diagnostic accuracy (STARD), Animal Research: Reporting In Vivo Experiments (ARRIVE), Consolidated Health Economic Evaluation Reporting Standards (CHEERS), and Meta-analysis of Observational Studies in Epidemiology (MOOSE) were examined. Our inclusion criteria included reviews published between January 1996 to September 2016 which investigated the adherence to reporting guidelines in the literature that addressed clinical trials, systematic reviews, observational studies, meta-analysis, diagnostic accuracy, economic evaluations, and preclinical animal studies that were in English. All reviews were found on Web of Science, Excerpta Medical Database (EMBASE), MEDLINE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Results: Among the general searching of 26,819 studies by using the designed searching method, 124 studies were included post screening. We found that 87.9% of the included studies reported suboptimal adherence to reporting guidelines. Factors associated with poor adherence included non-pharmacological interventions, year of publication, and trials concluding with significant results. Improved adherence was associated with better study designs such as allocation concealment, random sequence, large sample sizes, adequately powered studies, multiple authorships, and being published in journals endorsing guidelines. Conclusion: We conclude that the level of adherence to reporting guidelines remains suboptimal. Endorsement of reporting guidelines by journals is important and recommended. Keywords: guidelines, adherence, review, CONSORT

Atorvastatin calcium is a lipid-lowering agent. It has approximately 15% of bioavailability, remaining amount of drug showed adverse effect which is undesirable for patients. The objective of the study was to enhance the solubility and a dissolution profile of the atorvastatin (AT) calcium. Solid dispersion (SD) is a technique which enhances the solubility and a dissolution profile of poorly soluble drug. Various methods are being used for SDs such as microwave irradiation fusion, kneading, solvent evaporation, fusion, and dropping method. The authors have used here conventional fusion method using PEG 4000 as a hydrophilic carrier. The solubility of pure drug, physical mixture using PEG 4000 (1:3), and SD in phosphate buffer solutions (pH 6.8) was found to be 55.33 ± 0.66, 81.89 ± 2.35, and 93.66 ± 1.35, respectively. Fourier transform infrared and differential scanning calorimetry study showed the significant peak shift of drug in SD. It indicated that the nature of drug had been changed from crystalline form to amorphous form due to conversion into SD formulation. The dissolution rate was significantly increased when the drug polyethylene glycol 4000 ratio was 1:3. The mean cumulative percentage drugs release from pure drug, physical mixture, marketed tablet, and SD at 1 h was 28.92 ± 1.66%, 55.26 ± 0.95%, 72.16 ± 1.33%, and 91.66 ± 1.65%, respectively. It was concluded that the solubility and dissolution profile of SD of AT calcium showed the enhancement of solubility and dissolution when compared with marketed preparations.

Aralia species are used in traditional medicine to treat rheumatic arthritis, nephritis, lumbago, lameness, gastritis, inflammation and diabetes mellitus. Phytochemical investigation of the roots of Aralia cachemirica Decne (Araliaceae) collected from the Aharbal region of Kashmir afforded four new phytoconstituents identified as n-tetracont-19-enoic acid (1), 4α,4β,8β,10β,13β,17β-hexamethyl perhydrophenanthrenyl-3β-n-decanoate (3), tetrahydrocontinentalic acid (4) and 1β,4α,4β-trimethyl-6-(10,14,18-trimethyl-tridec-6-enyl)-cyclohexane-4β-ol (5) along with the known compounds continentalic acid (2), maltose (6) and sucrose (7). The structures of these phytoconstituents have been elucidated on the basis of spectral data analysis.

Purpose; Delayed presentation of lateral condylar fractures of the humerus is relatively common in the developing regions of the world. These fractures are difficult to manage because of the displacement and fibrosis around the condylar fragment secondary to the delay. There is a paucity of literature concerning the management of these fractures. An oft repeated finding is the requirement of extensive dissection around the fragment for proper reduction. The purpose of this study was to assess the efficacy of surgical management of lateral condylar fractures with delayed presentation. Methods; We assessed the results of lateral condylar fracture fixation in 20 cases with delayed presentation. Results; The lateral condylar fractures in patients with a delayed presentation can be managed surgically with good results. Conclusions; Open reduction and internal fixation should continue to be the method of choice for the management of lateral condylar fractures which report late for management.

Nutraceuticals are food or part of food that provides medical or health benefits including the prevention and/or treatment of a disease. Nutraceutical has advantage over the medicine because they avoid side effect, have naturally dietary supplement, etc. Nutraceutical; on the basis of their natural source, chemical grouping, categories into three key terms -nutrients, herbals, dietary supplements, dietary fiber, etc. The most rapidly growing segments of the industry were dietary supplements (19.5 percent per year) and natural/herbal products (11.6 percent per year). Global nutraceutical market is estimated as USD 117 billion. FDA regulated dietary supplements as foods to ensure that they were safe. In 2006, the Indian government passed Food Safety and Standard Act to regulate the nutraceutical industry. Herbal nutraceutical is used as a powerful instrument in maintaining health and to act against nutritionally induced acute and chronic diseases, thereby promoting optimal health, longevity, and quality of life.

Mutations in presenilin 1 (PS1) are the most common causes of familial Alzheimer's disease (FAD). We examined synaptic physiology in hippocampal brain slices of transgenic mice expressing the FAD-linked PS1 deletion of exon 9 variant. Basal excitatory transmission and paired-pulse facilitation in PS1 mutant mice were unchanged. Short- and long-term potentiation of excitatory transmission following high-frequency stimulation were greater in transgenic mice expressing mutant PS1. Mutants had enhanced synaptic inhibition, which may be a compensatory change offsetting an abnormally sensitized plasticity of excitatory transmission. Increasing inhibitory transmission in mutant animals even more with a benzodiazepine reverted synaptic potentiation to the levels of controls. These results support the potential use of benzodiazepines in the treatment of familial Alzheimer's disease.

Adults with Down syndrome develop the neuropathological hallmarks of Alzheimer's disease and are at very high risk of developing early-onset dementia, which is now the leading cause of death in this population. Diagnosis of dementia remains a clinical challenge because of the lack of validated diagnostic criteria in this population, and because symptoms are overshadowed by the intellectual disability associated with Down syndrome. In people with Down syndrome, fluid and imaging biomarkers have shown good diagnostic performances and a strikingly similar temporality of changes with respect to sporadic and autosomal dominant Alzheimer's disease. Most importantly, there are no treatments to prevent Alzheimer's disease, even though adults with Down syndrome could be an optimal population in whom to conduct Alzheimer's disease prevention trials. Unprecedented research activity in Down syndrome is rapidly changing this bleak scenario that will translate into disease-modifying therapies that could benefit other populations.

BackgroundAdults with Down syndrome are at an ultra-high risk of Alzheimer's disease, but diagnosis of Alzheimer's disease in this population is challenging. We aimed to validate the clinical utility of plasma neurofilament light chain (NfL) for the diagnosis of symptomatic Alzheimer's disease in Down syndrome, assess its prognostic value, and establish longitudinal changes in adults with Down syndrome.MethodsWe did a multicentre cohort study, including adults with Down syndrome (≥18 years), recruited from six hospitals and university medical centres in France, Germany, Spain, the UK, and the USA, who had been assessed, followed up, and provided at least two plasma samples. Participants were classified by local clinicians, who were masked to biomarker data, as asymptomatic (ie, no clinical suspicion of Alzheimer's disease), prodromal Alzheimer's disease, or Alzheimer's disease dementia. We classified individuals who progressed along the Alzheimer's disease continuum during follow-up as progressors. Plasma samples were analysed retrospectively; NfL concentrations were measured centrally using commercial kits for biomarker detection. We used ANOVA to evaluate differences in baseline NfL concentrations, Cox regression to study their prognostic value, and linear mixed models to estimate longitudinal changes. To account for potential confounders, we included age, sex, and intellectual disability as covariates in the analyses.FindingsBetween Aug 2, 2010, and July 16, 2019, we analysed 608 samples from 236 people with Down syndrome: 165 (70%) were asymptomatic, 32 (14%) had prodromal Alzheimer's disease, and 29 (12%) had Alzheimer's disease dementia; ten [4%] participants were excluded because their classification was uncertain. Mean follow-up was 3·6 years (SD 1·6, range 0·6-9·2). Baseline plasma NfL concentrations showed an area under the receiver operating characteristic curve of 0·83 (95% CI 0·76-0·91) in the prodromal group and 0·94 (0·90-0·97) in the dementia group for differentiating from participants who were asymptomatic. An increase of 1 pg/mL in baseline NfL concentrations was associated with a 1·04-fold risk of clinical progression (95% CI 1·01-1·07; p=0·0034). Plasma NfL concentrations showed an annual increase of 3·0% (95% CI 0·4-5·8) per year in the asymptomatic non-progressors group, 11·5% (4·9-18·5) per year in the asymptomatic progressors group, and 16·0% (8·4-24·0) per year in the prodromal Alzheimer's disease progressors group. In participants with Alzheimer's disease dementia, NfL concentrations increased by a mean of 24·3% (15·3-34·1).InterpretationPlasma NfL concentrations have excellent diagnostic and prognostic performance for symptomatic Alzheimer's disease in Down syndrome. The longitudinal trajectory of plasma NfL supports its use as a theragnostic marker in clinical trials.FundingAC Immune, La Caixa Foundation, Instituto de Salud Carlos III, National Institute on Aging, Wellcome Trust, Jérôme Lejeune Foundation, Medical Research Council, National Institute for Health Research, EU Joint Programme-Neurodegenerative Disease Research, Alzheimer's society, Deutsche Forschungsgemeinschaft, Stiftung für die Erforschung von Verhaltens und Umwelteinflüssen auf die menschliche Gesundheit, and NHS National Institute of Health Research Applied Research Collaborations East of England, UK.

Improved medical care of individuals with Down syndrome (DS) has led to an increase in life expectancy to over the age of 60 years. In conjunction, there has been an increase in age-related co-occurring conditions including Alzheimer's disease (AD). Understanding the factors that underlie symptom and age of clinical presentation of dementia in people with DS may provide insights into the mechanisms of sporadic and DS-associated AD (DS-AD). In March 2019, the Alzheimer's Association, Global Down Syndrome Foundation and the LuMind IDSC Foundation partnered to convene a workshop to explore the state of the research on the intersection of AD and DS research; to identify research gaps and unmet needs; and to consider how best to advance the field. This article provides a summary of discussions, including noting areas of emerging science and discovery, considerations for future studies, and identifying open gaps in our understanding for future focus.

INTRODUCTION: This study aimed to investigate the influence of the overall Alzheimer's disease (AD) genetic architecture on Down syndrome (DS) status, cognitive measures, and cerebrospinal fluid (CSF) biomarkers. METHODS: AD polygenic risk scores (PRS) were tested for association with DS‐related traits. RESULTS: The AD risk PRS was associated with disease status in several cohorts of sporadic late‐ and early‐onset and familial late‐onset AD, but not in familial early‐onset AD or DS. On the other hand, lower DS Mental Status Examination memory scores were associated with higher PRS, independent of intellectual disability and APOE (PRS including APOE, PRSAPOE, p = 2.84 × 10−4; PRS excluding APOE, PRSnonAPOE, p = 1.60 × 10−2). PRSAPOE exhibited significant associations with Aβ42, tTau, pTau, and Aβ42/40 ratio in DS. DISCUSSION: These data indicate that the AD genetic architecture influences cognitive and CSF phenotypes in DS adults, supporting common pathways that influence memory decline in both traits. Highlights: Examination of the polygenic risk of AD in DS presented here is the first of its kind.AD PRS influences memory aspects in DS individuals, independently of APOE genotype.These results point to an overlap between the genes and pathways that leads to AD and those that influence dementia and memory decline in the DS population.APOE ε4 is linked to DS cognitive decline, expanding cognitive insights in adults. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Almost all individuals with Down syndrome (DS) will develop neuropathological features of Alzheimer's disease (AD). Understanding AD biomarker trajectories is necessary for DS‐specific clinical interventions and interpretation of drug‐related changes in the disease trajectory. METHODS: A total of 177 adults with DS from the Alzheimer's Biomarker Consortium‐Down Syndrome (ABC‐DS) underwent positron emission tomography (PET) and MR imaging. Amyloid‐beta (Aβ) trajectories were modeled to provide individual‐level estimates of Aβ‐positive (A+) chronicity, which were compared against longitudinal tau change. RESULTS: Elevated tau was observed in all NFT regions following A+ and longitudinal tau increased with respect to A+ chronicity. Tau increases in NFT regions I‐III was observed 0–2.5 years following A+. Nearly all A+ individuals had tau increases in the medial temporal lobe. DISCUSSION: These findings highlight the rapid accumulation of amyloid and early onset of tau relative to amyloid in DS and provide a strategy for temporally characterizing AD neuropathology progression that is specific to the DS population and independent of chronological age. Highlights: Longitudinal amyloid trajectories reveal rapid Aβ accumulation in Down syndromeNFT stage tau was strongly associated with A+ chronicityEarly longitudinal tau increases were observed 2.5–5 years after reaching A+ [ABSTRACT FROM AUTHOR]