Association of brain amyloidosis with the incidence and frequency of neuropsychiatric symptoms in ADNI: a multisite observational cohort study

Objective To investigate the relationship between amyloid burden and frequency of existing and incidence of new neuropsychiatric symptoms (NPS) in elderly with and without cognitive decline. Methods 275 cognitively normal controls (NC), 100 subjective memory complaint (SMC), 559 mild cognitive impairment (MCI) and 143 Alzheimer’s disease dementia subjects from the Alzheimer’s Disease Neuroimaging Initiative received (18F)-florbetapir positron emission tomography (PET) scans. Yearly neuropsychiatric inventory (Neuropsychiatric Inventory (NPI)/NPI-Questionnaire) data were collected from the study partners at each visit. Mean standard uptake volume ratios (SUVR) normalised to whole cerebellum were obtained. Positive amyloid PET scan was defined as mean SUVR ≥1.17. Fisher’s exact test was used to compare frequency and incidence between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate of neuropsychiatric symptoms (NPS) between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate hazard ratios for developing the most common NPS by amyloid status. Results No differences in NPS frequency were seen between amyloid positive and amyloid negative NC, SMC, MCI or dementia groups. MCI subjects with amyloid pathology however tended to have greater frequency x severity (FxS) of anxiety, hallucinations, delusions, apathy, disinhibition, irritability, aberrant motor behavior, and appetite, but not agitation, depression, night-time disturbances, or elation. MCI subjects with amyloid pathology were at greater risk for developing apathy, anxiety and agitation over time. Baseline presence of agitation and apathy and new onset agitation, irritability and apathy predicted faster conversion to dementia among MCI subjects. Conclusions Amyloid pathology is associated with greater rate of development of new NPS in MCI. Anxiety and delusions are significant predictors of amyloid pathology. Agitation, irritability and apathy are significant predictors for conversion from MCI to dementia

The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism

INTRODUCTION: We analyzed the effects of the top 20 Alzheimer disease (AD) risk genes on gray-matter density (GMD) and metabolism. METHODS: We ran stepwise linear regression analysis using posterior cingulate hypometabolism and medial temporal GMD as outcomes and all risk variants as predictors while controlling for age, gender, and APOE ε4 genotype. We explored the results in 3D using Statistical Parametric Mapping 8. RESULTS: Significant predictors of brain GMD were SLC24A4/RIN3 in the pooled and mild cognitive impairment (MCI); ZCWPW1 in the MCI; and ABCA7, EPHA1, and INPP5D in the AD groups. Significant predictors of hypometabolism were EPHA1 in the pooled, and SLC24A4/RIN3, NME8, and CD2AP in the normal control group. DISCUSSION: Multiple variants showed associations with GMD and brain metabolism. For most genes, the effects were limited to specific stages of the cognitive continuum, indicating that the genetic influences on brain metabolism and GMD in AD are complex and stage dependent

Associations of the Top 20 Alzheimer Disease Risk Variants With Brain Amyloidosis

Importance: Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide association studies have identified more than 20 AD risk genes. The precise mechanism through which many of these genes are associated with AD remains unknown. Objective: To investigate the association of the top 20 AD risk variants with brain amyloidosis. Design, Setting, and Participants: This study analyzed the genetic and florbetapir F 18 data from 322 cognitively normal control individuals, 496 individuals with mild cognitive impairment, and 159 individuals with AD dementia who had genome-wide association studies and 18F-florbetapir positron emission tomographic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective, observational, multisite tertiary center clinical and biomarker study. This ongoing study began in 2005. Main Outcomes and Measures: The study tested the association of AD risk allele carrier status (exposure) with florbetapir mean standard uptake value ratio (outcome) using stepwise multivariable linear regression while controlling for age, sex, and apolipoprotein E ε4 genotype. The study also reports on an exploratory 3-dimensional stepwise regression model using an unbiased voxelwise approach in Statistical Parametric Mapping 8 with cluster and significance thresholds at 50 voxels and uncorrected P < .01. Results: This study included 977 participants (mean [SD] age, 74 [7.5] years; 535 [54.8%] male and 442 [45.2%] female) from the ADNI-1, ADNI-2, and ADNI-Grand Opportunity. The adenosine triphosphate-binding cassette subfamily A member 7 (ABCA7) gene had the strongest association with amyloid deposition (χ2 = 8.38, false discovery rate-corrected P < .001), after apolioprotein E ε4. Significant associations were found between ABCA7 in the asymptomatic and early symptomatic disease stages, suggesting an association with rapid amyloid accumulation. The fermitin family homolog 2 (FERMT2) gene had a stage-dependent association with brain amyloidosis (FERMT2 × diagnosis χ2 = 3.53, false discovery rate-corrected P = .05), which was most pronounced in the mild cognitive impairment stage. Conclusions and Relevance: This study found an association of several AD risk variants with brain amyloidosis. The data also suggest that AD genes might differentially regulate AD pathologic findings across the disease stages

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Association of a standardized measure of nasopharyngeal inflammation with Eustachian tube dysfunction questionnaire score.

BACKGROUND: Standardized diagnostic criteria for Eustachian tube (ET) dysfunction (ETD) have not been established. The purpose of this study was to characterize the relationship between ET inflammation and ETD symptoms and to determine the diagnostic performance of a quantitative score. METHODS: Patients were enrolled in a rhinology clinic between October 2018 and June 2019. Patients underwent nasal endoscopy and completed the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7). Nasopharyngeal inflammation identified on endoscopy was quantified using the Endoscopic Evaluation of the Eustachian Tube (3ET) score. Tympanometry was performed as indicated. Comorbid conditions were assigned during the patient encounter. RESULTS: A total of 414 patients were included in the study. Patients with clinically significant ETD symptoms (ETDQ-7 ≥2.1) had higher 3ET scores than those without symptoms. A 1-point increase in 3ET score was associated with a 1.7-fold increase in odds of clinically significant ETD symptoms (adjusted OR [aOR], 1.72; 95% CI, 1.46 to 2.05). The 3ET scores were correlated with ETDQ-7 scores (ρ = 0.54) and 22-item Sino-Nasal Outcome Test (SNOT-22) scores (ρ = 0.52). 3ET scores were not associated with tympanometric peak pressures. Patients with ETD symptoms were more likely to have laryngopharyngeal reflux (aOR, 2.71; 95% CI, 1.24 to 6.18). A 3ET score of 4 predicted symptomatic state in 80% of cases with a specificity of 97.8% and positive predictive value of 96.6%. CONCLUSION: Inflammatory findings at the nasopharyngeal ET orifice are associated with clinically significant ETD symptoms. The 3ET score is specific for a symptomatic state and has potential clinical utility in the evaluation of suspected ETD. ©2021 ARSAAOA, LLC

Neuromodulators for Atypical Facial Pain and Neuralgias: A Systematic Review and Meta-Analysis

Objective: To evaluate the effectiveness of neuromodulating agents for the management of atypical facial pain and primary facial neuralgias. Methods: We searched MEDLINE, Embase, CINAHL, and ClinicalTrials.gov databases for original research articles that examine the effectiveness and adverse reactions of pharmacologic therapy for the treatment of trigeminal neuralgia and atypical facial pain. Studies that included surgical interventions for atypical facial pain or facial pain secondary to other causes were excluded. Meta-analysis was conducted for reductions in symptom scores and adverse effects. Results: Of 3,409 articles screened, 73 full-text articles were included, consisting of 45 observational studies and 29 randomized controlled trials. Twenty-four different pharmacological agents were assessed; carbamazepine was the most frequently studied while botulinum toxin A demonstrated the highest consistency in reduction of symptom scores. Pooled estimate of three randomized controlled trials revealed that patients with trigeminal neuralgia who received botulinum toxin A had higher odds (odds ratio 7.46; 95% CI 3.53–15.78) of achieving a ≥50% reduction in visual analogue scale scores compared to controls. Pooled estimate of 15 observational studies showed that three-fourths of patients with trigeminal neuralgia who received carbamazepine experienced clinically significant pain reduction (prevalence proportion 0.75; 95% CI 0.66–0.83). Conclusions: Patients receiving botulinum toxin A for trigeminal neuralgia had higher odds of achieving ≥50% reduction in pain scores. A significant proportion of patients with trigeminal neuralgia experienced positive response to carbamazepine. There was moderate evidence for amitriptyline in patients with atypical facial pain. Standardization of outcome reporting would facilitate future quantitative comparisons of therapeutic effectiveness. Laryngoscope, 2020

Olfactory Training for Postviral Olfactory Dysfunction: Systematic Review and Meta-analysis

Objective: Olfactory dysfunction is a common problem that is most frequently attributed to upper respiratory infection. Postviral olfactory dysfunction (PVOD) can be prolonged and clinically challenging to treat. Olfactory training (OT) has demonstrated potential benefit for patients with nonspecific olfactory dysfunction. We sought to evaluate the efficacy of OT specifically for PVOD by pooled analysis of the existing evidence. Data Sources: PubMed, Embase, and Web of Science. Review Methods: Following PRISMA guidelines, PubMed, Embase, and Web of Science databases were queried and abstracts screened independently by 2 investigators. We included studies evaluating the efficacy of OT for PVOD and excluded studies evaluating pharmacologic interventions or olfactory loss from other causes. Results: Of the initial 1981 abstracts reviewed, 16 full-text articles were included. Sniffin’ Sticks olfactory testing results were reported in 15 (93%) studies as threshold (T), discrimination (D), and identification (I) subscores and TDI total scores. All studies reported clinically significant results after OT, defined as a score improvement of TDI >5.5. Four studies were included in the meta-analysis, in which pooled estimates revealed that patients with PVOD who received OT had a 2.77 (95% confidence interval, 1.67-4.58) higher odds of achieving a clinically important difference in TDI scores compared to controls. Conclusion: Meta-analysis of existing data demonstrates clinically significant improvements in PVOD associated with OT. Variability exists among OT protocols and may benefit from further optimization. Existing data supports the use of OT for the treatment of existing and newly emerging cases of PVOD

Survey of knowledge, attitude and practice of healthcare professionals on dengue transmission, diagnosis and clinical classification

Background:To investigate the knowledge, attitudes, and practices of the healthcare professionals (HCPs) including physicians and nurses regarding dengue transmission, diagnosis and clinical classification using the warning signs of World Health Organization (WHO) 2009 classification.Results: Out of 471 respondents from three countries, 80.9% of physicians and 74% of nurses did not receive previous training regarding the dengue infection. The majority of respondents could identify the primary dengue vector (86%), while only a third of HCPs knew the biting time of dengue mosquitoes. Only half of our respondents knew about immunity induced by serotypes; Moreover, half of our participants could determine the diagnostic tests. On the other hand, about 90% of the respondents took responsibility for talking to the patients about preventive measures. Our respondents also showed wide variations in definition of warning signs listed in the WHO 2009 classification. Multivariate analysis linked the impact of different cofactors including prior training on dengue infection, type of profession, frequency of taking care of dengue patients and country on how HCPs defined these warning signs.Conclusions: This study could declare the variation in employing the warning signs listed in the WHO 2009 classification. We have figured that most of the HCPs did not take prior training on the dengue viral infection; Also, we found gaps in the knowledge regarding various topics in dengue fever. This paper recommends the gathering of efforts to establish the proper knowledge of dengue infection and the warning signs listed by the WHO