Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them.

Longitudinal head-to-head comparison of C-PiB and F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer's disease.

Purpose: Pittsburgh Compound-B (C-PiB) and F-florbetapir are amyloid-β (Aβ) positron emission tomography (PET) radiotracers that have been used as endpoints in Alzheimer's disease (AD) clinical trials to evaluate the efficacy of anti-Aβ monoclonal antibodies. However, comparing drug effects between and within trials may become complicated if different Aβ radiotracers were used. To study the consequences of using different Aβ radiotracers to measure Aβ clearance, we performed a head-to-head comparison of C-PiB and F-florbetapir in a Phase 2/3 clinical trial of anti-Aβ monoclonal antibodies.

Amyloid-PET of the white matter: Relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease.

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (Aβ-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered Aβ-PET signal in WM regions.

Vascular burden and cognition: Mediating roles of neurodegeneration and amyloid PET.

It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aβ deposition ( F-AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or F fluorodeoxyglucose PET) in AD signature regions.

The Oral and Fecal Microbiota in a Canadian Cohort of Alzheimer's Disease.

Background: Despite decades of research, our understanding of Alzheimer's disease (AD) etiology remains incomplete. In recent years, appreciation has grown for potential roles for the microbiota in shaping neurological health.

Objective: This study aimed to examine associations between the microbiota and AD in a human cross-sectional cohort.

Consensus Statement Regarding the Application of Biogen to Health Canada for Approval of Aducanumab.

Alzheimer's disease is a major cause of morbidity and mortality. Currently, there are no disease-modifying pharmacotherapies for this condition. Aducanumab, an amyloid beta-directed monoclonal antibody that targets aggregated forms of amyloid-beta in the brains of people with Alzheimer's disease, has raised hopes that such a therapy has been discovered, but its approval by the US Food and Drug Administration has engendered a good deal of controversy.

In Vitro Properties of Potential Probiotic Indigenous Yeasts Originating from Fermented Food and Beverages in Taiwan.

Probiotics are live microorganisms that may be able to help prevent and treat some illnesses. Most probiotics on the market are bacterial, primarily Lactobacillus. Yeast are an inevitable part of the microbiota of various fermented foods and beverages and have several beneficial properties that bacteria do not have.

The Use of Random Forests to Identify Brain Regions on Amyloid and FDG PET Associated With MoCA Score.

Purpose: The aim of this study was to evaluate random forests (RFs) to identify ROIs on F-florbetapir and F-FDG PET associated with Montreal Cognitive Assessment (MoCA) score.

Materials And Methods: Fifty-seven subjects with significant white matter disease presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial, had MoCA and F-florbetapir PET; 55 had F-FDG PET. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter (F-florbetapir PET), or pons (F-FDG PET).

Utility of the global CDR plus NACC FTLD rating and development of scoring rules: Data from the ARTFL/LEFFTDS Consortium.

Introduction: We created global rating scoring rules for the CDR plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD.

Methods: The CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). Each of the eight domains of the CDR plus NACC FTLD was equally weighed in determining the global score.

Nonlinear Z-score modeling for improved detection of cognitive abnormality.

Introduction: Conventional Z-scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these "adjusted" Z-scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z-scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.

Assessment of Anastomotic Perfusion in Left-Sided Robotic Assisted Colorectal Resection by Indocyanine Green Fluorescence Angiography.

Background: Indocyanine green fluorescent angiography (IcGA) has been used with success in guiding intraoperative management to prevent colorectal anastomotic complications. Prior studies in open and laparoscopic colorectal surgery, such as PILLAR II, have demonstrated a low anastomotic leak rate (1.4%).

The Use of Random Forests to Classify Amyloid Brain PET.

Purpose: To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification.

Methods: The data set included 57 baseline F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with severe white matter disease, presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter, and clinically read by 2 nuclear medicine physicians with interpretation based on consensus (35 negative, 22 positive).

Adaptive crossover designs for assessment of symptomatic treatments targeting behaviour in neurodegenerative disease: a phase 2 clinical trial of intranasal oxytocin for frontotemporal dementia (FOXY).

Background: There are currently no treatments for empathy deficits in neuropsychiatric disorders. Acute administration of the hormone oxytocin has been associated with symptomatic improvements across animal models and several neuropsychiatric disorders, but results of the majority of oxytocin randomised controlled trials (RCTs) of longer duration have been negative or inconclusive. This lack of efficacy of may be due to rapid habituation to oxytocin with chronic dosing.

Development and validation of a novel dementia of Alzheimer's type (DAT) score based on metabolism FDG-PET imaging.

Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging based 3D topographic brain glucose metabolism patterns from normal controls (NC) and individuals with dementia of Alzheimer's type (DAT) are used to train a novel multi-scale ensemble classification model. This ensemble model outputs a FDG-PET DAT score (FPDS) between 0 and 1 denoting the probability of a subject to be clinically diagnosed with DAT based on their metabolism profile. A novel 7 group image stratification scheme is devised that groups images not only based on their associated clinical diagnosis but also on past and future trajectories of the clinical diagnoses, yielding a more continuous representation of the different stages of DAT spectrum that mimics a real-world clinical setting.

Study protocol for Vitality: a proof-of-concept randomised controlled trial of exercise training or complex mental and social activities to promote cognition in adults with chronic stroke.

Introduction: Cerebrovascular disease-such as stroke-is the second most common cause of dementia (ie, vascular dementia). Specifically, a stroke increases one's risk for dementia by a factor of two. Thus, stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia.

A Simulation Study to Evaluate Improvements in Anesthesia Work Environment Contamination After Implementation of an Infection Prevention Bundle.

Background: Microbiological contamination of the anesthesia work environment (AWE) is a potential source of health care-associated infections. Medication syringes, stopcocks, and many other areas are routinely contaminated during anesthetic care, and adherence to hand hygiene recommendations is poor. Using a simulation model, we investigated whether AWE contamination could be reduced by implementing an intervention bundle focused on infection prevention.

Corrigendum: The Impact of Aerobic Exercise on Fronto-Parietal Network Connectivity and Its Relation to Mobility: An Exploratory Analysis of a 6-Month Randomized Controlled Trial.

[This corrects the article on p. 344 in vol. 11, PMID: 28713255.

The Impact of Aerobic Exercise on Fronto-Parietal Network Connectivity and Its Relation to Mobility: An Exploratory Analysis of a 6-Month Randomized Controlled Trial.

Impaired mobility is a major concern for older adults and has significant consequences. While the widely accepted belief is that improved physical function underlies the effectiveness of targeted exercise training in improving mobility and reducing falls, recent evidence suggests cognitive and neural benefits gained through exercise may also play an important role in promoting mobility. However, the underlying neural mechanisms of this relationship are currently unclear.

First, Do No Harm: Referring Primary Care Patients with Depression to an Internet Support Group.

Background: Internet Support Groups (ISGs) offer people easy access to information regarding depression as well as support from others who are either currently suffering from depression or have previously suffered from depression. The safety and efficacy of ISGs for people with depression have not been thoroughly studied.

Introduction: The safety and helpfulness of a depression ISG were assessed by analyzing pre- and postintervention depressive symptoms, other psychological outcomes, and participant ratings of helpfulness.

Retropharyngeal Perforation With an Esophageal Dilator: A Case Report.

Esophageal "bougie" dilators are frequently used during esophageal surgeries to facilitate reconstruction and manipulation of the esophagus. Insertion of such dilators is usually a blind technique and not without risk. We present a case of retropharyngeal wall perforation resulting from esophageal dilator misplacement in a patient undergoing laparoscopic Heller myotomy and reconstruction.

Internal versus external motivation in referral of primary care patients with depression to an internet support group: randomized controlled trial.

Background: Depressive disorders and symptoms affect more than one-third of primary care patients, many of whom do not receive or do not complete treatment. Internet-based social support from peers could sustain depression treatment engagement and adherence. We do not know whether primary care patients will accept referral to such websites nor do we know which methods of referral would be most effective.