Structural Correlates of Overt Sentence Reading in Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease.

Background: Overt sentence reading in mild cognitive impairment (MCI) and mild-tomoderate Alzheimer's disease (AD) has been associated with slowness of speech, characterized by a higher number of pauses, shorter speech units and slower speech rate and attributed to reduced working memory/ attention and language capacity.

Objective: This preliminary case-control study investigates whether the temporal organization of speech is associated with the volume of brain regions involved in overt sentence reading and explores the discriminative ability of temporal speech parameters and standard volumetric MRI measures for the classification of MCI and AD.

Methods: Individuals with MCI, mild-to-moderate AD, and healthy controls (HC) had a structural MRI scan and read aloud sentences varying in cognitive-linguistic demand (length).

HALO: Study protocol for a single-case experimental design study evaluating the moderating impact of a befriending intervention on the association between loneliness and health in older adults.

: Loneliness in later life is often addressed with befriending interventions, yet evidence for their effectiveness is limited. Meanwhile it is known that loneliness has a deleterious impact on health. The aim of the study is to evaluate whether a befriending service for older adults mitigates the impact of loneliness on health outcomes, and to identify mechanisms through which befriending interventions might impact upon health.

Omega-3 fatty acid, carotenoid and vitamin E supplementation improves working memory in older adults: A randomised clinical trial.

Background & Aims: Accumulating evidence suggests that omega-3 fatty acids (ω-3FAs), carotenoids and vitamin E can improve cognitive performance. However, their collective impact on cognition has not yet been investigated in healthy individuals. This study investigated the combined effect of ω-3FA, carotenoid and vitamin E supplementation on the cognitive performance of older adults.

A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene.

We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We describe the clinical spectrum within this family and emphasize the association between MAPT gene variants and motor neuron disease.

Improvement in cognitive impairment following a 12-week aerobic exercise intervention in individuals with non-cirrhotic chronic hepatitis C.

Cognitive impairment occurs in 30%-50% of patients with non-cirrhotic chronic hepatitis C virus (HCV) infection. Exercise is beneficial in preventing and treating cognitive impairment and cardiometabolic abnormalities in many chronic inflammatory diseases, but there are few studies investigating the impact of exercise in HCV infection. The study aimed to assess the effect of a 12-week aerobic exercise intervention on cognition and extrahepatic manifestations in individuals with HCV.

Clinical utility of mild cognitive impairment subtypes and number of impaired cognitive domains at predicting progression to dementia: A 20-year retrospective study.

Objective: To determine the utility of mild cognitive impairment (MCI) subtypes and number of impaired cognitive domains on initial assessment at predicting progression to dementia in a sample of memory clinic patients over a 20-year period.

Methods: A retrospective analysis was conducted of those presenting to a memory clinic with MCI from 1 January 1999 to 31 December 2018 inclusive. Those with MCI were broken down into one of the four subtypes using recommended cut-off scores on the Cambridge Cognitive Assessment (CAMCOG).

Targeted Nutritional Intervention for Patients with Mild Cognitive Impairment: The Cognitive impAiRmEnt Study (CARES) Trial 1.

Omega-3 fatty acids (ω-3FAs), carotenoids, and vitamin E are important constituents of a healthy diet. While they are present in brain tissue, studies have shown that these key nutrients are depleted in individuals with mild cognitive impairment (MCI) in comparison to cognitively healthy individuals. Therefore, it is likely that these individuals will benefit from targeted nutritional intervention, given that poor nutrition is one of the many modifiable risk factors for MCI.

Synthetic Rhamnose Glycopolymer Cell-Surface Receptor for Endogenous Antibody Recruitment.

Synthetic materials capable of engineering the immune system are of great relevance in the fight against cancer to replace or complement the current monoclonal antibody and cell therapy-based immunotherapeutics. Here, we report on antibody recruiting glycopolymers (ARGPs). ARGPs consist of polymeric copies of a rhamnose motif, which can bind endogenous antirhamnose antibodies present in human serum.

Cell surface clicking of antibody-recruiting polymers to metabolically azide-labeled cancer cells.

Triggering antibody-mediated innate immune mechanisms to kill cancer cells is an attractive therapeutic avenue. In this context, recruitment of endogenous antibodies to the cancer cell surface could be a viable alternative to the use of monoclonal antibodies. We report on antibody-recruiting polymers containing multiple antibody-binding hapten motifs and cyclooctynes that can covalently conjugate to azides introduced onto the glycocalyx of cancer cells by metabolic labeling with azido sugars.

Is the Quick Mild Cognitive Impairment Screen (QMCI) more accurate at detecting mild cognitive impairment than existing short cognitive screening tests? A systematic review of the current literature.

Objectives: Differentiating normal cognition, mild cognitive impairment (MCI), and dementia is important, as these conditions differ in terms of their prognosis and treatment. Existing short cognitive screening tests vary widely in their accuracy, sensitivity, and specificity at detecting MCI and dementia. The Quick Mild Cognitive Impairment Screen (QMCI) was developed in 2012 as a fast and accurate "MCI specific" screening test.

Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer-Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists.

Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small-molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum-protein-binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid-polymer conjugates that suppress systemic inflammation but provoke potent lymph-node immune activation. This work provides a rational basis for the design of lipid-polymer amphiphiles for optimized lymphoid targeting.

Efficient Innate Immune Killing of Cancer Cells Triggered by Cell-Surface Anchoring of Multivalent Antibody-Recruiting Polymers.

Binding of monoclonal antibodies (mAbs) onto a cell surface triggers antibody-mediated effector killing by innate immune cells through complement activation. As an alternative to mAbs, synthetic systems that can recruit endogenous antibodies from the blood stream to a cancer cell surface could be of great relevance. Herein, we explore antibody-recruiting polymers (ARPs) as a novel class of immunotherapy.

Cognitive rehabilitation for early stage Alzheimer's disease: a pilot study with an Irish population.

Objectives: Research shows that cognitive rehabilitation (CR) has the potential to improve goal performance and enhance well-being for people with early stage Alzheimer's disease (AD). This single subject, multiple baseline design (MBD) research investigated the clinical efficacy of an 8-week individualised CR intervention for individuals with early stage AD.

Methods: Three participants with early stage AD were recruited to take part in the study.

Neuropolypathology as a result of severe traumatic brain injury?

A history of brain trauma has long been acknowledged as increasing an individual's risk of developing dementia in later life. The underlying mechanisms that belie this pre-disposition are, however, very poorly understood. Here, we report a clinical-neuropathological correlation of a man who presented at the age of 66 with a progressive complex atypical dementia with early and prominent neurobehavioral symptoms.

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

Background: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease.

Comprehensive Neuropsychological Assessment of Cognitive Functioning of Adults With Lower Limb Amputation in Rehabilitation.

Objective: To establish a comprehensive profile of cognitive functioning in people engaged in lower limb amputation (LLA) rehabilitation.

Design: Cross-sectional study as part of a longitudinal prospective cohort.

Setting: A national tertiary rehabilitation hospital.

Prosopagnosia as a Type of Conversion Disorder.

Background: Conversion disorder is a common and debilitating condition that remains poorly understood. We present a previously undescribed form of conversion disorder to highlight the complexity of the condition and consider the interplay of factors that produce conversion symptoms.

Case: A 50-year-old male presented with acquired prosopagnosia and language impairment.

Changes in Speech Chunking in Reading Aloud is a Marker of Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease.

Background: Speech and Language Impairments, generally attributed to lexico-semantic deficits, have been documented in Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). This study investigates the temporal organisation of speech (reflective of speech production planning) in reading aloud in relation to cognitive impairment, particularly working memory and attention deficits in MCI and AD. The discriminative ability of temporal features extracted from a newly designed read speech task is also evaluated for the detection of MCI and AD.

Semantic and Phonemic Verbal Fluency Discrepancy in Mild Cognitive Impairment: Potential Predictor of Progression to Alzheimer's Disease.

Objectives: To assess the utility of verbal fluency discrepancy scores in predicting progression to Alzheimer's disease (AD) in a cohort of individuals with mild cognitive impairment (MCI).

Design: Case control.

Setting: Cases identified from new referrals to a memory clinic and controls identified from The Irish Longitudinal Study on Ageing.

Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background: There is a biologically plausible rationale whereby the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are collectively referred to as macular pigment (MP) in the central retina (macula), support the maintenance of cognition via their antioxidant and anti-inflammatory properties.

Objective: To investigate the impact of supplemental L, Z, and MZ on memory, executive function, and verbal fluency among healthy individuals with low MP levels.

Methods: In this double-blind, placebo-controlled, randomized clinical trial, subjects (n = 91; mean±SD age = 45.

Tyrosine-Triazolinedione Bioconjugation as Site-Selective Protein Modification Starting from RAFT-Derived Polymers.

The electrophilic aromatic substitution (SAr) reaction of triazolinediones (TADs) with the phenol moiety of tyrosine amino acid residues is a potent method for the site-selective formation of polymer-protein conjugates. Herein, using poly(,-dimethylacrylamide) (pDMA) and bovine serum albumin (BSA) as model reagents, the performance of this tyrosine-TAD bioconjugation in aqueous solutions is explored. At first, reversible addition-fragmentation chain transfer (RAFT) polymerization with a functional urazole, a precursor for TAD, chain transfer agent is used for the synthesis of a TAD end-functionalized pDMA.

Transiently Thermoresponsive Acetal Polymers for Safe and Effective Administration of Amphotericin B as a Vaccine Adjuvant.

The quest for new potent and safe adjuvants with which to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll-like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, amphotericin B (AmpB), a Food and Drug Administration approved antifungal drug, has recently been discovered to possess TLR-triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant.

Rehabilitation of emergent awareness of errors post traumatic brain injury: A pilot intervention.

Impaired awareness of errors is common following traumatic brain injury (TBI) and can be a barrier to successful rehabilitation. The objective of this study was to develop and evaluate a computer-based intervention programme aimed at improving error awareness in individuals with TBI. A further aim was to explore its effects on metacognitive awareness and variability of performance.