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This cross-sectional study examined the biomechanical effects of two active chairs (AC1: had the feature to pedal and slide forward on the seat pan; AC2: a multiaxial motion seat pan) compared to a traditional office chair and standing workstation. Twenty-four healthy participants worked at each of the workstations for 60-min. The following equipment was used: Motion Capture, Electromyography, Ratings of Perceived Discomfort Questionnaire, and Exit Survey. The active protocol had positive effects on the body, including increased neuromuscular activity in the gastrocnemius, increased overall movement, and a more open trunk-thigh angle. Greater discomfort in the buttocks due to the lack of seat pan contour was reported for the AC1 which identified a need for a design modification. While standing, participants' shoulders were less flexed than when sitting in any of the three seats, however, greater discomfort was reported in the lower legs after 1 h of computer work.

Background: The uncompetitive NMDA antagonist, memantine (MEM), enhances prepulse inhibition of startle (PPI) across species. MEM is used to treat Alzheimer’s disease (AD); conceivably, its acute impact on PPI might be used to predict a patient’s sensitivity to MEM’s therapeutic effects. Objective: To begin to test this possibility, we studied MEM effects on PPI and related measures in AD patients. Methods: 18 carefully screened individuals with AD (mean age = 72.8 y; M:F=9 : 9) completed double-blind order-balanced testing with MEM (placebo versus 20 mg), assessing acoustic startle magnitude, habituation, PPI, and latency. Results: Fifteen out of 18 participants exhibited reliable startle responses. MEM did not significantly impact startle magnitude or habituation. Compared to placebo responses, PPI was significantly increased after MEM (p

Resume Introduction Pour la semaine de la securite des patients (SSP) 2018, axee sur les erreurs medicamenteuses (EM), notre etablissement a souhaite developper un outil de simulation en sante innovant, ludique et pragmatique. L’objectif etait de creer un jeu d’evasion (escape game) medicamenteux alliant reflexion sur les EM et travail collaboratif. Methodologie Un groupe de travail pluridisciplinaire a cree un scenario de prise en charge medicamenteuse (PECM) d’un patient necessitant une pose rapide d’antibiotherapie. Le groupe a defini quatre enigmes successives reprenant les principaux risques lies aux EM identifies dans notre etablissement. La seance de 45 minutes permettait d’immerger les equipes de 3 a 5 personnes suivant le format : instructions, mise en situation, analyse critique et evaluation de satisfaction. Resultats Soixante professionnels repartis en 14 equipes ont participe au jeu : 40 % d’infirmieres, 32 % d’aides-soignants, 18 % d’autres professionnels. Les equipes ont reussi le jeu en 21 min et 23 s et ont eu besoin de sept indices, en moyenne. Le niveau de difficulte a ete juge difficile (50 %) ou intermediaire (38 %) et le scenario decrit comme pertinent pour tous les participants. L’outil a repondu aux attentes de 88 % des participants et 81 % d’entre eux disent avoir acquis des connaissances. Conclusion Le jeu d’evasion medicamenteux permet de reprendre de facon ludique et pedagogique des erreurs pertinentes retrouvees dans le circuit de la PECM du patient. Apres un premier retour d’experience positif, ce format pedagogique sera integre a notre plan de formation 2019.

Background: Studies of cumulative anticholinergic drug burden on cognitive function and impairment are emerging, yet few for Hispanics/Latinos. Objective: To examine associations between anticholinergic use and neurocognitive performance outcomes among diverse Hispanics/Latinos. Methods: This prospective cohort study included diverse Hispanic/Latino participants, enrolled in the Study of Latinos-Investigation of Neurocognitive, from New York, Chicago, Miami, and San Diego (n = 6,249). Survey linear regression examined associations between anticholinergic use (measured during baseline [Visit 1] and average 7-year follow up [Visit 2]) with global cognition, episodic learning, memory, phonemic fluency, processing speed, executive functioning, and average 7-year change. Results: Anticholinergic use was associated with lower cognitive global cognition (β= –0.21; 95% CI [–0.36; –0.05]), learning (β= –0.27; 95% CI [–0.47; –0.07]), memory (β= –0.22; 95% CI [–0.41; –0.03]), and executive functioning (β= –0.22; 95% CI [–0.40; –0.03]) scores, particularly among those who took anticholinergics at both visits. Anticholinergic use was associated with faster decline in global cognition, learning, and verbal fluency (β: –0.28 [95% CI: –0.55, –0.01]; β: –0.28 [95% CI: –0.55, –0.01]; β: –0.25, [95% CI –0.47, –0.04], respectively). Sex modified associations between anticholinergic use with global cognition, learning, and executive functioning (F3 = 3.59, F3 = 2.84, F3 = 3.88, respectively). Conclusion: Anticholinergic use was associated with lower neurocognitive performance, especially among those who used anticholinergics at both visits, among a study population of diverse Hispanics/Latinos. Findings will support evidence-based decisions regarding anticholinergic prescriptions and efforts to minimize cognitive impact.

This chapter reviews the current information on the use of Positron emission tomography (PET) and movement disorders. Parkinson’s disease is a degenerative neurological disorder characterized by tremor, rigidity, bradykinesia, and postural instability. Therapy is aimed at replacing the neurochemical defect in this condition. L-dopa, the precursor of dopamine, has been used successfully in the treatment of patients with parkinsonism. Dopamine does not cross the blood brain barrier and cannot be used as a therapeutic agent. Parkinsonism may be present in conditions other than Parkinson’s disease. Disease processes that affect the substantia nigra or caudate nucleus and putamen may present with similar symptoms. Cerebral metabolism studies with fluorodeoxyglucose (FDG) have been performed in patients with unilateral and bilateral parkinsonism. PET may be employed to study the nigrostriatal dopamine pathway during life. PET studies of dopamine receptors in Parkinson’s disease have been very preliminary.

Background Biomarkers are being used increasingly to support the diagnosis of dementia with Lewy bodies (DLB). Novel biomarkers that increase diagnostic specificity of DLB are needed. We assessed previously known FDG-PET occipital cortex hypometabolism, and cingulate island sign biomarkers of DLB against a novel amygdala signature. Methods Retrospective analysis of 49 patients evaluated at one tertiary memory clinic. All had a FDG-PET brain scan performed as part of their diagnostic work up evaluating three common neurodegenerative etiologies: Alzheimer dementia (AD), Frontotemporal dementia (FTD) and DLB. A consensus diagnosis of dementia was made based on accepted clinical criteria for AD, FTD and DLB. FDG-PET regional metabolism was delineated by automatic segmentation as well as manual tracing of amygdala and posterior cingulate volumes of interest. Mean normalized values calculated for regional FDG-PET signatures of DLB: occipital cortex hypometabolism and preservation of posterior cingulate and amygdala metabolism relative to whole brain metabolism were evaluated. Results Significant overlap between DLB and AD patients (occipital, parietal, temporal and frontal hypometabolism) and between DLB and FTD (frontal hypometabolism and the posterior cingulate sign) were identified. Right amygdala (p = 0.028) and right posterior cingulate (p = 0.035) mean normalized regional metabolism levels were preserved in DLB compared to AD. Among subjects at less advanced stages of dementia (MoCA>10), relative preservation of regional metabolism was notable across both left (p = 0.006) and right (p = 0.020) amygdala. Conclusion Relative preservation of amygdala metabolism could complement previously described FDG-PET findings in earlier stages of DLB.

This cross-sectional study examined the physiological effects of two active chairs (AC1: had the feature to pedal and slide forward; AC2: was a multiaxial chair) compared to a traditional office chair and standing workstation. Twenty-four healthy participants computed at each of the workstations for 60 min. The active protocol was to alternate between a pedalling/side-to-side motion and sliding forward/front-to-back motion to the sound of a metronome operating at 40 bpm. The participants' physiological effects were recorded using near-infrared spectroscopy (NIRS); electrodermal activity (EDA) and a heart rate (HR) monitor for each collection period. Statistical analysis was conducted using a repeated measures analysis of variance for within-task and between-workstation comparisons. A Tukey's post hoc analysis was calculated for significant findings. Both active chairs significantly increased oxygenated blood in the gastrocnemius and participants' heart rate and EDA (stress) levels were affected slightly by task and time. However, participants felt more "productive" sitting in the control chair than in either of the active chairs.

Background and ObjectivePatients with earlier age at onset of sporadic Alzheimer disease (AD) are more likely than those with later onset to present with atypical clinical and cognitive features. We sought to determine whether this age-related clinical and cognitive heterogeneity is mediated by different topographic distributions of tau-aggregate neurofibrillary tangles (NFTs) or by variable amounts of concomitant non-AD neuropathology.MethodsThe relative distribution of NFT density in hippocampus and midfrontal neocortex was calculated, and α-synuclein, TAR DNA binding protein 43 (TDP-43), and microvascular copathologies were staged, in patients with severe AD and age at onset of 51–60 (n = 40), 61–70 (n = 41), and >70 (n = 40) years. Regression, mediation, and mixed effects models examined relationships of pathologic findings with clinical features and longitudinal cognitive decline.ResultsPatients with later age at onset of AD were less likely to present with nonmemory complaints (odds ratio [OR] 0.46 per decade, 95% confidence interval [CI] 0.22–0.88), psychiatric symptoms (β = −0.66, 95% CI −1.15 to −0.17), and functional impairment (β = −1.25, 95% CI −2.34 to −0.16). TDP-43 (OR 2.00, 95% CI 1.23–3.35) and microvascular copathology (OR 2.02, 95% CI 1.24–3.40) were more common in later onset AD, and α-synuclein copathology was not related to age at onset. NFT density in midfrontal cortex (β = −0.51, 95% CI −0.72 to −0.31) and midfrontal/hippocampal NFT ratio (β = −0.18, 95% CI −0.26 to −0.10) were lower in those with later age at onset. Executive function (β = 0.48, 95% CI 0.09–0.90) and visuospatial cognitive deficits (β = 0.97, 95% CI 0.46–1.46) were less impaired in patients with later age at onset. Mediation analyses showed that the effect of age at onset on severity of executive function deficits was mediated by midfrontal/hippocampal NFT ratio (β = 0.21, 95% CI 0.08–0.38) and not by concomitant non-AD pathologies. Midfrontal/hippocampal NFT ratio also mediated an association between earlier age at onset and faster decline on tests of global cognition, executive function, and visuospatial abilities.DiscussionWorse executive dysfunction and faster cognitive decline in people with sporadic AD with earlier rather than later age at onset is mediated by greater relative midfrontal neocortical to hippocampal NFT burden and not by concomitant non-AD neuropathology.

The decline of speech intelligibility in presbycusis can be regarded as resulting from the combined contribution of two main groups of factors: (1) audibility-related factors and (2) age-related factors. In particular, there is now an abundant scientific literature on the crucial role of suprathreshold auditory abilities and cognitive functions, which have been found to decline with age even in the absence of audiometric hearing loss. However, researchers investigating the direct effect of aging in presbycusis have to deal with the methodological issue that age and peripheral hearing loss covary to a large extent. In the present study, we analyzed a dataset of consonant-identification scores measured in quiet and in noise for a large cohort (n = 459, age = 42–92) of hearing-impaired (HI) and normal-hearing (NH) listeners. HI listeners were provided with a frequency-dependent amplification adjusted to their audiometric profile. Their scores in the two conditions were predicted from their pure-tone average (PTA) and age, as well as from their Extended Speech Intelligibility Index (ESII), a measure of the impact of audibility loss on speech intelligibility. We relied on a causal-inference approach combined with Bayesian modeling to disentangle the direct causal effects of age and audibility on intelligibility from the indirect effect of age on hearing loss. The analysis revealed that the direct effect of PTA on HI intelligibility scores was 5 times higher than the effect of age. This overwhelming effect of PTA was not due to a residual audibility loss despite amplification, as confirmed by a ESII-based model. More plausibly, the marginal role of age could be a consequence of the relatively little cognitively-demanding task used in this study. Furthermore, the amount of variance in intelligibility scores was smaller for NH than HI listeners, even after accounting for age and audibility, reflecting the presence of additional suprathreshold deficits in the latter group. Although the non-sense-syllable materials and the particular amplification settings used in this study potentially restrict the generalization of the findings, we think that these promising results call for a wider use of causal-inference analysis in audiology, e.g., as a way to disentangle the influence of the various cognitive factors and suprathreshold deficits associated to presbycusis.

International audience; Metal(loid)s found at many sites as a result of human activities induce contamination of ecosystems, which threatens the environment and public health. Several approaches can be used in order to reduce such negative impacts of pollutants, and among them, phytoremediation has gained attractive attention. The objective of the present study was to assess the capacity of Populus euramericana, Dorskamp cultivar, for the phytoremediation of metal(loid)s on a technosol (former mining site) highly contaminated mainly with Pb and As, and amended with biochars having different particle sizes. In a 46-day mesocosm glasshouse pot experiment, technosol was mixed at three ratios (0, 2, or 5% w/w) with four different hardwood-derived biochars (with various particle sizes) in order to study the biochar application rate and particle size effects on soil pore water (SPW) characteristics, on poplar growth, and on metal(loid) distribution and concentrations in the plant organs. The results showed that all biochars tested had a significant impact on several SPW physico-chemical parameters. Especially, biochar additions reduced available Pb concentrations but with no effect on As. In such conditions, Populus growth in amended technosol increased whatever rate and particle size of biochar used. Metal(loid) concentrations and repartition in plant organs showed the following: (1) for Pb, a higher root concentration with low aerial part translocation, which depended on biochar used, and (2) for As, mainly a root sequestration. We identified biochar with the finest particle size and combined with P. euramericana, Dorskamp, was the most suitable as remediation tools for Pb stabilization in post-mining contaminated soils.

Author(s): Boeve, Bradley F; Boxer, Adam L; Rosen, Howard J; Forsberg, Leah K; Heuer, Hilary W; Brushaber, Danielle; Appleby, Brian; Biernacka, Joanna M; Bordelon, Yvette M; Botha, Hugo; Brannelly, Patrick; Dickerson, Brad C; Dickson, Dennis W; Kimiko, Domoto‐Reilly; Faber, Kelley; Fagan, Anne; Fields, Julie A; Fishman, Ann; Foroud, Tatiana M; Galasko, Doug R; Gavrilova, Ralitza H; Gendron, Tania F; Geschwind, Daniel H; Ghoshal, Nupur; Goldman, Jill; Graff‐Radford, Jonathan; Graff‐Radford, Neill R; Grant, Ian; Grossman, Murray; Hsiung, Ging‐Yuek Robin; Huang, Eric J; Huey, Edward; Irwin, David J; Jones, David T; Kantarci, Kejal; Karydas, Anna M; Kaufer, Daniel; Knopman, David S; Kramer, Joel H; Kremers, Walter K; Kornak, John; Kukull, Walter A; Lagone, Emma; Leger, Gabriel C; Litvan, Irene; Ljubenkov, Peter A; Lucente, Diane E; Mackenzie, Ian R; Manoochehri, Masood; Masdeu, Joseph C; McGinnis, Scott; Mendez, Mario F; Miller, Bruce L; Miyagawa, Toji; Nelson, Kevin M; Onyike, Chiadi U; Pantelyat, Alex; Pascual, Belen; Pearlman, Rodney; Petrucelli, Leonard; Rademakers, Rosa; Ramos, Eliana Marisa; Rankin, Katherine; Rascovsky, Katya; Rexach, Jessica E; Ritter, Aaron; Roberson, Erik D; Rojas, Julio C; Sabbagh, Marwan N; Salmon, David P; Savica, Rodolfo; Seeley, William W; Staffaroni, Adam M; Syrjanen, Jeremy; Tartaglia, Carmela; Tatton, Nadine; Taylor, Joanne; Toga, Arthur W; Weintraub, Sandra; Wheaton, Diana; Wong, Bonnie; Wszolek, Zbigniew

Sensitivity to interaural time differences (ITDs) in envelope and temporal fine structure (TFS) of amplitude-modulated (AM) tones was assessed for young and older subjects, all with clinically normal hearing at the carrier frequencies of 250 and 500 Hz. Some subjects had hearing loss at higher frequencies. In experiment 1, thresholds for detecting changes in ITD were measured when the ITD was present in the TFS alone (ITD(TFS)), the envelope alone (ITD(ENV)), or both (ITD(TFS/ENV)). Thresholds tended to be higher for the older than for the young subjects. ITD(ENV) thresholds were much higher than ITD(TFS) thresholds, while ITD(TFS/ENV) thresholds were similar to ITD(TFS) thresholds. ITD(TFS) thresholds were lower than ITD thresholds obtained with an unmodulated pure tone, indicating that uninformative AM can improve ITD(TFS) discrimination. In experiment 2, equally detectable values of ITD(TFS) and ITD(ENV) were combined so as to give consistent or inconsistent lateralization. There were large individual differences, but several subjects gave scores that were much higher than would be expected from the optimal combination of independent sources of information, even for the inconsistent condition. It is suggested that ITD(TFS) and ITD(ENV) cues are processed partly independently, but that both cues influence lateralization judgments, even when one cue is uninformative.

Mitochondrial dysfunction in the spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but the neurometabolic alterations during early stages of the disease remain unknown. Here, we investigated the bioenergetic and proteomic changes in ALS mouse motor neurons and patients’ skin fibroblasts. We first observed that SODG93A mice presymptomatic motor neurons display alterations in the coupling efficiency of oxidative phosphorylation, along with fragmentation of the mitochondrial network. The proteome of presymptomatic ALS mice motor neurons also revealed a peculiar metabolic signature with upregulation of most energy-transducing enzymes, including the fatty acid oxidation (FAO) and the ketogenic components HADHA and ACAT2, respectively. Accordingly, FAO inhibition altered cell viability specifically in ALS mice motor neurons, while uncoupling protein 2 (UCP2) inhibition recovered cellular ATP levels and mitochondrial network morphology. These findings suggest a novel hypothesis of ALS bioenergetics linking FAO and UCP2. Lastly, we provide a unique set of data comparing the molecular alterations found in human ALS patients’ skin fibroblasts and SODG93A mouse motor neurons, revealing conserved changes in protein translation, folding and assembly, tRNA aminoacylation and cell adhesion processes.

Alzheimer's disease (AD) dementia refers to a particular onset and course of cognitive and functional decline associated with age together with a particular neuropathology. It was first described by Alois Alzheimer in 1906 about a patient whom he first encountered in 1901. Modern clinical diagnostic criteria have been developed, and criteria have also been proposed to recognize preclinical (or presymptomatic) stages of the disease with the use of biomarkers. The primary neuropathology was described by Alzheimer, and in the mid-1980s subsequently evolved into a more specific neuropathologic definition that recognizes the comorbid neuropathologies that frequently contribute to clinical dementia. Alzheimer's disease is now the most common form of neurodegenerative dementia in the United States with a disproportionate disease burden in minority populations. Deficits in the ability to encode and store new memories characterizes the initial stages of the disease. Subsequent progressive changes in cognition and behavior accompany the later stages. Changes in amyloid precursor protein (APP) cleavage and production of the APP fragment beta-amyloid (Aβ) along with hyperphosphorylated tau protein aggregation coalesce to cause reduction in synaptic strength, synaptic loss, and neurodegeneration. Metabolic, vascular, and inflammatory changes, as well as comorbid pathologies are key components of the disease process. Symptomatic treatment offers a modest, clinically measurable effect in cognition, but disease-modifying therapies are desperately needed.

Background Skin protectors Dexeryl (D) and Bepanthen (B) contain petroleum derivatives (PD) such as petroleum jelly and paraffin. These substances may favour cutaneous mycosis by triggering an epidermidis pH imbalance and development of fungal infection.1 This observation led our department to limit the use of D and B in favour of calcium hydroxyde liners (L) and care oil (O). In 2016, we initiated a change in practice by providing recommendations, analysis and follow-up of cutaneous topical prescriptions. Purpose The purpose of this study was to determine if there is a correlation between the prescription of PD and the consumption of a topical antifungal, Econazole (E). Material and methods Four-year retrospective analysis of consumption in a geriatrics ward: Skin protector with PD: D, B. Natural skin protector with: L, O. Topical antifungal: E. Comparison of consumption over two periods (period 1: 2014–2015; period 2: 2016–2017) with the Mann–Whitney log rank test. Results Average of mensual consumption, expressed in tubes (T): Period 1: B=117.5T (56; 177), D=52.4T (36; 103), E=79.4T (44; 121), L=2.5T (0; 24), O=171.5T (0; 337). Period 2: B=4.8T (0; 18), D=0.3T (0; 3), E=47.2T (22; 128), L=139.3T (59; 220), O=242T (153; 338). The consumption of B, D, E and L were significantly different between these two periods (p Conclusion A change in routine practice led to decreased consumption of B and D in favour of L. This correlated with a significantly decreased c consumption of E. These results are in agreement with those of a case control study that shows that the use of PD promoted an increase in the incidence of systemic candidiasis.1 From now on, B use is limited only to diaper dermatitis resistant to natural skin protectors in order to limit the risk of epidermitis deterioration. A prospective clinical follow-up is ongoing, with physicians from our department, to complete the data. Reference and/or acknowledgements Campbell J, et al. Systemic candidiasis in extremely low birthweight infants receiving topical petrolatum ointment for care: a case control study. Paediatrics 2000. No conflict of interest.

Acoustic speech is marked by time-varying changes in the amplitude envelope that may pose difficulties for hearing-impaired listeners. Removal of these variations (e.g., by the Hilbert transform) could improve speech reception for such listeners, particularly in fluctuating interference. Léger, Reed, Desloge, Swaminathan, and Braida [(2015b). J. Acoust. Soc. Am. 138, 389–403] observed that a normalized measure of masking release obtained for hearing-impaired listeners using speech processed to preserve temporal fine-structure (TFS) cues was larger than that for unprocessed or envelope-based speech. This study measured masking release for two other speech signals in which level variations were minimal: peak clipping and TFS processing of an envelope signal. Consonant identification was measured for hearing-impaired listeners in backgrounds of continuous and fluctuating speech-shaped noise. The normalized masking release obtained using speech with normal variations in overall level was substantially less than that observed using speech processed to achieve highly restricted level variations. These results suggest that the performance of hearing-impaired listeners in fluctuating noise may be improved by signal processing that leads to a decrease in stimulus level variations.

Introduction The Activities of Daily Living Questionnaire (ADL-Q) is an informant report questionnaire assessing functional impairment in daily living skills. Previous research has demonstrated correlations between ADL-Q and cognitive screening measures among patients with dementia. This study examined the relationship between ADL-Q and the Montreal Cognitive Assessment (MoCA), a brief cognitive screening. Methods Records of 448 individuals from an outpatient neurology clinic were reviewed. Pearson correlations were calculated between ADL-Q scores and MoCA scores. Linear regression models were fit using demographic information to predict ADL-Q scores. MoCA scores were then added to the models to determine the increase in predictive value of the MoCA. Results Lower MoCA scores were associated with higher levels of functional impairment. For each model, adding the MoCA significantly improved model fit. Discussion Low scores on the MoCA, among patient's presenting for memory complaints, should raise concerns about functional decline and prompt for further assessment of functional ability.

Consonant-identification ability was examined in normal-hearing (NH) and hearing-impaired (HI) listeners in the presence of steady-state and 10-Hz square-wave interrupted speech-shaped noise. The Hilbert transform was used to process speech stimuli (16 consonants in a-C-a syllables) to present envelope cues, temporal fine-structure (TFS) cues, or envelope cues recovered from TFS speech. The performance of the HI listeners was inferior to that of the NH listeners both in terms of lower levels of performance in the baseline condition and in the need for higher signal-to-noise ratio to yield a given level of performance. For NH listeners, scores were higher in interrupted noise than in steady-state noise for all speech types (indicating substantial masking release). For HI listeners, masking release was typically observed for TFS and recovered-envelope speech but not for unprocessed and envelope speech. For both groups of listeners, TFS and recovered-envelope speech yielded similar levels of performance and consonant confusion patterns. The masking release observed for TFS and recovered-envelope speech may be related to level effects associated with the manner in which the TFS processing interacts with the interrupted noise signal, rather than to the contributions of TFS cues per se.

The Montreal Cognitive Assessment (MoCA) has become widely used as a brief test of cognitive function in patients with neurological disease. More convenient application of the MoCA might increase its use and enhance its utility. An electronic version of the MoCA has recently been developed. To establish validity of the electronic version (eMoCA), discrepancy scores, concordance correlation coefficients (CCC), and root mean squared differences (RMSD) were calculated between each administration method in a sample of 43 new adult patients presenting with primary memory complaints. The CCC was 0.84 and the RMSD was 2.27, with 76% of the sample having a difference score within 2 points. Overall, this study establishes adequate convergent validity between the MoCA and eMoCA among an adult population presenting with memory concerns.

Narrowband speech can be separated into fast temporal cues [temporal fine structure (TFS)], and slow amplitude modulations (envelope). Speech processed to contain only TFS leads to envelope recovery through cochlear filtering, which has been suggested to account for TFS-speech intelligibility for normal-hearing listeners. Hearing-impaired listeners have deficits with TFS-speech identification, but the contribution of recovered-envelope cues to these deficits is unknown. This was assessed for hearing-impaired listeners by measuring identification of disyllables processed to contain TFS or recovered-envelope cues. Hearing-impaired listeners performed worse than normal-hearing listeners, but TFS-speech intelligibility was accounted for by recovered-envelope cues for both groups.

The auditory system processes temporal information at multiple scales, and disruptions to this temporal processing may lead to deficits in auditory tasks such as detecting and discriminating sounds in a noisy environment. Here, a modelling approach is used to study the temporal regularity of firing by chopper cells in the ventral cochlear nucleus, in both the normal and impaired auditory system. Chopper cells, which have a strikingly regular firing response, divide into two classes, sustained and transient, based on the time course of this regularity. Several hypotheses have been proposed to explain the behaviour of chopper cells, and the difference between sustained and transient cells in particular. However, there is no conclusive evidence so far. Here, a reduced mathematical model is developed and used to compare and test a wide range of hypotheses with a limited number of parameters. Simulation results show a continuum of cell types and behaviours: chopper-like behaviour arises for a wide range of parameters, suggesting that multiple mechanisms may underlie this behaviour. The model accounts for systematic trends in regularity as a function of stimulus level that have previously only been reported anecdotally. Finally, the model is used to predict the effects of a reduction in the number of auditory nerve fibres (deafferentation due to, for example, cochlear synaptopathy). An interactive version of this paper in which all the model parameters can be changed is available online.HighlightsA low parameter model reproduces chopper cell firing regularityMultiple factors can account for sustained vs transient chopper cell responseThe model explains stimulus level dependence of firing regularityThe model predicts chopper cells fire more irregularly after deafferentationAn interactive version of the paper allows readers to change parameters

The ability to identify syllables in the presence of speech-shaped noise and a single-talker background was measured for 18 normal-hearing (NH) listeners, and for eight hearing-impaired (HI) listeners with near-normal audiometric thresholds for frequencies up to 1.5 kHz and a moderate to severe hearing loss above 2 kHz. The stimulus components were restricted to the low-frequency (≤1.5 kHz) region, where audiometric thresholds were classified clinically as normal or near normal for all listeners. Syllable identification in a speech background was measured as a function of the fundamental-frequency (F0) difference between competing voices (ranging from 1 semitone to ~1 octave). HI listeners had poorer syllable intelligibility than NH listeners in all conditions. Intelligibility decreased by about the same amount for both groups when the F0 difference between competing voices was reduced. The results suggest that the ability to identify speech against noise or an interfering talker was disrupted in frequency regions of near-normal hearing for HI listeners, but that the ability to benefit from the tested F0 differences was not disrupted. This deficit was not predicted by the elevated absolute thresholds for speech in speech, but it was for speech in noise. It may result from supra-threshold auditory deficits associated with ageing.

This study aimed to assess whether the capacity of cochlear implant (CI) users to identify speech is determined by their capacity to perceive slow (20 Hz) temporal modulations.This was achieved by studying the correlation between (1) phoneme identification in quiet and in a steady-state or fluctuating (8 Hz) noises, and (2) amplitude-modulation detection thresholds (MDTs) at 8 Hz (i.e. slow temporal modulations).Twenty-one CI users, unilaterally implanted with the same device, were tested in free field with their everyday clinical processor.Extensive variability across subjects was observed for both phoneme identification and MDTs. Vowel and consonant identification scores in quiet were significantly correlated with MDTs at 8 Hz (r = - 0.47 for consonants, r = - 0.44 for vowels; p0.05). When the masker was a steady-state noise, only consonant identification scores tended to correlate with MDTs at 8 Hz (r = - 0.4; p = 0.07). When the masker was a fluctuating noise, consonant and vowel identification scores were not significantly correlated with MDTs at 8 Hz.Sensitivity to slow amplitude modulations is correlated with vowel and consonant perception in CI users. However, reduced sensitivity to slow modulations does not entirely explain the limited capacity of CI recipients to understand speech in noise.

Background: Behavioral variant frontotemporal dementia (bvFTD) is pathologically heterogeneous. With emerging therapeutics, determining underlying pathology during life is increasingly important. Neuropsychiatric symptoms are prevalent and diagnostic in bvFTD. Methods: We assessed the neuropsychiatric profile of patients with clinically diagnosed bvFTD as a function of pathology at autopsy. Patients with a clinical diagnosis of bvFTD at the initial visit were selected from the National Alzheimer's Coordinating Center (NACC) database. Neuropsychiatric symptoms endorsed on the Neuropsychiatric Inventory Questionnaire (NPI-Q) were analyzed. Results: Of 149 patients with clinically diagnosed bvFTD, pathology was primarily Alzheimer's disease (AD) in 20.5%. These patients differed from those with underlying frontotemporal lobar degeneration: patients with AD pathology (plaques and tangles) were more likely to have hallucinations, delusions, or agitation. Patients were further differentiated into tau-positive (30% of cases, including Pick's disease, FTD and parkinsonism with tau-positive or argyrophilic inclusions, and other tauopathies) or tau-negative cases (70% of cases, including bvFTD tau-negative ubiquitin-positive inclusions). These patients also differed in some of the neuropsychiatric symptoms seen. Tau-negative cases were more likely to demonstrate depression, delusions, and changes in appetite and eating. Conclusions: These preliminary findings contribute to our increasing ability to predict, using simple clinical tools, the neuropathological underpinnings of bvFTD during life.

Background/aims Differences in cognition between frontotemporal dementia (FTD) and Alzheimer disease (AD) are well described in clinical cohorts, but have rarely been confirmed in studies with pathologic verification. For emerging therapeutics to succeed, determining underlying pathology early in the disease course is increasingly important. Neuropsychological evaluation is an important component of the diagnostic workup for AD and FTD. Patients with FTD are thought to have greater deficits in language and executive function while patients with AD are more likely to have deficits in memory. Objectives To determine if performance on initial cognitive testing can reliably distinguish between patients with frontotemporal lobar degeneration (FTLD) and AD neuropathology. In addition, are there other factors of the neuropsychological assessment that can be used to enhance the accuracy of underlying pathology? Methods Using a logistic regression we retrospectively compared neurocognitive performance on initial evaluation of 106 patients with pathologically verified FTLD (pvFTLD), with 558 pathologically verified AD (pvAD) patients from the National Alzheimer's Coordinating Center using data from the Uniform Data Set (UDS) and the neuropathology data set. Results As expected, pvFTLD patients were younger, demonstrated better memory performance, and had more neuropsychiatric symptoms than pvAD patients. Other results were less predictable: pvFTLD patients performed better on one test of executive function (trail making test part B) but worse on another (digit span backward). Performance on language testing did not strongly distinguish the 2 groups. To determine what factors led to a misdiagnosis of AD in patients with FTLD, we further analyzed a small group of pvFTLD patients. These patients demonstrated older age and lower Neuropsychiatric Inventory Questionnaire counts compared with accurately diagnosed cases. Conclusions Other than memory, numerical scores of neurocognitive performance on the UDS are of limited value in differentiating FTLD from AD at the initial visit. These results highlight the difficulty of obtaining an accurate early diagnosis of FTLD and argue for adding supplemental tests to those included in the UDS to assess cognition in FTD and AD patients.

Our experiences, even as adults, shape our brains. Regional differences have been found in experts, with the regions associated with their particular skill-set. Functional differences have also been noted in brain activation patterns in some experts. This study uses multimodal techniques to assess structural and functional patterns that differ between experts and non-experts. Sommeliers are experts in wine and thus in olfaction. We assessed differences in Master Sommeliers’ brains, compared with controls, in structure and also in functional response to olfactory and visual judgment tasks. MRI data were analyzed using voxel-based morphometry as well as automated parcellation to assess structural properties, and group differences between tasks were calculated. Results indicate enhanced volume in the right insula and entorhinal cortex, with the cortical thickness of the entorhinal correlating with experience. There were regional activation differences in a large area involving the right olfactory and memory regions, with heightened activation specifically for sommeliers during an olfactory task. Our results indicate that sommeliers’ brains show specialization in the expected regions of the olfactory and memory networks, and also in regions important in integration of internal sensory stimuli and external cues. Overall, these differences suggest that specialized expertise and training might result in enhancements in the brain well into adulthood. This is particularly important given the regions involved, which are the first to be impacted by many neurodegenerative diseases.

Background: Patients with frontotemporal dementia (FTD) typically have initial deficits in language or changes in personality, while the defining characteristic of Alzheimer's disease (AD) is memory impairment. Neuropsychological findings in the two diseases tend to differ, but can be confounded by verbal impairment in FTD impacting performance on memory tests in these patients. Methods: Twenty-seven patients with FTD and 102 patients with AD underwent a neuropsychological assessment before diagnosis. By utilizing analogous versions of a verbal and nonverbal memory test, we demonstrated differences in these two modalities between AD and FTD. Discussion: Better differentiation between AD and FTD is found in a nonverbal memory test, possibly because it eliminates the confounding variable of language deficits found in patients with FTD. These results highlight the importance of nonverbal learning tests with multiple learning trials in diagnostic testing.

Recent studies suggest that normal-hearing listeners maintain robust speech intelligibility despite severe degradations of amplitude-modulation (AM) cues, by using temporal-envelope information recovered from broadband frequency-modulation (FM) speech cues at the output of cochlear filters. This study aimed to assess whether cochlear damage affects this capacity to reconstruct temporal-envelope information from FM. This was achieved by measuring the ability of 40 normal-hearing listeners and 41 listeners with mild-to-moderate hearing loss to identify syllables processed to degrade AM cues while leaving FM cues intact within three broad frequency bands spanning the range 65–3,645 Hz. Stimuli were presented at 65 dB SPL for both normal-hearing listeners and hearing-impaired listeners. They were presented as such or amplified using a modified half-gain rule for hearing-impaired listeners. Hearing-impaired listeners showed significantly poorer identification scores than normal-hearing listeners at both presentation levels. However, the deficit shown by hearing-impaired listeners for amplified stimuli was relatively modest. Overall, hearing-impaired data and the results of a simulation study were consistent with a poorer-than-normal ability to reconstruct temporal-envelope information resulting from a broadening of cochlear filters by a factor ranging from 2 to 4. These results suggest that mild-to-moderate cochlear hearing loss has only a modest detrimental effect on peripheral, temporal-envelope reconstruction mechanisms.

Léger et al. [J. Acoust. Soc. Am. 131, 1502-1514 (2012)] reported deficits in the identification of consonants in noise by hearing-impaired listeners using stimuli filtered into low- or mid-frequency regions in which audiometric thresholds were normal or near-normal. The deficits could not be fully explained in terms of reduced audibility or temporal-envelope processing. However, previous studies indicate that the listeners may have had reduced frequency selectivity, with auditory filters broadened by a factor of about 1.3, despite having normal or near-normal audiometric thresholds in the tested regions. The present study aimed to determine whether the speech-perception deficits could be explained by such a small reduction of frequency selectivity. Consonant identification was measured for normal-hearing listeners in quiet and in unmodulated and modulated noises using the same method as Léger et al. The signal-to-noise ratio was set to -3 dB for the masked conditions. Various amounts of reduced frequency selectivity were simulated using a spectral-smearing algorithm. Performance was reduced only for spectral-smearing factors greater than 1.7. For all conditions, identification scores for hearing-impaired listeners could not be explained by a mild reduction of frequency selectivity.

"Masking release" (MR), the improvement of speech intelligibility in modulated compared with unmodulated maskers, is typically smaller than normal for hearing-impaired listeners. The extent to which this is due to reduced audibility or to suprathreshold processing deficits is unclear. Here, the effects of audibility were controlled by using stimuli restricted to the low- (≤1.5 kHz) or mid-frequency (1-3 kHz) region for normal-hearing listeners and hearing-impaired listeners with near-normal hearing in the tested region. Previous work suggests that the latter may have suprathreshold deficits. Both spectral and temporal MR were measured. Consonant identification was measured in quiet and in the presence of unmodulated, amplitude-modulated, and spectrally modulated noise at three signal-to-noise ratios (the same ratios for the two groups). For both frequency regions, consonant identification was poorer for the hearing-impaired than for the normal-hearing listeners in all conditions. The results suggest the presence of suprathreshold deficits for the hearing-impaired listeners, despite near-normal audiometric thresholds over the tested frequency regions. However, spectral MR and temporal MR were similar for the two groups. Thus, the suprathreshold deficits for the hearing-impaired group did not lead to reduced MR.

Objective To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype. Methods Neuropsychological and neuropathological analyses of 23 consecutive PPA autopsies. All had qualitative determination of neurofibrillary tangle (NFT) density. Additional quantitation was done in four of the PPA/AD cases and four AD cases with the typical amnestic dementia of the Alzheimer type. Results The sample contained mostly logopenic, agrammatic, and mixed forms of PPA. All six agrammatics had frontotemporal lobar degeneration (five of six with tauopathy). Seven of the 11 logopenics had AD. In logopenics, lower memory scores increased the probability of AD, but there were exceptions. The PPA/AD group showed predominance of entorhinal NFT typical of the amnestic dementia of the Alzheimer type. In the small subgroup examined quantitatively, neocortical NFTs were more numerous in the left hemisphere of PPA/AD. However, the asymmetry was low and inconsistent. Neuritic plaques did not display consistent asymmetry. Apolipoprotein E4, a major risk factor for typical AD, did not predict AD pathology in PPA. Interpretation Subtyping PPA helps to predict AD versus frontotemporal lobar degeneration pathology at the group level. However, our results and the literature also indicate that no clinical predictor is completely reliable in individual patients. The inconsistent concordance of NFT distribution with the asymmetric atrophy and the nonamnestic phenotype also raises the possibility that the AD markers encountered at autopsy in PPA may not always reflect the nature of the initiating neurodegenerative process. Ann Neurol 2008

This article critically considers current diagnostic criteria for dementia and reports recommendations approved by at least 80% of experts attending the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD3). There was consensus that many of the features proposed as essential to a diagnosis of dementia in the 1980s no longer are relevant (for example, the requirements for memory impairment, electroencephalogram and cerebrospinal fluid studies, age-specific exclusions). In addition, other syndromes such as frontotemporal dementia have been recognized and need to inform new dementia criteria. It is also recognized that a diagnosis of depression need not exclude a dementia diagnosis. Other proposals, such as neuropathology should be considered as additional evidence and not as a gold standard or that some people with dementia have prolonged plateaus so that progressive decline need not be a criterion for Alzheimer's disease (AD), were more controversial and did not receive similar support. Given the evidence of the last three decades, there is merit in reconsidering the criteria by which dementia and AD are diagnosed.

The efficacy of levo-DOPA in the treatment of Parkinson's disease is potentiated by blockade of its peripheral metabolism with inhibitors of catechol-O-methyltransferase (COMT). Some COMT inhibitors may act entirely in the periphery (nitecapone, OR-462), while others may also have some activity in brain (entacapone, OR-611). We used positron emission tomography (PET) to test the effects of these two COMT inhibitors on the plasma kinetics and brain metabolism of the levo-DOPA analog 6-[18F]fluoro-L-dopa (FDOPA) in cynomolgus monkeys, employing a compartmental model for the assay of DOPA decarboxylase activity in living brain. Four monkeys each underwent two PET scans in the baseline condition, one PET scan after treatment with OR-462 (15 mg/kg, i.v.), and one PET scan after treatment with OR-611 (15 mg/kg, i.v.). Pharmacokinetic analysis of FDOPA metabolism in plasma indicated that these compounds blocked peripheral COMT activity by 80% for at least 60 minutes. Both COMT inhibitors increased the net availability of FDOPA in circulation, and increased the ratio of the radioactivity concentrations in striatum and occipital cortex, suggesting that [18F]fluorodopamine synthesis in striatum was potentiated. However, OR-611 treatment reduced the unidirectional (K1D) and net (Ki) blood-brain clearances of FDOPA, and also inhibited the rate of decarboxylation (k3D) of FDOPA in striatum. These observations suggest that high doses of OR-611 may partially antagonize the cerebral utilization of levo-DOPA. We used the present data to test the sensitivity of the compartmental model to the physiological constraint that the blood-brain permeabilities of the O-methylated plasma metabolite and FDOPA have a fixed ratio. In the groups with COMT inhibition, the estimates of k3D were insensitive to the magnitude of the permeability ratio. In the control group, the estimate of k3D increased by 40% as the magnitude of the constrained permeability ratio increased in the range of published estimates.

In this study, ceramic binary or ternary compounds were tested for their suitability to serve as inert matrices for transmutation of the minor actinides Np and Am, i.e. to achieve a reduction in their quantities by irradiation in nuclear reactors without formation of new actinides from the matrix. Five materials (MgAl 2 O 4 , ZrSiO 4 , CeO 2 , SiC and Si 3 N 4 ) were selected and produced without and with 241 Am using the well known soaking method. Special emphasis was put on the characterization of the materials and the measurement of thermal properties like heat capacity and thermal diffusivity. Irradiation damage was investigated by ion implantation experiments. X-ray diffraction measurements of MgAl 2 O 4 , CeO 2 and ZrSiO 4 were performed on the as-produced specimens to provide the basis for evaluating expected lattice parameter changes during self-irradiation by α-decay in future experiments. In addition, ceramic samples containing 20 wt % UO 2 were produced to demonstrate that matrix materials can accept large amounts of an oxide similar to americium oxide. An assessment of thermodynamic data for the systems SiC+UO 2 and Si 3 N 4 +UO 2 was used to calculate pseudobinary phase diagrams. Structural, thermal and thermodynamic aspects of all selected matrices, and the reasons for their selection are discussed.

Alzheimer's disease is the most common cause of dementia and is becoming a global health concern. Despite a well-established understanding of the molecular mechanism involved in its pathogenesis, and millions of dollars of investment in drug discovery and clinical trials, no single molecule has yet been approved for its treatment since the advent of cholinesterase inhibitors and memantine. This review examines first the optimal use of currently approved agents and then explores in detail the current Phase II and III clinical trial landscape, while spending some time on the mechanistic details. Driven by the increasing knowledge gleaned from numerous Phase III failures and improvements in early detection and biomarkers, there is renewed enthusiasm that a cure is taking shape along the visible horizon.

Cochlear synaptopathy, or “hidden hearing loss,” refers to a loss of synapses between inner hair cells and auditory nerve fibers, and affects primarily low-spontaneous-rate fibers that encode moderate-to-high intensity sounds. In rodent models, cochlear synaptopathy has been shown to occur as a result of noise exposure even when threshold sensitivity is unaffected. We tested 126 young humans with normal audiograms and a wide range of lifetime noise exposures quantified using a questionnaire. Our electrophysiological and behavioral measures were designed to be sensitive to the contribution of low-spontaneous-rate fibers. We predicted that our test battery would reveal that noise exposure is associated with attenuated electrophysiological responses, and elevated behavioural thresholds, especially at higher levels and frequencies. However, there was no relation between noise exposure history and auditory brainstem response wave I amplitude, nor performance on psychophysical tasks including modulation detecti...

Cochlear synaptopathy, or “hidden hearing loss,” refers to a loss of synapses between inner hair cells and auditory nerve fibers, and is observed in rodent models as a consequence of noise exposure and/or aging. In humans, cochlear synaptopathy is not thought to be detectable by pure tone audiometry, as thresholds to soft sounds in the rodent models are not permanently elevated. One hundred and forty audiometrically normal participants below the age of 35 and with a range of lifetime noise exposures performed an extensive battery of tests, including electrophysiological measures, psychophysical tests, and speech-in-noise tests. Inter-aural phase discrimination, amplitude modulation detection, and spatial release from masking on a speech task were found to be sensitive to noise exposure; however, these trends are weak and only the phase discrimination task followed the predicted direction (i.e., high noise exposed individuals showing elevated thresholds). None of the electrophysiological measures, including wave I of the ABR, showed a strong relation with noise exposure. The results suggest that either: (i) hidden hearing loss is not prevalent in young normally hearing adults, or (ii) even listeners with comparatively low levels of noise exposure have the disorder and that there is no additional consequence of high levels of exposure.

Objective: To review the different pharmacological approaches to the cognitive, functional, and behavioural manifestations of Alzheimer disease (AD). Methods: We searched and critically analyzed the most recent relevant literature on pharmacological treatment of AD. Results: The current pharmacological approach to AD treatment is based on vascular prevention and symptomatic therapy with cholinesterase inhibitors (ChEIs) and memantine, an N-methyl-d-aspartic acid antagonist. Clinical trials of 6– to 12–month duration have shown statistically significant benefits with ChEIs and memantine on cognitive, global, functional, and behavioural outcome measures. In general, these benefits are modest. However, they are dose-dependent and reproducible across studies. Most importantly, these benefits are symptomatic as they do not alter disease course. According to the third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, these agents are considered standard treatment options in AD. We will discuss practical issues related to current pharmacological management, such as setting realistic expectations, management of side effects, switching ChEIs, and the decision to discontinue treatment. The results of clinical trials studying potentially disease-modifying approaches in AD will also be reviewed. Unfortunately, although there remains much promise and enthusiasm, none of these agents has shown consistent benefits, and none are available for use in clinical practice. Conclusion: Pharmacological options are presently available for the symptomatic treatment of AD. These treatments provide mild but sustained benefits. Before disease-modifying approaches become available, optimizing the use of the available treatment options is crucial.

This chapter presents a case of a 67-year-old right-handed woman with a history of a 3 cm mid left parietal lobe intra-cerebral hemorrhage (ICH) of uncertain etiology admitted to the inpatient neurology service after an acute episode of witnessed productive aphasia and inability to obey commands during an outpatient neurology assessment. Cognitive history indicates that she has noticed minor deficits of short-term memory and word finding since her stroke, but denied any functional deficits associated with her cognition. The patient was started on citalopram with the goal of improving her initiative and a cholinesterase inhibitor for her vascular cognitive impairment (VCI). A trial of cholinesterase inhibitor with measurable outcomes identified at the outset is reasonable, particularly since a neurodegenerative process cannot be ruled out as a contributing factor. Ongoing partial seizures may contribute to cognitive impairment. This patient's lamotrigine should be titrated to minimize future seizures.