Language Decline Research Articles

Naming-related spectral responses predict neuropsychological outcome after epilepsy surgery.

This prospective study determined the use of intracranially recorded spectral responses during naming tasks in predicting neuropsychological performance following epilepsy surgery. We recruited 65 patients with drug-resistant focal epilepsy who underwent preoperative neuropsychological assessment and intracranial EEG recording. The Clinical Evaluation of Language Fundamentals evaluated the baseline and postoperative language function. During extra-operative intracranial EEG recording, we assigned patients to undergo auditory and picture naming tasks. Time-frequency analysis determined the spatiotemporal characteristics of naming-related amplitude modulations, including high gamma augmentation at 70-110 Hz. We surgically removed the presumed epileptogenic zone based on the intracranial EEG and MRI abnormalities while maximally preserving the eloquent areas defined by electrical stimulation mapping. The multivariate regression model incorporating auditory naming-related high gamma augmentation predicted the postoperative changes in Core Language Score with r2 of 0.37 and in Expressive Language Index with r2 of 0.32. Independently of the effects of epilepsy and neuroimaging profiles, higher high gamma augmentation at the resected language-dominant hemispheric area predicted a more severe postoperative decline in Core Language Score and Expressive Language Index. Conversely, the model incorporating picture naming-related high gamma augmentation predicted the change in Receptive Language Index with an r2 of 0.50. Higher high gamma augmentation independently predicted a more severe postoperative decline in Receptive Language Index. Ancillary regression analysis indicated that naming-related low gamma augmentation and alpha/beta attenuation likewise independently predicted a more severe Core Language Score decline. The machine learning-based prediction model suggested that naming-related high gamma augmentation, among all spectral responses used as predictors, most strongly contributed to the improved prediction of patients showing a >5-point Core Language Score decline (reflecting the lower 25th percentile among patients). We generated the model-based atlas visualizing sites, which, if resected, would lead to such a language decline. With a 5-fold cross-validation procedure, the auditory naming-based model predicted patients who had such a postoperative language decline with an accuracy of 0.80. The model indicated that virtual resection of an electrical stimulation mapping-defined language site would have increased the relative risk of the Core Language Score decline by 5.28 (95% confidence interval: 3.47-8.02). Especially, that of an electrical stimulation mapping-defined receptive language site would have maximized it to 15.90 (95% confidence interval: 9.59-26.33). In summary, naming-related spectral responses predict neuropsychological outcomes after epilepsy surgery. We have provided our prediction model as an open-source material, which will indicate the postoperative language function of future patients and facilitate external validation at tertiary epilepsy centres.

Structure and function of language networks in temporal lobe epilepsy.

Individuals with temporal lobe epilepsy (TLE) may have significant language deficits. Language capabilities may further decline following temporal lobe resections. The language network, comprising dispersed gray matter regions interconnected with white matter fibers, may be atypical in individuals with TLE. This review explores the structural changes to the language network and the functional reorganization of language abilities in TLE. We discuss the importance of detailed reporting of patient's characteristics, such as, left- and right-sided focal epilepsies as well as lesional and nonlesional pathological subtypes. These factors can affect the healthy functioning of gray and/or white matter. Dysfunction of white matter and displacement of gray matter function could concurrently impact their ability, in turn, producing an interactive effect on typical language organization and function. Surgical intervention can result in impairment of function if the resection includes parts of this structure-function network that are critical to language. In addition, impairment may occur if language function has been reorganized and is included in a resection. Conversely, resection of an epileptogenic zone may be associated with recovery of cortical function and thus improvement in language function. We explore the abnormality of functional regions in a clinically applicable framework and highlight the differences in the underlying language network. Avoidance of language decline following surgical intervention may depend on tailored resections to avoid critical areas of gray matter and their white matter connections. Further work is required to elucidate the plasticity of the language network in TLE and to identify sub-types of language representation, both of which will be useful in planning surgery to spare language function.

Can bilingualism increase neuroplasticity of language networks in epilepsy?

Individuals with left temporal lobe epilepsy (TLE) have a higher rate of atypical (i.e., bilateral or right hemisphere) language lateralization compared to healthy controls. In addition, bilinguals have been observed to have a less left-lateralized pattern of language representation. We examined the combined influence of bilingual language experience and side of seizure focus on language lateralization profiles in TLE to determine whether bilingualism promotes re-organization of language networks. Seventy-two monolingual speakers of English (21 left TLE; LTLE, 22 right TLE; RTLE, 29 age-matched healthy controls; HC) and 24 English-dominant bilinguals (6 LTLE, 7 RTLE, 11 HC) completed a lexical-semantic functional MRI task and standardized measures of language in English. Language lateralization was determined using laterality indices based on activations in left vs right homologous perisylvian regions-of-interest (ROIs). In a fronto-temporal ROI, LTLE showed the expected pattern of weaker left language lateralization relative to HC, and monolinguals showed a trend of weaker left language lateralization relative to bilinguals. Importantly, these effects were qualified by a significant group by language status interaction, revealing that bilinguals with LTLE had greater rightward language lateralization relative to monolingual LTLE, with a large effect size particularly in the lateral temporal region. Rightward language lateralization was associated with better language scores in bilingual LTLE. These preliminary findings suggest a combined effect of bilingual language experience and a left hemisphere neurologic insult, which may together increase the likelihood of language re-organization to the right hemisphere. Our data underscore the need to consider bilingualism as an important factor contributing to language laterality in patients with TLE. Bilingualism may be neuroprotective pre-surgically and may mitigate post-surgical language decline following left anterior temporal lobectomy, which will be important to test in larger samples.

Grey and white matter atrophy 1 year after stroke aphasia

Dynamic whole-brain changes occur following stroke, and not just in association with recovery. We tested the hypothesis that the presence of a specific behavioural deficit after stroke would be associated with structural decline (atrophy) in the brain regions supporting the affected function, by examining language deficits post-stroke. We quantified whole-brain structural volume changes longitudinally (3–12 months) in stroke participants with (N = 32) and without aphasia (N = 59) as assessed by the Token Test at 3 months post-stroke, compared with a healthy control group (N = 29). While no significant difference in language decline rates (change in Token Test scores from 3 to 12 months) was observed between groups and some participants in the aphasic group improved their scores, stroke participants with aphasia symptoms at 3 months showed significant atrophy (>2%, P = 0.0001) of the left inferior frontal gyrus not observed in either healthy control or non-aphasic groups over the 3–12 months period. We found significant group differences in the inferior frontal gyrus volume, accounting for age, sex, stroke severity at baseline, education and total intracranial volume (Bonferroni-corrected P = 0.0003). In a subset of participants (aphasic N = 14, non-aphasic N = 36, and healthy control N = 25) with available diffusion-weighted imaging data, we found significant atrophy in the corpus callosum and the left superior longitudinal fasciculus in the aphasic compared with the healthy control group. Language deficits at 3 months post-stroke are associated with accelerated structural decline specific to the left inferior frontal gyrus, highlighting that known functional brain reorganization underlying behavioural improvement may occur in parallel with atrophy of brain regions supporting the language function.

Alzheimer cafè: toward bridging the gap between cure and care in patients with dementia

Background Alzheimer’s disease (AD) is the most common form of degenerative dementia, whose symptoms usually appear in the pre-senile age. In the early stages, patients present social difficulties due to the general cognitive decline in memory, language and executive domains. These problems also affect patients’ quality of life, emotions, and mood, leading to social isolation. Objective The aim of this study is to evaluate the effects of Alzheimer’s Cafè (AC) on the cognitive and behavioral outcomes of AD patients. Methods Twenty patients diagnosed with AD, who attended the Cognitive and Behavioral Rehabilitation Laboratory of the IRCCS Centro Neurolesi ‘Bonino-Pulejo’ of Messina, Italy, from December 2017 to December 2018, were enrolled in this study. As these patients belonged to the experimental group (EG: n = 20), they received specific cognitive-behavior training using the AC modality. The patients were assessed by a neuropsychological evaluation at the beginning and at the end of the program. Their outcomes were compared to a matched group of patients with neurodegenerative dementia (CG: 20) receiving conventional cognitive training. Results The pre-post comparisons showed that both CG and EG had a significant improvement in global cognitive functioning (MoCA p < 0.001) and in perceived quality of life (<0.001). However, only in the EG, we observed a significant increase in social functioning (SASS p < 0.00), the perception of mental well-being (SF-12 Mental p < 0.00), and a reduction in the depressive state (GDS p < 0.00). Conclusions The present study suggests the importance of AC for patients with AD and the potential effect on psychological and social well-being.

Dual-Task nTMS Mapping to Visualize the Cortico-Subcortical Language Network and Capture Postoperative Outcome-A Patient Series in Neurosurgery.

BackgroundPerioperative assessment of language function in brain tumor patients commonly relies on administration of object naming during stimulation mapping. Ample research, however, points to the benefit of adding verb tasks to the testing paradigm in order to delineate and preserve postoperative language function more comprehensively. This research uses a case series approach to explore the feasibility and added value of a dual-task protocol that includes both a noun task (object naming) and a verb task (action naming) in perioperative delineation of language functions.Materials and MethodsSeven neurosurgical cases underwent perioperative language assessment with both object and action naming. This entailed preoperative baseline testing, preoperative stimulation mapping with navigated Transcranial Magnetic Stimulation (nTMS) with subsequent white matter visualization, intraoperative mapping with Direct Electrical Stimulation (DES) in 4 cases, and postoperative imaging and examination of language change.ResultsWe observed a divergent pattern of language organization and decline between cases who showed lesions close to the delineated language network and hence underwent DES mapping, and those that did not. The latter displayed no new impairment postoperatively consistent with an unharmed network for the neural circuits of both object and action naming. For the cases who underwent DES, on the other hand, a higher sensitivity was found for action naming over object naming. Firstly, action naming preferentially predicted the overall language state compared to aphasia batteries. Secondly, it more accurately predicted intraoperative positive language areas as revealed by DES. Thirdly, double dissociations between postoperatively unimpaired object naming and impaired action naming and vice versa indicate segregated skills and neural representation for noun versus verb processing, especially in the ventral stream. Overlaying postoperative imaging with object and action naming networks revealed that dual-task nTMS mapping can explain the drop in performance in those cases where the network appeared in proximity to the resection cavity.ConclusionUsing a dual-task protocol for visualization of cortical and subcortical language areas through nTMS mapping proved to be able to capture network-to-deficit relations in our case series. Ultimately, adding action naming to clinical nTMS and DES mapping may help prevent postoperative deficits of this seemingly segregated skill.

Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study.

IntroductionThe contribution of genetic and environmental factors to the relation between cerebrospinal fluid (CSF) biomarkers and cognitive decline in preclinical Alzheimer's disease remains unclear. We studied this in initially cognitively normal monozygotic twins.MethodsWe included 122 cognitively normal monozygotic twins (51 pairs) with a follow‐up of 4.3 ± 0.4 years. We first tested associations of baseline CSF Aβ1‐42/1‐40 ratio, total tau (t‐tau), and 181‐phosphorylated‐tau (p‐tau) status with subsequent cognitive decline using linear mixed models, and then performed twin specific analyses.ResultsBaseline abnormal amyloid‐β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid‐β and p‐tau markers in one twin predicted decline in memory in the co‐twin and tau markers in one twin predicted decline in language in the co‐twin (r range ‐0.26,0.39; p’s ≤ .02).DiscussionThese results suggest that memory and language decline are early features of AD that are in part determined by the same genetic factors that influence amyloid‐β and tau regulation.

A Potential New Alzheimer’s Treatment That May Function by Modulating the Gut Microbiota

Alzheimer’s disease (AD) is the most common form of dementia, and causes a progressive decline in memory, language, executive and visuospatial function, personality, and behaviour. For many years, there have been only four approved medications to help improve cognition in patients with AD, but these only address the symptoms, and do not affect the course of the underlying disease. Here we discuss information presented at the 13th and 14th Clinical Trials on Alzheimer’s Disease conferences about the GREEN MEMORY trial (NCT04520412) of GV-971® (sodium oligomannate). This treatment, as well as the recently approved aducanumab, provides hope that new therapeutics with novel mechanisms of action may provide disease-modifying effects and help slow disease progression in people with AD.

Pediatric GAD-65 Autoimmune Encephalitis: Assessing Clinical Characteristics and Response to Therapy With a Novel Assessment Scale

BackgroundGlutamic acid decarboxylase (GAD) encephalitis is a neuroinflammatory disease characterized by a broad range of symptoms including cognitive deficits, behavioral changes, and seizures. Children with this disorder have heterogeneous presentations, and little is known about symptom progression over time and response to immunotherapy. MethodsThis study reports 10 pediatric GAD encephalitis cases and symptoms found at presentation and follow-up. In addition, symptom severity was reported utilizing a novel scale evaluating functional outcomes across the domains affected by autoimmune encephalitis including cognition, language, seizures, psychiatric symptoms, sleep, and movement. Retrospective chart review was conducted for 10 patients aged <18 years, diagnosed with GAD encephalitis, and followed for one year or more. Chart review included clinical, imaging, and laboratory findings at time of diagnosis and at six- and 12-month follow-ups. ResultsAt presentation, cognitive deficits were found in all patients, seizures in six of 10, and language decline in seven of 10. Psychiatric symptoms were prominent for all but one patient with three of nine patients presenting with psychosis. Fatigue, sleep disruption, and movement disorders were less prominent symptoms, occurring in approximately half of the cohort. Cognition and fatigue improved significantly over time when compared with symptom severity, whereas seizures, psychiatric symptoms, and sleep did not. Language and sleep showed improvement only in early stages. Analysis of seizure frequency and type noted variability mirroring trends noted in adult studies of GAD encephalitis. ConclusionsThis study demonstrated the variability of symptom profiles of pediatric GAD encephalitis and benefits of symptom severity scales. Symptom profiles and progression vary in this population.

Abnormal functional connectivity profiles predict drug responsiveness in patients with temporal lobe epilepsy.

This work was undertaken to study the functional connectivity differences between non-seizure-free and seizure-free patients with temporal lobe epilepsy (TLE) and to identify imaging predictors for drug responsiveness in TLE. In this prospective study, 52 patients with TLE who presented undetermined antiseizure medication responsiveness and 55 demographically matched healthy controls were sequentially recruited from Xiangya Hospital. Functional magneticresonanceimaging data were acquired during a Chinese version of the verbal fluency task. The patients were followed up until the outcome could be classified. The subject groups were compared in terms of activation profile, task-residual functional connectivity (trFC), and generalized psychophysiological interaction (gPPI) analyses. Moreover, we extracted imaging characteristics for logistic regression and receiver operating characteristic evaluation. With a mean follow-up of 1.1years, we identified 27 non-seizure-free patients and 19seizure-free patients in the final analyses. The Chinese character verbal fluency task successfully activated the language network and cognitive control network (CCN) and deactivated the default mode network (DMN). In the non-seizure-freedom group, the trFC between the hippocampus and bilateral brain networks was attenuated (p<.05, familywise error corrected). For the gPPI analysis, group differences were mainly located in the precuneus, middle frontal gyrus, and inferior parietal lobule (p<.001, uncorrected; k ≥ 10). The regression model presented high accuracy when predicting non-seizure-free patients (area under the curve = .879, 95% confidence interval = .761-.998). In patients with TLE who would not achieve seizure freedom with current antiseizure medications, the functional connectivity between the hippocampus and central nodes of the DMN, CCN, and language network was disrupted, leading to language decline. Independent of hippocampal sclerosis, abnormalities, especially the effective connectivity from the hippocampus to the DMN, were predictive biomarkers of drug responsiveness in patients with TLE.

Effect of genetic and vascular AD risk factors on rate of cognitive decline in EOAD vs LOAD

AbstractBackground APOE ε4 and vascular factors are well‐known risk factors for developing AD. The effect of these risk factors on rate of cognitive decline in early‐ or late‐onset AD (EOAD and LOAD) is not well understood. We investigated the effect of known AD risk factors (APOE ε4, education, hypertension, diabetes, dyslipidemia, and obesity) on longitudinal cognitive decline in EOAD and LOAD.MethodCognitive and demographic data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study was used. We identified 203 EOAD and 1055 LOAD subjects based on age of onset of cognitive decline &lt; or ≥65. Language function was assessed using the Boston Naming Test. Visuospatial function was assessed using ADAS‐Cog constructional praxis. Verbal memory was assessed by summing the scores of word recall (ADAS‐WRT),Delayed Word recall and Word recognition (ADAS‐Word). Executive function was assessed by using the category fluency test. For general cognition we used Mini‐Mental Status Examination (MMSE) and clinical dementia rating sum of boxes (CDR‐SB). To evaluate whether the risk factors had differential effect on the rate of cognitive decline between EOAD and LOAD, we performed univariable analysis for three‐way interaction (risk factor*time*group) and in multivariable analyses, we included age, time, risk factor, group, two‐way interaction effect (risk factor*group, time*group), and three‐way interaction effect (risk factor*time*group) that showed significance in univariable analyses for three‐ways interaction (p&lt;.05).ResultBaseline characteristics and demographic of participants are described in (Table 1). APOE ε4 carrier status was associated with significantly faster decline in language, visuospatial, verbal memory, executive function and MMSE in LOAD (p&lt;0.05). In EOAD it was only associated with faster decline in language domain (p=0.046). LOAD carriers had slower rate of decline in CDR‐SB. Being overweight was associated with a significantly different rate of decline between EOAD and LOAD for visuospatial function (p=0.04) and MMSE(p=0.02). It was also significantly associated with faster decline in CDR‐SB(p=0.03) in EOAD. Obesity was significantly associated with faster decline in CDR‐SB in EOAD (p=0.004) but not LOAD (Table 2).ConclusionKnown risk factors for AD can have differential effect on type of cognitive trajectories based on age of onset of disease.

Baseline plasma total tau predicts longitudinal cognitive and functional decline in aging adults

AbstractBackgroundPlasma total‐tau (t‐tau) is an emerging biomarker of neurodegeneration and cognitive decline; however, findings are mixed regarding what specific cognitive domains are affected and it is unknown whether plasma t‐tau predicts early functional changes in aging adults at risk for dementia. This study examined baseline plasma t‐tau in relation to longitudinal cognitive and functional trajectories among community‐dwelling older adults.MethodVanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=332, 73±8 years, 40% mild cognitive impairment (MCI)) underwent baseline fasting venous blood draw and serially completed a comprehensive neuropsychological protocol and a 50‐item informant functional abilities questionnaire at study entry, 18‐month, 3‐year, and 5‐year intervals (mean 4.5±1.2 year follow‐up). Plasma t‐tau concentration was measured using single molecule array technology. Linear mixed effects models related baseline t‐tau to cognitive and functional trajectories through interaction with follow‐up time adjusting for baseline age, sex, education, race/ethnicity, apolipoprotein E (APOE) ∑4 status, modified Framingham Stroke Risk Profile, and cognitive diagnosis. Subsequent models assessed t‐tau x cognitive diagnosis and t‐tau x APOE‐∑4 interactions on cognitive and functional trajectories.ResultA higher baseline concentration of t‐tau was associated with faster decline in processing speed (p&lt;.05). Baseline t‐tau concentration interacted with diagnosis on longitudinal trajectories of processing speed (p‐values&lt;.03). After excluding outliers, higher baseline t‐tau was associated with faster decline in language, processing speed, and functional abilities (p‐values&lt;.05) with t‐tau interacting with diagnosis on each of these measures (p‐values&lt;.05). Baseline t‐tau interacted with APOE‐∑4 status on longitudinal trajectories of language after outlier exclusion (p‐values&lt;.04). Associations linking baseline t‐tau with faster decline were largely driven by participants with MCI (p‐values&lt;.05) and APOE‐∑4 carriers (p‐values&lt;.04).ConclusionAmong community‐dwelling aging adults free of clinical dementia, higher baseline plasma t‐tau concentration was associated with faster cognitive and functional decline over a mean 4.5‐year follow‐up. Processing speed was consistently implicated, especially in individuals with MCI. T‐tau may reflect non‐specific brain changes involving widely distributed neuronal networks, leading to slowed processing, a common complaint in aging adults. Taken together, results suggest that plasma t‐tau may be a useful biomarker for cognitive and functional decline in at‐risk individuals.

Lateralized tau deposition and speech, language, and cognition: A descriptive case report

AbstractBackgroundAsymmetric binding patterns in tau PET imaging are sometimes observed, but less is known about how this asymmetry might explain clinical phenotypes and AD variants, especially in a longitudinal context. Previous work has demonstrated that unilateral tau deposition in left frontal and temporal regions is common in logopenic progressive aphasia (lvPPA), an atypical AD variant. This work presents two descriptive case studies of participants with opposing laterality of [18F]MK‐6240, a PET radioligand for AD neurofibrillary tangles.MethodTwo participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), an ongoing, longitudinal cohort study of late middle‐aged adults enriched for AD risk, were identified based on unilateral MK‐6240 deposition. Topographic amyloid and tau burden was assessed with [11C]PiB and [18F]MK‐6240 PET imaging, respectively. Demographic data, cognitive diagnoses, health histories, and APOE status are described. Longitudinal neuropsychological assessments and digitally recorded connected speech samples were analyzed to create a descriptive profile of cognition and connected speech‐language (CSL). Cognitive test scores and language measures were then compared against the scores of the full WRAP sample, using a robust normative approach previously described by our group.ResultMK‐6240 tau‐PET imaging revealed right‐lateralized tau in Participant A and left‐lateralized tau in Participant B (Figure 1). Participants were identical on all demographics except age and APOE risk of developing AD (though both participants were ApoE‐4 allele carriers) (Table 1). Cognitive assessment Z‐scores (0=mean of demographically similar cognitively stable WRAP participants; Figs 2‐4) depict considerable between visit variability for Participant A on all measures, including language and CSL, with decline from baseline on all but letter fluency. Participant B showed isolated baseline deficits on memory tests (AVLT and story recall) at two standard deviations below the mean, which declined further across visits, whereas performances on Trails, naming, category fluency, and all measures of CSL remained stable and within normal expectations.ConclusionIn this case study, right&gt;left tau PET signal was associated with greater decline in language, particularly connected speech and naming. Future work will examine associations between volumetric MRI and asymmetric regional tau deposition, as well as additional relationships to language and cognition.

Staving off dementia through prevention of word retrieval problems in aging

AbstractBackgroundAfter the age of 40, everyone experiences instances of a temporary inability to retrieve a familiar word known as the annoying, and often embarrassing, tip‐of‐the‐tongue (TOT) phenomenon. The frequency of occurrence of TOTs is increased in individuals experiencing language decline associated with Alzheimer's disease. Current research demonstrates that building cognitive reserve may stave off the onset of dementia. Engaging in meaningful activities focused on word retrieval may afford the building of lexical reserve and, consequently, stave off the onset of language decline.Method30 cognitively healthy seniors (65+) engaged in a daily practice with word finding activities on a website built to improve word retrieval. They practiced for one hour on 20 consecutive days. Before and after the daily practice, they completed a category fluency task in which they generated responses to 11 semantic categories. The goal was to evaluate potential benefits of practice on reducing the frequency of TOTs and improving word retrieval abilities.ResultA paired‐samples t‐test performed on pre‐ and post‐intervention data showed a significant improvement in the total score across all categories, suggesting benefits from daily practice.ConclusionThe results suggest that in healthy seniors, engaging in activities focused on word retrieval may improve word finding and reduce TOTs. Ultimately, this could boost cognitive reserve necessary to stave off the onset of language decline in dementia. Practice effects on TOTs in spontaneous speech are currently being analyzed.

Family stories: Subjective cognitive decline profile associated with a familial history of Alzheimer’s disease

AbstractBackgroundSubjective Cognitive Decline (SCD) designates a self‐experienced worsening of cognition before that decline becomes detectable by objective cognitive assessment. SCD has been examined as an early stage of Alzheimer’s disease (AD), but the evidence linking self‐reported SCD features to clinical progression is inconsistent and the predictive validity of SCD presence and symptom burden remains uncertain. More nuanced measures of SCD which differentiate between domains of cognitive decline are needed. This study examined SCD across the domains of Memory, Language and Executive function to identify a pattern of decline associated with well‐established risk factors for AD: family history of AD, female gender, and older age.MethodCommunity‐dwelling participants aged &gt;50 years (M age=64, n=483) were recruited via the crowdsourcing website Amazon Mechanical Turk and completed a survey including demographic questions and the Subjective Cognitive Decline Questionnaire (SCD‐Q MyCog). Risk factors were binary (family history yes/no, female/male, age &lt;70/=&gt;70). Multivariate analysis of variance (MANOVA) was then performed for each risk factor grouping, with the three domains of SCD serving as dependent variables. Follow‐up discriminant analysis was performed on significant relationshipsResultThe sample included 27% of participants with a positive family history, 66.5% female, and 14.5% aged &gt;70 years. Those with a positive family history differed on a combination of SCD domain scores from those without family history, Pillai’s trace=‐.0.023, p=.011 (Memory M=2.6 vs. 1.8, Language M=2.0 vs. 1.4, Executive Function M=1.4 vs. 1.1). No other group differences reached statistical significance. Discriminant function coefficients showed that the memory domain was the strongest contributor (0.984), followed by language (0.849), and finally executive function (0.583).ConclusionA positive family history is a reliable predictor of future AD. We found that those with a positive family history reported a greater amount of subjectively experienced memory and language decline. Memory and language concerns may be helpful in assessing risk of AD in those endorsing SCD.

Early‐onset APOE‐ε4 carriers show greater decline in memory, language and executive function than late‐onset carriers

AbstractBackgroundApolipoprotein‐ε4 (APOE‐ε4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). However, whether APOE‐ε4 accelerates cognitive decline in AD has not been firmly established. We studied the rate of cognitive decline among early‐ (EOAD) and late‐onset (LOAD) APOE‐ε4 carriers vs non‐carriers on measures of memory, attention, language, and executive function.MethodEOAD and LOAD (onset‐age &lt; or ≥65) subjects were selected from the National Alzheimer’s Coordinating Center (NACC) database. Mixed‐effects models were run separately for EOAD and LOAD with longitudinal neuropsychological measures as dependent variables. APOE‐ε4 carrier status, follow‐up time, and an APOE*time interaction were included as independent variables adjusting for age, sex, education, and disease severity (CDR‐SB) at baseline. For measures where ε4‐carriers had significantly more decline in both groups, mixed‐effects models in the combined samples were used with a three‐way interaction among APOE status, follow‐up time and onset‐age variables to determine whether APOE‐ε4 associated decline was similar between EOAD and LOAD.ResultSubject demographics are shown in Table 1. The estimated differences in annual cognitive change between ε4‐carriers and non‐carriers are shown in Table 2. Both EOAD and LOAD APOE‐ε4 carriers showed significant decline in Craft Immediate (p=0.0065 and p=0.0134, respectively), semantic fluency (p=0.0001 and p&lt;0.0001, respectively), and Trail‐Making B scores (p=0.0028 and 0.0206, respectively) than non‐ε4 carriers. Only EOAD APOE‐ε4 carriers showed significantly greater decline in Craft Delayed recall than non‐ε4 carriers (p=0.0189). Only LOAD APOE‐ε4 carriers showed significantly greater decline on MoCA (p&lt;0.0001), MINT (p&lt;0.0001), and Trail‐Making A (p&lt;0.0001) than non‐carriers. The accelerated rate of decline in two of the three cognitive tests that showed faster decline in APOE‐ε4 carriers in both EOAD and LOAD was significantly greater in EOAD, while one was trending (Craft Immediate, p=0.0042; semantic fluency, p&lt;0.0001; Trail‐Making B, p=0.0942).ConclusionThese results suggest that APOE‐ε4 is associated with accelerated rate of decline in both LOAD and EOAD; however, the magnitude of the rate of decline is more pronounced in EOAD. Investigation in other large research consortia such as LEADS and ADNI can further characterize the genetic influences of APOE‐ε4 and other genetic risk factors on AD.

Comparative Evaluation of Cognitive Function among Indian Obese and Non-Obese Middle-Aged Subjects

Background: Obesity has become one of the common problems encountered by people of the present day. This condition is often accompanied by cardiovascular problems like hypertension, hyperlipidemia, is chemic heart disease. Also, that the relationship between obesity and cognitive impairment plays an important role in the development of neurodegenerative disorders. But reports on the association between obesity and working memory lack scientific evidence. So, the present study planned to assess the influence of obesity on cognitive functions and compare among obese and non - obese individuals.&#x0D; Objective: This study evaluated the changes in cognitive functions comparative between samples of obese and non-obese individuals from India.&#x0D; Methods: Based on the Body Mass Index (BMI), the participants were classified into 2 groups. Cognitive screening was done using MINI MENTAL STATE EXAMINATION and the parameters like level of orientation, registration, recall, language, copy art skills were analyzed and scores were calculated. The data was statistically analyzed using SPSS version 23 and the independent sample t test was used to analyze the differences in cognitive functions.&#x0D; Results: The study reported that there was statistically significant decline in language, recall and copy art skills in obese individuals compared to non-obese group.&#x0D; Conclusion: The study concluded an innovative finding that obesity is associated with impaired cognitive performance pertaining to recall, language and copy art and overall decreased MMSE scores indicating that accelerated cognitive decline and neurodegenerative pathologies such as dementia in later life is influenced by changes in body weight. Interventions that target mid-life obesity may be helpful in reducing the cognitive risks associated with obesity.

Language Decline Characterizes Amnestic Mild Cognitive Impairment Independent of Cognitive Decline.

Purpose This research investigated the nature of cognitive decline in prodromal Alzheimer's disease (AD), particularly in mild cognitive impairment, amnestic type (aMCI). We assessed language in aMCI as compared with healthy aging (HA) and healthy young (HY) with new psycholinguistic assessment of complex sentences, and we tested the degree to which deficits on this language measure relate to performance in other general cognitive domains such as memory. Method Sixty-one individuals with aMCI were compared with 24 HA and 10 HY adults on a psycholinguistic measure of complex sentence production (relative clauses). In addition, HA, HY, and a subset of the aMCI participants (n = 22) were also tested on a multidomain cognitive screen, the Addenbrooke's Cognitive Examination-Revised (ACE-R), and on a verbal working memory Brown-Peterson (BP) test. General and generalized linear mixed models were used to test psycholinguistic results and to test whether ACE-R and BP performance predicted performance on the psycholinguistic test similarly in the aMCI and HA groups. Results On the psycholinguistic measure, sentence imitation was significantly deficited in aMCI in comparison with that in HA and HY. Experimental factorial designs revealed that individuals with aMCI had particular difficulty repeating sentences that especially challenged syntax-semantics integration. As expected, the aMCI group also performed significantly below the HY and HA groups on the ACE-R. Neither the ACE-R Memory subtest nor the BP total scores predicted performance on the psycholinguistic task for either the aMCI or the HA group. However, the ACE-R total score significantly predicted psycholinguistic task performance, with increased ACE-R performance predicting increased psycholinguistic task performance only for the HA group, not for the aMCI group. Conclusions Results suggest a selective deterioration in language in aMCI, specifically a weakening of syntax-semantics integration in complex sentence processing, and a general independence of this language deficit and memory decline. Results cohere with previous assessments of the nature of difficulty in complex sentence formation in aMCI. We argue that clinical screening for prodromal AD can be strengthened by supplementary testing of language, as well as memory, and extended evaluation of strength of their relation.

Between Loss and Salvage: Kabyles and Syrian Christians Negotiate Heritage, Linguistic Authenticity and Identity in Europe

This paper brings together two different communities, Kabyles (Amazighs) and Syrian Christians, who are nevertheless marked by some commonalities: a strong diasporic dispersal as a historical experience, political, cultural and linguistic marginalization in their countries of origin, the deep association of collective identity with an “endangered” heritage language, a lived experience of multilingualism, and a post-emigration struggle of language maintenance and transmission. The Kabyles have roots in northern Algeria, and associate their language, Kabyle, with a pre-Arabized history of northern Africa, with claims to cultural authenticity and indigeneity. This paper focuses on research conducted in the UK, a relatively new immigrant setting for this community. The Syrian Christians originate from Turkey and have dispersed across different European countries since the 1960s. They make strong identity claims to Aramaic, “the language of Jesus”, yet have also found its preservation and intergenerational transmission challenging. This paper focuses on research conducted in the German speaking context. Drawing on ethnographic research with these communities, we bring their post-migration language preservation activisms into a dialogue. This shows the enduring significance of the heritage language for social, cultural and historical identity, despite considerable language decline. It also demonstrates that the current survival of the “mother tongue” hinges on multilingual and multi-sited language activisms which bear the hallmarks of both new creativities and diminishing fluencies.

PRIMARY EDUCATION ISSUES IN THE CREATIVE HERITAGE OF THE UKRAINIAN EDUCATOR NIKIFOR YAKOVICH GRIGORIYEV (1883–1953)

In the article, there is a list of contributions from a prominent teacher, historical, and community member of Ukraine – Nikifor Yakovich Grigoriyev. The contribution of the teacher to the process of Ukrainianization of the educational process has been grounded before the hour of his transfer to the seat of the Ministry of Education of the Ukrainian People's Republic in the office of the head of the People's Ministries of V. Golubovich. The manuals and books in the Ukrainian language with the help of educating the people about the formulation of their national consciousness have been analyzed. The assessment of the pedagogical study and methods of the study of the Ukrainian language and history decline was made.It is noted that N. Hryhoriyiv took a course on the revival of education, namely: primary education, native language, customs, and traditions in educational institutions. This period is characterized by the study of the Ukrainian language in primary school, the teaching of the Ukrainian language in teachers' seminaries, the creation of Ukrainian gymnasiums. The purpose of the article is to highlight the issues of primary education in the creative heritage of the Ukrainian teacher Nikifor Yakovlevich Hryhoriyiv (1883–1953). To write the article, we used the following methods: periodization – to determine in accordance with reasonable criteria for the selection of periods of educational activity of the scientist; method of reconstruction – to reproduce the socio-cultural and socio-political context of educational development; interpretations – for creative rethinking of pedagogical ideas of N. Grigoriev taking into account modern educational and organizational-pedagogical tasks. N. Hryhoriyiv's activity as the Minister of Education of the Ukrainian People's Republic was aimed at the nationalization of the public education system, which could educate a new generation of conscious citizens of Ukraine. After becoming the Minister of the Ukrainian People's Republic, in 1918 the teacher introduced compulsory teaching in schools in the Ukrainian language and issued a document “Schools in Ukraine”, which testified to the opening of schools in 39 settlements of Ukraine.