Language Decline Research Articles

NCOG-32. RELATIONSHIPS BETWEEN INTRAOPERATIVE TASK-BASED GAMMA BAND ELECTROCORTICOGRAMS, DIRECT ELECTRICAL STIMULATION, AND COGNITIVE-LINGUISTIC OUTCOME FOLLOWING AWAKE BRAIN TUMOR RESECTION

Abstract BACKGROUND As an adjunct to direct electrical stimulation (DES), intraoperative electrocorticography (ECoG) can aid detection of language-eloquent cortex. However, it is unclear how surgical impact upon mapping findings relates to cognitive-linguistic outcomes. METHODS Ten patients underwent awake craniotomy for tumor resection with ECoG and DES language mapping. Mapping utilized iPad stimulus presentation coupled to an electrode array capable of both recording ECoG activity and delivering DES. Time-frequency gamma band activations were visualized (Early, Long, Late, Double Peak) for 3 naming paradigms (Object, Action, Auditory). DES was also conducted for each task. Mapping results were overlayed on postoperative MRI to examine proximity to parenchymal trauma (cavity, sulcal displacement). Patients completed cognitive-linguistic testing [WAB-R (N=3) or Neuropsychological Assessment (N=7)] prior to surgery and <2 months postoperatively. Patients with persisting aphasia at 6-month follow-up were also identified. RESULTS Postoperative language decline was found in 50% of patients, with 30% showing worsening (>1SD) in Naming and Phonemic Fluency, and 60% in Semantic Fluency. Surgery impacted ECoG features in 60% of patients and DES arrest sites in 30%. A trend was observed where Early and Late Object naming ECoG features were associated with Semantic Fluency decline [rpb(5)=-.69, p=.067]. Arrest during Auditory naming DES <1 cm of surgical effect was associated with decline in Abstraction [rpb(5)=-.83, p=.042; FET, p=.029] and Semantic Fluency [rpb(5)=-.87, p=.012; FET, p=.024]. Excluding the 3 transsulcal surgeries, arrest during Auditory naming DES <1 cm of resection was associated with general language decline [FET, p=.047]. All 3 patients with persisting aphasia had Auditory naming arrest <1 cm of resection and 2/3 patients had Object naming ECoG features resected. CONCLUSIONS While preliminary, results suggest that surgical proximity to ECoG and DES mapping results may inform risk of surgically-acquired cognitive-linguistic decline. Findings support the potential of multimethod-multitask intraoperative language mapping.

The Current Treatment for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) refer to dysfunction of central nerve system, characterized by progressive loss of neuronal structure and function, ultimately resulting in decline in patients memory, motor ability, language and intelligence. The typical NDs include age related diseases like Aleimers disease (AD) and genetic diseases such as Huntingtons diseases (HD) and amyotrophic lateral sclerosis (ALS). NDs impose heavy economic burden and suffer to the enormous patients over the world, however, many types of NDs do not have a cure; existing treatments only aim to improve their symptoms. Under that condition, Gene therapy has shown potential for transporting some genetic products into the cells and correct faulty genes. Over the years, research have highlighted the promise of gene therapies using AAV vector in treating NDs. At the same time, a number of emerging therapeutic technologies for neurodegenerative diseases, such as epigenetic interventions through acetylation/deacetylation, gene therapies that target specific mRNAs or non-coding RNAs, and photo biomodulation therapies that can act on brain tissue, are also being studied. In this discussion, we explore the historical, present, and future outlook of gene therapies for neurodegenerative conditions.

Climate, Disease, and Upheaval in the Turkic World in the 14th-15th Centuries

This paper examines the role of climate and disease as a major factor resulting in disruption and upheaval in the Turkic world in the 14th-15th centuries. The first issue the paper addresses is the beginning of the climatic downturn in circa 1280, which will ultimately culminate in the Little Ice Age of the late 15th-18th centuries. The paper cites recent work on the role of climate in the history of Iran. While the author has explored this issue in detail for the history of the Golden Horde, the impact of climate change on Iran in the 14th-15th centuries is a topic which has yet to be investigated adequately by historians. More importantly, climate change is associated with the spread of the Black Death, both in the original point of its spread and especially in the lower Volga River delta. The paper addresses the role of the Black Death (1346- ) as a disruptive factor in the history of the Golden Horde and the Chağatay Khanate. Citing recent research, it also considers legacy of the Black Death in the political, socio-economic, and cultural history of the Il-Khanate and what it meant for the rise of the Aqqoyunlu state. In the Golden Horde, Central Asia, and the Ottoman Empire, the Black Death led to a decline or disappearance in the earlier Islamic Turkic literary language. The earlier archair literary language was replaced by a newer literary language closer to the vernacular or spoken language of the people. There is also evidence of cultural responses to plague written in the new language.

Clinicoradiological and neuropathological evaluation of primary progressive aphasia

BackgroundPrimary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding...

Early Symptoms and Treatment Outcomes in Neuronal Ceroid Lipofuscinosis Type 2: Croatian Experience.

Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative disease that generally appears in children between 2 and 4 years old, leading to seizures and a progressive loss of language and motor functions. As the disease progresses, affected individuals typically experience blindness and ultimately pass away in late childhood. Treatment with intracerebroventricular cerliponase alfa has been shown to slow the deterioration of motor and language functions compared to the natural progression of the disease. We aim to highlight the early symptoms of CLN2 which help with early diagnosis and timely treatment initiation in children with specific medical indications, as well as identify medical contraindications for enzyme replacement therapy. We describe five Croatian patients and one Bosnia and Herzegovinian patient with CLN2 disease, analyzing the clinical characteristics, neuroimaging findings, electroencephalogram results, genetic analysis, treatment indications and contraindications, and disease progression. All six patients presented with seizures: focal seizures (n = 1), myoclonic-atonic seizures (n = 1), febrile seizures (n = 2), and tonic-clonic seizures (n = 2), along with language delay (n = 6). Despite this, one patient refused treatment, two were initially included in the clinical trial and then continued treatment, one did not indicate starting treatment, and three continued treatment. One patient, after 4.5 years of treatment, no longer had medical indications for the therapy, which was discontinued. The other two patients who received treatment had a significant slowing of disease progression. The early onset of seizures between ages 2 and 4, alongside delayed language development, is a defining characteristic of CLN2 disease. Enzyme replacement therapy using cerliponase alfa represents the initial treatment for neuronal ceroid lipofuscinosis type 2, targeting the underlying cause of the disease. It effectively delays the progression of language and motor decline in patients diagnosed with this condition.

Subject-verb agreement inflection in Arabic-speaking individuals with Down syndrome

ABSTRACT This research examines the production of subject-verb agreement inflection in person, number, and gender in Urban Jordanian Arabic-speaking individuals with Down syndrome (DS). Third person singular masculine, third person singular feminine, and third person plural suffixes (3MS/3FS/3P) were investigated to achieve this objective. The research involved 60 participants, 30 males and 30 females, enrolled in Nazik Al Hariri Welfare Center for Special Education in Amman. The participants were divided into three groups by age, kindergarten 2 (7.1 to 12.5), school-age (13.10 to 17.6), and vocational training (18.3 to 27.3). Data were collected via a picture-naming task. The results showed that verb agreement constitutes a severe problem in individuals with DS. All three age groups showed some degree of language decline. The 3MS form was the most used and the most accurate form by the three DS groups (48.5%), followed by the 3FS (35.3%) and the 3P (22.8%). A significant finding of this study is that the acquisition of agreement for person, number, and gender by the DS groups is associated with inconsistency and atypical asynchrony. In addition, the results show that age significantly affects the DS groups’ production of subject-verb agreement. Thus, the study recommends early intervention for the verb system and subject-verb agreement.

Association of Basal Forebrain Volume with Amyloid, Tau, and Cognition in Alzheimer's Disease.

Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer's disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aβ]-negative cognitively unimpaired, 6 Aβ-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18F-florbetaben PET for Aβ, 18F-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated the baseline and longitudinal association of BF volume with Aβ and tau standardized uptake value ratio and cognition. Cross-sectionally, lower BF volume was not independently associated with higher cortical Aβ, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aβ accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aβ and tau burden. Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function.

Challenging Case: New-Onset Hallucinations and Developmental Regression in a Child with Autism Spectrum Disorder.

Nick is a 5-year-old boy who began displaying self-stimulating behaviors and decreased social interactions shortly before turning 3 years. At the age of 3.5 years, he was diagnosed with autism spectrum disorder by a local developmental-behavioral pediatrician. His parents recall that the physician described Nick to be "high functioning" and encouraged them to expect that he would attend college and live independently as an adult. Upon receiving the diagnosis, intervention was initiated using an applied behavioral analysis (ABA) approach. With this intervention, he demonstrated initial gains in the use of complex language and improved social interactions.Concerns regarding suspected psychosis emerged just before starting kindergarten when Nick began experiencing ego-dystonic visual and auditory hallucinations. Initially, Nick verbally responded to the hallucinations and vividly described what he was experiencing. Shortly after the onset of these hallucinations, Nick experienced a significant decrease in the frequency and complexity of his expressive language and became more withdrawn. Over time, his hallucinations intensified, and his parents became increasingly fearful for his safety. Various antipsychotic and mood-stabilizing medications, steroids, and immunotherapy have been trialed with limited improvement of his symptoms.An extensive medical evaluation yielded the following:1. Magnetic resonance imaging of the brain: dilated perivascular spaces.2. Urine organic acids: ketosis and increased lactic acid.3. Antinuclear antibody: minimally positive.4. Vitamin B12: elevated.All other studies, including lumbar puncture, electroencephalogram (awake and asleep), genetic studies (chromosomal microarray, fragile X testing, and whole exome sequencing), metabolic studies, inflammatory markers, and thyroid panel, were negative/normal.Nick is enrolled in a special education classroom within a school that utilizes an ABA-based approach for all students. As part of his educational programming, he receives 25 hours of ABA in a 1:1 setting, 2 hours of speech therapy, 3 hours of occupational therapy, 1 hour of physical therapy, and 30 minutes of music therapy weekly. Current concerns include significant head-banging and thrashing before falling asleep, hyperactivity, unsafe behaviors (e.g., banging on windows, climbing high to reach desired items), aggression toward caregivers, limited ability to complete self-care tasks (e.g., personal hygiene, toileting), significant decline in expressive language, and continued response to internal stimuli.Nick's parents now present to a multidisciplinary center seeking guidance regarding additional therapies/interventions to assist in management of his current developmental and behavioral challenges as well as information regarding his expected developmental trajectory as he reaches adulthood.

Naming fMRI-guided white matter language tract volumes influence naming decline after temporal lobe resection

ObjectiveThe aim of this study was to explore the relation of language functional MRI (fMRI)-guided tractography with postsurgical naming decline in people with temporal lobe epilepsy (TLE).MethodsTwenty patients with unilateral TLE (9 left) were studied with auditory and picture naming functional MRI tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole-brain fibre tractography. Clinical naming performance was assessed preoperatively, 4 months, and 12 months following temporal lobe resection. Volumes of white matter language tracts in both hemispheres as well as tract volume laterality indices were explored as moderators of postoperative naming decline using Pearson correlations and multiple linear regression with other clinical variables.ResultsLarger volumes of white matter language tracts derived from auditory and picture naming maxima in the hemisphere of subsequent surgery as well as stronger lateralization of picture naming tract volumes to the side of surgery correlated with greater language decline, which was independent of fMRI lateralization status. Multiple regression for picture naming tract volumes was associated with a significant decline of naming function with 100% sensitivity and 93% specificity at both short-term and long-term follow-up.InterpretationNaming fMRI-guided white matter language tract volumes relate to postoperative naming decline after temporal lobe resection in people with TLE. This can assist stratification of surgical outcome and minimize risk of postoperative language deficits in TLE.

Linguistic Imperialism as a Tool in Cultural Hegemony: Language Decline and Revitalization of Indigenous Communities in Canada

This paper provides an in-depth analysis of linguistic imperialism and its relationship to cultural hegemony, with a specific focus on Indigenous communities in Canada. Linguistic imperialism is defined as the suppression and marginalization of other languages by a dominant language, often stemming from historical colonization, which results in the imposition of cultural hegemony on diverse cultural groups. To analyze this noteworthy phenomenon, Edward Said's theory of Orientalism is applied in the paper. Furthermore, the study not only emphasizes the negative impact of linguistic domination but also proposes various methods with the aim of reversing language shift and fostering cultural and linguistic vitality. By analyzing the case of the Inuit community in Canada and introducing methods such as language revitalization programs, this paper presents strategies to counter the influence of linguistic imperialism, aiming to contribute to the creation of a more inclusive environment so as to safeguard linguistic and cultural diversity.

Alzheimer's Disease and Cognitive Decline in Patients with Cardiovascular Diseases Along the Heart-Brain Axis.

We hypothesize that Alzheimer's disease (AD)-related pathology may accelerate cognitive decline in patients with cardiovascular diseases. To investigate the association between blood-based biomarkers of AD, astrocyte activation, and neurodegeneration and cognitive decline. From the multi-center Heart-Brain study, we included 412 patients with heart failure, carotid occlusive disease or vascular cognitive impairment (age:68.6±9.0) and 128 reference participants (65.7±7.5). Baseline amyloid-β42/40 (Aβ42/40), phosphorylated-tau181 (pTau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were determined using SiMoA (Quanterix). Memory, attention, language, and executive functioning were evaluated (follow-up:2.1±0.3 years). We applied linear mixed models with terms for biomarker, time and biomarker*time interactions, adjusted for age, sex, education, and site, to assess associations between biomarkers and cognitive decline. Among patients, Aβ42/40 was not associated with cognitive performance at baseline. However, lower Aβ42/40 was associated with steeper decline in global cognition (β±SE:0.04±0.02). Higher pTau181 was associated with worse baseline performance on global cognition (-0.14±0.04) and memory (-0.31±0.09) and with steeper decline in global cognition (-0.07±0.02), memory (-0.09±0.04), attention (-0.05±0.02), and language (-0.10±0.03). Higher GFAP was associated with worse baseline performance on global cognition (-0.22±0.05), memory (-0.43±0.10), attention (-0.14±0.06), language (-0.15±0.05), and executive functioning (-0.15±0.05) and steeper decline in global cognition (-0.05±0.01). Higher NfL was associated with worse baseline performance on global cognition (-0.16±0.04), memory (-0.28±0.09), attention (-0.20±0.06), and executive functioning (-0.10±0.04), but was not associated with performance over time. In reference participants, no associations were found. Our findings suggest that blood-based biomarkers of AD-related pathology predict cognitive decline in patients with cardiovascular diseases.

Language attitudes: sociolinguistic aspect

Language attitudes are pivotal in shaping spheres of language use, impacting language change and policy. They reflect how communities perceive and value languages, influencing language choice, education, and social interactions. Studies on language attitudes explore preferences in language instruction, societal perceptions, and the potential for language discrimination. Positive attitudes can elevate language prestige, while negative ones may contribute to language decline. Loyalty to a language or a variety can resist influences from a dominant language, especially if a minority language prestige is high. The article comprises reviews on ‘language attitudes’ as a term, an overview of the history of research on the perceptions of a language, analysis of related changes occurring among speakers. The objective of the article is to provide a forecast for the future fate of Karelian, Kalmyk, and Yakut languages by analyzing language attitudes. The focus of the study was on the perceptions of a language held by members of a speech community, i.e., those who have no command of the studied language, as these perceptions were deemed highly significant. When the overall sentiment toward a language is positive, and speech community members recognize the importance of having at least a basic proficiency in it, the prospects for the language's growth appear promising. Such favorable attitudes may lead speech community members to actively encourage language study among their children or grandchildren or even decide to learn the language themselves later in life, creating a potentially fertile environment for a language to flourish.

Longitudinal Cognitive Trajectories in Older Adults with Restless Legs Syndrome or Willis-Ekbom Disease.

Background: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia and with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the participants. Generalized estimating equation analyses were used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results: A total of 1003 predominantly female (59.5%), older (72.9 ± 4.9 years) participants with follow-up evaluations after a mean of 3.09 ± 0.85 years and without dementia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, and executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by a standard deviation of 0.249, while demonstrating a mitigated language decline over time, by a standard deviation of 0.063. The unadjusted models yielded similar results. Conclusions: Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time.

Defining economic impact on minority languages: the case of Wales

ABSTRACT The relationship between economy and language is thought to be key to language revitalisation efforts, although the nature of the relationship is often discussed only in general terms. Royles sets out to address this ambiguity by defining the different dimensions of this relationship, however the resultant framework is based on a limited body of evidence. Using the case of Wales, we undertake a systematic review of what is known about the impact of economic variables upon language, thus generating a wider body of evidence to verify Royles’ framework. Our investigation reveals that of the 15,414 references generated as part of the review, 73 were found to satisfy the search criteria and all of which were successfully allocated within Royles’ categories. In validating Royles’ framework we advance a new understanding of economic impact on minority languages by moving from general to definitive terms and suggest that the clarity that this provides can be utilised by policy practitioners in their efforts to halt language decline.

Polygenic burden and its association with baseline cognitive function and postoperative cognitive outcome in temporal lobe epilepsy

ObjectiveDemographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer’s disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. Methods202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n = 116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. ResultsNo significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. SignificanceWe did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects.

Национальные имена, личные песни и семейные предания как способы трансляции семейно-родовой истории в культуре коряков-чавчувенов

The paper explores how the Koryak culture preserves and transmits family and ancestral values despite challenges such as assimilation, language decline, and economic structure transformations. Until the 1920s, the Chavchuven and Nymylan Koryak descendants, even those from mixed marriages, possessed both national names and names recorded in official documents. The choice of name is conditioned by the idea of reincarnation that implies the soul of an ancestor to be reborn in a descendant. The recollection of older relatives can be preserved by performing their personal songs. In the context of rituals, such a performance of ancestors’ songs is regarded as a form of communication with them. This study analyzes the compositional and harmonic features of personal songs of relatives performed by N. S. Kuznetsova-Kerguvie (Nuteŋewyt, 1949–2023). The paper provides the notes of the songs accompanied by links to audio and video illustrations. Family narratives under analysis offer a comprehensive account of the life histories of ancestors, reflecting traditional Koryak cultural practices such as matchmaking, bride kidnapping, conspiracy, and marriage under the law of levirate. The peculiarity of family narratives lies in the specifics of their functioning: they are the heritage of a narrow family circle. The enduring relevance of borderline life situations experienced by ancestors persists within the descendants of the family, thereby ensuring their transmission from one generation to the next.

The Impact of the Risk of Losing the Betawi Language on Society

The Betawi language, like many other global languages, faces the threat of extinction caused by various factors, including the evolution of civilization. This threat threatens various aspects of indigenous Betawi culture. Therefore, maintaining and preserving the Betawi language is very important. The challenge is to understand the breadth of the Betawi linguistic and textual context. It is important to develop targeted strategies that highlight the main elements affected by language degradation, especially in the Betawi community. This study identified these elements after conducting intensive field research for more than a year with continuous observations. This research shows that sociological qualitative analysis, especially in evaluating people's social interactions, is the most effective method. Five main areas were identified to analyze the impact of language decline: linguistic aspects, individual identity, intergenerational communication, knowledge transfer, and economic implications

A REVIEW OF THE LITERATURE ON HIV AND NEUROPSYCHOLOGICAL FUNCTIONING IN OLDER ADULTS: IS MORE RESEARCH NEEDED?

The increase in the number of ageing people living with HIV and the documented neurocognitive impairments have highlighted the need to illuminate the existing findings and evaluate the impact that HIV has on older individuals. A review of the evidence for neuropsychological declines in memory, executive functions, attention and language in people aged 60 years or more was conducted. The databases MEDLINE, PsychINFO and Pubmed were searched for eligible studies based on keywords. Eight studies of low to high quality that looked at HIV+ older adults (≥ 60) were identified. The majority of older HIV+ adults experienced severe declines in all the cognitive domains under study. There were mixed results regarding the association among advancing age, functioning decline and HIV. Comparisons between HIV-infected and HIV-uninfected older adults showed that HIV+ subjects demonstrate higher scores of cognitive decline in memory, attention, language and executive functions. Further, comparisons among HIV+ adults, demographically matched individuals with mild cognitive impairment of the Alzheimer's type and healthy controls demonstrated that both disease groups perform worse, but the Alzheimer’s type group reports a greater decline in memory and language. Neuropsychological functioning in HIV+ adults presents great decline but studies on this population are limited. As individuals with HIV are increasingly living longer, studies should pay attention to these individuals and examine predictors of neuropsychological decline in the face of well-controlled interventions and treatments. Keywords: HIV, memory, neuropsychological function, executive functions, older adults

EEG complexity-based algorithm using Multiscale Fuzzy Entropy: Towards a detection of Alzheimer’s disease

Alzheimer’s Disease (AD) is a progressive neurodegenerative condition causing memory, attention, and language decline. Current AD diagnostic methods lack objectivity and non-invasiveness. While electroencephalography (EEG) holds promise for AD research, conventional EEG analysis methods have proven unsatisfactory. Non-linear dynamical approaches are considered more effective in assessing the brain’s complex nature. Starting from these considerations, this study presents an entropy-based algorithm utilizing Multiscale Fuzzy Entropy (MFE) as a promising, effective AD diagnostic method. Computed across 20 different time scales for a public dataset, MFE showed a significant discriminative power. Notably, a trend inversion was observed in the results: AD subjects displayed higher complexity values for slow frequency bands compared to healthy controls, while the opposite was found in fast frequency bands. These findings underscore the potential of MFE in effectively distinguishing AD patients from healthy individuals, marking a significant advance towards more objective and reliable AD diagnosis strategies.

Serum biomarkers for prognosis and monitoring in asymptomatic Alzheimer’s Disease

AbstractBackgroundPrognostic and monitoring capabilities of blood‐based biomarkers for early cognitive decline, amyloid‐β (Aβ) accumulation and grey matter (GM) loss in the asymptomatic phase of Alzheimer disease require further investigation over extended time periods. This longitudinal study investigated serum glial fibrillary acidic protein (GFAP), neurofilament light (NfL) and Aβ1‐42/Aβ1‐40 as potential prognostic and monitoring biomarkers in cognitively unimpaired (CU) elderly.MethodWe included 184 CU older adults (Table 1) who underwent baseline serum sampling and 2‐yearly neuropsychological assessment for up to 10 years (median: 6 years, Figure 1). A subset (N = 109) underwent serial blood sampling, Aβ‐PET and structural MRI at 2 (N = 73), 3 (N = 34), or 4 (N = 2) time points (time interval: 2‐10 years, median: 6 years). Cognition was evaluated in memory, language and executive functioning domains through conversion of neuropsychological tests scores to standardised z‐scores and subsequent averaging per domain. Aβ‐accumulation and GM loss were analysed in a voxelwise manner using Voxelstats with cluster‐level p RFT<.05 and voxel‐level puncorrected<.001 significance thresholds.[1] Aβ1‐42/Aβ1‐40 was inverted to facilitate biomarker comparison. Linear‐mixed effects models were used to (i) identify the predictive value of serum biomarkers for longitudinal cognitive decline, Aβ‐accumulation and GM loss, (ii) calculate annual serum biomarker rates of change and (iii) investigate associations between longitudinal biomarker changes and longitudinal changes in cognition, Aβ‐PET and GM volume.ResultHigh baseline GFAP and NfL predicted a longitudinal decline in memory (βGFAP*time = ‐0.020, pFDR = 0.03; βNfL*time = ‐0.031, pFDR = 0.002) and language (βGFAP*time = ‐0.025, pFDR<0.001, βNfL*time = ‐0.017, pFDR = 0.04), and longitudinal GM loss within the hippocampus. Low Aβ1‐42/Aβ1‐40 predicted memory decline (βAβ1‐42/Aβ1‐40*time = ‐0.022, pFDR = 0.03) as well as Aβ accumulation within Aβ‐vulnerable regions (Figure 1). Serum GFAP (βtime = 0.022, pFDR<.001) and NfL (βtime = 0.040, pFDR<.001) increased over time. Longitudinal serum NfL increases were associated with a concomitant decline in memory (β∆NfL*time = ‐0.031, pFDR= .004), language (β∆NfL*time = ‐0.022, pFDR= .01) and GM volume (Figure 2). Serum GFAP increases were associated with precuneal Aβ accumulation. Aβ1‐42/Aβ1‐40 decreases were stronger in Aβ‐ subjects (pFDR<.001) and did not associate with Aβ accumulation, nor any other longitudinal marker.ConclusionSerum GFAP, NfL and Aβ1‐42/Aβ1‐40 are prognostic and/or monitoring biomarkers providing complementary information by reflecting different Aβ‐dependent or ‐independent pathophysiological processes.REFERENCE[1] Mathotaarachchi et al. Front Neuroinform 2016.