Prodromal Research Articles

A Multidimensional, Person-Centered Framework for Functional Assessment in Dementia: Insights from the 'What', 'How', 'To Whom', and 'How Much' Questions.

Dementia is a syndrome characterized by cognitive and neuropsychiatric symptoms associated with progressive functional decline (FD). FD is a core diagnostic criterion for dementia, setting the threshold between its prodromal stages and the full-blown disease. The operationalization of FD continues to generate a great deal of controversy. For instance, the threshold of FD for the diagnosis of dementia varies across diagnostic criteria, supporting the need for standardization of this construct. Moreover, there is a need to reconsider how we are measuring FD to set boundaries between normal aging, mild cognitive impairment, and dementia. In this paper, we propose a multidimensional framework that addresses outstanding issues in the assessment of FD: i) What activities of daily living (ADLs) are necessary to sustain an independent living in aging? ii) How to assess FD in individuals with suspected neurocognitive disorders? iii) To whom is the assessment directed? and iv) How much does FD differentiate healthy aging from mild and major neurocognitive disorders? Importantly, the To Whom Question introduces a person-centered approach that regards patients and caregivers as active agents in the assessment process of FD. Thus, once impaired ADLs have been identified, patients can indicate how significant such impairments are for them in daily life. We envisage that this new framework will guide future strategies to enhance functional assessment and treatment of patients with dementia and their caregivers.

Pollinator Diversity and Phenological Interplay: Exploring Mineral, Hormonal, Sugar, and Vitamin Contents in Vitis vinifera L. cv Bozcaada Çavuşu.

Unraveling the intricate physiological and biochemical intricacies associated with female dominance in grape berries across diverse developmental stages is imperative for optimizing grape production and ensuring the attainment of high-quality yields. This study conducted a thorough analysis of grape berries across phenological stages (BBCH-79, BBCH-81, BBCH-89) and cultivars. At BBCH-89, Bozcaada Çavuşu*Vasilâki demonstrated the highest berry weight and total soluble solids (TSS) levels, emphasizing its enological potential. Acidity peaked at BBCH-79 (28.16) and declined at BBCH-89 (6.11), signaling a shift towards lower acidity in later stages. Bozcaada Çavuşu*Vasilâki consistently showed the highest maturity index (MI). Mineral content variations were observed across nitrogen (N), calcium (Ca), potassium (K), phosphorus (P), magnesium (Mg), sulfur (S), iron (Fe), manganese (Mn), boron (B), zinc (Zn), and copper (Cu), with Bozcaada Çavuşu*Vasilâki often having the highest concentrations, particularly in potassium, calcium, and boron. Hormonal analysis revealed a significant surge in concentrations at BBCH-89, with Bozcaada Çavuşu*Vasilâki standing out. Notably, Indole-3-acetic acid (IAA) concentrations increased by 106%, and abscisic acid (ABA) levels peaked at BBCH-79 with a 38% increase in Bozcaada Çavuşu*Kuntra. Sugar content analysis showed variations in fructose, glucose, sucrose, rhamnose, xylose, galactose, and arabinose levels across sampling times and cultivars. Bozcaada Çavuşu*Vasilâki consistently exhibited higher sugar levels, especially at BBCH-81 and BBCH-89. Vitamin concentrations varied temporally and among cultivars, with BBCH-89 displaying the highest vitamin A concentration (6.24 mg/100 g FW), and Bozcaada Çavuşu*Vasilâki often exhibiting maximum values for vitamin B1, B2, B6, and C. Further research and targeted cultivation practices focusing on the unique attributes of Bozcaada Çavuşu*Vasilâki could enhance grape production efficiency, emphasizing its potential contribution to achieving consistently high-quality yields across various phenological stages.

Explanations for Gender Differences in Preferences for Submissive Sexual Fantasies.

Women have a stronger preference for sexualsubmission than men do. In the current studies, we investigated gender differences in fantasies about sexual submission. Replicating previous research, in twostudies we found that women expressed a stronger affinityfor fantasies about sexual submission than men did. However,controlling for age and several sociocultural factorsmade the relationship between gender and preference for sexual submission non-significant-that is, we could statistically eliminate the gender difference. These analyses suggest the multiple factorsthat may influencesexual preferences and the multiple ways that gender differences in preference for submissive sexual fantasies can be eliminated by easily assessed demographic and contextual differences in the experiences of women and men.

Characteristics and Usefulness of Neurophysiological Monitoring in Corrective Procedures for Abnormally Curved Spine in Young Patients.

To identify and characterize events of deterioration in intraoperative neuromonitoring data during correction procedures for thoracic and lumbar abnormal spinal curvature in young patients. Records of 1,127 cases were retrospectively reviewed to identify events with deterioration of the neuromonitoring data. General etiological and demographic variables were summarized, and neuromonitoring events were studied and characterized. Adolescent idiopathic cases were associated with female dominance and older age. Nonadolescent idiopathic cases were associated with a higher rate of neuromonitoring events. The neuromonitoring events evolved during the different procedural stages, were primarily reflected in the motor-evoked potential data and affected a range of neural structures to varying degrees. Most of the events were resolved, partially or completely, following a corresponding intervention by the surgical team, before the end of the procedure. Significant immediate weakness of the lower extremities was demonstrated in patients with unresolved neuromonitoring events, most of them were nonadolescent idiopathic patients. Neurophysiological monitoring enables the intraoperative assessment of the integrity of neural pathways and allows the detection of surgery-related impending neural injuries. Neuromonitoring contributes to intraoperative decision making, either when data are uneventful and allow confident continuation or when data deteriorate and lead to corresponding intervention. Further awareness should be paid to the vulnerable characteristics of the patient, surgery course, and neuromonitoring data. Proper interpretation of the neuromonitoring data, together with corresponding intervention by the surgeon when necessary, has the potential to reduce postoperative neurological insults and improve clinical outcomes.

Serious outcomes among emergency department patients with presyncope: A systematic review

AbstractBackgroundSyncope is transient loss of consciousness, and in presyncope, patients experience same prodromal symptoms without losing consciousness. While studies have extensively reported the risk of serious outcome among emergency department (ED) syncope, the outcome for patients with presyncope and their management are not well studied. We undertook a systematic review to assess the occurrence/identification of short‐term (30‐day) serious outcomes among ED patients with presyncope.MethodsED studies that enrolled patients with presyncope and reported any short‐term serious outcome were included. Studies that enrolled patients without presyncope (e.g., hypoglycemia, seizure, and stroke) were excluded. We restricted our study to only English publications and searched the MEDLINE, Embase, Scopus, and Web of Science from the inception date to July 2023. We used SIGN 50 tool for assessment of risk of bias.ResultsIn total, 1788 articles were screened by two reviewers and 32 articles were selected for full‐text assessment. Five (four prospective and one retrospective) studies with 2741 presyncope patients were included. Four studies were from North America and the fifth one was from Europe. Included studies had weaknesses due to risk of bias, but all had acceptable quality. The prevalence of overall adverse outcome varied 4.4%–26.8% for all adults and 5.5%–18.7% among older patients; arrhythmia was the most prevalent (17.4% in one study), followed by anemia/hemorrhage as reported in different studies. Among older patients, myocardial infarction was the third most common serious outcome reported in one study.ConclusionsThe prevalence of short‐term serious outcomes varies from 4% to 27% among ED patients with presyncope in our review, with arrhythmia being the most common serious outcome. Our review indicates that presyncope may carry a similar risk to syncope, and hence, the same level of caution should be exercised for ED presyncope management as syncope.

Mitochondrial alterations in fibroblasts from sporadic Alzheimer's disease (AD) patients correlate with AD-related clinical hallmarks

Mitochondrial dysfunctions are key features of Alzheimer’s disease (AD). The occurrence of these disturbances in the peripheral cells of AD patients and their potential correlation with disease progression are underinvestigated. We studied mitochondrial structure, function and mitophagy in fibroblasts from healthy volunteers and AD patients at the prodromal (AD-MCI) or demented (AD-D) stages. We carried out correlation studies with clinical cognitive scores, namely, (i) Mini-Mental State Examination (MMSE) and (ii) Dementia Rating-Scale Sum of Boxes (CDR-SOB), and with (iii) amyloid beta (Aβ) plaque burden (PiB-PET imaging) and (iv) the accumulation of peripheral amyloid precursor protein C-terminal fragments (APP-CTFs). We revealed alterations in mitochondrial structure as well as specific mitochondrial dysfunction signatures in AD-MCI and AD-D fibroblasts and revealed that defective mitophagy and autophagy are linked to impaired lysosomal activity in AD-D fibroblasts. We reported significant correlations of a subset of these dysfunctions with cognitive decline, AD-related clinical hallmarks and peripheral APP-CTFs accumulation. This study emphasizes the potential use of peripheral cells for investigating AD pathophysiology.

In a circuit necessary for cognition and emotional affect, Alzheimer's-like pathology associates with neuroinflammation, cognitive and motivational deficits in the young adult TgF344-AD rat

In addition to extracellular amyloid plaques, intracellular neurofibrillary tau tangles, and inflammation, cognitive and emotional affect perturbations are characteristic of Alzheimer's disease (AD). The cognitive and emotional domains impaired by AD include several forms of decision making (such as intertemporal choice), blunted motivation (increased apathy), and impaired executive function (such as working memory and cognitive flexibility). However, the interaction between these domains of the mind and their supporting neurobiological substrates at prodromal stages of AD, or whether these interactions can be predictive of AD severity (individual variability), remain unclear. In this study, we employed a battery of cognitive and emotional tests in the young adult (5–7 mo) transgenic Fisher-344 AD (TgF344-AD; TgAD) rat model of AD. We also assessed whether markers of inflammation or AD-like pathology in the prelimbic cortex (PrL) of the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), or nucleus accumbens (NAc), all structures that directly support the aforementioned behaviors, were predictive of behavioral deficits. We found TgAD rats displayed maladaptive decision making, greater apathy, and impaired working memory that was indeed predicted by AD-like pathology in the relevant brain structures, even at an early age. Moreover, we report that the BLA is an early epicenter of inflammation, and notably, AD-like pathology in the PrL, BLA, and NAc was predictive of BLA inflammation. These results suggest that operant-based battery testing may be sensitive enough to determine pathology trajectories, including neuroinflammation, from early stages of AD.

The clinical course of individuals with 22q11.2 deletion syndrome converting to psychotic disorders: a long-term retrospective follow-up.

This retrospective study aims to investigate the evolution and clinical course of psychotic disorders from three large international cohorts of individuals with 22q11.2 deletion syndrome (22q11.2DS) (Tel Aviv, Philadelphia, and Geneva). We followed 118 individuals with 22q11.2DS from several years before the onset to several years after the onset of psychotic disorders. Data from structured baseline assessment of psychiatric disorders, symptoms of prodrome, indicators and types of psychotic disorders were collected. Additionally, cognitive evaluation was conducted using the age-appropriate Wechsler Intelligence Scale. Electronic medical records were reviewed for medication usage, occupational status, living situation, and psychiatric hospitalizations. At baseline evaluation, the most common psychiatric disorders were anxiety disorder (80%) and attention/deficit hyperactivity disorder (50%). The age of onset of prodromal symptoms and conversion to psychotic disorders were 18.6 ± 6.8 and 20.3 ± 7.2, respectively. The most common prodromal symptoms were exacerbation of anxiety symptoms and social isolation. Of the psychotic disorders, schizophrenia was the most common, occurring in 49% of cases. History of at least one psychiatric hospitalization was present in 43% of participants, and the number of psychiatric hospitalizations was 2.1 ± 1.4. Compared to the normalized chart, IQ scores in our cohort were lower after vs. before conversion to psychosis. Following conversion there was a decrease in the use of stimulants and antidepressants and an increase in antipsychotics use, and most individuals with 22q11.2DS were unemployed and lived with their parents. Our results indicate that 22q11.2DS psychosis is like non-22q11.2DS in its course, symptoms, and cognitive and functional impairments.

Compensatory thickening of cortical thickness in early stage of schizophrenia.

Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.

An Overview of Appropriate Medical Practice and Preparedness in Radiation Emergency Response.

Radiation emergencies involving high doses of nuclear radiation pose significant risks from exposure to ionizing radiation in various scenarios. These situations include transportation accidents involving radioactive materials, occupational exposure, nuclear detonations, dirty bombs, and nuclear power plant accidents. In addition to the immediate risks of acute radiation syndrome (ARS) and related diseases, long-term exposure can increase the risk of other health issues such as cardiovascular disease and cancer. Vulnerable populations, including pregnant women and children, face particular concern due to potential impacts on their health and the health of unborn babies. The severity of ARS depends on several factors such as radiation dose, quality, dose rate, exposure uniformity, and individual biological responses. Bioindicators are biological responses or markers that help assess the severity and effects of radiation exposure on an individual. Bioindicators can include physical symptoms such as nausea, vomiting, and diarrhea, or laboratory tests such as changes in blood cell counts and gene expression that can help in assessing and treating exposed individuals. Additionally, early prodromal symptoms such as vomiting, diarrhea, and erythema can provide important clues for diagnosis and treatment. Developing a comprehensive plan for radiation emergencies is vital for safeguarding public health, infrastructure, and the environment. First responders play a critical role in establishing safety perimeters, triage, and coordination with various stakeholders. Education and training are essential for medical personnel and the public. This article provides general recommendations and identifies challenges to effective radiation emergency preparedness and response.

Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

Allostatic load measures in older adults with subjective cognitive decline and mild cognitive impairment: A cross-sectional analysis from the Brazilian Memory and Aging Study

IntroductionAn increasing body of research suggests that stress and allostatic load are related to cognitive dysfunction and neurodegeneration. Objectivesto determine the relationship between allostatic load (AL) and cognitive status in older adults classified with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). MethodologyUsing the Brazilian Memory and Aging Study (BRAMS) database, we analyzed data from 57 older adults with SCD and MCI. Blood neuroendocrine (cortisol, DHEA-s), inflammatory (C-reactive protein, fibrinogen), metabolic (HbA1c, HDL-cholesterol, total cholesterol, creatinine), and cardiovascular (blood pressure, waist/hip ratio) were transformed into an AL index. ResultsDespite a significant difference in the univariate analysis between waist/hip ratio (0.94 in the MCI group vs. 0, 88 in the SCD group, p = 0.03), total cholesterol levels (194 vs. 160, p = 0.02), and AL index (36.9 % in the MCI group vs. 27.2 % in the SCD group, p = 0.04), AL was not associated with SCD or MCI in the multivariate analysis. ConclusionOur data suggest that different profiles of AL in MCI compared to individuals with SCD could be due to cofounding factors. These findings need to be confirmed in longitudinal studies investigating profiles of AL changes at preclinical and prodromal stages of Alzheimer’s disease.

Stemming the Tide: The Proactive Role of Allied Health Therapy in Parkinson's Disease.

Motor and nonmotor symptoms occur in early Parkinson's disease (PD), or even in the prodromal stage. Many of these symptoms can be addressed by allied health therapies, including physical therapy, occupational therapy, speech therapy, and psychological therapies. However, referrals to these services early in the disease are low. We provide a review summarizing the efficacy of proactive allied health interventions on motor and nonmotor symptoms and daily function in prodromal and early disease. We also highlight areas for additional research and provide recommendations to improve care for individuals with early PD within each discipline. We recognize the overlapping roles of the allied health disciplines and support integrated or transdisciplinary care beginning soon after diagnosis to help stem the tide in the progression of PD symptoms and disability.

Ophthalmological traits in older adult and risk of Alzheimer's disease: results from a French geriatric cohort

Ophthalmological changes have been reported in Alzheimer's patients. Our objectives were to determine whether: i) GCC (ganglion cell complex) and RNFL (retinal nerve fibre layer) thickness were associated with different stages of AD (i.e., no AD, prodromal AD, dementia-stage AD), and ii) GCC and RNFL thickness predicted disease progression in older non-demented patients with subjective memory complaints followed for four years. Ninety-one French older community-dwellers with memory complaint and without open-angle glaucoma or age-related macular degeneration (mean, 71.60 ±4,73 years; 44% women) from the GAIT study underwent examination with HD-OCT, measuring the thickness of the macula, the macular GCC and the RNFL. They also had a complete cognitive diagnosis (i.e., cognitively healthy, prodromal AD, or dementia AD), and a cognitive follow-up 4 years later looking for a possible conversion. Age, sex, body mass index (BMI), number of comorbidities, and Instrumental activities of daily living (IADL) score were considered as potential confounders. At baseline, 37 (40.7%) patients were diagnosed as cognitively healthy, 47 (51.6%) as MCI, and 7 (7.7%) as AD. Mean GCC thickness was higher in cognitively healthy patients than in MCI patients (79.23 vs. 76.27μm, p =0.023), particularly in the inferior and nasal fields (p =0.023 and p =0.005, respectively). This difference was also found between cognitively healthy patients and others (MCI and AD) in the superior, inferior and nasal fields (p =0.030, p =0.014 and p =0.002, respectively). There was no difference in RNFL thickness between the different cognitive statuses. After 4 years of follow-up, 12patients (70.6%) of the 17 followed had not changed their cognitive status, while 5 (29.4%) had converted to a more advanced stage of AD. There were no significant differences between the two groups in either GCC thickness (p =0.429) or RNFL thickness (p =0.286). We found decreased CGG thicknesses in Alzheimer's patients at prodromal and dementia stages, compared with cognitively healthy participants. There was no association between RNFL thickness and cognitive status, nor between CCG or RNFL thicknesses and the risk of progressing to AD stages after 4 years of follow-up.

Self Identifying Mental Health Status and Get Guidance For Support Using AI

In recent years, an awareness has emerged about the importance of the individual in mental health and treatment. Mental health problems are common among college students around the world; Therefore, identifying at-risk groups will help provide services. Self-diagnosis of mental illness is an important step in recognizing and addressing personal health. Our goal is to develop a screening tool to identify students at risk for mental illness. Students are taught to use assessment tools to distinguish between those at reduced and increased risk of mental illness. Psychological services should be provided to students at risk. Despite the prevalence of psychological problems, problems such as fear of decision-making and lack of information often make it difficult for people to define themselves. The person may deny or ignore symptoms, which may delay the person's intervention and make the situation worse. Empowering people with mental health knowledge and resources can enable them to take part in their own health. As well as personal benefits, self-expression can promote understanding and acceptance and contribute to a culture of empathy and support. Artificial Intelligence (AI) technology holds both great promise and potential pitfalls in transforming mental health. This article discusses the current limitations of artificial intelligence, areas where further research is needed, and how it can improve healthcare by considering the ethical fairness of intellectual technology. As AI technology continues to evolve and improve, it may be able to help psychiatrists reclassify mental disorders beyond what is currently specified in the DSM-5, identifying these problems in their early or prodromal stages so that interventions can be implemented. . Quality and personalized treatment based on individual characteristics. However, caution must be exercised to avoid overinterpretation of preliminary results, and more studies must be conducted to close the gap in scientific expertise on mental health and treatment.

Non-linear relationship between serum cholesterol levels and cognitive change among older people in the preclinical and prodromal stages of dementia: a retrospective longitudinal study in Taiwan

BackgroundAdverse effects of rigorously lowering low-density lipoprotein cholesterol on cognition have been reported; therefore, we aimed to study the contribution of serum cholesterol in cognitive decline in older people with or without dementia.MethodsCognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI). We investigated associations between serum cholesterol with cognitive decline using multiple regressions controlling for the effects of demographics, vascular risk factors, and treatments.ResultsMost associations between cholesterol and CASI scores could be explained by non-linear and inverted U-shaped relationships (R2 = 0.003–0.006, p < 0.016, Šidákcorrection). The relationships were most evident between changes in cholesterol and CASI scores in older people at the preclinical or prodromal stages of dementia (R2 = 0.02–0.064, p values < 0.016). There were no differences in level of changes in CASI scores between individuals in 1st decile and 10th decile groups of changes in cholesterol (p = 0.266–0.972). However, individuals in the 1st decile of triglyceride changes and with stable and normal cognitive functions showed significant improvement in CASI scores compared to those in the 10th decile (t(202) = 2.275, p values < 0.05).ConclusionThese findings could implicate that rigorously lowering cholesterol may not be suitable for the prevention of cognitive decline among older people, especially among individuals in preclinical or prodromal stages of dementia.

Parkinson's disease with hyposmia and dysautonomia: does it represent a distinct subtype?

Olfactory dysfunction or dysautonomia is one of the earliest prodromal nonmotor symptoms of Parkinson's disease (PD). We aimed to investigate whether PD patients with dysautonomia and hyposmia at the de novo stage present different prognoses regarding PD dementia (PDD) conversion, motor complication development, and change in levodopa-equivalent doses (LED). In this retrograde cohort study, we included 105 patients with newly diagnosed PD patients who underwent cross-cultural smell identification test (CC-SIT), autonomic function tests (AFT), and dopamine transporter (DAT) scan at the de novo stage. PD patients were divided into Hyposmia + /Dysautonomia + (H + /D +) and Hyposmia - /Dysautonomia - (H - /D -) groups depending on the result of AFT and CC-SIT. Baseline clinical, cognitive, imaging characteristics, longitudinal risks of PDD development and motor complication occurrence, and longitudinal LED changes were compared between the two groups. When compared with the H - /D - group, the H + /D + group showed lower standardized uptake value ratios in all subregions, lower asymmetry index, and steeper ventral - dorsal gradient in the DAT scan. The H + /D + group exhibited poorer performance in frontal/executive function and a higher risk of PDD development. The risk of motor complications including levodopa-induced dyskinesia, wearing off, and freezing of gait, was comparable between the two groups. The analysis of longitudinal changes in LED using a linear mixed model showed that the increase of LED in the H + /D + group was more rapid. Our results suggest that PD patients with dysautonomia and hyposmia at the de novo stage show a higher risk of PD dementia conversion and rapid progression of motor symptoms.

Gait Variability as a Potential Motor Marker of Cerebellar Disease-Relationship between Variability of Stride, Arm Swing and Trunk Movements, and Walking Speed.

Excessive stride variability is a characteristic feature of cerebellar ataxias, even in pre-ataxic or prodromal disease stages. This study explores the relation of variability of arm swing and trunk deflection in relationship to stride length and gait speed in previously described cohorts of cerebellar disease and healthy elderly: we examined 10 patients with spinocerebellar ataxia type 14 (SCA), 12 patients with essential tremor (ET), and 67 healthy elderly (HE). Using inertial sensors, recordings of gait performance were conducted at different subjective walking speeds to delineate gait parameters and respective coefficients of variability (CoV). Comparisons across cohorts and walking speed categories revealed slower stride velocities in SCA and ET patients compared to HE, which was paralleled by reduced arm swing range of motion (RoM), peak velocity, and increased CoV of stride length, while no group differences were found for trunk deflections and their variability. Larger arm swing RoM, peak velocity, and stride length were predicted by higher gait velocity in all cohorts. Lower gait velocity predicted higher CoV values of trunk sagittal and horizontal deflections, as well as arm swing and stride length in ET and SCA patients, but not in HE. These findings highlight the role of arm movements in ataxic gait and the impact of gait velocity on variability, which are essential for defining disease manifestation and disease-related changes in longitudinal observations.

Identification of youth at clinical high-risk for psychosis: A community-based study from India.

A two-stage process, wherein self-report screening precedes the structured interview, is suggested for identifying individuals at clinical high-risk for psychosis (CHR-P) in community samples. Aim of this study was to screen a community youth sample from India for CHR-P using the two-stage method. Specific objectives were to assess concordant validity of the self-report measure and predictive validity of the two-stage method. Based on probability sampling, 2025 youth aged 15-24 years were recruited from one rural and one urban area of Telangana, a Telugu-speaking state in India. Telugu version of the PRIME Screen-Revised (PS-R) and structured interview for psychosis-risk syndromes (SIPS) were used. CHR-P positive and negative cohorts were followed-up for transition to psychosis at 3-monthly intervals. One hundred ten individuals screened positive on PS-R. SIPS conducted on 67 out of 110 individuals confirmed 62 (92.54%) to be CHR-P positive. PS-R showed 98.41% sensitivity and 90.74% specificity. Among CHR-P positive, three participants transitioned to psychosis in 15 months. The hazard ratio for psychosis transition was 11.4. Screening accuracy of PS-R in the community youth sample in Telangana is optimum. The hazard ratio for psychosis transition in the community identified CHR-P indicates good predictive validity for the two-stage method.

A multimodal approach to automated hierarchical assessment of bulbar involvement in amyotrophic lateral sclerosis.

As a hallmark feature of amyotrophic lateral sclerosis (ALS), bulbar involvement leads to progressive declines of speech and swallowing functions, significantly impacting social, emotional, and physical health, and quality of life. Standard clinical tools for bulbar assessment focus primarily on clinical symptoms and functional outcomes. However, ALS is known to have a long, clinically silent prodromal stage characterized by complex subclinical changes at various levels of the bulbar motor system. These changes accumulate over time and eventually culminate in clinical symptoms and functional declines. Detection of these subclinical changes is critical, both for mechanistic understanding of bulbar neuromuscular pathology and for optimal clinical management of bulbar dysfunction in ALS. To this end, we developed a novel multimodal measurement tool based on two clinically readily available, noninvasive instruments-facial surface electromyography (sEMG) and acoustic techniques-to hierarchically assess seven constructs of bulbar/speech motor control at the neuromuscular and acoustic levels. These constructs, including prosody, pause, functional connectivity, amplitude, rhythm, complexity, and regularity, are both mechanically and clinically relevant to bulbar involvement. Using a custom-developed, fully automated data analytic algorithm, a variety of features were extracted from the sEMG and acoustic recordings of a speech task performed by 13 individuals with ALS and 10 neurologically healthy controls. These features were then factorized into 10 composite outcome measures using confirmatory factor analysis. Statistical and machine learning techniques were applied to these composite outcome measures to evaluate their reliability (internal consistency), validity (concurrent and construct), and efficacy for early detection and progress monitoring of bulbar involvement in ALS. The composite outcome measures were demonstrated to (1) be internally consistent and structurally valid in measuring the targeted constructs; (2) hold concurrent validity with the existing clinical and functional criteria for bulbar assessment; and (3) outperform the outcome measures obtained from each constituent modality in differentiating individuals with ALS from healthy controls. Moreover, the composite outcome measures combined demonstrated high efficacy for detecting subclinical changes in the targeted constructs, both during the prodromal stage and during the transition from prodromal to symptomatic stages. The findings provided compelling initial evidence for the utility of the multimodal measurement tool for improving early detection and progress monitoring of bulbar involvement in ALS, which have important implications in facilitating timely access to and delivery of optimal clinical care of bulbar dysfunction.