Steklov problem on differential forms

In this paper we study spectral properties of Dirichlet-to-Neumann map on differential forms obtained by a slight modification of the definition due to Belishev and Sharafutdinov. The resulting operator $\Lambda$ is shown to be self-adjoint on the subspace of coclosed forms and to have purely discrete spectrum there.We investigate properies of eigenvalues of $\Lambda$ and prove a Hersch-Payne-Schiffer type inequality relating products of those eigenvalues to eigenvalues of Hodge Laplacian on the boundary. Moreover, non-trivial eigenvalues of $\Lambda$ are always at least as large as eigenvalues of Dirichlet-to-Neumann map defined by Raulot and Savo. Finally, we remark that a particular case of $p$-forms on the boundary of $2p+2$-dimensional manifold shares a lot of important properties with the classical Steklov eigenvalue problem on surfaces.Comment: 18 page

A composite measure of cognitive and functional progression in Alzheimer's disease: Design of the Capturing Changes in Cognition study

markdownabstract__Introduction__ Cognitive testing in Alzheimer's disease (AD) is essential for establishing diagnosis, monitoring progression, and evaluating treatments. Assessments should ideally be brief, reliable, valid, and reflect clinically meaningful changes. There is a lack of instruments that meet all these criteria. In the Capturing Changes in Cognition (Catch-Cog) study, we seek to correct these deficiencies through the development and validation of a composite measure combining cognition and function: the cognitive-functional composite (CFC). We expect that the CFC is able to detect clinically relevant changes over time in early dementia stages of AD. __Methods/Design__ We will include patients (n = 350) with mild cognitive impairment or mild dementia due to AD from memory clinics in the Netherlands and the United Kingdom. We will include cognitively healthy volunteers (n = 30) as a control group. The CFC is based on the “cognitive composite” and the Amsterdam instrumental activities of daily living questionnaire. We will investigate test–retest reliability with baseline and 2- to 3-week follow-up assessments (n = 50 patients and n = 30 healthy controls). We will involve experts and participants to evaluate the initial feasibility and refine the CFC if needed. Subsequently, we will perform a longitudinal construct validation study in a prospective cohort (n = 300) with baseline, 3-, 6-, and 12-month follow-up assessments. The main outcome is cognitive and functional progression measured by the CFC. Reference measures for progression include traditional cognitive and functional tests, disease burden measures, and brain imaging methods. Using linear mixed modeling, we will investigate longitudinal changes on the CFC and relate these to the reference measures. Using linear regression analyses, we will evaluate the influence of possible confounders such as age, gender, and education on the CFC. __Discussion__ By performing an independent longitudinal construct validation, the Catch-Cog study of the novel CFC will contribute to the improvement of disease monitoring and treatment evaluation in early dementia stages of AD

Detecting functional decline from normal aging to dementia: Development and validation of a short version of the Amsterdam IADL Questionnaire

Introduction Detecting functional decline from normal aging to dementia is relevant for diagnostic and prognostic purposes. Therefore, the Amsterdam IADL Questionnaire (A-IADL-Q) was developed: a 70-item proxy-based tool with good psychometric properties. We aimed to design a short version while preserving its psychometric quality. Methods Study partners of subjects (n = 1355), ranging from cognitively normal to dementia subjects, completed the original A-IADL-Q. We selected the short version items using a stepwise procedure combining missing data, Item Response Theory, and input from respondents and experts. We investigated internal consistency of the short version and concordance with the original version. To assess its construct validity, we additionally investigated concordance between the short version and the Mini–Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD). Finally, we investigated differences in instrumental activities of daily living (IADL) scores between diagnostic groups across the dementia spectrum. Results We selected 30 items covering the entire spectrum of IADL functioning. Internal consistency (0.98) and concordance with the original version (0.97) were very high. Concordance with the MMSE (0.72) and DAD (0.87) scores was high. IADL impairment scores increased across the spectrum from normal cognition to dementia. Discussion The A-IADL-Q short version (A-IADL-Q-SV) consists of 30 items and has maintained the psychometric quality of the original A-IADL-Q. As such, the A-IADL-Q-SV is a concise measure of functional decline

Assessing cognition and daily function in early dementia using the cognitive-functional composite:findings from the Catch-Cog study cohort

BackgroundThe cognitive-functional composite (CFC) was designed to improve the measurement of clinically relevant changes in predementia and early dementia stages. We have previously demonstrated its good test-retest reliability and feasibility of use. The current study aimed to evaluate several quality aspects of the CFC, including construct validity, clinical relevance, and suitability for the target population.MethodsBaseline data of the Capturing Changes in Cognition study was used: an international, prospective cohort study including participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer's disease (AD) dementia, and dementia with Lewy bodies (DLB). The CFC comprises seven existing cognitive tests focusing on memory and executive functions (EF) and the informant-based Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). Construct validity and clinical relevance were assessed by (1) confirmatory factor analyses (CFA) using all CFC subtests and (2) linear regression analyses relating the CFC score (independent) to reference measures of disease severity (dependent), correcting for age, sex, and education. To assess the suitability for the target population, we compared score distributions of the CFC to those of traditional tests (Alzheimer's Disease Assessment Scale-Cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, and Clinical Dementia Rating scale).ResultsA total of 184 participants were included (age 71.88.4; 42% female; n=14 SCD, n=80 MCI, n=78AD, and n=12 DLB). CFA showed that the hypothesized three-factor model (memory, EF, and IADL) had adequate fit (CFI=.931, RMSEA=.091, SRMR=.06). Moreover, worse CFC performance was associated with more cognitive decline as reported by the informant (=.61, p</p

What's in a score:A longitudinal investigation of scores based on item response theory and classical test theory for the Amsterdam Instrumental Activities of Daily Living Questionnaire in cognitively normal and impaired older adults

OBJECTIVE:We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire. METHOD: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time.RESULTS: Two thousand two hundred ninety-four participants were included (66.6 ± 7.7 years, 54% female): n = 2,032 (89%) with normal cognition, n = 93 (4%) with subjective cognitive decline, n = 79 (3%) with mild cognitive impairment, and n = 91 (4%) with dementia. At baseline, IRT-based and CTT-based scores were highly correlated (r = -0.92). IRT-based scores showed less scale attenuation than CTT-based scores. In a subsample of n = 1,145 (62%) who were followed for a mean of 1.3 (SD = 0.6) years, IRT-based scores declined significantly among cognitively normal individuals (unstandardized coefficient [B] = -0.15, 95% confidence interval, 95% CI [-0.28, -0.03], effect size = -0.02), whereas CTT-based scores did not (B = 0.20, 95% CI [-0.02, 0.41], effect size = 0.02). In the other diagnostic groups, effect sizes of change over time were similar. CONCLUSIONS: IRT-based scores were less affected by scale attenuation than CTT-based scores. With regard to responsiveness, IRT-based scores showed more signal than CTT-based scores in early disease stages, highlighting the IRT-based scores' superior suitability for use in preclinical populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).</p

Cross-cultural adaptation and validation of the Amsterdam Instrumental Activities of Daily Living questionnaire short version German for Switzerland

Background Instrumental Activities of Daily Living (IADL) limitations are associated with reduced health-related quality of life for people with mild cognitive impairment (MCI). For these people, the assessment of IADL is crucial to the diagnostic process, as well as for the evaluation of new interventions addressing MCI. The Amsterdam IADL Questionnaire Short Version (A-IADL-Q-SV) is an established assessment tool with good psychometric properties that has been shown to be robust to cultural differences in Western countries. The aims of this study were to: (1) cross-culturally adapt and validate the A-IADL-Q-SV for the German-speaking population of Switzerland; (2) investigate its cultural comparability; and (3) evaluate further psychometric properties. Methods The A-IADL-Q-SV German was pretested on clinicians and participants in a memory clinic setting. The psychometric properties and cultural comparability of the questionnaire were investigated in memory clinic settings including participants with MCI or mild dementia, as well as participants with normal cognition recruited from the community. Item response theory (IRT) was applied to investigate measurement invariance by means of differential item functioning to assess item bias. Additionally, the test–retest reliability on scale level, the construct validity through hypothesis testing and the discriminant validity of the A-IADL-Q-SV German were evaluated. Results Ninety-six informants of participants with normal cognition, MCI or mild dementia completed the A-IADL-Q-SV German. The basic assumptions for IRT scoring were met. No meaningful differential item functioning for culture was detected between the Swiss and Dutch reference samples. High test–retest reliability on scale level (ICC 0.93; 95% CI 0.9–0.96) was found. More than 75% of the observed correlations between the A-IADL-Q-SV German and clinical measures of cognition and functional status were found to be in the direction and of the magnitude hypothesized. The A-IADL-Q-SV German was shown to be able to discriminate between participants with normal cognition and MCI, as well as MCI and mild dementia. Conclusions The A-IADL-Q-SV German is a psychometrically robust measurement tool for a Swiss population with normal cognition, MCI and mild dementia. Thus, it provides a valuable tool to assess IADL functioning in clinical practices and research settings in Switzerland

Perspectives on ethnic and racial disparities in Alzheimer\u27s disease and related dementias: Update and areas of immediate need

Alzheimer\u27s disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer\u27s Association International Society to Advance Alzheimer\u27s Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise “state-of-the-science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations. © 2018 The Author

Discontinuation and nonpublication of interventional clinical trials conducted in patients with mild cognitive impairment and Alzheimer's disease

Introduction: Discontinuation and nonpublication of interventional clinical trials represents a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in patients afflicted by mild cognitive impairment and Alzheimer's disease. Methods: We conducted a retrospective, cross-sectional study on mild cognitive impairment and Alzheimer's disease–based interventional clinical trials in ClinicalTrials.gov dating back to 1995. The analyzed data included trial phase, intervention type, enrollment, and funding sources. Fisher's exact and χ2 tests were used to determine any potential associations between trial characteristics and completion. Results: A total of 744 studies were identified, of which 502 (67%) were industry-sponsored ones. A total of 127 (17%) were discontinued prematurely. Of the 617 completed trials, 450 (73%) were not published, representing approximately 66,655 participants who incurred the risks of trial participation without subsequently contributing to the medical literature. Similarly, there were 18,246 patients from unpublished, discontinued trials. Of the 744 trials examined, 247 publications from 167 trials could be identified via PubMed/MEDLINE and EMBASE searches. Most notably, the odds of nonpublication among industry-sponsored trials were more than 75% higher than those in studies funded by academia (odds ratio = 1.78; 95% confidence interval, 1.14–2.78; P =.01). Furthermore, industry-sponsored trials had a 50% greater odds of study discontinuation compared with trials funded by academia (odds ratio = 1.50; 95% confidence interval, 1.04–2.16; P =.03). Discussion: The nonpublication of many trials and preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Publication of inconclusive or negative results ensures that all research activities, regardless of outcome, contribute to global medical knowledge

Impairment in complex activities of daily living is related to neurodegeneration in Alzheimer's disease-specific regions

Impairment in instrumental activities of daily living (IADL) is an early clinical feature of Alzheimer's disease (AD). The neurobiology underlying IADL disruptions is still unclear. We aimed to investigate the relationship between IADL functioning and cortical atrophy across the AD spectrum. We selected 162 memory-clinic subjects with subjective cognitive decline (n = 49), mild cognitive impairment (n = 26) or AD dementia (n = 87), and an available structural MRI acquired at 3.0 Tesla and Amsterdam IADL Questionnaire (A-IADL-Q) assessment. We used linear regression correcting for age, sex, education, vascular injuries, and total intracranial volume to investigate the association between gray matter volume and A-IADL-Q score, and voxel-based morphometry to investigate whether any associations were specific for distinct regions. Less gray matter volume was associated with lower A-IADL-Q scores (β = 0.346, 95% CI = [0.185-0.507], p < 0.001), specifically in cortical regions covering the medial temporal lobes, cingulate cortex, and precuneus (all p(familywise error-corrected) < 0.05). Results were similar when repeating the analyses in amyloid-positive subjects (n = 78). Our findings illustrate that the A-IADL-Q detects functional impairment related to AD-specific neurodegeneration

Detecting functional decline from normal aging to dementia: Development and validation of a short version of the Amsterdam IADL Questionnaire

Introduction Detecting functional decline from normal aging to dementia is relevant for diagnostic and prognostic purposes. Therefore, the Amsterdam IADL Questionnaire (A-IADL-Q) was developed: a 70-item proxy-based tool with good psychometric properties. We aimed to design a short version while preserving its psychometric quality. Methods Study partners of subjects (n = 1355), ranging from cognitively normal to dementia subjects, completed the original A-IADL-Q. We selected the short version items using a stepwise procedure combining missing data, Item Response Theory, and input from respondents and experts. We investigated internal consistency of the short version and concordance with the original version. To assess its construct validity, we additionally investigated concordance between the short version and the Mini–Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD). Finally, we investigated differences in instrumental activities of daily living (IADL) scores between diagnostic groups across the dementia spectrum. Results We selected 30 items covering the entire spectrum of IADL functioning. Internal consistency (0.98) and concordance with the original version (0.97) were very high. Concordance with the MMSE (0.72) and DAD (0.87) scores was high. IADL impairment scores increased across the spectrum from normal cognition to dementia. Discussion The A-IADL-Q short version (A-IADL-Q-SV) consists of 30 items and has maintained the psychometric quality of the original A-IADL-Q. As such, the A-IADL-Q-SV is a concise measure of functional decline