Teaching Microscopy: A Changing Paradigm

IMPACT. 1: Integrate the technical expertise and research capabilities at the Center for Electron Microscopy and Analysis (CEMAS) with the curriculum at Metro High school. -- 2. Ability to provide a revolutionary learning experience in a newly designed digital theater with remote access to several million dollars worth of microscopy equipment. -- 3. No one else is able to offer a similar program because our facility at CEMAS is uniquely positioned to provide excellent on-site microscopy experiences as well as the teaching/research expertise.OSU PARTNERS: College of Engineering; Materials Science and Engineering; Center for Electron Microscopy and AnalysisCOMMUNITY PARTNERS: Metro High SchoolPRIMARY CONTACT: Isabel Boona ([email protected]); Frank Scheltens ([email protected])This program will be one of the first collaborations between a multidisciplinary microscopy facility and a local high school. The intent is to introduce high school students to the concept of microscopy based materials examination through the development of teaching modules that can be incorporated into a curriculum as part of an existing course or as stand-alone senior level projects. The program will make use of CEMAS developed digital theater and remote instrument access capabilities

Teaching Microscopy: A Changing Paradigm

IMPACT. 1: Integrate the technical expertise and research capabilities at the Center for Electron Microscopy and Analysis (CEMAS) with the curriculum at Metro High school. -- 2. Ability to provide a revolutionary learning experience in a newly designed digital theater with remote access to several million dollars worth of microscopy equipment. -- 3. No one else is able to offer a similar program because our facility at CEMAS is uniquely positioned to provide excellent on-site microscopy experiences as well as the teaching/research expertise.OSU PARTNERS: College of Engineering; Materials Science and Engineering; Center for Electron Microscopy and AnalysisCOMMUNITY PARTNERS: Metro High SchoolPRIMARY CONTACT: Isabel Boona ([email protected]); Frank Scheltens ([email protected])This program will be one of the first collaborations between a multidisciplinary microscopy facility and a local high school. The intent is to introduce high school students to the concept of microscopy based materials examination through the development of teaching modules that can be incorporated into a curriculum as part of an existing course or as stand-alone senior level projects. The program will make use of CEMAS developed digital theater and remote instrument access capabilities

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

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

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

Brain Health Services: organization, structure, and challenges for implementation. A user manual for Brain Health Services-part 1 of 6.

Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy.An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population.We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services

Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6.

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions

Analysis of Psychological Symptoms Following Disclosure of Amyloid-Positron Emission Tomography Imaging Results to Adults With Subjective Cognitive Decline

IMPORTANCE: Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks. OBJECTIVE: To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022. EXPOSURES: Disclosure of amyloid-PET result. MAIN OUTCOMES AND MEASURES: Psychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale-Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms). RESULTS: After disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30]) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2]; P < .001), IES-R avoidance (0.00 [0.00 to 0.69] vs 0.00 [0.00 to 0.00]; P < .001), IES-R intrusions (0.50 [0.13 to 0.75] vs 0.00 [0.00 to 0.25]; P < .001), and IES-R hyperarousal (0.33 [0.00 to 0.67] vs 0.00 [0.00 to 0.00]; P < .001) scores than the 78 patients who were amyloid-negative (median [IQR], age, 67 [64 to 74] years, 45 men [58%], median [IQR] education: 15 [12 to 17] years, median [IQR] MMSE score: 29 [28 to 30]). There were no observed differences between amyloid-positive and amyloid-negative patients in the median (IQR) HADS Anxiety (-1.0 [-3.0 to 1.8] vs -2.0 [-4.8 to 1.0]; P = .06) and Depression (-1.0 [-2.0 to 0.0] vs -1.0 [-3.0 to 0.0]; P = .46) deltas (score after disclosure - scores at baseline). In patients with amyloid-positive SCD+, despite the small sample size, higher education was associated with lower disclosure-related distress (ρ = -0.43; P = .02) whereas the presence of study partner was associated with higher disclosure-related distress (W = 7.5; P = .03). No participants with amyloid-positive SCD+ showed probable presence of PTSD or severe anxiety or depression symptoms at follow-up. CONCLUSIONS AND RELEVANCE: The disclosure of a positive amyloid-PET result to patients with SCD+ was associated with a bigger psychological change, yet such change did not reach the threshold for clinical concern