BACKGROUND: Associations between longitudinal changes of plasma biomarkers and cerebral magnetic resonance (MR)-derived measurements in Alzheimer’s disease (AD) remain unclear. METHODS: In a study population (n = 127) of healthy older adults and patients within the AD continuum, we examined associations between longitudinal plasma amyloid beta 42/40 ratio, tau phosphorylated at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and 7T structural and functional MR imaging and spectroscopy using linear mixed models. RESULTS: Increases in both p-tau181 and GFAP showed the strongest associations to 7T MR-derived measurements, particularly with decreasing parietal cortical thickness, decreasing connectivity of the salience network, and increasing neuroinflammation as determined by MR spectroscopy (MRS) myo-inositol. DISCUSSION: Both plasma p-tau181 and GFAP appear to reflect disease progression, as indicated by 7T MR-derived brain changes which are not limited to areas known to be affected by tau pathology and neuroinflammation measured by MRS myo-inositol, respectively. Highlights: This study leverages high-resolution 7T magnetic resonance (MR) imaging and MR spectroscopy (MRS) for Alzheimer’s disease (AD) plasma biomarker insights. Tau phosphorylated at threonine 181 (p-tau181) and glial fibrillary acidic protein (GFAP) showed the largest changes over time, particularly in the AD group. p-tau181 and GFAP are robust in reflecting 7T MR-based changes in AD. The strongest associations were for frontal/parietal MR changes and MRS neuroinflammation. 

Why?

Society's need for knowledge about experiences, feelings, behaviours and abilities is increasing. It is important to know how people and society feel or how a product or service is perceived, and to be able to compare how these change over time and between different areas, for example when making decisions about priorities, efforts and effects. In order for measurements of experiences, feelings, behaviours and abilities to be useful and provide reliable data, quality-assured measurement is required for socalled category based measurements1. It is therefore necessary that basic measurement principles are applied, which is often not the case today in this field. For the physical quantities (length, mass, time, etc.) there has long been an internationally established measurement quality infrastructure. In Sweden, it is mainly RISE as the National Metrological Institute which, through its national measurement sites, is responsible for ensuring access to quality-assured and traceable measurements for society. However, the corresponding measurement quality infrastructure is so far missing for category based measurements.

What?

RISE has been working for several years to develop methodology and working methods for measurement quality assurance of experiences, feelings, behaviours and abilities. Through dialogue over several years with actors at various levels, including in health care and academia, it has emerged that there is a great need for support for this development. RISE has therefore produced a first draft of a possible sustainable organization for measurement quality assurance of category based measurements. A national centre for quality assurance of category based measurements would be tasked with coordinating and ensuring reliable and comparable measurements of experiences, feelings, behaviours and abilities. Such infrastructural support must make methodologies available to enable quality assurance for category based measurements. The organization must meet society's need for support by offering services based on internationally accepted metrological principles and scientific methods, as well as adopting a neutral and independent role.

How?

We have humility about the fact that it is a long process to establish an organization for category based measurements and that it needs to happen through a dynamic and iterative development in co-creation with the actors involved. We look forward to continuing to develop ideas and revise the proposal in dialogue in the coming years. It is also important to start a dialogue together with relevant actors about how the implementation of the organization can take place in the future.

Varför?

Samhällets behov av kunskap om upplevelser, känslor, beteenden och förmågor ökar. Det är viktigt att veta hur personer och samhället mår eller hur en produkt eller tjänst upplevs samt att kunna jämföra hur detta förändras över tid och mellan olika områden, för att exempelvis fatta beslut om prioriteringar, insatser och effekter. För att mätningar av upplevelser, känslor, beteenden och förmågor ska vara användbara och ge tillförlitliga underlag krävs kvalitetssäkrad mätteknik för s.k. kategoribaserade mätningar. Det är alltså nödvändigt att grundläggande mättekniska principer tillämpas, vilket ofta inte är fallet i dag inom detta område. För de fysikaliska storheterna (längd, massa, tid etc.) finns sedan länge en internationellt etablerad mätkvalitetsinfrastruktur. I Sverige är det huvudsakligen RISE som Nationellt Metrologiskt Institut som genom sina riksmätplatser ansvarar för att säkerställa tillgång till kvalitetssäkrade och spårbara mätningar för samhället. Motsvarande mätkvalitetsinfrastruktur saknas dock för kategoribaserade mätningar.

Vad?

RISE arbetar sedan flera år för att utveckla metoder och arbetssätt för mätkvalitetssäkring av upplevelser, känslor, beteenden och förmågor. Genom dialoger med aktörer på olika nivåer, bland annat inom hälso- och sjukvården och akademin, som pågått under flera års tid har det framkommit att det finns ett stort behov av stöd för denna utveckling. RISE har därför tagit fram ett första utkast för en möjlig hållbar organisering för mätkvalitetssäkring av kategoribaserade mätningar. Ett nationellt centrum för mätkvalitetssäkring av kategoribaserade mätningar skulle ha i uppdrag att samordna och säkerställa tillförlitliga och jämförbara mätningar av upplevelser, känslor, beteenden och förmågor. Ett sådant infrastrukturellt stöd ska tillgängliggöra metodiker för att möjliggöra mätkvalitetssäkring för kategoribaserade mätningar. Organiseringen ska möta samhällets behov av stöd genom att erbjuda tjänster baserade på internationellt vedertagna mättekniska principer och vetenskapliga metoder samt ha en neutral och oberoende roll.

Hur?

Det finns en stor ödmjukhet kring att det är en lång process att etablera en organisering för kategoribaserade mätningar och att det behöver ske genom en dynamisk och iterativ utveckling i samskapande med berörda aktörer. Vi ser fram emot att fortsätta utveckla tankar och revidera förslaget i dialog under kommande år. Det är också viktigt att påbörja en dialog tillsammans med relevanta aktörer om hur implementeringen av organiseringen kan ske i framtiden.

Both construct specification equations (CSEs) and entropy can be used to provide a specific, causal, and rigorously mathematical conceptualization of item attributes in order to provide fit-for-purpose measurements of person abilities. This has been previously demonstrated for memory measurements. It can also be reasonably expected to be applicable to other kinds of measures of human abilities and task difficulty in health care, but further exploration is needed about how to incorporate qualitative explanatory variables in the CSE formulation. In this paper we report two case studies exploring the possibilities of advancing CSE and entropy to include human functional balance measurements. In case study I, physiotherapists have formulated a CSE for balance task difficulty by principal component regression of empirical balance task difficulty values from Berg’s Balance Scale transformed using the Rasch model. In case study II, four balance tasks of increasing difficulty due to diminishing bases of support and vision were briefly investigated in relation to entropy as a measure of the amount of information and order as well as physical thermodynamics. The pilot study has explored both methodological and conceptual possibilities and concerns to be considered in further work. The results should not be considered as fully comprehensive or absolute, but rather open up for further discussion and investigations to advance measurements of person balance ability in clinical practice, research, and trials. © 2023 by the authors.

There are different views in the literature about the number and inter-relationships of cognitive domains (such as memory and executive function) and a lack of understanding of the cognitive processes underlying these domains. In previous publications, we demonstrated a methodology for formulating and testing cognitive constructs for visuo-spatial and verbal recall tasks, particularly for working memory task difficulty where entropy is found to play a major role. In the present paper, we applied those insights to a new set of such memory tasks, namely, backward recalling block tapping and digit sequences. Once again, we saw clear and strong entropy-based construct specification equations (CSEs) for task difficulty. In fact, the entropy contributions in the CSEs for the different tasks were of similar magnitudes (within the measurement uncertainties), which may indicate a shared factor in what is being measured with both forward and backward sequences, as well as visuo-spatial and verbal memory recalling tasks more generally. On the other hand, the analyses of dimensionality and the larger measurement uncertainties in the CSEs for the backward sequences suggest that caution is needed when attempting to unify a single unidimensional construct based on forward and backward sequences with visuo-spatial and verbal memory tasks.

Better metrics of cognition can be formed by carefully combining selected items from legacy short-term memory tests so as to enhance coherence in item design while not jeopardizing validity. In this paper, we report on how Rasch Measurement Theory and Construct specification equations (CSE) have been brought together when composing the NeuroMET Memory Metric (NMM). The NMM is guided by: i) entropy-based equivalence criteria; ii) a comprehensive understanding of the construct purported to be measured; and iii) how a collection of items works together. CSEs play a major role in ensuring the metrological legitimacy of the NMM in a way analogous to certified reference materials in more established areas of metrology. The resulting NMM for short-term memory recall has up to a five-fold reduction in measurement uncertainties for memory ability compared with an individual legacy test, and the entropy-based CSEs should enable more efficient and valid assessment. © 2022 The Authors

The justification for making a measurement can be sought in asking what decisions are based on measurement, such as in assessing the compliance of a quality characteristic of an entity in relation to a specification limit, SL. The relative performance of testing devices and classification algorithms used in assessing compliance is often evaluated using the venerable and ever popular receiver operating characteristic (ROC). However, the ROC tool has potentially all the limitations of classic test theory (CTT) such as the non-linearity, effects of ordinality and confounding task difficulty and instrument ability. These limitations, inherent and often unacknowledged when using the ROC tool, are tackled here for the first time with a modernised approach combining measurement system analysis (MSA) and item response theory (IRT), using data from pregnancy testing as an example. The new method of assessing device ability from separate Rasch IRT regressions for each axis of ROC curves is found to perform significantly better, with correlation coefficients with traditional area-under-curve metrics of at least 0.92 which exceeds that of linearised ROC plots, such as Linacre’s, and is recommended to replace other approaches for device assessment. The resulting improved measurement quality of each ROC curve achieved with this original approach should enable more reliable decision-making in conformity assessment in many scenarios, including machine learning, where its use as a metric for assessing classification algorithms has become almost indispensable.

Background: The ability to measure, track over time, and compare memory ability for people with neurodegeneration is important. However, currently, full comparability of memory test data is limited by a lack of quality assurance of memory measurements. At AAIC 2021, we presented a preliminary item bank to assess memory, composed by selecting items from legacy tests according to metrological principles through use of the Rasch model and with item equivalence based on entropy. Method: Here, we demonstrate direct comparability of measurements generated from different tests, with the new NeuroMET Memory Metric comprising 87 selected items for task difficulty from: the Corsi Block Test, Digit Span Test, Rey’s Auditory Verbal Learning Test, Word Learning List from the CERAD test battery and the Mini Mental State Examination. Data were collected from the European EMPIR NeuroMET and the SmartAge studies recruited at Charité Hospital (Healthy controls n = 92; Subjective cognitive decline n = 160; Mild Cognitive Impairment n = 50; and Alzheimer’s Disease n = 58; age range 55-87). Results: The Rasch analysis showed well-targeted items for all participants’ abilities; good fit to the measurement model, with 83 items (95%) having fit residuals within the expected range and satisfactory unidimensionality, and item reliability of 0.96. The full item bank comprising 87 short-term memory items gave a person reliability of 0.85. Subsequently, a conversion table was created linking the raw scores from the legacy tests to the common NeuroMET Memory Metric and to individual legacy tests. Conclusion: Legacy memory tests have previously proven useful in clinical practice and research, and will continue to be used, but have to date been metrologically limited. The provided conversion table, linking these legacy memory tests to a metrologically assured scale, viz., the NeuroMET memory metric, remedies this deficiency. The NeuroMET memory metric will be included in the first ever prototype of a metrological validated app used to deliver memory tests. Clinicians and researchers will be able to select sets of items to produce data, via a scoring algorithm for transforming patient responses to measures, in a common frame of reference.

Accurate assessment of memory ability for persons on the continuum of Alzheimer’s disease (AD) is vital for early diagnosis, monitoring of disease progression and evaluation of new therapies. However, currently available neuropsychological tests suffer from a lack of standardization and metrological quality assurance. Improved metrics of memory can be created by carefully combining selected items from legacy short-term memory tests, whilst at the same time retaining validity, and reducing patient burden. In psychometrics, this is known as “crosswalks” to link items empirically. The aim of this paper is to link items from different types of memory tests. Memory test data were collected from the European EMPIR NeuroMET and the SmartAge studies recruited at Charité Hospital (Healthy controls n = 92; Subjective cognitive decline n = 160; Mild cognitive impairment n = 50; and AD n = 58; age range 55–87). A bank of items (n = 57) was developed based on legacy short-term memory items (i.e., Corsi Block Test, Digit Span Test, Rey’s Auditory Verbal Learning Test, Word Learning Lists from the CERAD test battery and Mini Mental State Examination; MMSE). The NeuroMET Memory Metric (NMM) is a composite metric that comprises 57 dichotomous items (right/wrong). We previously reported on a preliminary item bank to assess memory based on immediate recall, and have now demonstrated direct comparability of measurements generated from the different legacy tests. We created crosswalks between the NMM and the legacy tests and between the NMM and the full MMSE using Rasch analysis (RUMM2030) and produced two conversion tables. Measurement uncertainties for estimates of person memory ability with the NMM across the full span were smaller than all individual legacy tests, which demonstrates the added value of the NMM. Comparisons with one (MMSE) of the legacy tests showed however higher measurement uncertainties of the NMM for people with a very low memory ability (raw score ≤ 19). The conversion tables developed through crosswalks in this paper provide clinicians and researchers with a practical tool to: (i) compensate for ordinality in raw scores, (ii) ensure traceability to make reliable and valid comparisons when measuring person ability, and (iii) enable comparability between test results from different legacy tests. © 2023, The Author(s).

New candidate diagnostics for cognitive decline and dementia have recently been proposed based on effects such as primacy and recency in word learning memory list tests. The diagnostic value is, however, currently limited by the multiple ways in which raw scores, and in particular these serial position effects (SPE), have been defined and analyzed to date. In this work, we build on previous analyses taking a metrological approach to the 10-item word learning list. We show i) how the variation in task difficulty reduces successively for trials 2 and 3, ii) how SPE change with repeated trials as predicted with our entropy-based theory, and iii) how possibilities to separate cohort members according to cognitive health status are limited. These findings mainly depend on the test design itself: A test with only 10 words, where SPE do not dominate over trials, requires more challenging words to increase the variation in task difficulty, and in turn to challenge the test persons. The work is novel and also contributes to the endeavour to develop for more consistent ways of defining and analyzing memory task difficulty, and in turn opens up for more practical and accurate measurement in clinical practice, research and trials.