Authors: Petrazzuoli, Ferdinando | Vestberg, Susanna | Midlöv, Patrik | Thulesius, Hans | Stomrud, Erik | Palmqvist, Sebastian
Article Type: Research Article
Abstract: Background: Differentiating mild cognitive impairment (MCI) from subjective cognitive decline (SCD) is important because of the higher progression rate to dementia for MCI and when considering future disease-modifying drugs that will have treatment indications at the MCI stage. Objective: We examined if the two most widely-used cognitive tests, the Mini-Mental State Examination (MMSE) and clock-drawing test (CDT), and a test of attention/executive function (AQT) accurately can differentiate MCI from SCD. Methods: We included 466 consecutively recruited non-demented patients with cognitive complaints from the BioFINDER study who had been referred to memory clinics, predominantly from primary care. They were classified as …MCI (n = 258) or SCD (n = 208) after thorough neuropsychological assessments. The accuracy of MMSE, CDT, and AQT for identifying MCI was examined both in training and validation samples and in the whole population. Results: As a single test, MMSE had the highest accuracy (sensitivity 73%, specificity 60%). The best combination of two tests was MMSE < 27 points or AQT > 91 seconds (sensitivity 56%, specificity 78%), but in logistic regression models, their AUC (0.76) was not significantly better than MMSE alone (AUC 0.75). CDT and AQT performed significantly worse (AUC 0.71; p < 0.001–0.05); otherwise no differences were seen between any combination of two or three tests. Conclusion: Neither single nor combinations of tests could differentiate MCI from SCD with adequately high accuracy. There is a great need to further develop, validate, and implement accurate screening-tests for primary care to improve accurate identification of MCI among individuals that seek medical care due to cognitive symptoms. Show more
Keywords: AQT, clock drawing test, cognitive screening, diagnostic accuracy, mild cognitive impairment, Mini-Mental State Examination, subjective cognitive decline
DOI: 10.3233/JAD-191191
Citation: Journal of Alzheimer's Disease, vol. 75, no. 4, pp. 1191-1201, 2020
Authors: Nägga, Katarina | Bränsvik, Vanja | Stomrud, Erik | Melander, Olle | Nilsson, Peter M. | Gustavsson, Anna-Märta | Hansson, Oskar
Article Type: Research Article
Abstract: Background: Register diagnoses, both hospital-based and from open clinic care, are often used in research studies in Sweden. The validity of such diagnoses has been debated and a validation assessment can improve the diagnostic accuracy for use in research studies. Objective: The aim of this study was to investigate the quality of register-derived dementia diagnoses in the Malmö Diet and Cancer population study (MDCS) and to validate these diagnoses using systematic criteria. Methods: MDCS is a population-based prospective study comprising 30,446 participants. Register diagnoses of dementia for the MDCS population were derived from the Swedish National Patient Register (NPR) and …validated through re-evaluation of available medical records by physicians. Results: In the MDCS cohort, 2,206 participants were diagnosed with dementia according to the NPR during a mean follow-up of 18.1 years. The general dementia diagnosis was valid in 96% of the cases, but 40% of the specific dementia diagnoses were changed during the process of reevaluation. The diagnostic validity varied between 25.2% and 82.9% for the different diagnoses. The results from the validity assessment per diagnostic category revealed that the validity of the NPR diagnoses was higher for the more specific diagnoses and lower for unspecified dementia. The major diagnostic shift during the re-evaluation was from unspecified dementia to more specific diagnoses. Conclusion: Validation of dementia diagnoses using medical records results in more precise diagnoses. Dementia diagnoses derived from registers should be validated in order to study associations between influential factors and different dementia diagnoses. Show more
Keywords: Alzheimer’s disease, dementia, register, risk factors, validation study
DOI: 10.3233/ADR-220003
Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 529-538, 2022
Authors: Hansson, Oskar | Stomrud, Erik | Vanmechelen, Eugeen | Östling, Svante | Gustafson, Deborah R | Zetterberg, Henrik | Blennow, Kaj | Skoog, Ingmar
Article Type: Research Article
Abstract: Amyloid-β (Aβ) pathology is a major component in the mechanisms behind Alzheimer's disease (AD). Measurement of Aβ42 in cerebrospinal fluid predicts cognitive decline in patients with mild cognitive impairment and identifies AD in patients with dementia. However, studies on Aβ in plasma are contradictory. In this prospective population-based study, plasma Aβ42 and Aβ40 were measured at baseline in 730 adults aged 70 years or older and without dementia. After five years, plasma levels were analyzed again and participants were assessed for development of dementia. During follow-up, 53 individuals (7%) developed dementia of which 37 (5%) were classified as AD. No …difference in baseline plasma Aβ42 , Aβ40 , or Aβ42 /Aβ40 ratio levels were observed between converters to dementia or AD compared to the cognitively stable individuals. However, individuals with plasma Aβ40 levels above the median level for the group at baseline had an increased risk of developing dementia and AD during the follow-up, even after adjustment for age, gender, APOE genotype, and educational level (odds ratio = 2.2, 95% confidence interval = 1.0–4.7, p < 0.05). Neither plasma Aβ42 nor the Aβ42 /Aβ40 ratio influenced the risk of developing dementia or AD. Moreover, Aβ42 and Aβ40 levels increased over the 5 years, whereas the Aβ42 /Aβ40 ratio decreased (p < 0.001). In conclusion, this study suggests that measurement of plasma Aβ should not be used clinically to predict dementia or AD. However, plasma Aβ40 may possibly be regarded as a moderate risk marker comparable to other risk markers for AD such as first-degree family history of dementia. Show more
Keywords: Alzheimer's disease, amyloid-β 40, amyloid-β 42, biological markers, cohort studies, dementia, plasma
DOI: 10.3233/JAD-2011-111418
Citation: Journal of Alzheimer's Disease, vol. 28, no. 1, pp. 231-238, 2012
Authors: Lindh-Rengifo, Magnus | Jonasson, Stina B. | Ullén, Susann | Palmqvist, Sebastian | van Westen, Danielle | Stomrud, Erik | Mattsson-Carlgren, Niklas | Nilsson, Maria H. | Hansson, Oskar
Article Type: Research Article
Abstract: Background: Impaired gait can precede dementia. The associations between gait parameters and brain pathologies are therefore of interest. Objective: To explore how different brain pathologies (i.e., vascular and Alzheimer’s) are associated with specific gait parameters from various gait components in persons with mild cognitive impairment (MCI), who have an increased risk of developing dementia. Methods: This cross-sectional study included 96 patients with MCI (mean 72, ±7.5 years; 52% women). Gait was evaluated by using an electronic walkway, GAITRite® . Four gait parameters (step velocity variability; step length; step time; stance time asymmetry) were used as dependent variables in multivariable linear …regression analyses. Independent variables included Alzheimer’s disease pathologies (amyloid-β and tau) by using PET imaging and white matter hyperintensities (WMH) by using MRI. Covariates included age, sex, comorbidities (and intracranial volume in analyses that includedWMH). Results: Increased tau-PET (Braak I–IV region of interest [ROI]) was associated with step velocity variability (standardized regression coefficient, β= 0.383, p < 0.001) and step length (β= 0.336, p < 0.001), which remained significant when using different Braak ROIs (I-II, III-IV, V-VI). The associations remained significant when adjusting for WMH (p < 0.001). When also controlling for gait speed, tau was no longer significantly (p = 0.168) associated with an increased step length. No significant associations between gait and Aβ-PET load or WMH were identified. Conclusions: The results indicate that one should pay specific attention to assess step velocity variability when targeting single task gait in patients with MCI. Future studies should address additional gait variability measures and dual tasking in larger cohorts. Show more
Keywords: Alzheimer’s disease, Alzheimer’s disease pathology, amyloid-β, electronic walkway, gait, gait variability, mild cognitive impairment, tau, white matter hyperintensities
DOI: 10.3233/JAD-221303
Citation: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 161-171, 2023
Authors: Pavlik, Valory N. | Burnham, Samantha C. | Kass, Joseph S. | Helmer, Catherine | Palmqvist, Sebastian | Vassilaki, Maria | Dartigues, Jean-François | Hansson, Oskar | Masters, Colin L. | Pérès, Karine | Petersen, Ronald C. | Stomrud, Erik | Butler, Lesley | Coloma, Preciosa M. | Teitsma, Xavier M. | Doody, Rachelle | Sano, Mary | for the CONCORD-AD investigators
Article Type: Review Article
Abstract: Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer’s disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer’s Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding …of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed. Show more
Keywords: Alzheimer’s disease, biomarkers, cognitive function, cohort, CONCORD-AD network, dementia, observational study, population characteristics
DOI: 10.3233/JAD-210525
Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 31-45, 2022
Authors: Wimo, Anders | Belger, Mark | Bon, Jaka | Jessen, Frank | Dumas, Annette | Kramberger, Milica G. | Jamilis, Laura | Johansson, Gunilla | Rodrigo Salas, Adrián | Rodríguez Gómez, Octavio | Sannemann, Lena | Stoekenbroek, Malou | Gurruchaga Telleria, Miren | Valero, Sergi | Vermunt, Lisa | Waterink, Lisa | Winblad, Bengt | Visser, Peter Jelle | Zwan, Marissa | Boada, Mercè | Escher, Claus | Müller, Theresa | Bogdanovic, Nenad | Andersen, Pia | Spulber, Gabriela | Sundström, Maria | Westman, Eric | Ferreira, Daniel | Jelic, Vesna | Haglund, Anders | Stomrud, Erik | Nelvig, Anders | Saha, Samir | Petek, Davorina | Serné, Erik
Article Type: Research Article
Abstract: Background: For care planning and support, under-detection and late diagnosis of Alzheimer’s disease (AD) is a great challenge. Models of Patient-Engagement for Alzheimer’s Disease (MOPEAD) is an EU-funded project aiming at testing different strategies to improve this situation. Objective: To make a cost-consequence analysis of MOPEAD. Methods: Four screening strategies were tested in five countries (Germany, the Netherlands, Slovenia, Spain, and Sweden): 1) a web-approach; 2) Open-House initiative; 3) in primary care; and 4) by diabetes specialists. Persons-at-risk of AD in all strategies were offered referral to a hospital-based specialist. The primary health-economic outcome was the cost per true-positive case …(TP) of AD from the screened population. Results: Of 2,847 screened persons, 1,121 screened positive (39%), 402 were evaluated at memory clinics (14%), and 236 got an AD diagnosis (8%). The cost per TP of those screened was €3,115 with the web-approach, €2,722 with the Open-House, €1,530 in primary care, and €1,190 by diabetes specialists. Sensitivity analyses that more likely reflect the real-world situation confirmed the results. The number-needed-to-screen was 30 with the web-approach, 8 with the Open-House and primary care, and 6 with the diabetes specialists. There were country differences in terms of screening rates, referrals to memory clinics, staff-types involved, and costs per TP. Conclusion: In primary care and by the diabetes specialist, the costs per TP/screened population were lowest, but the capacity of such settings to identify cases with AD-risk must be discussed. Hence new diagnostic strategies such as web-solutions and Open-House initiatives may be valuable after modifications. Show more
Keywords: Alzheimer’s disease, cost-consequence analysis, cost analysis, costs, dementia, diagnosis, diagnostic work-up, screening
DOI: 10.3233/JAD-210303
Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1149-1159, 2021
