Health utility in preclinical and prodromal Alzheimer's disease for establishing the value of new disease‐modifying treatments—EQ‐5D data from the Swedish BioFINDER study

Gustavsson, Anders; Rakêt, Lars Lau; Lilja, Mathias; Rutten-Jacobs, Loes C.A.; Wahl, Hanna Fues; Bagijn, Marloes; Stomrud, Erik; Hansson, Oskar; Palmqvist, Sebastian

doi:10.1002/alz.12355

Cited by 5 publications

(6 citation statements)

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“…A recent cross-sectional study among biomarker-confirmed AD patients in the SCD and MCI stages showed no significant difference in EQ-5D score between amyloid-positive and amyloid-negative SCD patients and a somewhat counter-intuitively higher EQ-5D score in amyloid-positive MCI patients compared to amyloid-negative MCI [ 10 ]. We confirmed these results and we also observed higher GDS in amyloid-negative MCI patients compared to amyloid-positive patients (Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…A recent cross-sectional study among biomarker-confirmed AD patients in the SCD and MCI stages showed no difference in the EQ-5D utilities between amyloid-positive and amyloid-negative individuals with subjective cognitive decline (SCD) and a higher EQ-5D utility in amyloid-positive mild cognitive impairment (MCI) patients compared to amyloid-negative MCI [ 10 ]. However, the cross-sectional nature of this former study does not allow insight in the trajectory of QoL over time in individuals.…”

Section: Introductionmentioning

confidence: 99%

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A longitudinal study on quality of life along the spectrum of Alzheimer’s disease

et al. 2022

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Background Quality of life (QoL) is an important outcome from the perspective of patients and their caregivers, in both dementia and pre-dementia stages. Yet, little is known about the long-term changes in QoL over time. We aimed to compare the trajectories of QoL between amyloid-positive and amyloid-negative SCD or MCI patients and to evaluate QoL trajectories along the Alzheimer’s disease (AD) continuum of cognitively normal to dementia. Methods We included longitudinal data of 447 subjective cognitive decline (SCD), 276 mild cognitive impairment (MCI), and 417 AD dementia patients from the Amsterdam Dementia Cohort. We compared QoL trajectories (EQ-5D and visual analog scale (VAS)) between (1) amyloid-positive and amyloid-negative SCD or MCI patients and (2) amyloid-positive SCD, MCI, and dementia patients with linear mixed-effect models. The models were adjusted for age, sex, Charlson Comorbidity Index (CCI), education, and EQ-5D scale (3 or 5 level). Results In SCD, amyloid-positive participants had a higher VAS at baseline but showed a steeper decline over time in EQ-5D and VAS than amyloid-negative participants. Also, in MCI, amyloid-positive patients had higher QoL at baseline but subsequently showed a steeper decline in QoL over time compared to amyloid-negative patients. When we compared amyloid-positive patients along the Alzheimer continuum, we found no difference between SCD, MCI, or dementia in baseline QoL, but QoL decreased at a faster rate in the dementia stage compared with the of SCD and MCI stages. Conclusions QoL decreased at a faster rate over time in amyloid-positive SCD or MCI patients than amyloid-negative patients. QoL decreases over time along the entire AD continuum of SCD, MCI and dementia, with the strongest decrease in dementia patients. Knowledge of QoL trajectories is essential for the future evaluation of treatments in AD. Supplementary Information The online version contains supplementary material available at 10.1186/s13195-022-01075-8.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A longitudinal study on quality of life along the spectrum of Alzheimer’s disease

et al. 2022

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“…13 CSF amyloid-β (Aβ) 40 and Aβ42 were analyzed by EURO-IMMUN ELISAs (EUROIMMUN AG Lübeck, Germany). Pathologic Aβ accumulation was considered as present using a previously established CSF Aβ42/40 cutoff <0.088, 20 i.e., determined by using mixture modeling statistics in the healthy controls and participants with SCD and MCI in BioFINDER. 21,22 Tau phosphorylated at Thr181 (P-tau) were analyzed with INNOTEST ELISA (Fujirebio Gent, Belgium).…”

Section: Biomarkersmentioning

confidence: 99%

Spatial Navigation and Its Association With Biomarkers and Future Dementia in Memory Clinic Patients Without Dementia

et al. 2022

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Background and Objectives:Impaired spatial navigation is considered an early sign in many neurodegenerative diseases. We aimed to determine if spatial navigation was associated with future dementia in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI), and to explore associations between spatial navigation and biomarkers of Alzheimer’s disease (AD) and neurodegeneration.Methods:The study included memory clinic patients without dementia in the longitudinal BioFINDER cohort. The Floor Maze Test (FMT) was used to assess spatial navigation at baseline. Conversion to dementia were evaluated at 2- and 4-year follow-ups. At baseline, amyloid-β 42/40 ratio, phosphorylated-tau (p-tau) and neurofilament light (NfL) were analysed in CSF. Cortical thickness and volume of regions relevant for navigation, and white matter lesion volume were quantified from MRI. The predictive role of the FMT for conversion to all-cause dementia was analysed using logistic regression analyses in two models; 1) controlled for age, sex and education, and 2) adding baseline cognitive status and MMSE. Associations between FMT and biomarkers were adjusted for age, sex, and cognitive status (SCD or MCI).Results:156 patients with SCD and 176 patients with MCI were included. FMT total time was associated with progression to all-cause dementia in model 2 at 2-year (OR 1.10, 95% CI 1.04, 1.16) and at 4-year follow-up (OR 1.10, 95% CI 1.04, 1.16), i.e., a 10 % increase in odds of developing dementia per every 10 sec increase in FMT. In the adjusted analyses, P-tau and NfL was associated with FMT total time, as well as hippocampal volume, parahippocampal and inferior parietal cortical thickness. Amyloid-β 42/40 ratio was not associated with FMT total time.Discussion:Impaired spatial navigation was associated with conversion to dementia within 2 and 4 years, and with key CSF and MRI biomarkers for AD and neurodegeneration in patients with SCD and MCI. This supports its use in early cognitive assessments, but the predictive accuracy should be validated in other cohorts.Classification of Evidence:This is a Class 1 prospective cohort study demonstrating association of baseline markers of spatial recognition with development of dementia in patients with SCD or MCI at baseline.

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“…Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder and a primary cause of dementia resulting in reduced life expectancy [ 1 , 2 ], loss of function and autonomy [ 1 , 3 ], impaired quality of life (QoL) [ 4 ], care partner burden [ 5 – 7 ], and high costs to society [ 8 , 9 ]. Recent estimates suggest that 32 million people have dementia due to AD worldwide and 69 million mild cognitive impairment (MCI) due to AD [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Progression analysis versus traditional methods to quantify slowing of disease progression in Alzheimer’s disease

Jönsson,

Ivkovic,

Atri

et al. 2024

Alz Res Therapy

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Background The clinical meaningfulness of the effects of recently approved disease-modifying treatments (DMT) in Alzheimer’s disease is under debate. Available evidence is limited to short-term effects on clinical rating scales which may be difficult to interpret and have limited intrinsic meaning to patients. The main value of DMTs accrues over the long term as they are expected to cause a delay or slowing of disease progression. While awaiting such evidence, the translation of short-term effects to time delays or slowing of progression could offer a powerful and readily interpretable representation of clinical outcomes. Methods We simulated disease progression trajectories representing two arms, active and placebo, of a hypothetical clinical trial of a DMT. The placebo arm was simulated based on estimated mean trajectories of clinical dementia rating scale–sum of boxes (CDR-SB) recordings from amyloid-positive subjects with mild cognitive impairment (MCI) from Alzheimer’s Disease Neuroimaging Initiative (ADNI). The active arm was simulated to show an average slowing of disease progression versus placebo of 20% at each visit. The treatment effects in the simulated trials were estimated with a progression model for repeated measures (PMRM) and a mixed model for repeated measures (MMRM) for comparison. For PMRM, the treatment effect is expressed in units of time (e.g., days) and for MMRM in units of the outcome (e.g., CDR-SB points). PMRM results were implemented in a health economics Markov model extrapolating disease progression and death over 15 years. Results The PMRM model estimated a 19% delay in disease progression at 18 months and 20% (~ 7 months delay) at 36 months, while the MMRM model estimated a 25% reduction in CDR-SB (~ 0.5 points) at 36 months. The PMRM model had slightly greater power compared to MMRM. The health economic model based on the estimated time delay suggested an increase in life expectancy (10 months) without extending time in severe stages of disease. Conclusion PMRM methods can be used to estimate treatment effects in terms of slowing of progression which translates to time metrics that can be readily interpreted and appreciated as meaningful outcomes for patients, care partners, and health care practitioners.

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Health utility in preclinical and prodromal Alzheimer's disease for establishing the value of new disease‐modifying treatments—EQ‐5D data from the Swedish BioFINDER study

Cited by 5 publications

References 35 publications

A longitudinal study on quality of life along the spectrum of Alzheimer’s disease

A longitudinal study on quality of life along the spectrum of Alzheimer’s disease

Spatial Navigation and Its Association With Biomarkers and Future Dementia in Memory Clinic Patients Without Dementia

Progression analysis versus traditional methods to quantify slowing of disease progression in Alzheimer’s disease

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