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- Dubbelman, MA, et al.
(författare)
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Decline in cognitively complex everyday activities accelerates along the Alzheimer's disease continuum
- 2020
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1, s. 138-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundImpairment in daily functioning is a clinical hallmark of dementia. Difficulties with “instrumental activities of daily living” (IADL) seem to increase gradually over the course of Alzheimer’s disease (AD), before dementia onset. However, it is currently not well established how difficulties develop along the preclinical and prodromal stages of AD. We aimed to investigate the trajectories of decline in IADL performance, as reported by a study partner, along the early stages of AD.MethodsIn a longitudinal multicenter study, combining data from community-based and memory clinic cohorts, we included 1555 individuals (mean age 72.5 ± 7.8 years; 50% female) based on availability of amyloid biomarkers, longitudinal IADL data, and clinical information at baseline. Median follow-up duration was 2.1 years. All amyloid-positive participants (n = 982) were classified into the National Institute on Aging–Alzheimer’s Association (NIA-AA) clinical stages ranging from preclinical AD (1) to overt dementia (4+). Cognitively normal amyloid-negative individuals (n = 573) served as a comparison group. The total scores of three study-partner reported IADL questionnaires were standardized.ResultsThe rate of decline in cognitively normal (stage 1) individuals with and without abnormal amyloid did not differ (p = .453). However, from stage 2 onwards, decline was significantly faster in individuals on the AD continuum (B [95%CI] = − 0.32 [− 0.55, − 0.09],p = .007). The rate of decline increased with each successive stage: one standard deviation (SD) unit per year in stage 3 (− 1.06 [− 1.27, − 0.85],p < .001) and nearly two SD units per year in stage 4+ (1.93 [− 2.19, − 1.67],p < .001). Overall, results were similar between community-based and memory clinic study cohorts.ConclusionsOur results suggest that the rate of functional decline accelerates along the AD continuum, as shown by steeper rates of decline in each successive NIA-AA clinical stage. These results imply that incremental changes in function are a meaningful measure for early disease monitoring. Combined with the low-cost assessment, this advocates the use of these functional questionnaires for capturing the effects of early AD-related cognitive decline on daily life.
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- Hagenbeek, FA, et al.
(författare)
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Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 39-
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
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- Mank, A, et al.
(författare)
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A longitudinal study on quality of life along the spectrum of Alzheimer's disease
- 2022
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1, s. 132-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundQuality 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.MethodsWe 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).ResultsIn 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.ConclusionsQoL 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.
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