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- Coley, Nicola, et al.
(författare)
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Plasma p-tau181 as an outcome and predictor of multidomain intervention effects: a secondary analysis of a randomised, controlled, dementia prevention trial
- 2024
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Ingår i: The Lancet Healthy Longevity. - 2666-7568. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unknown whether multidomain interventions, which might preserve late-life cognition, affect Alzheimer's disease pathology. Previous studies measured cerebrospinal fluid and imaging Alzheimer's disease biomarkers in small subsamples of multidomain trial participants. Newly developed assays enable the measurement of blood-based Alzheimer's disease biomarkers in larger samples. We aimed to assess whether plasma tau phosphorylated at threonine 181 (p-tau181) was able to detect or predict 3-year multidomain intervention effects. Methods: This is a secondary analysis of the randomised, controlled, Multidomain Alzheimer Prevention Trial (MAPT) testing a 3-year multidomain intervention, omega-3 fatty acid supplementation, or both versus placebo, in individuals aged 70 years and older in 13 memory centres in France and Monaco. Plasma p-tau181 was measured in stored blood samples in a subsample of 527 participants on an intention-to-treat basis. Changes in cognitive score were calculated as a composite measure using the average of Z scores for the following tests: Mini Mental State Examination orientation items, Free and Cued Selective Reminding Test (sum of free and total recall scores), category fluency, and Digit Symbol Substitution Test. Intervention effects on 3-year change in p-tau181 concentration were estimated by use of a linear mixed model with centre-specific random intercepts. Findings: Recruitment took place between May 30, 2008, and Feb 24, 2011. Median baseline plasma p-tau181 was 8·8 pg/mL (IQR 6·7–11·9) in the total sample, and significantly higher in older individuals, men, APOE ε4 carriers, and participants with renal dysfunction or a positive PET amyloid scan. During 3-year follow-up, individuals with raised baseline p-tau181 underwent greater cognitive decline (eg, mean difference in 3-year change on the composite cognitive score between control group participants with normal and abnormal baseline levels of p-tau was −0·34 [effect size −0·52; 95% CI −0·61 to 0·07] in the fully adjusted model using a 12·4 pg/mL cutoff for abnormal baseline p-tau181), but there were no intervention effects on change in p-tau181 either in this subgroup or the total population, and no effect on cognitive change in individuals with raised baseline p-tau181 (eg, in the fully adjusted model using the 12·4 pg/mL cutoff for p-tau181 abnormality, the mean difference [95% CI] in this subgroup in 3-year decline on the composite cognitive score between the control group and the multidomain + omega-3 group, the omega-3 group, and the multidomain intervention group, was, respectively: 0·13 [−0·21 to 0·47], 0·03 [−0·30 to 0·36], and 0·10 [−0·26 to 0·46]). Surprisingly, individuals with raised baseline p-tau181 showed a decrease in p-tau181 during follow-up (eg, unadjusted mean [95% CI] 3-year change was −3·01 pg/mL (−4·45 to −1·56) in control group subjects with abnormal baseline p-tau181 [using the 12·4 pg/mL abnormal p-tau cutoff]). Interpretation: Our results support the utility of p-tau181 as a prognostic biomarker, but it did not predict or detect intervention effects in this study. Further investigation of its usefulness as a prevention trial outcome measure is required.
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| 2. |
- de Mauleon, Adelaide, et al.
(författare)
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Associated Factors With Antipsychotic Use in Long-Term Institutional Care in Eight European Countries: Results From the RightTimePlaceCare Study
- 2014
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Ingår i: Journal of the American Medical Directors Association. - Philadelphia : Elsevier. - 1525-8610 .- 1538-9375. ; 15:11, s. 812-818
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine factors associated with the antipsychotic (AP) prescription for people with dementia (PwD) recently admitted to institutional long-term carefacilities (LTCFs) and to ascertain differences in the use of this medication in 8 European countries.Design: An exploratory cross-sectional study.Setting: LTCFs from 8 European countries (Estonia, Finland, France, Germany, The Netherlands, Spain, Sweden, and England).Participants: A total of 791 PwD recently admitted to an LTCF and their caregivers.Measurements: Baseline data from RightTimePlaceCare survey was used. Patients' medical conditions, neuropsychiatric symptoms, physical and cognitive status, and medications were recorded. Multiple logistic regression models were used to assess associations with the AP use. Results: A group of 296 patients (37.4%) of 791 patients recently admitted received AP medication. The prevalence of the use of 1 or more APs varied between study countries, ranging from 12% in Sweden to 54% inSpain. Factors independently associated with the AP use were living in Sweden [odds ratio (OR) 0.12, 95% confidence interval (CI) 0.05-0.30], Finland (OR 0.26, 95% CI 0.14-0.48), Germany (OR 2.75, 95% CI 1.55-4.86) and Estonia (OR 6.79, 95% CI 3.84-12.0). The odds of AP use decreased with the presence of a dementia specific unit inthe LTCF (OR 0.60, 95% CI 0.39-0.92), but was higher among residents with a hyperactivity behavior (OR 2.12, 95% CI 1.41-3.18).Conclusion: The current study shows that more than one-third of the residents recently admitted received APs and that prescription frequency across countries varied significantly. This study raises the possibility that the presence of a dementia-specific unit might play a role in the AP use. Further studies should investigate this association and seek better understanding of what will achieve optimal quality of AP use among newly admitted residents in LTCF. © 2014 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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