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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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- Haapanen, Markus J., et al.
(författare)
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Early growth, stress, and socioeconomic factors as predictors of the rate of multimorbidity accumulation across the life course : a longitudinal birth cohort study
- 2024
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Ingår i: Lancet healthy longevity. - 2666-7568. ; 5:1, s. e56-e65
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early growth, stress, and socioeconomic factors are associated with future risk of individual chronic diseases. It is uncertain whether they also affect the rate of multimorbidity accumulation later in life. This study aimed to explore whether early life factors are associated with the rate at which chronic diseases are accumulated across older age.Methods: In this national birth cohort study, we studied people born at Helsinki University Central Hospital, Helsinki, Finland between Jan 1, 1934, and Dec 31, 1944, who attended child welfare clinics in the city, and were living in Finland in 1971. Individuals who had died or emigrated from Finland before 1987 were excluded, alongside participants without any registry data and who died before the end of the registry follow-up on Dec 31, 2017. Early anthropometry, growth, wartime parental separation, and socioeconomic factors were recorded from birth, child welfare clinic, or school health-care records, and Finnish National Archives. International Classification of Diseases codes of diagnoses for chronic diseases were obtained from the Care Register for Health Care starting from 1987 (when participants were aged 42-53 years) until 2017. Linear mixed models were used to study the association between early-life factors and the rate of change in the number of chronic diseases over 10-year periods.Findings: From Jan 1, 1934, to Dec 31, 2017, 11 689 people (6064 [51 center dot 9%] men and 5625 [48 center dot 1%] women) were included in the study. Individuals born to mothers younger than 25 years (beta 0 center dot 09; 95% CI 0 center dot 06-0 center dot 12), mothers with a BMI of 25-30 kg/m2 (0 center dot 08; 0 center dot 05-0 center dot 10), and mothers with a BMI more than 30 kg/m2 (0 center dot 26; 0 center dot 21-0 center dot 31) in late pregnancy accumulated chronic diseases faster than those born to older mothers (25-30 years) and those with a BMI of less than 25 kg/m2. Individuals with a birthweight less than 2 center dot 5 kg (0 center dot 17; 0 center dot 10-0 center dot 25) and those with a rapid growth in height and weight from birth until age 11 years accumulated chronic diseases faster during their life course. Additionally, paternal occupational class (manual workers vs upper-middle class 0 center dot 27; 0 center dot 23-0 center dot 30) and wartime parental separation (0 center dot 24; 0 center dot 19-0 center dot 29 for boys; 0 center dot 31; 0 center dot 25-0 center dot 36 for girls) were associated with a faster rate of chronic disease accumulation. Interpretation Our findings suggest that the foundation for accumulating chronic diseases is established early in life. Early interventions might be needed for vulnerable populations, including war evacuee children and children with lower socioeconomic status.
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