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- Röhr, Susanne, et al.
(author)
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Impact of the COVID-19 pandemic on statistical design and analysis plans for multidomain intervention clinical trials : Experience from World-Wide FINGERS
- 2021
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In: Alzheimer’s & Dementia. - : Wiley. - 2352-8737. ; 7:1
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Journal article (peer-reviewed)abstract
- Introduction: The coronavirus disease-19 (COVID-19) pandemic presents challenges to the conduct of randomized clinical trials of lifestyle interventions.Methods: World-Wide FINGERS is an international network of clinical trials to assess the impact of multidomain lifestyle intervention on cognitive decline in at-risk adults. Individual trials are tailoring successful approaches from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) to local cultures and environments. The network convened a forum for researchers to discuss statistical design and analysis issues they faced during the pandemic. We report on experiences of three trials that, at various stages of conduct, altered designs and analysis plans to navigate these issues. We provide recommendations for future trials to consider as they develop and launch behavioral intervention trials.Results: The pandemic led researchers to change recruitment plans, interrupt timelines for assessments and intervention delivery, and move to remote intervention and assessment protocols. The necessity of these changes add emphasis to the importance, in study design and analysis, of intention to treat approaches, flexibility, within-site stratification, interim power projections, and sensitivity analyses.Discussion: Robust approaches to study design and analysis are critical to negotiate issues related to the intervention. The world-wide network of similarly oriented clinical trials will allow us to evaluate the effectiveness of responses to the pandemic across cultures, local environments, and phases of the pandemic.
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| 2. |
- Röhr, Susanne, et al.
(author)
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Multidomain interventions for risk reduction and prevention of cognitive decline and dementia : current developments
- 2022
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In: Current Opinion in Psychiatry. - 0951-7367 .- 1473-6578. ; 35:4, s. 285-292
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Research review (peer-reviewed)abstract
- Purpose of review The potential for dementia prevention is deemed substantial if modifiable risk factors were addressed. First large-scale multidomain lifestyle interventions aiming at reducing risk of cognitive decline and dementia have yielded mixed but promising evidence.Recent findings Despite the impact of the COVID-19 pandemic on trials conduction, causing interruptions and delays, the research landscape on multidomain interventions is growing rapidly. The successful Finish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) has led to an adaptation of the FINGER model in trials underway or being planned in over 40 countries. Recent studies identified barriers and facilitators of and adherence to multidomain interventions, showed the suitability of dementia risk scores as surrogate outcomes, and suggested mechanisms. Multidomain interventions are increasingly conducted in the Global South, and study protocols are increasingly testing expanded FINGER models, for example, with pharmacological components, in digital/remote settings and co-designed personalized interventions.Summary Though results remain mixed, the many ongoing trials will provide more conclusive evidence within the next few years and help to optimize interventions. Continued international collaboration is pivotal to scale and accelerate the development and implementation of effective multidomain interventions as part of larger public health strategies to counteract the global dementia increase.
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| 3. |
- van Dalen, Jan Willem, et al.
(author)
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Association of Systolic Blood Pressure With Dementia Risk and the Role of Age, U-Shaped Associations, and Mortality.
- 2022
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In: JAMA internal medicine. - : American Medical Association (AMA). - 2168-6114 .- 2168-6106. ; 182:2, s. 142-152
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Journal article (peer-reviewed)abstract
- The optimal systolic blood pressure (SBP) to minimize the risk of dementia in older age is unknown.To investigate whether the association between SBP and dementia risk is U-shaped and whether age and comorbidity play a role in this association.This cohort study used an individual participant data approach to analyze 7 prospective, observational, population-based cohort studies that were designed to evaluate incident dementia in older adults. These studies started between 1987 and 2006 in Europe and the US. Participants had no dementia diagnosis and had SBP and/or diastolic blood pressure (BP) data at baseline and incident dementia status during follow-up. Data analysis was conducted from November 7, 2019, to October 3, 2021.Baseline systolic BP.All-cause dementia (defined using Diagnostic and Statistical Manual of Mental Disorders [Third Edition Revised] or Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] and established at follow-up measurements or in clinical practice), mortality, and combined dementia and mortality were the outcomes. Covariates included baseline antihypertensive medication use, sex, educational level, body mass index, smoking status, diabetes, stroke history, myocardial infarction history, and polypharmacy. Cox proportional hazards regression models were used, and nonlinear associations were explored using natural splines.The study analyzed 7 cohort studies with a total of 17286 participants, among whom 10393 were women (60.1%) and the mean (SD) baseline age was 74.5 (7.3) years. Overall, dementia risk was lower for individuals with higher SBP, with the lowest risk associated with an SBP of approximately 185 mm Hg (95% CI, 161-230 mm Hg; P=.001). Stratified by overlapping 10-year baseline age groups, the lowest dementia risk was observed at somewhat lower systolic BP levels in those older than 75 years (158 [95% CI, 152-178] mm Hg to 170 [95% CI, 160-260] mm Hg). For mortality, there was a clear U-shaped association, with the lowest risk at 160 mm Hg (95% CI, 154-181 mm Hg; P<.001). This U-shape occurred across all age groups, with the lowest dementia risk associated with an SBP of 134 mm Hg (95% CI, 102-149 mm Hg; P=.03) in those aged 60 to 70 years and increasing to between 155 mm Hg (95% CI, 150-166 mm Hg; P<.001) and 166 mm Hg (95% CI, 154-260 mm Hg; P=.02) for age groups between 70 and 95 years. Combined dementia and mortality risk curves closely resembled those for mortality. Associations of diastolic BP with dementia risk were generally similar but were less distinct.This cohort study found that dementia risk was lower for older individuals with higher SBP levels and that more distinctly U-shaped associations appeared for those older than 75 years, but these associations cannot be explained by SBP-associated changes in mortality risk. The findings may warrant future trials on tailored BP management in older age groups that take life expectancy and health context into consideration.
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