Shireen Sindi

Changes in sleep patterns are common among people with dementia, however why short (≤6hrs) or long sleep (≥9hrs) duration is less favorable for dementia, remains unknown. Given that approximately 46% & 44% of variability in sleep duration is explained by genetics, it is pertinent to consider genetic influences when understanding the mechanisms contributing to sleep-related risk for dementia. In addition to sleep, there is growing interest in the relationship between circadian rhythms, the 24-hour cycles of body & dementia. Links between Alzheimer’s’ dementia and the circadian system are suggested by common observations that an early symptom of Alzheimer’s’ dementia is fragmented sleep/wake patterns with increasing night\time activity and daytime naps. Even among individuals who are cognitively intact, altered circadian rhythms of motor activity have been linked to amyloid pathology

the hallmark of Alzheimer’s’ dementia. There is some evidence linking weakening circadian rhythm to dementia, yet it is not clear whether disruption of clock contributes to incidence dementia. In CLOCKED, I will use data from the Swedish Twin Registry with over 20 years of follow-up, the largest twin registry in the world to assess if sleep polygenic risk score influences the risk of incident dementia (overall, Alzheimer’s’, vascular) & examine whether differences in dementia risk are influenced by a genetically predicted sleep or sleep driven mainly by non-genetic factors, i.e., environmental lifestyle factors. Using accelerometry data on around 100,000 participants from the UK Biobank data, I will assess the relation of accelerometer-assessed circadian rhythmicity with incident dementia & quantify dementia risk stratified by sex, ethnicity, socioeconomic status, shift work, lifestyle factors, & metabolic status

and determine whether a risk score consisting of circadian factors (i.e., circadian syndrome) is a more accurate predictor for dementia than existing risk scores.

The purpose is to better understand how exposure to different kinds of stressors (factors that cause stress) across the life course is associated with mental health and loneliness in older adults. What are the relations between stressors, mental health, and loneliness across the life course? Can the negative impact of stressors be counteracted through social resources and lifestyle factors?The project will run for 4 years with participating researchers from Jönköping University (coordinators), Karolinska Institutet, Stockholm University, University of Gothenburg, University of Southern California, and Swansea University. Longitudinal data will be used to assess stressors in childhood e.g., family conflicts, adulthood e.g., work stressors, late adulthood e.g., death of a spouse, and stressors that may play a role from childhood to older age, e.g., financial strain. Outcomes include anxiety, depressive symptoms, psychiatric disorders, quality of life, and loneliness. We will also study how social resources and lifestyle factors can impact these associations, and the role that gender and socioeconomic position play. Advanced statistical modelling will be used, e.g., structural equation models and growth curve models.The results can support practical recommendations on stress-buffering factors that can be implemented at strategic points in the life course, which can be promoted at a societal level, and, ultimately, help to reach the goals of sustainable and healthy aging for all.

Research problem, specific questionsMaintaining cognitive and functional ability into late life is a lifelong process and health promotion/early intervention are the vital components of public health efforts to achieve healthy aging. The FINGER multidomain intervention trial, which integrates five healthy behaviour domains—nutrition, exercise, cognitive training, social activity, and vascular risk monitoring and management, was the first large-scale randomized controlled trial in the world showing evidence for cognitive benefit in older adults at-risk for dementia. The benefit was also extended to physical function, cardiovascular health, quality of life, and health economic aspects. Despite the compelling evidence, more questions remain to be answered: Are the findings from the FINGER trial generalizable to different settings in the Swedish context (e.g., memory clinic, primary care, and municipality)? Can the FINGER model contribute to additional parameters central for healthy aging? Is there an evidence-based need to further refine the FINGER model? How can the FINGER model be adapted and implemented across socioeconomically diverse populations? In this 6-year program, we address these questions by adapting and implementing the FINGER model in different settings and sociocultural contexts.Data and methodWe plan six interrelated work packages: a) Adapting and implementing the FINGER model across different settings in Swedish society

b) Testing the FINGER model for healthy aging

c) Refining the FINGER model with novel risk factors and sex differences in the response to lifestyle interventions

d) Adapting and implementing the FINGER model in sociocultural contexts

e) Health economic assessment, payment models and sustainment

and f) Knowledge dissemination, implementation of findings and public involvement. We use data from a) existing FINGER and FINGER-based trials in many countries (e.g., MIND-AD, MIND-China)

b) ongoing FINGER-based implementation studies in different contexts: specialist (Brain Health Clinic), primary care (STRONGER), and municipality (Train your Brain)

and c) pilot studies to capture younger people and family caregivers (Family FINGERS).Relevance and utilisationThe program will generate new knowledge on tailored intervention approaches at individual and population levels to support longer and healthier lives in different settings and sociocultural contexts. This knowledge is critical knowledge for the development of health policies to promote of healthy aging and equal health care.Plan for programme realisationThe program is carried out by an interdisciplinary team of experts with expertise in relevant disciplines, e.g., epidemiology, gerontology, clinical geriatrics, clinical trials, implementation research, psychology, health economics, biostatistics, and care science. The budget is used for supporting researchers to implement the study plan and collect new data. The applicant will coordinate all research activities.

Research problem and specific questionsPopulation aging in Sweden and worldwide makes it essential to increase our knowledge of mechanisms underlying older peoples’ mental health and loneliness to identify preventive strategies. Stress has a clear impact on mental health. Yet, little is known about how different stressors (experiences that cause stress) in different contexts throughout the life course impact mental health problems and loneliness in older adults. Moreover, the stress-mental health-loneliness nexus throughout the life course is not well understood. The overall goal of this project is to better understand how exposure to different kinds of stressors across the life course is associated with mental health and loneliness in older adults. What are the relations between stressors, mental health, and loneliness across the life course? Are there ways to counteract the negative impact of stressors through social resources and lifestyle factors?Data and methodLongitudinal data will be used to assess age-based and life-long stressors: childhood e.g., family conflicts, adulthood e.g., work stressors, late adulthood e.g., conflict with children or grandchildren, and stressors that may play a role from childhood to older age, e.g., financial strain, death of relatives, loved ones, or close friends. Outcomes: anxiety, depressive symptoms, self-reported psychiatric disorder, quality of life, suicidal thoughts, and perceived loneliness. Importantly, we will also study how social resources and lifestyle factors can impact these associations, and the role that gender and socioeconomic position play across the life course. Advanced statistical modelling will be used, e.g., structural equation models and growth curve models.Relevance and utilisationThis project aims to identify at-risk groups and modifiable factors that can buffer against stress. The results can support practical recommendations on stress-buffering factors that can be implemented at strategic points in the life course, which can be promoted at a societal level, and, ultimately, help to reach the goals of sustainable and healthy aging for all.Plan for project realisationThe researchers have extensive knowledge of the proposed data sets, as well as access to them. The main costs for the project are for salaries. We will work in close collaboration with Dr. Martin Hyde from Swansea University. To enable this, costs are included in the budget for several research visits during the project period.