Publications by authors named "Miia Kivipelto"

270 Publications

Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people: the FINGER trial.

Eur Heart J 2022 Jan 20. Epub 2022 Jan 20.

Department of Public Health and Welfare, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Aims: Joint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome).

Methods And Results: FINGER enrolled 1259 individuals aged 60-77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51-0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56-1.26) and total CVD events 0.80 (95% CI: 0.61-1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28-0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20-0.81) was lower in the intervention than the control group.

Conclusion: A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD.

Key Question: Can a 2-year multi-domain lifestyle intervention, primarily designed for prevention of cognitive impairment, prevent new cardiovascular events among older adults over an extended follow-up?

Key Finding: Among the 1259 participants aged 60-77 years, the intervention resulted in 13-20% lower cardiovascular disease (CVD) event rates (unadjusted and adjusted analyses), but with large degree of uncertainty. Cerebrovascular event rates were lower but for total CVD only among those with earlier CVD events.

Take-home Message: A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those with a history of CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab922DOI Listing
January 2022

Personal Social Networks of Community-Dwelling Oldest Old During the Covid-19 Pandemic-A Qualitative Study.

Front Public Health 2021 24;9:770965. Epub 2021 Dec 24.

Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.

The COVID-19 pandemic and its related restrictions have affected the everyday life of older people. Advanced age is a significant predisposing factor for a more severe COVID-19 infection, increasing the risk for hospitalization and mortality. Even though restrictions have been, thus, well-grounded, they may also have had detrimental effects on the social well-being of older people. Personal networks and social activity are known protective factors against the premature decline in health and functioning, and it is widely acknowledged that social isolation increases feelings of loneliness, poor quality of life, and even the risk for diseases and disabilities among older adults. This qualitative study investigated changes in personal networks among community-dwelling oldest-old individuals (persons aged 80 and over) during the first and second waves of the COVID-19 pandemic in Finland. The data is part of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE85+) study, which is an ongoing large longitudinal population-based study in Finland. In this qualitative sub-study, we analyzed fifteen in-depth telephone interviews using directed content analyses and identified five types of changes in personal social networks during the pandemic. In type 1, all social contacts were significantly reduced due to official recommendations and fear of the virus. Type 2 included modified ways of being socially active i.e., by deploying new technology, and in type 3, social contacts increased during the lockdown. In type 4, personal social networks were changed unexpectedly or dramatically due to a death of a spouse, for example. In type 5, we observed stable social networks, which had not been affected by the pandemic. At an individual level, one person could have had different types of changes during the pandemic. These results highlight the heterogeneity of the oldest olds' personal social networks and changes related to them during the exceptional times of the COVID-19 pandemic. Social activity and personal networks play an important role in the well-being of the oldest old, but individual situations, needs, and preferences toward personal social networks should be taken into account when planning social activities, policies, and interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2021.770965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739883PMC
January 2022

Trials and Treatments for Vascular Brain Health: Risk Factor Modification and Cognitive Outcomes.

Stroke 2022 Jan 10:STROKEAHA121032614. Epub 2022 Jan 10.

Departments of Psychiatry, Neurology, and Epidemiology; University of California, San Francisco (K.Y.).

There is robust evidence linking vascular health to brain health, cognition, and dementia. In this article, we present evidence from trials of vascular risk factor treatment on cognitive outcomes. We summarize findings from randomized controlled trials of antihypertensives, lipid-lowering medications, diabetes treatments (including antidiabetic drugs versus placebo, and intensive versus standard glycemic control), and multidomain interventions (that target several domains simultaneously such as control of vascular and metabolic factors, nutrition, physical activity, and cognitive stimulation etc). We report that evidence on the efficacy of vascular risk reduction interventions is promising, but not yet conclusive, and several methodological limitations hamper interpretation. Evidence mainly comes from high-income countries and, as cognition and dementia have not been the primary outcomes of many trials, evaluation of cognitive changes have often been limited. As the cognitive aging process occurs over decades, it is unclear whether treatment during the late-life window is optimal for dementia prevention, yet older individuals have been the target of most trials thus far. Further, many trials have not been powered to explore interactions with modifiers such as age, race, and apolipoprotein E, even though sub-analyses from some trials indicate that the success of interventions differs depending on patient characteristics. Due to the complex multifactorial etiology of dementia, and variations in risk factors between individuals, multidomain interventions targeting several risk factors and mechanisms are likely to be needed and the long-term sustainability of preventive interventions will require personalized approaches that could be facilitated by digital health tools. This is especially relevant during the coronavirus disease 2019 (COVID-19) pandemic, where intervention strategies will need to be adapted to the new normal, when face-to-face engagement with participants is limited and public health measures may create changes in lifestyle that affect individuals' vascular risk profiles and subsequent risk of cognitive decline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.121.032614DOI Listing
January 2022

Can Exercise Training Teach Us How to Treat Alzheimer's disease?

Ageing Res Rev 2022 Jan 6:101559. Epub 2022 Jan 6.

Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address:

Alzheimer's disease (AD) is the most common cause of dementia and there is currently no cure. Novel approaches to treat AD and curb the rapidly increasing worldwide prevalence and costs of dementia are needed. Physical inactivity is a significant modifiable risk factor for AD, estimated to contribute to 12.7% of AD cases worldwide. Exercise interventions in humans and animals have shown beneficial effects of exercise on brain plasticity and cognitive functions. In animal studies, exercise also improved AD pathology. The mechanisms underlying these effects of exercise seem to be associated mainly with exercise performance or cardiorespiratory fitness. In addition, exercise-induced molecules of peripheral origin seem to play an important role. Since exercise affects the whole body, there likely is no single therapeutic target that could mimic all the benefits of exercise. However, systemic strategies may be a viable means to convey broad therapeutic effects in AD patients. Here, we review the potential of physical activity and exercise training in AD prevention and treatment, shining light on recently discovered underlying mechanisms and concluding with a view on future development of exercise-free treatment strategies for AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arr.2022.101559DOI Listing
January 2022

Effects of Physical and Cognitive Training on Falls and Concern about Falling in Older Adults: Results from a Randomized Controlled Trial.

J Gerontol A Biol Sci Med Sci 2021 Dec 15. Epub 2021 Dec 15.

Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

Background: The aim of this study is to investigate whether combined cognitive and physical training provides additional benefits to fall prevention when compared with physical training alone in older adults.

Methods: This is a prespecified secondary analysis of a single-blind, randomized controlled trial involving community-dwelling men and women aged 70 to 85 years who did not meet the physical activity guidelines. The participants were randomized into combined physical and cognitive training (PTCT, n=155) and physical training (PT, n=159) groups. PT included supervised and home-based physical exercises following the physical activity recommendations. PTCT included PT and computer-based cognitive training. The outcome was the rate of falls over the 12-month intervention (PTCT, n=151 and PT, n=155) and 12-month postintervention follow-up (PTCT, n=143 and PT, n=148). Falls were ascertained from monthly diaries. Exploratory outcomes included the rate of injurious falls, faller/recurrent faller/fall-related fracture status, and concern about falling.

Results: Estimated incidence rates of falls per person-year were 0.8 (95% CI 0.7-1.1) in the PTCT and 1.1 (95% CI 0.9-1.3) in the PT during the intervention and 0.8 (95% CI 0.7-1.0) versus 1.0 (95% CI 0.8-1.1), respectively, during the postintervention follow-up. There was no significant difference in the rate of falls during the intervention (incidence rate ratio [IRR] 0.78; 95% CI 0.56-1.10, p=0.152) or in the follow-up (IRR=0.83; 95% CI 0.59-1.15, p=0.263). No significant between-group differences were observed in any exploratory outcomes.

Conclusion: A yearlong PTCT intervention did not result in a significantly lower rate of falls or concern about falling than PT alone in older community-dwelling adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glab375DOI Listing
December 2021

Health, Lifestyle, and Psycho-Social Determinants of Poor Sleep Quality During the Early Phase of the COVID-19 Pandemic: A Focus on UK Older Adults Deemed Clinically Extremely Vulnerable.

Front Public Health 2021 28;9:753964. Epub 2021 Oct 28.

Ageing Epidemiology Research Unit (AGE), School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.

Several studies have assessed the impact of COVID-19-related lockdowns on sleep quality across global populations. However, no study to date has specifically assessed populations, particularly those at highest risk of complications from coronavirus infection deemed "clinically-extremely-vulnerable-(COVID-19CEV)" (as defined by Public Health England). In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio-demographic factors. We examined associations between these variables and sleep quality; and explored interactions of COVID-19CEV status with significant predictors of poor sleep, to identify potential moderating factors. Thirty-seven percent of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep. Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a "clinically-extremely-vulnerable" population and the sex differences identified within this group. Male and female older adults deemed COVID-19CEV may benefit from targeted mental health and dietary interventions, respectively. This work extends the available evidence on the notable impact of lack of social interactions during the COVID-19 pandemic on sleep, and provides recommendations toward areas for future work, including research into vulnerability factors impacting sleep disruption and COVID-19-related complications. Study results may inform tailored interventions targeted at modifiable risk factors to promote optimal sleep; additionally, providing empirical data to support health policy development in this area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2021.753964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637825PMC
December 2021

Development of the First WHO Guidelines for Risk Reduction of Cognitive Decline and Dementia: Lessons Learned and Future Directions.

Front Neurol 2021 26;12:763573. Epub 2021 Oct 26.

The Ageing Epidemiology Research Unit, Faculty of Medicine, School of Public Health, Imperial College London, London, United Kingdom.

The first WHO guidelines for risk reduction of cognitive decline and dementia marked an important milestone in the field of dementia prevention. In this paper, we discuss the evidence reviewed as part of the guidelines development and present the main themes emerged from its synthesis, to inform future research and policies on dementia risk reduction. The role of intervention effect-size; the mismatch between observational and intervention-based evidence; the heterogeneity of evidence among intervention trials; the importance of intervention duration; the role of timing of exposure to a certain risk factor and interventions; the relationship between intervention intensity and response; the link between individual risk factors and specific dementia pathologies; and the need for tailored interventions emerged as the main themes. The interaction and clustering of individual risk factors, including genetics, was identified as the overarching theme. The evidence collected indicates that multidomain approaches targeting simultaneously multiple risk factors and tailored at both individual and population level, are likely to be most effective and feasible in dementia risk reduction. The current status of multidomain intervention trials aimed to cognitive impairment/dementia prevention was also briefly reviewed. Primary results were presented focusing on methodological differences and the potential of design harmonization for improving evidence quality. Since multidomain intervention trials address a condition with slow clinical manifestation-like dementia-in a relatively short time frame, the need for surrogate outcomes was also discussed, with a specific focus on the potential utility of dementia risk scores. Finally, we considered how multidomain intervention could be most effectively implemented in a public health context and the implications world-wide for other non-communicable diseases targeting common risk factors, taking into account the limited evidence in low-middle income countries. In conclusion, the evidence from the first WHO guidelines for risk reduction of cognitive decline and dementia indicated that "one size does not fit all," and multidomain approaches adaptable to different populations and individuals are likely to be the most effective. Harmonization in trial design, the use of appropriate outcome measures, and sustainability in large at-risk populations in the context of other chronic disorders also emerged as key elements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.763573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577650PMC
October 2021

Acute and post-acute neurological manifestations of COVID-19: present findings, critical appraisal, and future directions.

J Neurol 2021 Oct 21. Epub 2021 Oct 21.

Department of Neurology, Centre for Global Health, Technical University of Munich, Munich, Germany.

Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-021-10848-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528941PMC
October 2021

The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER).

Alzheimers Dement 2021 Oct 20. Epub 2021 Oct 20.

Department of Public Health and Welfare, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Introduction: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses).

Methods: FINGER is a multicenter randomized controlled trial examining the efficacy of multidomain lifestyle intervention (ClinicalTrials.gov NCT01041989). A total of 1260 participants aged 60 to 77 with increased dementia risk were randomized to a lifestyle intervention and control groups. Percentage of completed intervention sessions, and change in multidomain lifestyle score (self-reported diet; physical, cognitive, and social activity; vascular risk) were examined in relation to change in Neuropsychological Test Battery (NTB) scores.

Results: Active participation was associated with better trajectories in NTB total and all cognitive subdomains. Improvement in lifestyle was associated with improvement in NTB total and executive function.

Discussion: Multidomain lifestyle changes are beneficial for cognitive functioning, but future interventions should be intensive enough, and supporting adherence is essential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alz.12492DOI Listing
October 2021

The effects of a physical and cognitive training intervention vs. physical training alone on older adults' physical activity: A randomized controlled trial with extended follow-up during COVID-19.

PLoS One 2021 13;16(10):e0258559. Epub 2021 Oct 13.

Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

Background: Executive functions underlie self-regulation and are thus important for physical activity and adaptation to new situations. The aim was to investigate, if yearlong physical and cognitive training (PTCT) had greater effects on physical activity among older adults than physical training (PT) alone, and if executive functions predicted physical activity at baseline, after six (6m) and twelve months (12m) of the interventions, one-year post-intervention follow-up and an extended follow-up during COVID-19 lockdown.

Methods: Data from a single-blinded, parallel-group randomized controlled trial (PASSWORD-study, ISRCTN52388040) were utilized. Participants were 70-85 years old community-dwelling men and women from Jyväskylä, Finland. PT (n = 159) included supervised resistance, walking and balance training, home-exercises and self-administered moderate activity. PTCT (n = 155) included PT and cognitive training targeting executive functions on a computer program. Physical activity was assessed with a one-item, seven-scale question. Executive functions were assessed with color-word Stroop, Trail Making Test (TMT) B-A and Letter Fluency. Changes in physical activity were modeled with multinomial logistic models and the impact of executive functions on physical activity with latent change score models.

Results: No significant group-by-time interaction was observed for physical activity (p>0.1). The subjects were likely to select an activity category higher than baseline throughout the study (pooled data: B = 0.720-1.614, p<0.001-0.046). Higher baseline Stroop predicted higher physical activity through all subsequent time-points (pooled data: B = 0.011-0.013, p = 0.015-0.030). Higher baseline TMT B-A predicted higher physical activity at 6m (pooled data: B = 0.007, p = 0.006) and during COVID-19 (B = 0.005, p = 0.030). In the PT group, higher baseline Letter Fluency predicted higher physical activity at 12m (B = -0.028, p = 0.030) and follow-up (B = -0.042, p = 0.002).

Conclusions: Cognitive training did not have additive effects over physical training alone on physical activity, but multicomponent training and higher executive function at baseline may support adaptation to and maintenance of a physically active lifestyle among older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258559PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513828PMC
October 2021

Multidomain interventions: state-of-the-art and future directions for protocols to implement precision dementia risk reduction. A user manual for Brain Health Services-part 4 of 6.

Alzheimers Res Ther 2021 10 11;13(1):171. Epub 2021 Oct 11.

Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-021-00875-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507202PMC
October 2021

Everyday Life Meaningfulness for the Community-Dwelling Oldest Old During the COVID-19 Pandemic.

Front Psychol 2021 9;12:716428. Epub 2021 Sep 9.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

In many countries, the COVID-19 pandemic has led to strong restrictions and changed the everyday lives of older people. In Finland, people aged 70 and over were instructed to stay at home under quarantine-like conditions. Existing studies from other countries have reported increases in negative experiences and symptoms as a result of such restrictions, including psychosocial stress. However, little focus has been given to older people's experiences of meaningfulness during the pandemic. Using survey and interview data, we ask to what extent have community-dwelling oldest old (80+) experienced meaningfulness during the pandemic, what background factors are associated with meaningfulness and what factors have contributed to everyday life meaningfulness during the pandemic. The data was collected as part of the COVID-19 sub-study of the third follow-up of the Cardiovascular Risk Factors, Aging and Dementia (CAIDE85+) study, a Finnish population-based cohort study carried out in the eastern part of the country. In the quantitative analyses, meaningfulness was assessed as part of the Experiences of Social Inclusion Scale. The association of meaningfulness with different background factors (gender, age, living alone, self-chosen quarantine or physical isolation, self-rated health, physical functioning, and cognitive capacity) was explored with the Chi-square test. The quantitative findings indicate that the majority of the participants experienced meaningfulness during the pandemic. Participants who did not practice any physical isolation measures and participants with higher self-rated health experienced more meaningfulness. There was no evidence for difference in the prevalence of meaningfulness and other background factors. The qualitative data was analyzed using thematic analysis. The findings indicated that factors contributing to meaningfulness in everyday life were social contacts, daily chores and activities, familiar places and seasonal changes. The small sample size does not provide possibilities for generalizing the results into the wider population of older adults. However, the results provide new understanding of the oldest old's experiences of meaningfulness in everyday life during the global pandemic. The findings may help find ways to support older people's meaningfulness in challenging times.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.716428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459014PMC
September 2021

Influence of Cognitive Reserve on Cognitive Trajectories: Role of Brain Pathologies.

Neurology 2021 10 7;97(17):e1695-e1706. Epub 2021 Sep 7.

From the Department of Epidemiology and Biostatistics (X.L., R.S., X.Q., W.Y., W.X.), School of Public Health, Tianjin Medical University; Tianjin Key Laboratory of Environment, Nutrition and Public Health (X.L., R.S., X.Q., W.Y., W.X.); Center for International Collaborative Research on Environment, Nutrition and Public Health (X.L., R.S., X.Q., W.Y., W.X.), Tianjin; Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine (R.S.), Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan; Big Data and Engineering Research Center (H.X.), Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China; Division of Clinical Geriatrics, Center for Alzheimer Research (M.K.), and Aging Research Center (W.X.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet; Theme Aging (M.K.), Karolinska University Hospital, Stockholm, Sweden; Ageing and Epidemiology (AGE) Research Unit (M.K.), School of Public Health, Imperial College London, UK; and Rush Alzheimer's Disease Center (D.A.B.), Rush University Medical Center, Chicago, IL.

Background And Objectives: Evidence on the association of cognitive reserve (CR) with the cognitive trajectories is limited. We aimed to examine the influence of CR indicator on domain-specific cognitive trajectories taking brain pathologies into account.

Methods: Within the Rush Memory and Aging Project, 1,697 participants without dementia (mean age 79.6 years) were followed up to 21 years. CR indicator encompassing education, early-life, mid-life, and late-life cognitive activities and late-life social activity was ascertained at baseline and categorized as tertiles (lowest, middle, and highest). Global cognition, episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with 19 tests, from which composite scores were derived. During the follow-up, 648 participants died and underwent autopsies to evaluate brain pathologies. Data were analyzed using linear mixed-effect models.

Results: Among the participants, the score of the CR indicator ranged from -8.00 to 5.74 (mean 0.00 ± 2.23). In multi-adjusted mixed-effect models, compared to the lowest CR, the highest was related to a slower decline in global cognition (β = 0.028, 95% confidence interval [CI] 0.012-0.043), episodic memory (β = 0.028, 95% CI 0.010-0.047), and working memory (β = 0.019, 95% CI 0.005-0.033) during the follow-up. In brain pathologic data analysis, the association of the highest CR with cognitive function changes remained significant among participants with high Alzheimer disease pathology or gross infarcts.

Discussion: High CR indicator is associated with preserved global cognitive function, episodic memory, and working memory, even in the presence of brain pathologies. Our findings highlight the important role of high CR accumulation in the prevention of cognitive decline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605617PMC
October 2021

Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF: Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults.

Front Aging Neurosci 2021 20;13:716594. Epub 2021 Aug 20.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC). Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65-75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0-2 h to changes in BDNF at 0-4 h). ICC estimates were calculated from baseline levels from the three study days. proBDNF increased more in vs. between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07-0.44; = 0.007). Individual change in BHB 0-2 h, predicted change in proBDNF 0-4 h, (β = 0.40, CI 0.12-0.67; = 0.006). Change in mBDNF was lower in vs. at 0-2 h (β = -0.88, CI -1.37 to -0.40; < 0.001) and cumulatively 0-4 h (β = -1.01, CI -1.75 to -0.27; = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92-0.99) for proBDNF, and 0.72 (CI 0.47-0.89) for mBDNF. The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health. ClinicalTrials.gov, NCT03904433.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2021.716594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417778PMC
August 2021

Facilitators and barriers to implementing lifestyle intervention programme to prevent cognitive decline.

Eur J Public Health 2021 10;31(4):816-822

Department of Public Health and Welfare, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Background: The Finnish Intervention Study to Prevent Cognitive Impairment and Disability is a randomized controlled trial that has tested the efficacy of a multidomain intervention targeting modifiable risk factors to prevent cognitive impairment/dementia. A combination of healthy diet, physical, social and cognitive activity, and management of cardiovascular risks was shown to be an effective model to promote brain health among older people. The aim of this qualitative study was to explore healthcare professionals' perceptions of facilitators and barriers to implementing this lifestyle programme into health care.

Methods: Four semi-structured focus group interviews were conducted among healthcare professionals working in primary care and in non-governmental organizations (N=27). Participants were asked to discuss their perceptions of facilitators and barriers for implementing the multidomain intervention into clinical practice. Interviews were analyzed using content analysis.

Results: Barriers and facilitators described by the healthcare professionals were related to infrastructure and resources, client's personal characteristics and the lifestyle intervention itself. These main categories included several sub-categories related to knowledge, motivation, resources, individualization and collaboration. The interviewees pointed out that more education on dementia prevention is needed, the work should be coordinated efficiently, resources to provide preventive health care should be adequate and multiprofessional collaboration is needed.

Conclusions: Transferring a lifestyle intervention from a trial-setting to real life requires knowledge about the factors that influence effective implementation. Identifying drivers and constraints of successful implementation helps to design and tailor future prevention programmes, increases motivation and adherence and supports system change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurpub/ckab087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505000PMC
October 2021

Red Cell Distribution Width and Dementia Among Rural-Dwelling Older Adults: The MIND-China Study.

J Alzheimers Dis 2021 ;83(3):1187-1198

Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Background: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse.

Objective: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status.

Methods: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer's disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models.

Results: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87-2.44), 1.00 (reference), 1.77 (1.07-2.93), and 2.28 (1.40-3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and β-coefficients of MMSE score.

Conclusion: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-210517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543291PMC
December 2021

Sex differences in dementia and response to a lifestyle intervention: Evidence from Nordic population-based studies and a prevention trial.

Alzheimers Dement 2021 07;17(7):1166-1178

Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

Introduction: Evidence on sex differences in the risk for dementia has been mixed. The goal was to assess sex differences in the development of dementia, and in the effects of a lifestyle intervention.

Methods: Two strategies were adopted, one using combined data from three large Nordic population-based cohort studies (n = 2289), adopting dementia as outcome, and 2-year multidomain lifestyle intervention (n = 1260), adopting cognitive change as outcome.

Results: There was higher risk for dementia after age 80 years in women. The positive effects of the lifestyle intervention on cognition did not significantly differ between men and women. Sex-specific analyses suggested that different vascular, lifestyle, and psychosocial risk factors are important for women and men in mid- and late-life.

Conclusion: Women had higher risk for dementia among the oldest individuals. Lifestyle interventions may be effectively implemented among older men and women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alz.12279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361986PMC
July 2021

Association Between Iron-Related Protein Lipocalin 2 and Cognitive Impairment in Cerebrospinal Fluid and Serum.

Front Aging Neurosci 2021 25;13:663837. Epub 2021 Jun 25.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

A worldwide increase in longevity is bringing novel challenges to public health and health care professionals. Cognitive impairment in the elderly may compromise living conditions and precede Alzheimer's disease (AD), the most prevalent form of dementia. Therefore, finding molecular markers associated with cognitive impairment is of crucial importance. Lipocalin 2 (LCN2), an iron-related protein, has been suggested as a potential marker for mild cognitive impairment (MCI) and AD. This study aimed at investigating the association between LCN2 measured in serum and cerebrospinal fluid (CSF) with cognitive impairment. A cross-sectional design based on two aging cohorts was used: individuals diagnosed with subjective cognitive complaints (SCC), MCI, and AD from a Swedish memory clinic-based cohort, and individuals diagnosed with SCC and AD from a Portuguese cohort. Binary logistic [for the outcome cognitive impairment (MCI + AD) in the Swedish cohort and AD in the Portuguese cohort] and multinomial logistic (for the outcomes MCI and AD) regression analyses were used. No associations were found in both cohorts when controlling for sex, education, and age. This explanatory study suggests that the association between serum and CSF LCN2 concentrations with cognitive impairment reported in the literature must be further analyzed for confounders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnagi.2021.663837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267056PMC
June 2021

Decreased Mortality Over Time During the First Wave in Patients With COVID-19 in Geriatric Care: Data From the Stockholm GeroCovid Study.

J Am Med Dir Assoc 2021 08 12;22(8):1565-1573.e4. Epub 2021 Jun 12.

Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Aging, Karolinska University Hospital, Stockholm, Sweden.

Objective: To describe temporal changes in treatment, care, and short-term mortality outcomes of geriatric patients during the first wave of the COVID-19 pandemic.

Design: Observational study.

Setting And Participants: Altogether 1785 patients diagnosed with COVID-19 and 6744 hospitalized for non-COVID-19 causes at 7 geriatric clinics in Stockholm from March 6 to July 31, 2020, were included.

Methods: Across admission month, patient vital signs and pharmacological treatment in relationship to risk for in-hospital death were analyzed using the Poisson regression model. Incidence rates (IRs) and incidence rate ratios (IRRs) of death are presented.

Results: In patients with COVID-19, the IR of mortality were 27%, 17%, 10%, 8%, and 2% from March to July, respectively, after standardization for demographics and vital signs. Compared with patients admitted in March, the risk of in-hospital death decreased by 29% [IRR 0.71, 95% confidence interval (CI) 0.51-0.99] in April, 61% (0.39, 0.26-0.58) in May, 68% (0.32, 0.19-0.55) in June, and 86% (0.14, 0.03-0.58) in July. The proportion of patients admitted for geriatric care with oxygen saturation <90% decreased from 13% to 1%, which partly explains the improvement of COVID-19 patient survival. In non-COVID-19 patients during the pandemic, mortality rates remained relatively stable (IR 1.3%-2.3%). Compared with non-COVID-19 geriatric patients, the IRR of death declined from 11 times higher (IRR 11.7, 95% CI 6.11-22.3) to 1.6 times (2.61, 0.50-13.7) between March and July in patients with COVID-19.

Conclusions And Implications: Mortality risk in geriatric patients from the Stockholm region declined over time throughout the first pandemic wave of COVID-19. The improved survival rate over time was only partly related to improvement in saturation status at the admission of the patients hospitalized later throughout the pandemic. Lower incidence during the later months could have led to less severe hospitalized cases driving down mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamda.2021.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196313PMC
August 2021

Excess Mortality After COVID-19 in Swedish Long-Term Care Facilities.

J Am Med Dir Assoc 2021 08 24;22(8):1574-1580.e8. Epub 2021 Jun 24.

Department of Community Medicine and Rehabilitation, Unit of Geriatric Medicine, Umeå University, Umeå, Sweden. Electronic address:

Objective: To compare 30-day mortality in long-term care facility (LTCF) residents with and without COVID-19 and to investigate the impact of 31 potential risk factors for mortality in COVID-19 cases.

Design: Retrospective cohort study.

Setting And Participants: All residents of LTCFs registered in Senior Alert, a Swedish national database of health examinations in older adults, during 2019-2020.

Methods: We selected residents with confirmed COVID-19 until September 15, 2020, along with time-dependent propensity score-matched controls without COVID-19. Exposures were COVID-19, age, sex, comorbidities, medications, and other patient characteristics. The outcome was all-cause 30-day mortality.

Results: A total of 3731 residents (median age 87 years, 64.5% female) with COVID-19 were matched to 3731 controls without COVID-19. Thirty-day mortality was 39.9% in COVID-19 cases and 5.7% in controls [relative risk 7.05, 95% confidence interval (CI) 6.10-8.14]. In COVID-19 cases, the odds ratio (OR) for 30-day mortality was 2.44 (95% CI 1.57-3.81) in cases aged 80-84 years, 2.99 (95% CI 1.93-4.65) in cases aged 85-89 years, and 3.28 (95% CI 2.11-5.10) in cases aged ≥90 years, as compared with cases aged <70 years. Other risk factors for mortality among COVID-19 cases included male sex (OR, 2.60, 95% CI 2.22-3.05), neuropsychological conditions (OR, 2.18; 95% CI 1.76-2.71), impaired walking ability (OR, 1.45, 95% CI 1.17-1.78), urinary and bowel incontinence (OR 1.51, 95% CI 1.22-1.85), diabetes (OR 1.36, 95% CI 1.14-1.62), chronic kidney disease (OR 1.37, 95% CI 1.11-1.68) and previous pneumonia (OR 1.57, 95% CI 1.32-1.85). Nutritional factors, cardiovascular diseases, and antihypertensive medications were not significantly associated with mortality.

Conclusions And Implications: In Swedish LTCFs, COVID-19 was associated with a large excess in mortality after controlling for an extensive number of risk factors. Beyond older age and male sex, several prevalent clinical risk factors independently contributed to higher mortality. These findings suggest that reducing transmission of COVID-19 in LTCFs will likely prevent a considerable number of deaths.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamda.2021.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223135PMC
August 2021

Protocol of the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy.

BMJ Open 2021 06 24;11(6):e043114. Epub 2021 Jun 24.

Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK.

Introduction: The Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy (CPSS), sponsored by Janssen Pharmaceutical Research & Development LLC, is an Alzheimer's disease (AD) biomarker enriched observational study that began 3 July 2015 CPSS aims to identify and validate determinants of AD, alongside cognitive, functional and biological changes in older adults with or without detectable evidence of AD pathology at baseline.

Methods And Analysis: CPSS is a dual-site longitudinal cohort (3.5 years) assessed quarterly. Cognitively normal participants (60-85 years) were recruited across Greater London and Edinburgh. Participants are classified as high, medium (amnestic or non-amnestic) or low risk for developing mild cognitive impairment-Alzheimer's disease based on their Repeatable Battery for the Assessment of Neuropsychological Status performance at screening. Additional AD-related assessments include: a novel cognitive composite, the Global Preclinical Alzheimer's Cognitive Composite, brain MRI and positron emission tomography and cerebrospinal fluid analysis. Lifestyle, other cognitive and functional data, as well as biosamples (blood, urine, and saliva) are collected. Primarily, study analyses will evaluate longitudinal change in cognitive and functional outcomes. Annual interim analyses for descriptive data occur throughout the course of the study, although inferential statistics are conducted as required.

Ethics And Dissemination: CPSS received ethical approvals from the London-Central Research Ethics Committee (15/LO/0711) and the Administration of Radioactive Substances Advisory Committee (RPC 630/3764/33110) The study is at the forefront of global AD prevention efforts, with frequent and robust sampling of the well-characterised cohort, allowing for detection of incipient pathophysiological, cognitive and functional changes that could inform therapeutic strategies to prevent and/or delay cognitive impairment and dementia. Dissemination of results will target the scientific community, research participants, volunteer community, public, industry, regulatory authorities and policymakers. On study completion, and following a predetermined embargo period, CPSS data are planned to be made accessible for analysis to facilitate further research into the determinants of AD pathology, onset of symptomatology and progression.

Trial Registration Number: The CHARIOT:PRO SubStudy is registered with clinicaltrials.gov (NCT02114372). Notices of protocol modifications will be made available through this trial registry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-043114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230926PMC
June 2021

Effect of a Multidomain Lifestyle Intervention on Estimated Dementia Risk.

J Alzheimers Dis 2021 ;82(4):1461-1466

Karolinska Institutet, NVS, Division of Clinical Geriatrics, Solna, Stockholm, Sweden.

We investigated the effect of a multidomain lifestyle intervention on the risk of dementia estimated using the validated CAIDE risk score (post-hoc analysis). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a 2-year randomized controlled trial among 1,260 at-risk older adults (60-77 years). Difference in the estimated mean change in CAIDE score at 2 years in the intervention compared to the control group was -0.16 (95 %CI -0.31 to 0.00) (p = 0.013), corresponding to a relative dementia risk reduction between 6.04-6.50%. This could be interpreted as a reflection of the prevention potential of the intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-210331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461663PMC
November 2021

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Nat Commun 2021 06 7;12(1):3417. Epub 2021 Jun 7.

Servei de Neurologia, Hospital Universitari i Politècnic La Fe, Valencia, Spain.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22491-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184987PMC
June 2021

Multidomain Intervention for Reversal of Cognitive Frailty, Towards a Personalized Approach (AGELESS Trial): Study Design.

J Alzheimers Dis 2021 ;82(2):673-687

Division of Clinical Geriatrics, Alzheimer Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Sweden.

Background: Cognitive frailty (CF) is identified as one of the main precursors of dementia. Multidomain intervention has been found to delay or prevent the onset of CF.

Objective: The aim of our present study is to determine the effectiveness of a comprehensive, multidomain intervention on CF; to evaluate its cost effectiveness and the factors influencing adherence toward this intensive intervention.

Methods: A total of 1,000 community dwelling older adults, aged 60 years and above will be screened for CF. This randomized controlled trial involves recruitment of 330 older adults with CF from urban, semi-urban, and rural areas in Malaysia. Multidomain intervention comprised of physical, nutritional, cognitive, and psychosocial aspects will be provided to participants in the experimental group (n = 165). The control group (n = 165) will continue their usual care with their physician. Primary outcomes include CF status, physical function, psychosocial and nutritional status as well as cognitive performance. Vascular health and gut microbiome will be assessed using blood and stool samples. A 24-month intensive intervention will be prescribed to the participants and its sustainability will be assessed for the following 12 months. The effective intervention strategies will be integrated as a personalized telerehabilitation package for the reversal of CF for future use.

Results: The multidomain intervention developed from this trial is expected to be cost effective compared to usual care as well as able is to reverse CF.

Conclusion: This project will be part of the World-Wide FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) Network, of which common identifiable data will be shared and harmonized among the consortia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-201607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385532PMC
September 2021

Change in CAIDE Dementia Risk Score and Neuroimaging Biomarkers During a 2-Year Multidomain Lifestyle Randomized Controlled Trial: Results of a Post-Hoc Subgroup Analysis.

J Gerontol A Biol Sci Med Sci 2021 07;76(8):1407-1414

Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland.

The CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Risk Score is a validated tool estimating dementia risk. It was previously associated with imaging biomarkers. However, associations between dementia risk scores (including CAIDE) and dementia-related biomarkers have not been studied in the context of an intervention. This study investigated associations between change in CAIDE score and change in neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B-positron emission tomography [PiB-PET] measures) during the 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (post-hoc analyses). FINGER targeted at-risk older adults, aged 60-77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB-PET) data from baseline and 2-year visits were used. A toal of 112 participants had repeated brain MRI measures (hippocampal, total gray matter, and white matter lesion volumes, and Alzheimer's disease signature cortical thickness). Repeated PiB-PET scans were available for 39 participants. Reduction in CAIDE score (indicating lower dementia risk) during the intervention was associated with less decline in hippocampus volume in the intervention group, but not the control group (Randomization group × CAIDE change interaction β coefficient = -0.40, p = .02). Associations for other neuroimaging measures were not significant. The intervention may have benefits on hippocampal volume in individuals who succeed in improving their overall risk level as indicated by a reduction in CAIDE score. This exploratory finding requires further testing and validation in larger studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glab130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277089PMC
July 2021

Effects of physical and cognitive training on gait speed and cognition in older adults: A randomized controlled trial.

Scand J Med Sci Sports 2021 Jul 6;31(7):1518-1533. Epub 2021 Apr 6.

Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.

Gait speed is a measure of health and functioning. Physical and cognitive determinants of gait are amenable to interventions, but best practices remain unclear. We investigated the effects of a 12-month physical and cognitive training (PTCT) on gait speed, dual-task cost in gait speed, and executive functions (EFs) compared with physical training (PT) (ISRCTN52388040). Community-dwelling older adults, who did not meet physical activity recommendations, were recruited (n = 314). PT included supervised walking/balance (once weekly) and resistance/balance training (once weekly), home exercises (2-3 times weekly), and moderate aerobic activity 150 min/week in bouts of >10 min. PTCT included the PT and computer training (CT) on EFs 15-20 min, 3-4 times weekly. The primary outcome was gait speed. Secondary outcomes were 6-min walking distance, dual-task cost in gait speed, and EF (Stroop and Trail Making B-A). The trial was completed by 93% of the participants (age 74.5 [SD3.8] years; 60% women). Mean adherence to supervised sessions was 59%-72% in PT and 62%-77% in PTCT. Home exercises and CT were performed on average 1.9 times/week. Weekly minutes spent in aerobic activities were 188 (median 169) in PT and 207 (median 180) in PTCT. No significant interactions were observed for gait speed (PTCT-PT, 0.02; 95%CI -0.03, 0.08), walking distance (-3.8; -16.9, 9.3) or dual-task cost (-0.22; -1.74, 1.30). Stroop improvement was greater after PTCT than PT (-6.9; -13.0, -0.8). Complementing physical training with EFs training is not essential for promotion of gait speed. For EF's, complementing physical training with targeted cognitive training provides additional benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/sms.13960DOI Listing
July 2021

Research diagnostic criteria for Alzheimer's disease: findings from the LipiDiDiet randomized controlled trial.

Alzheimers Res Ther 2021 03 25;13(1):64. Epub 2021 Mar 25.

Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Background: To explore the utility of the International Working Group (IWG)-1 criteria in recruitment for Alzheimer's disease (AD) clinical trials, we applied the more recently proposed research diagnostic criteria to individuals enrolled in a randomized controlled prevention trial (RCT) and assessed their disease progression.

Methods: The multinational LipiDiDiet RCT targeted 311 individuals with IWG-1 defined prodromal AD. Based on centrally analyzed baseline biomarkers, participants were classified according to the IWG-2 and National Institute on Aging-Alzheimer's Association (NIA-AA) 2011 and 2018 criteria. Linear mixed models were used to investigate the 2-year change in cognitive and functional performance (Neuropsychological Test Battery NTB Z scores, Clinical Dementia Rating-Sum of Boxes CDR-SB) (criteria × time interactions; baseline score, randomization group, sex, Mini-Mental State Examination (MMSE), and age also included in the models). Cox models adjusted for randomization group, MMSE, sex, age, and study site were used to investigate the risk of progression to dementia over 2 years.

Results: In total, 88%, 86%, and 69% of participants had abnormal cerebrospinal fluid (CSF) β-amyloid, total tau, and phosphorylated tau, respectively; 64% had an A+T+N+ profile (CSF available for N = 107). Cognitive-functional decline appeared to be more pronounced in the IWG-2 prodromal AD, NIA-AA 2011 high and intermediate AD likelihood, and NIA-AA 2018 AD groups, but few significant differences were observed between the groups within each set of criteria. Hazard ratio (95% CI) for dementia was 4.6 (1.6-13.7) for IWG-2 prodromal AD (reference group no prodromal AD), 7.4 (1.0-54.7) for NIA-AA 2011 high AD likelihood (reference group suspected non-AD pathology SNAP), and 9.4 (1.2-72.7) for NIA-AA 2018 AD (reference group non-Alzheimer's pathologic change). Compared with the NIA-AA 2011 high AD likelihood group (abnormal β-amyloid and neuronal injury markers), disease progression was similar in the intermediate AD likelihood group (medial temporal lobe atrophy; no CSF available).

Conclusions: Despite being less restrictive than the other criteria, the IWG-1 criteria reliably identified individuals with AD pathology. More pragmatic and easily applicable selection criteria might be preferred due to feasibility in certain situations, e.g., in multidomain prevention trials that do not specifically target β-amyloid/tau pathologies.

Trial Registration: Netherlands Trial Register, NL1620 . Registered on 9 March 2009.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-021-00799-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995792PMC
March 2021

A competing risk joint model for dealing with different types of missing data in an intervention trial in prodromal Alzheimer's disease.

Alzheimers Res Ther 2021 03 22;13(1):63. Epub 2021 Mar 22.

Department of Biostatistics, Erasmus Medical Center, PO Box 2040, 3000, Rotterdam, CA, the Netherlands.

Background: Missing data can complicate the interpretability of a clinical trial, especially if the proportion is substantial and if there are different, potentially outcome-dependent causes.

Methods: We aimed to obtain unbiased estimates, in the presence of a high level of missing data, for the intervention effects in a prodromal Alzheimer's disease trial: the LipiDiDiet study. We used a competing risk joint model that can simultaneously model each patient's longitudinal outcome trajectory in combination with the timing and type of missingness.

Results: Using the competing risk joint model, we were able to provide unbiased estimates of the intervention effects in the presence of the different types of missingness. For the LipiDiDiet study, the intervention effects remained statistically significant after this correction for the timing and type of missingness.

Conclusion: Missing data is a common problem in (Alzheimer) clinical trials. It is important to realize that statistical techniques make specific assumptions about the missing data mechanisms. When there are different missing data sources, a competing risk joint model is a powerful method because it can explicitly model the association between the longitudinal data and each type of missingness.

Trial Registration: Dutch Trial Register, NTR1705 . Registered on 9 March 2009.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-021-00801-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983401PMC
March 2021
-->