The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER).
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;(7):1325-1334
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.
Psychosocial determinants for adherence to a healthy lifestyle and intervention participation in the FINGER trial: an exploratory analysis of a randomised clinical trial.
Aging clinical and experimental research. 2022;(8):1793-1805
BACKGROUND AND AIMS Psychosocial factors may affect adherence to lifestyle interventions and lifestyle changes. The role of psychosocial factors in dementia prevention needs more research. We aimed at clarify the issue in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). METHODS The population included 1260 participants aged 60-77 years at risk for cognitive decline, randomised to a multidomain lifestyle intervention or regular health advice for 2 years. Adherence was evaluated as participation in the provided activities and actual lifestyle changes, separately for each domain (diet, exercise, social/cognitive activity, vascular risk management) and combined into multidomain. Psychosocial factors were measured at trial baseline (depressive symptoms; study perception; health-related quality of life, HRQoL) and earlier life (hopelessness; satisfaction with family life, achievements, and financial situation). RESULTS Depressive symptoms, hopelessness, and nonpositive study perception were negatively and HRQoL positively associated with participation in the multidomain intervention. Depressive symptoms, lower HRQoL, hopelessness and dissatisfaction with financial situation were associated with unhealthier lifestyles at baseline. Baseline depressive symptoms and lower HRQoL predicted less improvement in lifestyle, but did not modify the intervention effect on lifestyle change. DISCUSSION AND CONCLUSIONS Several psychosocial factors were associated with participation in lifestyle intervention, while fewer of them contributed to lifestyle changes. Although the intervention was beneficial for lifestyle changes independent of psychosocial factors, those most in need of lifestyle improvement were less likely to be active. Tailoring lifestyle-modifying strategies based on the need for psychosocial support may add efficacy in future trials. TRIAL REGISTRY ClinicalTrials.gov NCT01041989 2010-01-05.
Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people: the FINGER trial.
European heart journal. 2022;(21):2054-2061
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.
Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.
Nature genetics. 2021;(5):762
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.
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;(8):1407-1414
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.
Quantifying dementia prevention potential in the FINGER randomized controlled trial using the LIBRA prevention index.
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021;17(7):1205-1212
Plain language summary
Lifestyle interventions are being increasingly recognised to delay or prevent the onset of dementia. Scientific research targeting one lifestyle factor has continually failed to show any benefits and therefore interventions targeting several lifestyle factors, before disease onset may be more beneficial. The Lifestyle for BRAin Health (LIBRA) score is a tool which assesses peoples risk of dementia based on several lifestyle factors and this trial used this tool to determine the dementia risk of individuals who entered The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). This study was the first randomised control trial showing benefits to cognition following multi-domain lifestyle interventions. The results showed that higher LIBRA score at the start of the trial was associated with poorer brain function over time and that the multi-domain lifestyle intervention was effective at decreasing LIBRA score, regardless of the risk at the start of the trial. It was concluded that LIBRA may be a useful tool to determine risk of dementia and that the FINGER intervention was of benefit to individuals regardless of their risk of dementia.
INTRODUCTION Individuals in early dementia prevention trials may differ in how much they benefit from interventions depending on their initial risk level. Additionally, modifiable dementia risk scores might be used as surrogate/intermediate outcomes. METHODS In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated in post hoc analyses (N = 1207) whether the cognitive benefits of the 2-year multi-domain lifestyle intervention differed by baseline dementia risk measured with the "LIfestyle for BRAin Health" (LIBRA) score. We also investigated intervention effects on change in LIBRA score over time. RESULTS Overall, higher baseline LIBRA was related to less cognitive improvement over time. This association did not differ between the intervention and control groups. The intervention was effective in decreasing LIBRA scores over time, regardless of baseline demographics or cognition. DISCUSSION The cognitive benefit of the FINGER intervention was similar across individuals with different LIBRA scores at baseline. Furthermore, LIBRA may be useful as a surrogate/intermediate endpoint and surveillance tool to monitor intervention success during trial execution.
Effect of a Multidomain Lifestyle Intervention on Estimated Dementia Risk.
Journal of Alzheimer's disease : JAD. 2021;(4):1461-1466
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.
27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial.
Alzheimer's research & therapy. 2021;(1):56
BACKGROUND 27-Hydroxycholesterol (27-OH), the main circulating oxysterol in humans and the potential missing link between peripheral hypercholesterolemia and Alzheimer's disease (AD), has not been investigated previously in relation to cognition and neuroimaging markers in the context of preventive interventions. METHODS The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older individuals (60-77 years) at increased risk for dementia but without dementia or substantial cognitive impairment from the general population. Participants were randomized to a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice) in a 1:1 ratio. Outcome assessors were masked to group allocation. This FINGER exploratory sub-study included 47 participants with measures of 27-OH, cognition, brain MRI, brain FDG-PET, and PiB-PET. Linear regression models were used to assess the cross-sectional and longitudinal associations between 27-OH, cognition, and neuroimaging markers, considering several potential confounders/intervention effect modifiers. RESULTS 27-OH reduction during the intervention was associated with improvement in cognition (especially memory). This was not observed in the control group. The intervention reduced 27-OH particularly in individuals with the highest 27-OH levels and younger age. No associations were found between changes in 27-OH levels and neuroimaging markers. However, at baseline, a higher 27-OH was associated with lower total gray matter and hippocampal volume, and lower cognitive scores. These associations were unaffected by total cholesterol levels. While sex seemed to influence associations at baseline, it did not affect longitudinal associations. CONCLUSION 27-OH appears to be a marker not only for dementia/AD risk, but also for monitoring the effects of preventive interventions on cholesterol metabolism. TRIAL REGISTRATION ClinicalTrials.gov , NCT01041989 . Registered on 4 January 2010.
Facilitators and barriers to implementing lifestyle intervention programme to prevent cognitive decline.
European journal of public health. 2021;(4):816-822
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.
Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial.
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;(3):491-498
BACKGROUND Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). METHODS Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989). RESULTS This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264). CONCLUSIONS This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits. CLINICAL TRIALS REGISTRATION NUMBER NCT01041989.