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The Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) score as a predictor for cognitive decline and potential surrogate outcome in the FINGER lifestyle randomized controlled trial.
Hall, A, Barbera, M, Lehtisalo, J, Antikainen, R, Huque, H, Laatikainen, T, Ngandu, T, Soininen, H, Stephen, R, Strandberg, T, et al
European journal of neurology. 2024;:e16238
Abstract
BACKGROUND AND PURPOSE The complex aetiology of Alzheimer's disease suggests prevention potential. Risk scores have potential as risk stratification tools and surrogate outcomes in multimodal interventions targeting specific at-risk populations. The Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) was tested in relation to cognition and its suitability as a surrogate outcome in a multidomain lifestyle randomized controlled trial, in older adults at risk of dementia. METHODS In this post hoc analysis of the Finnish Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), ANU-ADRI was calculated at baseline, 12, and 24 months (n = 1174). The association between ANU-ADRI and cognition (at baseline and over time), the intervention effect on changes in ANU-ADRI, and the potential impact of baseline ANU-ADRI on the intervention effect on changes in cognition were assessed using linear mixed models with maximum likelihood estimation. RESULTS A higher ANU-ADRI was significantly related to worse cognition, at baseline (e.g., estimate for global cognition [95% confidence interval] was -0.028 [-0.032 to -0.025]) and over the 2-year study (e.g., estimate for 2-year changes in ANU-ADRI and per-year changes in global cognition [95% confidence interval] was -0.068 [-0.026 to -0.108]). No significant beneficial intervention effect was reported for ANU-ADRI, and baseline ANU-ADRI did not significantly affect the response to the intervention on changes in cognition. CONCLUSIONS The ANU-ADRI was effective for the risk prediction of cognitive decline. Risk scores may be crucial for the success of novel dementia prevention strategies, but their algorithm, the target population, and the intervention design should be carefully considered when choosing the appropriate tool for each context.
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A short history from Karelia study to biodiversity and public health interventions.
Haahtela, T, Alenius, H, Auvinen, P, Fyhrquist, N, von Hertzen, L, Jousilahti, P, Karisola, P, Laatikainen, T, Lehtimäki, J, Paalanen, L, et al
Frontiers in allergy. 2023;:1152927
Abstract
Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy & asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia. The Karelia Allergy Study 2002-2022 showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwide Finnish Allergy Programme 2008-2018 implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme, Nature Step to Health 2022-2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit of Planetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.
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Psychosocial determinants for adherence to a healthy lifestyle and intervention participation in the FINGER trial: an exploratory analysis of a randomised clinical trial.
Neuvonen, E, Lehtisalo, J, Solomon, A, Antikainen, R, Havulinna, S, Hänninen, T, Laatikainen, T, Lindström, J, Rautio, N, Soininen, H, et al
Aging clinical and experimental research. 2022;(8):1793-1805
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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.
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The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER).
Ngandu, T, Lehtisalo, J, Korkki, S, Solomon, A, Coley, N, Antikainen, R, Bäckman, L, Hänninen, T, Lindström, J, Laatikainen, T, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;(7):1325-1334
Abstract
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.
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Family socioeconomic status and childhood adiposity in Europe - A scoping review.
Sares-Jäske, L, Grönqvist, A, Mäki, P, Tolonen, H, Laatikainen, T
Preventive medicine. 2022;:107095
Abstract
Childhood obesity is a considerable public health problem worldwide. In Europe, lower parental socioeconomic status (SES) relates to higher childhood adiposity. This scoping review strives to discover, which SES indicators are the most commonly used and meaningful determinants of childhood adiposity (greater level of continuous adiposity indicator, e.g. body mass index z-score, or overweight or obesity categorized by established definitions). The review focused on studies about European general populations from the 21st century (January 2000-April 2021) considering children and adolescents aged 0-17 years. PubMed and reference lists of articles were searched in February-April 2021. Total of 53 studies with 121 association analyses between different SES indicators and adiposity indicators, were identified and reviewed. Different SES indicators were grouped to 25 indicators and further to six indicator groups. The most used indicator was mother's education (n of association analyses = 24) and the most used indicator group was parental education (n of association analyses = 51). Of all association analyses, 55% were inverse, 36% were non-significant, and 8% were positive. Composite SES (80%), parental education (69%) and parental occupation (64%) indicators showed most frequently inverse associations with obesity measures (i.e. lower parental SES associating with higher adiposity), while parental income (50% inverse; 50% non-significant) and property and affluence (42% inverse; 50% nonsignificant) indicators showed approximately even number of inverse and non-significant associations. Instead, majority of parental employment (60%) indicators, showed non-significant associations and 33% showed positive associations (i.e. higher parental SES associating with higher adiposity). Despite some variation in percentages, majority of the associations were inverse in each age group and with different outcome categorizations. In girls and in boys, non-significant associations predominated. It seems that children with parents of higher SES have lower likelihood of adiposity in Europe. Parents' employment appears to differ from other SES indicators, so that having an employed parent(s) does not associate with lower likelihood of adiposity. Positive associations seem to occur more frequently in poorer countries. Criteria for uniform childhood SES and adiposity measures should be established and used in studies in order to be able to produce comparable results across countries.
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Occupational complexity and cognition in the FINGER multidomain intervention trial.
Rydström, A, Darin-Mattsson, A, Kåreholt, I, Ngandu, T, Lehtisalo, J, Solomon, A, Antikainen, R, Bäckman, L, Hänninen, T, Laatikainen, T, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;(12):2438-2447
Abstract
INTRODUCTION Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. METHODS In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. RESULTS Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. DISCUSSION In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies.
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27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial.
Sandebring-Matton, A, Goikolea, J, Björkhem, I, Paternain, L, Kemppainen, N, Laatikainen, T, Ngandu, T, Rinne, J, Soininen, H, Cedazo-Minguez, A, et al
Alzheimer's research & therapy. 2021;(1):56
Abstract
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.
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Long-term trends in blood pressure and hypertension in Russia: an analysis of data from 14 health surveys conducted in 1975-2017.
Churilova, E, Shkolnikov, VM, Shalnova, SA, Kudryavtsev, AV, Malyutina, S, Nilssen, O, Laatikainen, T, Leon, DA
BMC public health. 2021;(1):2226
Abstract
BACKGROUND Hypertension is recognized as an important contributor to high cardiovascular mortality in Russia. A comprehensive analysis of data from Russian studies that measured blood pressure in population-based samples has not been previously undertaken. This study aims to identify trends and patterns in mean blood pressure and the prevalence of hypertension in Russia over the most recent 40 years. METHODS We obtained anonymized individual records of blood pressure measurements from 14 surveys conducted in Russia in 1975-2017 relating to a total of 137,687 individuals. For comparative purposes we obtained equivalent data from 4 surveys in the USA and England for 23,864 individuals. A meta-regression on aggregated data adjusted for education was undertaken to estimate time trends in mean systolic and diastolic blood pressure, the prevalence of elevated blood pressure (> 140/90 mmHg), and hypertension (defined as elevated blood pressure and/or the use of blood pressure-lowering) medication. A meta-analysis of pooled individual-level data was used to assess male-female differences in blood pressure and hypertension. RESULTS During the period 1975-2017 mean blood pressure, the prevalence of elevated blood pressure and hypertension remained stable among Russian men. Among Russian women, mean systolic blood pressure decreased at an annual rate of 0.25 mmHg (p < 0.1) at age 35-54 years and by 0.8 mmHg (p < 0.01) at ages 55 and over. The prevalence of elevated blood pressure also decreased by 0.8% per year (p < 0.01), but the prevalence of hypertension remained stable. Mean blood pressure and prevalence of hypertension were higher in Russia compared to the USA and England at all ages and for both sexes. CONCLUSIONS In contrast to the generally observed downward trend in elevated blood pressure in many other countries, levels in Russia have changed little over the past 40 years, although there are some positive trends among women. Improved strategies to bring down the high levels of mean blood pressure and hypertension in Russia compared to countries such as England and the USA are important to further reduce the high burden of CVD in Russia.
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The Finnish Allergy Program 2008-2018: Society-wide proactive program for change of management to mitigate allergy burden.
Haahtela, T, Valovirta, E, Saarinen, K, Jantunen, J, Lindström, I, Kauppi, P, Laatikainen, T, Pelkonen, A, Salava, A, Tommila, E, et al
The Journal of allergy and clinical immunology. 2021;(2):319-326.e4
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A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 billion to €1.8 billion, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education.
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Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial.
Sindi, S, Solomon, A, Kåreholt, I, Hovatta, I, Antikainen, R, Hänninen, T, Levälahti, E, Laatikainen, T, Lehtisalo, J, Lindström, J, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;(3):491-498
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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.