Multidomain Lifestyle Intervention Research Articles

Enhancing Dementia Risk Mitigation: Standardized Digital Monitoring in Clinical Trials and Platform Design for At-Risk Elderly Individuals.

Dementia is becoming a significant public health concern, affecting approximately 130,000 individuals in Austria, whereby nearly 40% of the cases are attributed to modifiable risk factors. Multidomain lifestyle interventions have thereby demonstrated significant effects in reducing the risk of dementia. The goal was to define an interoperability framework to conduct standardized monitoring in clinical trials for enhancing dementia risk mitigation. In addition, the identified standards should be integrated into the components of the project. A step-by-step approach was used, where initially data collection, aggregation and harmonization was carried out with retrospective data from various clinical centers. Afterwards, the interoperability framework was defined including the prospective data that is gathered during a clinical trial. A guideline for integrating healthcare standards was developed and incorporated into the technical components for the clinical trial. The interoperability framework was designed in a scalable way and will be regularly updated for future needs.

Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial.

We assessed a genetic risk score for Alzheimer's disease (AD-GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial. 1260 at-risk older individuals without dementia were randomized to multidomain lifestyle intervention or health advice. N=126 participants underwent magnetic resonance imaging (MRI), and N=47 positron emission tomography (PET) scans (Pittsburgh Compund B [PiB], Fluorodeoxyglucose) at baseline; N=107 and N=38 had repeated 2-year scans. The APOE4 allele, but not AD-GRS, was associated with baseline lower hippocampus volume (β=-0.27, p=0.001), greater amyloid deposition (β=0.48, p=0.001), 2-year decline in hippocampus (β=-0.27, p=0.01), total gray matter volume (β=-0.25, p=0.01), and cortical thickness (β=-0.28, p=0.003). In analyses stratified by AD-GRS (below vs above median), the PiB composite score increased less in intervention versus control in the higher AD-GRS group (β=-0.60, p=0.03). AD-GRS and APOE4 may have different impacts on potential intervention effects on amyloid, that is, less accumulation in the higher-risk group (AD-GRS) versus lower-risk group (APOE). First study of neuroimaging and AD genetics in a multidomain lifestyle intervention. Possible intervention effect on brain amyloid deposition may rely on genetic risk. AD-GRS and APOE4 allele may have different impacts on amyloid during intervention.

A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol

BackgroundCombining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer’s Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence).MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60–79 years) at increased risk of dementia.MethodsMET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes.The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded.ConclusionMET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field.Trial registrationClinicalTrials.gov (NCT05109169).

Programme Dementia Prevention (pdp): A Nationwide Program for Personalized Prevention in Luxembourg.

With continuously aging societies, an increase in the number of people with cognitive decline is to be expected. Aside from the development of causative treatments, the successful implementation of prevention strategies is of utmost importance to reduce the high societal burden caused by neurodegenerative diseases leading to dementia among which the most common cause is Alzheimer's disease. The aim of the Luxembourgish "programme dementia prevention (pdp)" is to prevent or at least delay dementia in an at-risk population through personalized multi-domain lifestyle interventions. The current work aims to provide a detailed overview of the methodology and presents initial results regarding the cohort characteristics and the implementation process. In the frame of the pdp, an extensive neuropsychological evaluation and risk factor assessment are conducted for each participant. Based on the results, individualized multi-domain lifestyle interventions are suggested. A total number of 450 participants (Mean age = 69.5 years; SD = 10.8) have been screened at different recruitment sites throughout the country, among whom 425 participants (94.4%) met the selection criteria. We provide evidence supporting the feasibility of implementing a nationwide dementia prevention program and achieving successful recruitment of the target population by establishing a network of different healthcare providers.

The Multi-domain Lifestyle Intervention for Cognitive Impairment in Community-Dwelling Older Adults in Hangzhou (The Heritage Study): Study Design and Protocol.

The globe has been working to promote a multi-domain lifestyle intervention for dementia prevention in older adults, referring to the Worldwide-FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) initiative. In China, the multi-domain lifestyle intervention has been implemented in rural communities (MIND-China), yet the adaptability of such intervention based on the urban communities in China has not been verified. To examine the effectiveness and feasibility of the multi-domain lifestyle intervention on dementia prevention in at-risk community-dwelling older adults in China. The multi-domain lifestyle intervention study is a community-based 2-year cluster randomized controlled trial (RCT). A total of 1200 participants aged 60-80 years old will be recruited from twelve communities in Hangzhou, Zhejiang. Inclusion criteria were the Montreal Cognitive Assessment 5 minutes protocol (5 min MoCA) score of 6-9 or the Ascertain Dementia 8 (AD 8) score of ≥2, and having modifiable lifestyle factors. Participating communities will be randomized into either the structured multi-domain intervention (SMI) arm or the self-guided intervention (SGI, general health education) arm. The SMI consists of cognitive training, physical exercise, and nutritional and dietary instruction for the first 12 months; and vascular risks monitoring and control for 24 months. The primary outcome is the global cognitive performance, measured by the comprehensive Neuropsychological Test Battery (NTB). The secondary outcomes include domain-specific cognitive performances, physical function, mental health, physiological and biochemical indices, adherence to healthy lifestyles, and neuroimaging metrics. The feasibility of intervention will be evaluated around the five dimensions of the RE-AIM framework and in conjunction with quantitative data, operational data and results of focus group discussions. Following the Worldwide-FINGERS, this cluster RCT will verify the adaptability of the multi-domain lifestyle intervention in the urban community settings in China. This study will add evidence for global dementia prevention and management among older adults.

Impact of genetic risk in multidomain lifestyle preventive interventions

AbstractBackgroundInteractions between genetic and lifestyle‐related risk factors for dementia have been investigated mainly in observational studies, with conflicting results. Less is known about whether genetic risk factors for dementia (not just APOE4 allele but also polygenic risk beyond APOE4) have an impact on the effects of multidomain lifestyle preventive interventions on cognition. Although there is overlap between risk factors for dementia and e.g. cardiovascular diseases (CVD), it is unclear if CVD genetic risk may also have an impact on potential intervention benefits.MethodThe FINGER randomized controlled trial included 1260 participants aged 60‐77 years and at risk for dementia from the general Finnish population. Cognition improved more during 2 years in the multidomain lifestyle intervention (diet, exercise, cognitive training, social activities and cardiovascular risk monitoring) compared with control (regular health advice) group. Genetic risk scores for Alzheimer’s disease (AD‐GRS, excluding APOE) and CVD‐GRS were selected based on existing literature, and calculated using GWAS data from FINGER participants.ResultPrevious findings indicated that the FINGER intervention had clear cognitive benefits among APOE4 carriers. Preliminary results suggested a less straightforward impact of AD‐GRS, especially after adjustment for APOE4. There seemed to be a pattern of more intervention‐related cognitive benefit among participants with lower compared with higher CVD‐GRS.ConclusionAPOE4, AD‐GRS and CVD‐GRS may have different impact on the cognitive benefits of multidomain lifestyle interventions for dementia prevention. Ongoing World‐Wide FINGERS trials in populations with a variety of genetic profiles will create opportunities for more detailed investigation of genetic‐lifestyle interactions in the context of preventive interventions.

Study Design of FINGER‐NL: a Multidomain Lifestyle Intervention in Dutch Older Adults to Maintain Optimal Cognitive Functioning

AbstractBackgroundEvidence on the effectiveness of multidomain lifestyle interventions to prevent cognitive decline in non‐demented older individuals is mixed. The multidomain FINGER study1 found small positive effects on cognition among older people at risk for dementia. As part of the World‐Wide FINGERS initiative to replicate and build on these results, FINGER‐NL aims to investigate the effectiveness of a 2‐year high versus low intensive multidomain lifestyle intervention on cognitive functioning in Dutch older at‐risk individuals.MethodFINGER‐NL is a Dutch multi‐center, randomized, controlled, multidomain lifestyle intervention trial aiming to include 1,206 adults at risk for cognitive decline. Adults aged 60‐80 years with at least 3 modifiable dementia risk factors (based on ‘LIfestyle for BRAin Health’ (LIBRA))2 and either a family history of dementia or self‐reported cognitive decline are eligible for inclusion. Participants are randomized (1:1 ratio) to either a high (HI‐group) or low‐intensity (LI‐group) intervention group. The multi‐domain intervention comprises a combination of 7 lifestyle components (physical exercise, cognitive training, cardiovascular risk management, nutritional counseling (with a specific focus on the MIND diet), sleep counseling, stress management, social activities) and 1 nutritional product (Souvenaid, 125ml). The HI‐group receives a personalized, supervised and hybrid intervention consisting of group meetings and individual sessions guided by a lifestyle coach. The LI‐group receives online lifestyle‐related health education. Primary outcome is 2‐year change from baseline on the cognitive composite score covering processing speed, executive function and memory. Secondary outcomes including changes in specific cognitive domains, instrumental activities of daily living, LIBRA score, and lifestyle component specific outcomes. For recruitment, we use the Dutch Brain Research Registry.3 ResultParticipant recruitment started in January 2022. So far, 2405 people were interested, 1711 individuals have been screened for eligibility, 949 underwent baseline testing and 880 participants (73% of target sample) have been randomized and started with the intervention. The intervention is well‐accepted based on drop‐out rate (0.5%) and use of the online intervention portal. We expect to finalize randomization in Q2 of 2023 and complete the two‐year trial in 2025.ConclusionResults so far show that FINGER‐NL is well on track, the intervention is well‐accepted and the trial will reach its inclusion target.

Role of nutrition and metabolic regulation in multidomain trials for dementia risk reduction: findings from FINGER and FINGER 2.0 studies

AbstractBackgroundThe successful FINGER multidomain intervention model combined dietary intervention (healthy Nordic diet) with exercise, cognitive training, social activities, and cardiovascular risk monitoring. The FINGER model is being tested and optimized in the World‐Wide FINGERS network of multidomain dementia prevention trials (45+ countries). Advanced FINGER 2.0 models combine lifestyle interventions with multi‐nutrients and/or putative disease‐modifying drugs.MethodThe 11‐year extended follow‐up of FINGER trial participants (N:1260, at‐risk general population) was completed in Q1‐2023. The MIND‐AD pilot‐trial (N:93, prodromal Alzheimer’s disease (AD)) included medical food (Fortasyn Connect), tested alone or in combination with multidomain lifestyle intervention for 6 months. The MET‐FINGER trial (N:600, at‐risk general population enriched with APOE4‐carriers, 2‐year intervention) includes different dosages of metformin (in combination with upgraded FINGER lifestyle intervention).ResultNew nutrition/metabolic related data will be presented from FINGER where eg. adherence to healthier diet was still relatively high in the multidomain arm after the extended follow‐up. Higher adherence was also related to better cognition. Several dietary and metabolic biomarkers have been analyzed revealing underlying mechanisms and responders (eg persons with insulin resistance, higher HOMA, responded less). In the MIND‐AD trial, participants from 4 European countries were randomized to the multidomain lifestyle intervention alone (N:32), or in combination with medical food (N:31), and 30 to the control group. Adherence was high for all intervention domains (78‐87%). Compared with the control group, the group with lifestyle+medical food showed a decrease in vascular risk burden (P = 0.027) and an increase in healthy diet patterns (P = 0.045), and better cognition after the intervention (CDR‐SOB). There were no significant differences between the lifestyle only and control group. MET‐FINGER trial recruitment started in January 2023 (preliminary data presented).ConclusionLonger‐term dietary and lifestyle changes are feasible and effective in older adults in the at‐risk spectrum of AD/dementia. Beneficial effects (adherence to and effects of interventions) seemed to improve with the inclusion of medical food in prodromal AD. The unique long follow‐up of FINGER provides important information about long‐term effects and methodological aspects. The MET‐FINGER trial will provide data on synergistic effects between FINGER intervention and a drug targeting both glucose metabolism and AD pathology.

LatAm‐FINGERS and U.S. POINTER: Design and Cohort Characteristics of Parallel Harmonized Trials of Multidomain Lifestyle Interventions Targeting Cognition

AbstractBackgroundMultidomain lifestyle interventions hold great promise world‐wide as interventions to slow cognitive aging, and delay and prevent Alzheimer’s Disease and Related Disorders (ADRD). To have the greatest reach, they must be tailored for and assessed within local cultures in clinical trials. For trials to have the greatest impact, it’s important that they are designed with common features that promote comparisons and potential harmonization.MethodWorld‐Wide FINGERS was launched in 2017 as a global network of multidomain lifestyle intervention trials to adapt, test, and optimize multidomain lifestyle intervention trials in regions worldwide. Two participating trials, the Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm‐FINGERS) and the U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) have collaborated to promote harmonization to support joint initiatives. This presentation is organized to describe, in parallel, their study protocols, and cohort characteristics, and demonstrate how cross‐trial collaboration may expand the impact of individual trials.ResultThe trials have overlapping aims, eligibility criteria, interventions, and assessment protocols. LatAm‐FINGERS and U.S. POINTER will enroll 1,200 and 2,000 participants, respectively. Table 1 describes sample characteristics. The samples of the two studies share similar sociodemographic and clinical characteristics with a few exceptions. In U.S. POINTER, there is a larger proportion of participants with a family history of memory impairment and physical inactivity, and a higher frequency of White participants. Additionally, mild memory impairment (Clinical Dementia Rating = 0.5) is more common in LatAm‐FINGERS participants.ConclusionHarmonization of LatAm‐FINGERS and U.S. POINTER protocols provides unique opportunities for collaborative science for identifying effective strategies to promote cognitive resilience and reduce risks for Alzheimer’s disease, and significantly expand the potential for scientific investigation in diverse populations.

What are the most prevalent combinations of modifiable dementia risk factors that can be targeted in multidomain lifestyle intervention in Canada?

AbstractBackgroundNot all risk factors have the same weight in dementia development, and the combinations of common risk factors differs across individuals and populations. The goal of this study is to estimate the potential population impact of modifiable risk factors for dementia in Canada, and to identify the combinations of the modifiable risk factors that could prevent many dementia cases in Canadian adults.MethodThis is a secondary analysis of data from the Canadian Longitudinal Study on Aging Comprehensive Cohort (n = 30,009). The prevalence and population attributable fraction (PAF) of 12 modifiable lifestyle risk factors established in the Lancet Commission Report 2020 were calculated using baseline data. The prevalence of every possible dyad, triad, and tetrad combination of the risk factors was estimated. All analyses were stratified by 2 sex strata (male, female) and 4 age strata (45‐54, 55‐64, 65‐74, 75+).ResultThe combined PAF of the 12 lifestyle risk factors was 49% in the Canadian population. The single risk factors that contributed the most were physical inactivity (11.3%), hearing loss (6.9%), and obesity (6.9%) in Canada, whereas social isolation (0.4%), alcohol (1.1%), and smoking (1.4%) had substantially smaller effects (Table 1). The most prevalent risk factor dyad was physical inactivity and sleep disturbance (34%). Obesity, physical inactivity, and sleep disturbance was the most prevalent risk factor triad (14%). The tetrad of hearing loss, obesity, physical inactivity, and sleep disturbance had the highest prevalence (4.9%). The prevalent risk factor combinations were similar in the two younger age groups and both sexes, but not in the two older age groups (Table 2).ConclusionNearly 50% of dementia cases in Canada can be prevented by modifying 12 lifestyle risk factors. The most prevalent combinations of risk factors differ before and after the age of 65, but not by sex. The most prevalent risk factor combinations consist of physical inactivity, sleep disturbance and obesity in the two younger age groups, and hearing loss, sleep disturbance and obesity in the two older age groups. These findings may help strategically target tailoring multidomain dementia intervention programs to have the greatest impact in the Canadian population.

Background and Design of the U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER)

AbstractBackgroundU.S. POINTER is a Phase 3, multicenter, randomized 2‐year clinical trial of two multidomain lifestyle interventions in 2111 older adults who are at increased risk of cognitive decline and dementia due sedentary lifestyle, poor diet, and other factors such as family history of memory impairment and suboptimum cardiovascular health.MethodEnrollment took place at five geographically diverse sites, beginning in 2019 and completing in early 2023. Participants are randomly assigned to one of two lifestyle intervention groups that differ in format, intensity, and accountability. Those randomized to the Self‐Guided Lifestyle Intervention receive annual medical monitoring and health education information, tools, and support to encourage increased physical and cognitive activity and a healthier diet through 2‐3 annual group meetings. Those randomized to the Structured Lifestyle Intervention receive frequent medical monitoring of cardiovascular health and a structured program of exercise (primarily aerobic), nutritional counseling, cognitive training and social engagement initially through weekly and then monthly group meetings. U.S. POINTER includes partnerships with local chapters of the Alzheimer’s Association and lifestyle specialists to assist with intervention delivery. The primary outcome is 2‐year change in cognitive function measured with a global cognition composite score that permits harmonization with FINGER and other trials. Secondary and tertiary outcomes include measures of executive function and episodic memory, physical activity, diet, cognitive and physical activity, cardiometabolic disease risks, mood, quality of life, health care costs, and health care utilization.ResultU.S. POINTER is generating a richly phenotyped cohort that will provide a rigorous comparison of two lifestyle interventions designed to preserve cognitive function. It has nurtured 4 ancillary studies to assess intervention effects on outcomes related to sleep quality, brain structure and pathology, peripheral and neurovascular function, and the microbiome. It also partners with clinical trials within the World‐Wide FINGERS international network. The study is generating an archive of biospecimens and de‐identified public use data. Plans for a post‐intervention observational study of the U.S. POINTER cohort are underway.ConclusionU.S. POINTER provides an important national resource to advance the field in understanding the role of nonpharmacological interventions in reducing risk for cognitive decline and Alzheimer’s disease and related dementia.

Importance of individual dietary factors for cognitive performance in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, FINGER

AbstractBackgroundFinnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized trial that showed beneficial effect on cognition with a 2‐year multidomain lifestyle intervention. One of the four multidomain intervention components was diet and we have earlier shown that overall adherence to the FINGER dietary intervention goals was associated with better cognition. Here our aim is to investigate how the individual components of the dietary adherence score are associated with cognitive performance during the 2‐year period.MethodThe FINGER cohort included 1259 individuals at risk of dementia aged 60‐77 years at baseline, randomized into the multidomain intervention (n = 631) or the control group (n = 628). They underwent extensive data collection annually (total of 3 assessments), including detailed neuropsychological test battery (NTB) and a 3‐day food record. Adherence to dietary intervention was evaluated on 9 items based on dietary recommendations: intake of saturated fat, polyunsaturated fat, sucrose, fiber, protein, alcohol, vegetables, fruits, and fish. Data analyses were completed with mixed‐effects regression.ResultThe goal for low alcohol intake was inversely associated with cognition at baseline, but no other dietary items showed cross‐sectional associations. Reaching the goal for saturated fat, fiber, vegetables, fruits, and fish predicted better cognitive change at two years (p <0.05 for goal*time each). Results were similar when continuous variables rather than dichotomized goals were investigated. Intake of polyunsaturated fats additionally predicted better cognitive change and vegetable intake showed positive cross‐sectional association with cognition. There were no significant interactions with the study group.ConclusionSix out of nine FINGER dietary goals predicted a favorable cognitive change over time, indicating that a dietary pattern adherence with general dietary recommendations is beneficial for brain health. However, alcohol intake goal, i.e. lower alcohol intake, was associated with worse cognition; and cut‐offs for polyunsaturated fats based on the recommendations appeared suboptimal. The FINGER dietary adherence score should be compared with food‐based dietary patterns like Mediterranean Diet to investigate if nutrient intakes should be better taken into account when analyzing diet in relation to cognitive performance.

Impact of multidomain lifestyle intervention on white matter integrity: theSUPERBRAIN exploratory sub‐study

AbstractBackgroundIn the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), we evaluated the impact of a 24‐week facility‐based multidomain intervention (FMI) and home‐based MI (HMI) on white matter integrity.MethodTotally, 152 participants, aged 60‐79 years without dementia, were randomly assigned to the FMI, HMI, or control groups. Among them, 55 participants (20 FMI, 19 HMI, and 16 controls) underwent brain MRI at baseline and 24 weeks. The dtifit tool was used to fit the diffusion tensor model and computed diffusion scalar maps for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Individual FA, MD, AD, and RD at baseline were compared among groups using one‐way analyses of covariance (ANCOVA) with age, sex, years of education, and imaging site effects added as covariates of no interest. In addition, to compare changes in the FA, MD, AD, and RD from baseline to the study endpoint, we used two statistical analyses. First, ROI‐wise paired t‐tests were used to analyze longitudinal changes in white matter integrity for control and intervention group. The statistical significance level was set at bonferroni corrected p‐value < 0.05. And then, significant brain image measures in previous paired t‐test were compared between each group pair (FMI vs. control; HMI vs. control; FMI+HMI vs. control) using ANCOVA with changes as dependent variables and age, sex, education, and site as covariates.ResultThe FA, MD, AD, and RD at each ROI at the baseline were not different among groups after bonferroni correction. In cingulum regions, the FA and AD were increased and the MD and AD were decreased significantly in the intervention group. The AD in right uncinate fasciculus was also increased in intervention group. Finally, among the significant regions in paired t‐test, compared with the control group, the FMI, HMI, and intervention group yielded significantly more beneficial effects on the AD of the cingulum regionsConclusionThe change of white matter integrity in the intervention group suggests that multidomain lifestyle intervention may be beneficial through structural neuroplastic changes in highly complex tract.

Health care service use in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) during an extended follow‐up period

AbstractBackgroundFinnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized trial aiming to prevent cognitive decline with a 2‐year multidomain lifestyle intervention. Beneficial effects were detected not only in cognition, but also for co‐morbidity, as reported earlier. Aim of this work was to investigate, if the multidomain intervention also had an impact on the health care use and to evaluate possible cost‐effectiveness of the interventions in terms of health care costs.MethodThe FINGER trial recruited a population‐based cohort of 1259 at‐risk individuals aged 60‐77 living in six areas of Finland. They were randomized into a multidomain lifestyle intervention consisting of diet, exercise, cognitive training and vascular risk management (n = 631) or a regular health advice (control) (n = 628) group for two years and followed on average for 8 years. Health care use was obtained from nationwide registers where all primary and specialized care visits are recorded. We calculated days spent in hospital, ambulatory visits, outpatient visits in hospitals and primary care, and home care. Costs will be evaluated based on national reference prices.ResultAltogether 99% of the population used some health care services and 66% were hospitalized at least for one day during the 8 years. 128 (10%) participants died during the follow‐up. Preliminary data indicated that the intervention group spent less days in the hospital, but there were no differences in outpatient visits. Further analyses are ongoing to evaluate the costs related to these visits.ConclusionMultidomain lifestyle intervention which is effective in prevention of cognitive decline can also help in reducing health care use at least in terms of hospital stays.

The Look AHEAD Aging Study: design, cohort characteristics, and cognitive function

AbstractBackgroundData on cognitive trajectories and characteristics associated with cognitive resilience among older individuals with type 2 diabetes and overweight or obesity are scant. To date, the NIA‐funded Action for Health in Diabetes (Look AHEAD) Aging Study has enrolled 1245 individuals, ages 64 to 95 years, who have been richly characterized over 18 years of prior follow‐up with factors associated with cognitive aging.MethodVolunteers from the Look AHEAD clinical trial of a multidomain lifestyle intervention and its subsequent clinic‐based post‐trial observational phase were invited to join a 4‐year telephone‐based observational study that includes annual cognitive assessments to assess memory, attention/processing speed, executive function, and global cognitive function. A composite measure of cognitive function based on the average standardized cognitive function tests was used to capture global cognitive function. Mild cognitive impairment and probable dementia will be centrally adjudicated. Additional measures include depressive symptoms, physical function and abilities, medical events, medication use, and health related quality of life. Recruitment will be completed in early 2023.ResultThe enrolled cohort to date (N = 1590) includes 62% women, 32% individuals from traditionally under‐represented racial/ethnic minorities, 49% without college education, and 52% who had been randomly assigned to the lifestyle intervention. The mean (SD) age is 76.3 (5.6) and years of diabetes is 25.5 (5.5). When last measured, the mean BMI was 33.8 (6.3) kg/m2 and 4 m walk speed was 0.86 (0.22) m/sec. Of 1060 who were tested, 20.6% have one apoE‐e4 allele and 1.1% have two apoE‐e4 alleles. Modified Telephone Interview for Cognitive Status (TICSm) scores ranged from 12 to 48, with mean 34.7 (4.7), with no difference between intervention groups (p = 0.66). While TICSm scores tended to be lower for older participants, many still demonstrated relatively high levels of cognitive functioning, even into the 8th decade of life (attached figure).ConclusionThe Look AHEAD Aging study holds great promise to identify factors across two decades of follow‐up that are associated with cognitive resilience in a large cohort with type 2 diabetes and overweight or obesity. Our presentation will provide data on the full cohort and cognitive battery.

Higher glucose parameters at baseline are related to hippocampal volume decline after a 2‐year multidomain lifestyle intervention to prevent cognitive decline in people at risk of developing Alzheimer’s disease: Exploratory results from the FINGER study

AbstractBackgroundLifestyle interventions for preventing cognitive decline have provided promising results in older at‐risk individuals. Two modifiable risk factors are insulin resistance and diabetes mellitus, since they’ve been associated with higher risk of cognitive decline. However, it remains unclear if healthy individuals with higher normal glucose levels are free from suffering the negative effect of pathological glucose values on brain and cognition. The Oral Glucose Tolerance Test (OGTT) is a sensitive measurement for non‐detected glucose metabolism disorders and might be related with changes in brain structure and cognition. In this study we hypothesised that changes in glucose parameters will be associated with brain structural changes.Method1.259 participants of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) were included [Table 1]. A sample of 132 participants had brain MRI scans, and 47 also underwent PiB‐PET and FDG‐PET scans. Global GMv, hippocampal volumes, WMHv and cortical thickness measurements were analysed to assess the association between brain structural changes and glucose homeostasis. AD‐signature composites were also calculated from FDG‐PET and PiB‐PET scans data for the analysis. SPSS was used for linear regression models.ResultsBaseline AUC‐OGTT, 120min‐OGTT and fasting glucose were negatively associated (p<0.05) with 2‐year change in hippocampal volume [Table 2]. A negative association was also found between baseline AUC and change in FDG‐PET‐AD‐composite (p = 0.028). Three negative associations were additionally found at baseline between AUC‐OGTT and cortical thickness (p = 0.015), fasting glucose and total GMv (p = 0.015), and HbA1c and FDG‐PET‐AD‐composite (p = 0.033) [Table 3]. Interestingly, a positive association was found in a smaller sample (n = 38) between the TyG index and change in PiB‐PET‐AD‐composite (0.014). No associations were found between glucose parameters and the remaining imaging data.ConclusionIn a sample of participants at risk for dementia, baseline higher measures of peripheral glucose metabolism such as AUC‐OGTT and 120min‐OGTT glucose were related to greater decline in hippocampal volume, irrespective of the randomisation group and after considering abnormal glucose metabolism. These results suggest that glucose homeostasis might have an impact on brain structure in participants with higher normal glucose parameters measurements.

Grassroots Approaches to Community‐Based Representative Recruitment in a Large Multidomain Lifestyle Intervention Trial

AbstractBackgroundU.S. POINTER is a randomized, controlled, multi‐domain 2‐year clinical trial in 2000 older Americans to slow cognitive decline via culturally‐appropriate healthy lifestyle interventions. Participant diversity is essential, with targeted enrollment of 50% women and 23% enrollees from communities of color (reflecting the U.S. population in the 2016 Census). Other recruitment priorities include individuals with lower traditional educational attainment, older age within our eligibility range (75‐79 years old), and rural residence. This diversification aims to (1) better represent our communities particularly affected by ADRD, and (2) help ensure that this intervention can be successful across broad cultural differences for long‐term implementation.MethodU.S. POINTER developed and deployed a community‐based recruitment strategy via a centrally‐coordinated grassroots outreach team at each site. The strategy includes evidence‐based and innovative community engagement tactics and is a multi‐faceted, agile approach that accounts for variations in: demographics across sites’ respective communities; levels of home institution‐community connectedness/integration; and outreach experience across team members. Tactics include: employing a multi‐tiered outreach framework that leverages existing community networks in order to augment team outreach capacity and ensure continuous community engagement; innovating approval procedures with central IRB to reduce barriers to producing timely outreach materials as needed; and standardizing onboarding for new team members across experience levels.ResultThe POINTER grassroots recruitment strategy has accounted for 22% of the trial’s overall enrollment. As of Jan 18, 2023, POINTER has enrolled 1879 participants, 29% of whom are from communities of color, 30% are men, 30% do not hold college degrees, and 13% are over 75 years old. Lessons learned include navigating local institutional reputations, retaining consistent team personnel for long‐term relationship building, setting trajectories for mutually‐beneficial long‐term community investment, and employing a formidable equity lens at all levels of staffing, outreach, and intervention design to better identify and eliminate barriers to participation, amongst others.ConclusionKey recommendations emerging from recruitment success in enrolling a diverse cohort include: approaching recruitment with long‐term vision and commitment toward community investment; leveraging existing community assets and working in partnership with respected community voices; and employing consistent, diverse, multimodal community outreach touchpoints for traction.

Impact of a multidomain lifestyle intervention on white matter integrity: the SUPERBRAIN exploratory sub-study.

In the South Korean study to prevent cognitive impairment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and home-based MI (HMI) on white matter integrity. Among 152 participants, aged 60-79 years without dementia but with ≥1 modifiable dementia risk factor, 19 FMI, 20 HMI, and 16 controls underwent brain MRI at baseline and 24 weeks. Between the intervention and control groups, we compared changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at regions-of-interest (ROI) including the cingulum cingulate gyrus (CgC), cingulum hippocampus (CgH), superior longitudinal fasciculus (SLF), as well as the uncinate fasciculus (UF). In addition, correlations between total and standard scores cognitive domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or serum brain-derived neurotrophic factor (BDNF) and changes in brain image measures were evaluated at a statistical significance level of p < 0.05 (uncorrected for multiple corrections). The FA, MD, AD, and RD at each ROI at the baseline were not different among groups after Bonferroni correction. In the statistical analysis using two-way repeated measures ANOVA, any significant difference in longitudinal changes in the FA, MD, AD, and RD was not revealed. The statistical analysis, among the significant regions in paired t-test of the intervention group, compared with the control group, the FMI, HMI, and intervention group yielded significantly more beneficial effects on the AD of the CgC. In addition, longitudinal AD changes of the left CgC correlated with the BDNF changes (r = 0.280, p = 0.048). In this study, enhanced cognitive reserve after the multidomain lifestyle intervention could be revealed by changes in brain imaging for white matter integrity.

LETHE: A Digital Intervention for Cognitive Decline.

Dementia is the main cause of disability in elderly populations. It has been shown that the risk factors of dementia are a mixture of pathological, lifestyle and heritable factors, with some of those being provably modifiable. Early diagnosis of dementia and approaches to slow down its evolution are currently the most prominent management methodologies due to lack of a cure. For that reason, a plethora of home-based assistive technologies for dementia management do exist, with most of them focusing on the improvement of memory and thinking. The main objective of LETHE is prevention in the whole spectrum of cognitive decline in the elderly population at risk reaching from asymptomatic to subjective or mild cognitive impairment to prodromal Dementia. LETHE will provide a Big Data collection platform and analysis system, that will allow prevention, personalized risk detection and intervention on cognitive decline. Through the subsequent 2-year clinical trial, the LETHE system, as well as the respective knowledge gained will be evaluated and validated. The scope of the current paper is to introduce the LETHE study and its respective novel platform as a holistic approach to multidomain lifestyle intervention trial studies. The present work depicts the architectural perspective and extends beyond state-of-the-art guidelines and approaches to health management systems and cloud platform development.Clinical Relevance - Patient Management Systems as well as lifestyle management platforms have significant clinical relevance as they allow for remote and continuous monitoring of patients' health status. LETHE aims to improve patient outcomes by providing predictive models for cognitive decline and patient adherence to the multimodal lifestyle intervention, enabling prompt and appropriate medical decisions.

Protocol development to study launch: The Australian‐multidomain approach to reduce dementia risk by protecting brain health With lifestyle intervention (AU‐ARROW) study

AbstractBackgroundThe Finnish Geriatric Intervention Study (FINGER) reported that a multidomain lifestyle intervention could provide an effective and accessible means of protecting against age‐related cognitive decline and dementia. This led to the global dementia risk reduction initiative: World‐Wide FINGERS (WW‐FINGERS). As part of WW‐FINGERS, the AU‐ARROW study mirrors aspects of FINGER, as well as the U.S. study (US‐POINTER, also part of WW‐FINGERS), while allowing for Australian cultural and dietary adaptations.MethodAU‐ARROW is a randomised, single‐blind, 2‐year clinical trial, recruiting 600 participants aged 60‐79, who satisfy study‐specific eligibility inclusion/exclusion criteria. Participants will be recruited at (a) Macquarie University, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and randomised into either the multimodal lifestyle intervention (ML) group or the Health Education and Coaching (HC) group. The ML group will engage in a) aerobic exercise, resistance training and stretching facilitated by local gym memberships, b) monthly telehealth diet monitoring and advice, to encourage MIND diet adherence whilst aligning with Australian Dietary Guidelines, c) online BrainHQ cognitive training sessions, and d) medical monitoring and health education sessions. The HC group will receive occasional health education sessions. All participants receive heart rate trackers, 6‐monthly blood tests, regular health monitoring and clinician advice.ResultAU‐ARROW’s primary outcome measure involves assessment of changes in a global composite cognitive score, measured using neurocognitive tests as in US‐POINTER. Further neurocognitive tests, lifestyle questionnaires, physical function tests, diet and sleep monitoring will determine specific contributions of the various lifestyle changes. Extra value will emanate from Alzheimer’s disease (AD) biomarker analysis of blood and urine samples collected yearly, as well as AD Aβ amyloid‐specific ligand‐PET imaging, brain MRI and retinal biomarker tests at 0 and 24 months. The final AU‐ARROW protocol design and methods will be presented. Initial recruitment data may also be presented.ConclusionThe finalised AU‐ARROW protocol is expected to facilitate study completion and maximise data sources, and allow a) development of an evidence‐based innovative treatment plan to reduce cognitive decline and dementia risk, b) effective transfer of research outcomes into Australian health policy, and c) validation of emerging blood and retinal diagnostic biomarkers in preclinical screening.