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Background: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them. Method: A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records. Results: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake. Conclusion: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density. Trial registration: ClinicalTrials.gov NCT03249688, 2017–07-08. [ABSTRACT FROM AUTHOR]

Background: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them. Method: A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records. Results: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake. Conclusion: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density. Trial registration: ClinicalTrials.gov NCT03249688, 2017–07-08. [ABSTRACT FROM AUTHOR]

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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). Highlights: 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. [ABSTRACT FROM AUTHOR]

Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. Methods: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. Trial registration: ClinicalTrials.gov NCT03249688. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Combining 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. Methods: MET-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. Conclusion: MET-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 registration: ClinicalTrials.gov (NCT05109169). [ABSTRACT FROM AUTHOR]

Background: Lifestyle 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. Method: 1.259 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. Results: Baseline 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. Conclusion: In 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. [ABSTRACT FROM AUTHOR]

Introduction: Mechanisms underlying the positive association between occupational mental demands and late-life cognition are poorly understood. The objective of this study was to assess whether the association between occupational complexity and cognition is related to and moderated by brain integrity in individuals at risk for dementia. Brain integrity was appraised throughout structural measures (magnetic resonance imaging, MRI) and amyloid accumulation (Pittsburgh compound B (PiB)-positron emission tomography, PiB-PET). Methods: Participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) neuroimaging sample – MRI (N = 126), PiB-PET (N = 41) – were included in a post hoc cross-sectional analysis. Neuroimaging parameters comprised the Alzheimer's disease signature (ADS) cortical thickness (FreeSurfer 5.3), medial temporal atrophy (MTA), and amyloid accumulation (PiB-PET). Cognition was assessed using the neuropsychological test battery. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Linear regression models included cognition as dependent variable, and occupational complexity, measures of brain integrity, and their interaction terms as predictors. Results: Occupational complexity with data and substantive complexity were associated with better cognition (overall cognition, executive function) when adjusting for ADS and MTA (independent association). Significant interaction effects between occupational complexity and brain integrity were also found, indicating that, for some indicators of brain integrity and cognition (e.g., overall cognition, processing speed), the positive association between occupational complexity and cognition occurred only among persons with higher brain integrity (moderated association). Conclusions: Among individuals at risk for dementia, occupational complexity does not seem to contribute toward resilience against neuropathology. These exploratory findings require validation in larger populations. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to estimate the potential cost‐effectiveness of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) program. Methods: A life‐time Markov model with societal perspective, simulating a cohort of people at risk of dementia reflecting usual care and the FINGER program. Results: Costs were 1,653,275 and 1,635,346 SEK and quality‐adjusted life years (QALYs) were 8.636 and 8.679 for usual care and the FINGER program, respectively, resulting in savings of 16,928 SEK (2023 US$) and 0.043 QALY gains per person, supporting extended dominance for the FINGER program. A total of 1623 dementia cases were avoided with 0.17 fewer person‐years living with dementia. The sensitivity analysis confirmed the conclusions in most scenarios. Discussion: The model provides support that programs like FINGER have the potential to be cost‐effective in preventing dementia. Results at the individual level are rather modest, but the societal benefits can be substantial because of the large potential target population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Naloxone as emergency treatment for opioid overdosing can be administered via several routes. However, the available administration methods are invasive or may be associated with incomplete or slow naloxone absorption. We evaluated pharmacokinetics and local tolerance of naloxone ocular drops in healthy beagle dogs. Naloxone administration as eye drops produced fast absorption with time to maximum plasma concentration (tmax) achieved in 14 to 28 min, high plasma exposure (Cmax 10.3 ng/mL to 12.7 ng/mL), and good bioavailability (41% to 56%). No signs of ocular irritability were observed in the scored ocular tolerability parameters, and the reactions of dogs suggesting immediate ocular discomfort after the dosing were sporadic and short lasting. Slight and transient increase in the intraocular pressure and transient decrease in the tear production were recorded. The results suggest that eye drops may provide a fast and an effective non-invasive route for naloxone administration to reverse opioid overdosing, and clinical studies in the human are warranted. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) has beneficial effects on older age physical functioning, but longitudinal studies with follow-ups extending up to decades are few. We investigated the association between leisure-time PA (LTPA) and occupational PA (OPA) from early to late adulthood in relation to later life performance-based physical functioning. Methods: The study involved 1260 people aged 60 to 79 years who took part in assessments of physical functioning (Short Physical Performance Battery [SPPB] test, 10-m maximal walking test, and grip strength test). Participants' data on earlier life LTPA/OPA (age range 25 to 74 years) were received from the previous studies (average follow-up 13.4 years). Logistic, linear, and censored regression models were used to assess the associations between LTPA/OPA earlier in life and subsequent physical functioning. Results: A high level of LTPA earlier in life was associated with a lower risk of having difficulties on the SPPB test (odds ratio [OR]: 0.37; 95% confidence interval [CI], 0.24-0.58) and especially on the chair rise test (OR: 0.42; 95% CI, 0.27-0.64) in old age. Heavy manual work predicted difficulties on SPPB (OR: 1.91; 95% CI, 1.22-2.98) and the chair rise test (OR: 1.75; 95% CI, 1.14-2.69) and poorer walking speed (β= .10, P = .005). Conclusions: This study highlights the importance of LTPA on later life functioning, but also indicates the inverse effects that may be caused by heavy manual work. [ABSTRACT FROM AUTHOR]

Background: Finnish 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. Method: The 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. Result: The 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. Conclusion: Six 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. [ABSTRACT FROM AUTHOR]

Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a 2‐year multidomain lifestyle intervention to prevent cognitive decline. We have earlier reported that lifestyles improved during the original intervention period, both as participation in the intervention during the 2‐year period and adherence to goals of the intervention. Our aim was to study how these lifestyle changes are maintained during the long‐term period following the active intervention. Method: Total of 1259 older adults aged 60‐77 participated in the FINGER trial and were randomized into multidomain intervention (n = 631) or control groups (n = 628). A multidomain lifestyle index (MHLI) was calculated based on self‐reported questionnaire using 12 items to obtain a total score representing all four domains of the intervention: diet, physical activity, cognitive activity, and cardiovascular risk factors (range 0 to 24). The questionnaire was repeated annually during the active intervention period and three times thereafter, total of 6 assessments over 11 years. Mixed‐effects regression analyses were executed. Result: Among the 1259 participants 1117 (88%) completed the original study period and preliminary data were available for 484 at the 11‐year visit (38% of the original cohort; 58% of those invited). Mean MHLI was 13.5 at baseline and lower MHLI score predicted drop‐out during the post‐intervention follow‐up. In the intervention group the MHLI improved during the active period and maintained higher up to 7 years (within‐group change and difference compared with the control group p <0.05 for each year) but no longer at the 11‐year follow‐up. There were no changes in the control group. Age, education, sex, and baseline cognition were all associated with MHLI but did not modify the intervention effect. Conclusion: A multidomain lifestyle intervention among at‐risk older adults can have an impact on multidomain healthy lifestyle up to 5 years after the active intervention. Interestingly, average lifestyle did not decrease in the control group either, which would have been expected due to aging. Ongoing detailed analyses will show if this is explained by selective dropout or if participation in the control group may have had some benefits from the participation as well. [ABSTRACT FROM AUTHOR]

Background: Dementia prevention is a global public health priority. The FINGER multimodal lifestyle intervention is the only intervention model so far that has demonstrated significant cognitive and other health benefits in at‐risk older adults. LETHE proposes a new multimodal precision prevention approach where FINGER intervention is complemented with digital tools to optimize intervention delivery, personalize recommendations based on individual risk profile, and support risk factor self‐management. The multinational 2‐year randomized controlled LETHE pilot trial aims to test the feasibility of a digitally supported, adapted FINGER intervention among older adults at risk of cognitive decline and dementia. Method: A total of 160 individuals aged 60‐77 years and with risk factors for dementia but no substantial cognitive impairment are recruited at four sites (Austria, Finland, Italy, Sweden; N = 40 per country). Digital readiness and experience with smart devices are required. Participants are randomized 1:1 to 1) structured multimodal lifestyle intervention (dietary guidance, exercise, cognitive training, vascular/metabolic risk management, social stimulation, sleep/stress management) where in‐person individual and group‐based activities are supported with the LETHE smartphone app developed in the project; or 2) self‐guided lifestyle intervention (regular health advice and access to a simplified app with no personalized/interactive content). Both groups wear a smartwatch to gather passive data (e.g., activity, sleep). Primary outcomes are retention rate, adherence to intervention and engagement with the app, and change in dementia risk based on validated risk scores (CAIDE, LIBRA). Secondary outcomes are lifestyle changes and changes in cognition, stress‐related symptoms, sleep, health‐related quality of life, and health literacy. Participant experiences will also be explored. The LETHE Advisory Board (members of the public) provided feedback on the trial protocol. Result: Trial is registered at ClinicalTrials.gov (NCT05565170), and ethical approval has been obtained in each country. Recruitment started in September 2022 and will be completed in Spring 2023. Updates and results on study progress will be presented. Conclusion: LETHE pilot trial will inform about the feasibility of technological solutions and a digitally assisted lifestyle program to support brain health among older adults. If proved to induce sustained behavioural changes, digital tools could offer potential for large‐scale, cost‐effective dementia prevention programs. [ABSTRACT FROM AUTHOR]

Background: The 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. Method: The 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). Result: New 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). Conclusion: Longer‐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. [ABSTRACT FROM AUTHOR]

Background: A comprehensive genetic risk score (GRS) for Alzheimer's disease (AD‐GRS) was recently developed based on 83 genome‐wide significant variants (Bellenguez et al. Nat Genet. 2022), excluding APOE. This study investigated AD‐GRS and APOE4 in relation to neuroimaging biomarkers in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Method: FINGER included at‐risk individuals without dementia from the general population, aged 60‐77 years. Participants were randomized to either 2‐year multidomain lifestyle‐based intervention or regular health advice. At baseline, 132 participants underwent MRI scans, of which 48 also underwent PET scans (PiB/FDG). Two years later, 112 and 39 repeated their scans, respectively. MRI measures included hippocampus, total gray matter and white matter lesion volumes, and cortical thickness. Composite indices were calculated for PiB and FDG uptake values. We report preliminary results from linear regressions (standardized β‐coefficients, p‐values). Result: At baseline, higher AD‐GRS tended to relate to lower hippocampus volume (β = ‐0.15, p = 0.07) and FDG‐PET index (β = ‐0.23, p = 0.08); this remained after APOE adjustment. APOE4 was associated with lower hippocampus volume (β = ‐0.27, p = 0.001) and higher PiB‐PET index (β = 0.48, p = 0.001). Overall, AD‐GRS was not related to the 2‐year change in neuroimaging measures, while APOE4 was related to decreasing hippocampus (β = ‐0.27, p = 0.01) and total gray matter (β = ‐0.25, p = 0.01) volumes, and cortical thickness (β = ‐0.28, p = 0.003). There were no significant interactions of AD‐GRS or APOE4 with randomization group in relation to neuroimaging changes. However, in analyses stratified by AD‐GRS (below vs above median), there was less PIB index increase in intervention vs control in the higher AD‐GRS group (β = ‐0.60, p = 0.03); no intervention control‐difference was found in the lower AD‐GRS group (β = 0.04, p = 0.86). In analyses stratified by APOE4, PIB index tended to increase less in intervention vs control in non‐carriers (β = ‐0.38, p = 0.078), with no intervention‐control difference in carriers (β = 0.05, p = 0.89). Conclusion: Unlike APOE4, AD‐GRS was not related to 2‐year change in AD‐related neuroimaging measures. AD‐GRS and APOE4 may also have very different impact on potential intervention effects on amyloid, i.e. less accumulation in the higher‐risk group (AD‐GRS) vs lower‐risk group (APOE). However, these exploratory findings need to be verified in larger studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to describe how the first phase of the coronavirus disease 2019 (COVID-19) pandemic affected older persons from the general Finnish population who are at risk of developing or have cognitive impairment, specifically, to describe whether participants experienced a change in risk factors that are relevant for the prevention of cognitive decline including diet, physical activity, access to medical care, socially and cognitively stimulating activities, and emotional health and well-being. Method: A postal survey was sent in June 2020 to 859 participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), an ongoing longitudinal study. The survey was developed to assess the effect of the COVID-19 pandemic and related infection-control measures on daily life, specifically commitment to distancing measures, access to health care and social services, daily activities, and changes in cognitive and social activities. Results: By September 2020, 613 (71%) participants responded (mean age = 77.7 years, 32% lived alone, and 80% had at least one chronic condition). Three quarters adopted some distancing practices during the first months of the pandemic. Older participants were more likely to practice total isolation than younger ones (29 vs. 19%; p = 0.003). Non-acute health-care visits were canceled for 5% of the participants who needed appointments, but cancellations in dental health care (43%), home aid (30%), and rehabilitative services (53%) were more common. Pandemic-related changes were reported in social engagements, for example, less contact with friends (55%) and family (31%), or less frequent attendance in cultural events (38%) or associations (25%), although remote contact with others increased for 40%. Feelings of loneliness increased for 21%, particularly those who were older (p = 0.023) or living alone (p < 0.001). Physical activity reduced for 34%, but dietary habits remained stable or improved. Pandemic-related changes in lifestyle and activities were more evident among those living alone. Conclusions: Finnish older persons generally reported less negative changes in lifestyles and behaviors during the pandemic than expected. Older people and those living alone seemed more susceptible to negative changes. It is important to compare how coping strategies may compare with other European countries to identify factors that may help older individuals to maintain healthy lifestyles during future waves of COVID-19. [ABSTRACT FROM AUTHOR]

Background frailty syndrome is common amongst older people. Low physical activity is part of frailty, but long-term prospective studies investigating leisure-time physical activity (LTPA) during the life course as a predictor of frailty are still warranted. The aim of this study is to investigate whether earlier life LTPA predicts frailty in older age. Methods the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older adults (aged 60–77 years) from the general population who were at increased risk of cognitive decline. Frailty was assessed for 1,137 participants at a baseline visit using a modified version of Fried's phenotype, including five criteria: weight loss, exhaustion, weakness, slowness and low physical activity. Self-reported data on earlier life LTPA were available from previous population-based studies (average follow-up time 13.6 years). A binomial logistic regression analysis was used to investigate the association between earlier life LTPA and pre-frailty/frailty in older age. Results the prevalence of frailty and pre-frailty was 0.8% and 27.3%, respectively. In the analyses, pre-frail and frail groups were combined. People who had been physically very active (OR 0.37, 95% CI 0.23–0.60) or moderately active (OR 0.45, 95% CI 0.32–0.65) earlier in life had lower odds of becoming pre-frail/frail than individuals who had been sedentary. Conclusions frailty was rare in this relatively healthy study population, but almost a third of the participants were pre-frail. Earlier life LTPA was associated with lower levels of pre-frailty/frailty. The results highlight the importance of physical activity when aiming to promote healthy old age. [ABSTRACT FROM AUTHOR]

Background: Finnish 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. Method: The 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. Result: Altogether 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. Conclusion: Multidomain 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. [ABSTRACT FROM AUTHOR]

Background: Multimodal lifestyle interventions have proven successful with at‐risk populations; however, little is known of the interventions effect on patients with prodromal Alzheimer's disease. Even less is known of feasibility and adherence to dietary recommendations within the population. Method: A 6‐month pilot trial was conducted with 93 participants randomized into three intervention arms. Two groups received physical exercise, cognitive training, nutritional guidance, monitoring and management of vascular and metabolic risk factors, and social stimulation, with one group receiving a medical food product. The third group was a self‐guided control group. Intake of individual macro‐ and micronutrients were analyzed from 3‐day food records. Adherence to recommendations assessed from food frequency questionnaires and by using a healthy diet index. Result: For macro‐ and micronutrient intake there were no differences at the end of the intervention and intake was in line with other national food surveys. The group who received intervention and medical food product has significantly better healthy diet index score compared to the other groups. Conclusion: There were few longitudinal significant differences on macro‐ and micronutrient intake, however, dietary intake improved significantly in itself when the intervention was complemented with a medical food product. [ABSTRACT FROM AUTHOR]

Background: This exploratory study investigated associations between physical function and 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). Method: FINGER targeted 60–77‐year‐old general population at‐risk and without dementia or substantial cognitive impairment. Measures of physical function (activities of daily living (ADL), hand grip strength, physical performance, Fried's frailty phenotype index and self‐rated health) from baseline and 2‐year visits were used. Baseline neuroimaging measures, MRI (hippocampus, total gray matter volumes, Alzheimer's disease (AD) signature cortical thickness) were available for 115‐132 participants and PiB‐PET (composite score) for 44‐48 participants. Linear and logistic regressions were used to test the cross‐sectional associations and the impact of baseline imaging measures on changes in physical function. Models were adjusted for site, sex and education. Result: Cross‐sectionally, higher ADL were associated with higher hippocampus volume (β = 0.18 p = 0.048), total gray matter volume (β = 0.15 p = 0.005) and AD signature cortical thickness (β = 0.25 p = 0.006) while stronger hand grip and was associated with higher total gray matter volume (β = 0.20 p = 0.041) significantly. Baseline imaging measures were associated with changes in physical function: higher baseline hippocampus volume was associated with maintenance/improvement in the ADL (OR = 0.56 p = 0.039) while lower hippocampus at baseline predicted poorer physical performance over time (OR = 1.66 p = 0.036). Conclusion: Higher brain integrity is associated with better physical function while lower baseline brain integrity predicts poorer physical function over time. [ABSTRACT FROM AUTHOR]

Background: Dementia risk scores could be instrumental in the implementation of multidomain lifestyle interventions for dementia prevention. However, as relatively new tools, their performance requires further validation. Given the extensive overlap between risk factors for dementia and cardiovascular disease (CVD), multidomain interventions usually have an important vascular component and better‐established cardiovascular risk scores could become useful in this context. More evidence is needed on their ability to predict the risk of cognitive decline and dementia. SCORE/SCORE‐Older People (OP) are the official tools of the European Society of Cardiology to estimate the 10‐year CVD‐mortality risk. In this study, we investigated the association between SCORE/SCORE‐OP and cognitive function within FINGER, the first large trial showing the efficacy of a multidomain lifestyle‐ and vascular‐based intervention in preventing cognitive decline. Method: SCORE (age<65) and SCORE‐OP (age≥65) were calculated in the population of the 2‐year FINGER trial (N = 1236, baseline and 24 months). The cognitive outcomes (baseline, 12 and 24 months) were the overall z‐score from a Neuropsychological Test Battery (NTB, 14 tests, primary outcome) and the z‐scores of the NTB cognitive domains (Memory, Executive Function, and Processing Speed, secondary outcomes). The associations between (i) SCORE/SCORE‐OP and cognition, (ii) SCORE/SCORE‐OP and changes in cognition, and (iii) changes SCORE‐OP and changes in cognition were assessed using linear mixed‐models repeated‐measures with maximum likelihood estimation. Result: Higher baseline risk of CVD‐mortality, estimated with SCORE/SCORE‐OP, was significantly and consistently associated with worse cognition, (NTB total composite: Estimate = ‐0.036; CI: ‐0.042 to ‐0.030; P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001) and yearly lower improvement in cognitive performance (NTB total composite: Estimate = ‐0.009, CI: ‐0.011 to ‐0.007, P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001). 2‐year change in SCORE‐OP was not significantly associated with changes in cognition during the FINGER study period. Conclusion: SCORE/SCORE‐OP could be useful in predicting the risk of cognitive decline in a trial aimed at improving lifestyle and vascular‐related risk factors of dementia. However, more evidence is needed on their efficacy in predicting dementia risk and the response to multidomain lifestyle‐ and vascular‐ based interventions. Future studies on other well‐established and easy‐access cardiovascular risk scores could also provide relevant findings. [ABSTRACT FROM AUTHOR]

Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable. Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2‐year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3‐year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega‐3 supplement or placebo. Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega‐3 supplement, and lowest for unsupervised computer‐based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms. Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face‐to‐face contacts, and taking into account participant characteristics may increase adherence in future trials. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effect of a 2‐year multidomain lifestyle intervention on daily functioning of older people. DESIGN: A 2‐year randomized controlled trial (ClinicalTrials.gov, NCT01041989). SETTING: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability. PARTICIPANTS: A total of 1260 older adults, with a mean age of 69 years at the baseline, who were at risk of cognitive decline. INTERVENTION: A multidomain intervention, including simultaneous physical activity intervention, nutritional counseling, vascular risk monitoring and management, and cognitive training and social activity. MEASUREMENTS: The ability to perform daily activities (activities of daily living [ADLs] and instrumental ADLs) and physical performance (Short Physical Performance Battery). RESULTS: The mean baseline ADL score was 18.1 (SD = 2.6) points; the scale ranges from 17 (no difficulties) to 85 (total ADL dependence). During the 2‐year intervention, the ADL disability score slightly increased in the control group, while in the intervention group, it remained relatively stable. Based on the latent growth curve model, the difference in the change between the intervention and control groups was −0.95 (95% confidence interval [CI] = −1.61 to −0.28) after 1 year and −1.20 (95% CI = −2.02 to −0.38) after 2 years. In terms of physical performance, the intervention group had a slightly higher probability of improvement (from score 3 to score 4; P = .041) and a lower probability of decline (from score 3 to scores 0‐2; P = .043) for chair rise compared to the control group. CONCLUSION: A 2‐year lifestyle intervention was able to maintain the daily functioning of the at‐risk older population. The clinical significance of these results in this fairly well‐functioning population remains uncertain, but the study results hold promise that healthy eating, exercise, and cognitive and social activity may have favorable effects on functional independence in older people. [ABSTRACT FROM AUTHOR]

Background: global population aging and forecasted trends of modifiable risk factors for dementia and Alzheimer's disease (AD) make prevention of these conditions an urgent priority. The World‐Wide FINGERS (WW‐FINGERS) global network of multidomain trials for dementia risk reduction and prevention is at the forefront of efforts to find effective and sustainable solutions for diverse population. The COVID‐19 pandemic has caused changes in the mental and physical health of older adults, which can influence dementia risk and prevention opportunities. Methods: The WW‐FINGERS‐SARS‐CoV‐2 survey was developed to assess direct and indirect effects of the COVID‐19 pandemic in older adults. The questionnaire measures changes in lifestyle factors (e.g., diet, physical activity), management of chronic noncommunicable diseases (e.g., diabetes, hypertension), and psychosocial factors ‐including depressive symptoms, sleep disorders, social isolation‐ that are relevant to cognition. Both a pen‐and‐paper and a digital version of the survey have been developed in several languages. The digital version is supported through REDCap (Research Electronic Data Capture), which is used also for harmonized data collection. Results: 30 countries are participating in the survey. As for January 2022, data have been collected from 20 countries, with 23000+ participants. Local adaptations and piloting were done to optimize implementation in clinical‐based and population‐based settings. Participants are in the at‐risk spectrum for dementia: from normal cognition to pre‐dementia cognitive symptoms. Timing of the survey implementation varies across populations, allowing to capture short, medium and long‐term effects of the pandemic and restrictions measures. Some countries have used the survey to recruit participants in multimodal prevention trials. An updated report of the survey status and main results will be presented. Conclusion: The WW‐FINGERS‐SARS‐CoV2 survey is a joint global action of the WW‐FINGERS network which can inform better care of older adults in the context of a pandemic. The survey is also a valuable tool for pre‐screening of participants for prevention trials, and results can inform adaptions to ensure successful recruitment and adherence in forthcoming multidomain trials for dementia prevention in older adults. [ABSTRACT FROM AUTHOR]

Background: The positive results of the landmark Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability ‐ FINGER, 2‐year lifestyle‐based intervention and up to 11 years follow‐up ‐, followed by the Multimodal Preventive Trial for Alzheimer's Disease ‐ MIND‐ADmini, 6‐month lifestyle‐based + medical food, up to 1‐year follow‐up ‐, provided the foundation to advance multimodal trials for dementia prevention within the World‐Wide FINGERS (WW‐FINGERS) network. Innovative trials should involve tailored approaches, combining non‐pharmacological and pharmacological interventions, to optimize interventions´ adherence and efficacy. Method: Through a drug‐repurposing approach, metformin has been identified as a potential disease‐modifying drug for Alzheimer´s disease (AD) and dementia in subjects without type‐2 diabetes, with a robust pharmacological safety profile. Analysis on genetic factors (APOE, AD Polygenic‐Risk‐Score) and intervention effects from the FINGER trial indicated clear cognitive benefits in participants with genetic susceptibility to AD and dementia. Feasibility data (adherence, retention rate) from FINGER and MIND‐ADmini, including extended follow‐up data analysis, have informed the upgrade of the lifestyle‐based intervention implemented in MET‐FINGER. Result: An update on the trial status will be presented. The MET‐FINGER phase‐IIb trial population includes an APOE‐enriched population of 600 subjects aged 60‐79 years, with increased risk of dementia due to modifiable risk factors. Participants are recruited in three countries (Finland, Sweden, United Kingdom), and randomized to either an upgraded FINGER lifestyle‐based intervention, alone or in association with metformin (up to 2000mg/day), or the reference group, which follows a self‐guided lifestyle program. MET‐FINGER trial outcomes are harmonized with WW‐FINGERS guidelines, and include cognition and biological measures to detect disease‐modifying effects of metformin. Conclusion: MET‐FINGER pioneering trial leverages and expands on successful experiences from WW‐FINGERS core trials, embodying the next generation of clinical trials for dementia risk reduction and prevention within the framework of precision prevention. The MET‐FINGER trial protocol is the first in its kind, providing the basis for forthcoming trials combining non‐pharmacological and pharmacological interventions. MET‐FINGER results can inform AD drug development and reduce intervention failure rate of new trials. [ABSTRACT FROM AUTHOR]

Background: Older adults have a higher risk of Alzheimer´s disease (AD) and dementia. In terms of morbidity and mortality, they also represent the group most severely affected by the SARS‐CoV‐2 (COVID‐19) pandemic. Since February 2020, the Swedish government recommended different general measures limiting mobility and social contact, to contain the spread of infection. Pandemic‐related changes in lifestyle and access to healthcare could have a negative impact on modifiable factors for AD and dementia. Methods: A digital survey was distributed to the general population (multiple distribution channels, voluntary participation) during the last waves of the COVID‐19 pandemic in Sweden (May/2021 – December/2021). Participants were people aged 60+ years, free of dementia, and living in Sweden. The survey aimed to measure changes in lifestyle (e.g., diet, physical activity), care of vascular/metabolic risk factors (e.g., diabetes, hypertension), as well as psychosocial factors (e.g., depressive symptoms, sleep quality, social isolation) relevant for AD and dementia. The survey is part of the World‐Wide‐FINGERS‐SARS‐CoV‐2 initiative. Results: 6,918 participants completed the survey, mean age was 67.9 (5.11 SD), 58% were female, 71.6% were from urban areas. Preliminary results showed that, during the pandemic, 27% of participants decreased their physical activity, 26.3% increased intake of unhealthy snacks, 25.7% experienced increased sleep problems. Also, 58.7% had less contact with family, 40.4% experienced loneliness, 24.7% experienced worsening of memory, and 26.8% rated their health worse than before the pandemic. On the other hand, the reported increase in consumption of vegetables and fruits was 14.1% and 15.7%, respectively, and 65.2% of people had increased the use of digital services to keep in contact with family and friends. Also, 2.6% of participants decreased smoking, and 11.2% reduced their alcohol consumption. The occurrence of chronic vascular and metabolic diseases and related disruption in access to healthcare is presented in Table 1. Conclusion: The COVID‐19 pandemic has had an effect on modifiable factors for AD and dementia in Swedish older adults. These changes can affect future AD/dementia occurrence and should be addressed in forthcoming interventions for AD/dementia risk reduction and prevention. The survey can also be used for pre‐screening participants for prevention trials. [ABSTRACT FROM AUTHOR]

Advancing age increases the risk for diseases and health concerns like cognitive decline, constituting a major public health challenge. Lifestyle, especially healthy diet, affects many risk factors related to chronic diseases, and thus lifestyle interventions among older adults may be beneficial in promoting successful ageing. We completed a randomised 2-year multi-domain lifestyle intervention trial aiming at prevention of cognitive decline among 631 participants in the intervention and 629 in the control group, aged 60-77 years at baseline. Dietary counselling was one of the intervention domains together with strength exercise, cognitive training and management of CVD risk factors. The aim of this paper was to describe success of the intervention -- that is, how an intervention based on national dietary recommendations affected dietary habits as a part of multi-intervention. Composite dietary intervention adherence score comprising nine distinct goals (range 0--9 points from none to achieving all goals) was 5·0 at baseline, and increased in the intervention group after the 1st (P<0⋅001) and 2nd (P =0⋅005) year. The difference in change compared with the control group was significant at both years (P <0⋅001 and P=0⋅018). Intake of several vitamins and minerals decreased in the control group but remained unchanged or increased in the intervention group during the 2 years. Well-targeted dietary counselling may prevent age-related decline in diet quality and help in preventing cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies, but these observations are limited by lack of data on the exact timing of diabetes onset. We investigated diabetes, dysglycaemia, and cognition in the Finnish Diabetes Prevention Study, in which the timing and duration of diabetes are well documented.Methods: The Finnish Diabetes Prevention Study comprised middle-aged, overweight participants with impaired glucose tolerance but no diabetes at baseline (n = 522), randomized to lifestyle intervention or a control group. After an intervention period (mean duration 4 years) and follow-up (additional 9 years), cognitive assessment with the CERAD test battery and Trail Making Test A (TMT) was executed twice within a 2-year interval. Of the 364 (70%) participants with cognitive assessments, 171 (47%) had developed diabetes.Results: Cognitive function did not differ between those who developed diabetes and those who did not. Lower mean 2-h glucose at an oral glucose tolerance test (OGTT) and HbA1C during the intervention period predicted better performance in the TMT (p = 0.012 and 0.024, respectively). Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessments (p = 0.001) whereas those with long duration of diabetes did not (p = 0.844).Conclusions: Better glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9 years later in this secondary analysis of the Finnish Diabetes Prevention Study population. In addition, learning effects in cognitive testing were not evident in people with long diabetes duration. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Given the complex and multi‐factorial aetiology of dementia, preventive interventions targeting several risk‐factors simultaneously and tailored on specific risk‐profiles are likely to be most beneficial. To date, trials testing lifestyle‐ and vascular‐based multidomain interventions for dementia and cognitive decline prevention have shown inconsistent results. In particular, achieving sufficient level of intervention intensity, accurately assessing adherence, and identifying the optimal target population have been highlighted among the key challenges. Within FINGER, the first large trial showing the efficacy of a multidomain intervention in preventing cognitive decline, we aimed to develop a Healthy Lifestyle Index (HLI) as a potential easy‐access indicator of adherence, and to assess its association with cognition. Method: The HLI (score 0‐24) was developed based on a brief set of self‐reported questions collected at baseline, 12, and 24 months within the FINGER trial (N=1260) and across four lifestyle components: physical activity, diet, smoking and alcohol, and social and cognitive activity. The FINGER cognitive outcomes were the overall z‐score from a Neuropsychological Test Battery (NTB, 14 tests, primary outcome) and the z‐scores of the NTB cognitive domains (secondary outcomes). Linear mixed‐models repeated‐measures with maximum likelihood estimation were used to assess the effect of the intervention on change in the HLI and associations between HLI and cognition over the 2‐year study period. Result: The intervention led to an increase in HLI (P<0.001). At baseline, the HLI was directly associated with the overall NTB z‐score (b=0.024; 95% CI: 0.014‐0.033; P<0.001) and individual cognitive domains. Baseline HLI was significantly associated with 2‐year changes in the NTB z‐score (0.006; 95% CI: 0.003‐0.010; P<0.001), as well as the memory domain. Changes in HLI were not significantly associated with 2‐year changes in cognitive outcomes. Conclusion: The FINGER HLI may potentially help measure and monitor adherence to multidomain interventions aimed at prevention of cognitive decline. Being developed as an easy‐access tool, its application could be especially relevant for those settings where more complex assessments are not feasible, such as implementation trials in clinical practice, and primary care in particular. More evidence is needed to determine its efficacy in predicting response to such interventions. [ABSTRACT FROM AUTHOR]

Background: Finnish 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. During the post‐intervention follow‐up, COVID19 pandemic emerged resulting in lockdown and reduced services. Our aim is to investigate how lifestyle and behavior changes during the pandemic are related to lifestyle earlier in the study. Method: The FINGER cohort included 1260 individuals aged 60‐77 years at baseline and at risk of dementia, randomized into multidomain intervention or control groups. A postal survey was sent to all eligible participants from the FINGER study in June 2020 (end of the first wave of the pandemic in Finland), on average 10 year after the baseline. 859 (68%) were still alive and eligible for the survey. Result: Total of 735 responders (85% of the eligible participants) were on average 78 years old. They were younger, had higher baseline cognition, and were more often from the former control group than non‐responders (p<0.05 for all). The intervention allocation showed no association with self‐reported lifestyle changes during the pandemic in diet, exercise, or cognitive activity. Among older participants (>78 y), the intervention group reported more increase in remote contact with friends and relatives (p=0.013) and health care (p=0.042) than the control, and also less pandemic‐related reduction in overall contact with friends (p=0.045). Among all, reductions in physical exercise were reported among those who were less physically active earlier in the study. Both increase and decrease in contact with friends and family were reported by those more cognitively active earlier in the study. They also had more increase in remote contacts. Changes in diet were positive (increase in fruit and vegetable intake), but they were not related to earlier diet. Conclusion: The FINGER participants reported only minor change in their lifestyle and behavior during the first wave of the COVID pandemic related lockdown. For physical activity, the pandemic appeared to have negative effect particularly among those with lower levels earlier, possibly adding inequalities. Intervention was related to more remote contacts, probably due to better computer literacy after the cognitive training. [ABSTRACT FROM AUTHOR]

Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER; NCT01041989), a two-year multidomain lifestyle trial. One thousand two-hundred and sixty individuals (60–77 years) at risk for dementia were randomised into a multidomain intervention (diet, exercise, cognitive training, and vascular/metabolic risk monitoring) or control group (regular health advice). Depressive symptoms (Zung scale) and cognition (modified Neuropsychological Test Battery) were evaluated at baseline, 12, and 24 months. One thousand one-hundred and twenty-five participants had baseline Zung data. Mean Zung score decreased 0.73 (SD 5.6) points in the intervention and 0.36 (5.6) points in the control group, with nonsignificant between-group difference (group × time coefficient −0.006, 95% CI −0.019 to 0.007). Overall, higher baseline Zung score was associated with less improvement in global cognition (−0.140, p = 0.005) and memory (−0.231, p = 0.005). Participants with clinically significant baseline depressive symptoms (Zung ≥ 40 points) had less intervention benefit to executive functioning (group × time × Zung −0.096, 95% CI −0.163 to −0.028). Change in Zung score was not associated with change in cognition. Clinically significant depressive symptoms warrant more attention when designing dementia-prevention interventions. [ABSTRACT FROM AUTHOR]