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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]

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]

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]

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]

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]

Diet is an important modifiable lifestyle factor related to dementia risk. Yet, the role of midlife dietary changes is unclear. The goal is to investigate whether midlife healthy dietary changes are associated with late-life dementia risk. Data were collected within the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) population-based cohort study (n = 2000) (mean baseline age = 56 years). Participants returned for two late-life re-examinations (mean age = 70 and 78 years). Self-reported midlife diet was measured in a sub-sample (n = 341) (mean total follow-up = 16.8 years). Changes in specific dietary components (fats, vegetables, sugar, salt) were measured in midlife. Dementia diagnoses were ascertained with detailed examinations. Analyses adjusted for potential confounders. Total midlife healthy dietary changes (improving quality of fats, increasing vegetables, decreasing sugar and salt) were associated with a reduced risk of dementia (fully adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) = 0.20–0.85). In contrast, when each factor was assessed individually, associations were not significant. This study is the first to show that beneficial midlife dietary changes are associated with a reduced dementia risk later in life. The results highlight the importance of targeting dietary patterns, where various food items may have synergistic effects. [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-AD mini 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., (© 2024. The Author(s).)

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., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

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-AD mini 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 (β Lifestyle×Time  = 1.11, P = 0.038; β Lifestyle+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., (© 2024. The Author(s).)

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., Competing Interests: KA is an advisor to Staying Sharp. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stephen, Barbera, Peters, Ee, Zheng, Lehtisalo, Kulmala, Håkansson, Chowdhary, Dua, Solomon, Anstey and Kivipelto.)