The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER)

Ngandu, Tiia; Lehtisalo, Jenni; Korkki, Saana M.; Solomon, Alina; Coley, Nicola; Antikaínen, Riitta; Bäckman, Lars; Hänninen, Tuomo; Lindström, Jaana; Laatikainen, Tiina; Paajanen, Teemu; Havulinna, Satu; Peltonen, Markku; Neely, Anna Stigsdotter; Strandberg, Timo; Tuomilehto, Jaakko; Kivipelto, Miia

doi:10.1002/alz.12492

Cited by 45 publications

(34 citation statements)

References 34 publications

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“…The Rotterdam Study is a prospective, population-based cohort study among individuals living in the Ommoord district in the city of Rotterdam (the Netherlands) 25 , offering metabolomics for 2,949 participants with a median age of 74 years (IQR [70][71][72][73][74][75][76][77][78][79]. The Leiden Longevity PAROFF Study (LLS) 26 comprises offspring and spouses of long-lived individuals, with metabolomics available for 1,655 individuals with a mean age of 59 years (IQR [54][55][56][57][58][59][60][61][62][63]. Finally, the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a clinical trial investigating pravastatin effects 27 , of which 960 samples with a median age of 76 years (IQR [73][74][75][76][77][78] are included in the BBMRI-NL platform.…”

Section: Resultsmentioning

confidence: 99%

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Metabolomic profiles predict individual multidisease outcomes

Buergel

Steinfeldt

Ruyoga

et al. 2022

Nat Med

195

106

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Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic, vascular, respiratory, musculoskeletal and neurological diseases and cancers. Specifically, we trained a neural network to learn disease-specific metabolomic states from 168 circulating metabolic markers measured in 117,981 participants with ~1.4 million person-years of follow-up from the UK Biobank and validated the model in four independent cohorts. We found metabolomic states to be associated with incident event rates in all the investigated conditions, except breast cancer. For 10-year outcome prediction for 15 endpoints, with and without established metabolic contribution, a combination of age and sex and the metabolomic state equaled or outperformed established predictors. Moreover, metabolomic state added predictive information over comprehensive clinical variables for eight common diseases, including type 2 diabetes, dementia and heart failure. Decision curve analyses showed that predictive improvements translated into clinical utility for a wide range of potential decision thresholds. Taken together, our study demonstrates both the potential and limitations of NMR-derived metabolomic profiles as a multidisease assay to inform on the risk of many common diseases simultaneously.

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Section: Resultsmentioning

confidence: 99%

“…This is particularly compelling because today's pharmacological treatment options for dementia are scarce. However, the efficacy of various lifestyle interventions 58,59 is disputed, calling for further experimental investigation.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiles predict individual multidisease outcomes

Buergel

Steinfeldt

Ruyoga

et al. 2022

Nat Med

195

106

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“…Given the increasing acceptance of multimodal interventions — to the point where they may now be considered to be the most effective intervention for ADRD — we do not in this manuscript thoroughly review the literature. The FINGER trial is the most recognized trial demonstrating the effectiveness of multimodal interventions (Ngandu et al, 2022). More recent studies, including the Chicago Health and Aging Project (CHAP) and the Rush Memory and Aging Project (MAP), validate these findings (e.g., Dhana et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A multimodal intervention for Alzheimer’s disease results in multifaceted systemic effects reflected in blood and ameliorates functional and cognitive outcomes

Roach¹,

Edens²,

Markewych³

et al. 2022

Preprint

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Introduction. Comprehensive treatment of Alzheimer's disease and related dementias (ADRD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and exercise. The Coaching for Cognition in Alzheimer's (COCOA) trial was a prospective randomized controlled trial (RCT) to test the hypothesis that a remotely coached multimodal lifestyle intervention would improve early-stage Alzheimer's disease (AD). AD results from the interplay of multiple interacting dysfunctional biological systems. Specific causes of AD differ between individuals. Personalized, multimodal therapies are needed to best prevent and treat AD. COCOA collected psychometric, clinical, lifestyle, genomic, proteomic, metabolomic and microbiome data at multiple timepoints across two years for each participant. These data enable systems-biology analyses. We report analyses of the first COCOA data freeze. This analysis includes an evaluation of the effect of the intervention on outcome measures. It also includes systems analyses to identify molecular mediators that convey the effect of personalized multimodal lifestyle interventions on amelioration of cognitive trajectory. Methods. A total of 55 participants with early-stage AD from Southern California were randomized into two parallel arms. Arm 1 (control; N=24) received standard of care. Arm 2 (intervention; N=31) also received telephonic personalized coaching for multiple lifestyle interventions including diet, exercise, and cognitive training. COCOA's overarching aim was to gather dense molecular data from an AD cohort to improve understanding of pathophysiology and advance treatment. For the RCT, COCOA's objective was to test the hypothesis that the Memory Performance Index (MPI) trajectory would be better in the intervention arm than in the control arm. The Functional Assessment Staging Test (FAST) was assessed for a secondary outcome. Assessments were blinded. The nature of the intervention precluded participant blinding. Results. The intervention arm ameliorated 2.6 ± 0.8 MPI points (p = 0.0007; N = 48) compared to the control arm over the two-year intervention. Top-ranked candidate mediators included: albumin, propionylcarnitine, sphingomyelin, hexadecanedioate, acetylkynurenine, tiglylcarnitine, IL18R1, palmitoyl-sphingosine-phosphoethanolamine, acetyltryptophan, and IL17D. These individual molecules implicated inflammatory and nitrogen/tryptophan metabolism pathways. No important adverse events or side effects were observed. Conclusions. Clinical trials should include frequent assessment of dense data to maximize knowledge gained. Such knowledge is useful not only in testing a primary hypothesis, but also in advancing basic biological and pathophysiological knowledge, understanding mechanisms explaining trial results, generating synergistic knowledge tangential to preconceived hypotheses, and refining interventions for clinical translation. Data from every trial should allow an intervention to be refined and then tested in future trials, driving iterative improvement. Multimodal lifestyle interventions are effective for ameliorating cognitive decline and may have an effect size larger than pharmacological interventions. Effects may be molecularly idiosyncratic; personalization of interventions is important. Dietary changes and exercise are likely to be beneficial components of multimodal interventions in many individuals. Remote coaching is an effective intervention for early stage ADRD. Remote interventions were effective during the COVID pandemic.

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“…Thus, diet should rather be regarded as one part of a multidomain intervention with respect to cognitive performance. [8][9][10] This study, on the other hand, does not completely exclude the possibility that there may be an effect of dietary habits more specifically on cognition. The inherent limitations of such a large study should be considered: Misreporting and changes of dietary habits cannot be excluded, and baseline assessments constitute a "snap-shot," followed by a long period of time over 2 decades with numerous changing confounders over time.…”

mentioning

confidence: 82%

The Implications of Dietary Habits for Dementia

Peters

Nacmias

2023

Neurology

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Dementia imposes a substantial medical and psychosocial burden on affected individuals and their caregivers, and it constitutes an overall socioeconomic challenge. Based on the demographic changes in many parts of the world, these issues will most likely gain even more importance in the near future. Therapeutic and especially preventive strategies are therefore essential. These approaches naturally focus on modifiable factors that may have an impact on the development of cognitive decline and dementia. 1 Such factors not only include various cardiovascular and cerebrovascular risk factors, such as arterial hypertension or diabetes, but also include broader aspects, which may be addressed by the individuals themselves, such as physical activity and dietary habits. The latter has been subject of investigation in various previous studies, indicating a potential benefit of Mediterranean diet with respect to cognition. 2-4 However, the results have been ambiguous, and interpretation has been hampered by heterogeneous approaches.

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The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER)

Abstract: Introduction: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses).

Cited by 45 publications

References 34 publications

Metabolomic profiles predict individual multidisease outcomes

Metabolomic profiles predict individual multidisease outcomes

A multimodal intervention for Alzheimer’s disease results in multifaceted systemic effects reflected in blood and ameliorates functional and cognitive outcomes

The Implications of Dietary Habits for Dementia

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