24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial

Soininen, Hilkka; Solomon, Alina; Visser, Pieter Jelle; Hendrix, Suzanne; Blennow, Kaj; Kivipelto, Miia; Hartmann, Tobias; Hallikainen, Ilona; Hallikainen, Merja; Helisalmi, Seppo; Lappalainen, Tarja; Liu, Yawu; Paajanen, Teemu; Wahlund, Lars‐Olof; Freund‐Levi, Yvonne; Andreasen, Niels; Hagman, Göran; Lindblom, Stina; Faßbender, Klaus; Riemenschneider, Matthias; Grimm, Marcus O.W.; Klees-Rollmann, Aline; Luley, Maxine; Lyros, Epameinondas; Schomburg, Robert; Kennel, Jennifer; Ramelli, Daniela; Frölich, Lutz; Hausner, Lucrezia; Laske, Christoph; Leyhe, Thomas; Mychajliw, Christian; Koehler, Niklas; Schiekofer, Stephan; Klünemann, Hans H.; Schröder, Johannes; Lütjohann, Dieter; Scheltens, Philip; Rossum, Ineke van; Scheltens, Nienke M.E.; Bertens, Daniela; Kate, Mara ten; Barkhof, Frederik; Henselmans, J.M.L.; Roks, Gerwin; Hees, Anneke M.J. van; Ellison, Noel

doi:10.1016/s1474-4422(17)30332-0

Cited by 192 publications

(246 citation statements)

References 37 publications

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“…Also in mild AD, Scheltens et al [6] showed an improvement on the neuropsychological test battery memory domain and electroencephalography functional connectivity in the delta band after 24 weeks. In contrast, a recent large study by Soininen et al [26] investigated the effect of Souvenaid in prodromal AD subjects, a population close to the current population with MCI or mild dementia due to AD. In this study, a positive effect on the clinical dementia rating sum of boxes and hippocampal and ventricular volume on MRI was found after 2 years of treatment, although the effects were not yet observed at the study's 1-year half-way point.…”

Section: Discussionmentioning

confidence: 98%

Exploring effects of Souvenaid on cerebral glucose metabolism in Alzheimer's disease

Scheltens

Briels

Yaqub

et al. 2019

A&D Transl Res & Clin Interv

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IntroductionAlzheimer's disease (AD) is associated with synapse loss. Souvenaid, containing the specific nutrient combination Fortasyn Connect, was designed to improve synapse formation and function. The NL-ENIGMA study explored the effect of Souvenaid on synapse function in early AD by assessing cerebral glucose metabolism (CMRglc) with 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET).MethodsWe conducted an exploratory double-blind randomized controlled single-center trial. Fifty patients with mild cognitive impairment or mild dementia with evidence of amyloid pathology (cerebrospinal fluid or PET) were stratified for MMSE (20–24 and 25–30) and randomly 1:1 allocated to 24-week daily administration of 125 mL Souvenaid (n = 25) or placebo (n = 25). Dynamic 60-minute [18F]FDG-PET scans (21 frames) with arterial sampling were acquired at baseline and 24 weeks. CMRglc was estimated by quantitative (Ki) and semiquantitative (standardized uptake value ratio, reference cerebellar gray matter) measurements in five predefined regions of interest and a composite region of interest. Change from baseline in CMRglc was compared between treatment groups by analysis of variance, adjusted for baseline CMRglc and MMSE stratum. Additional exploratory outcome parameters included voxel-based analyses by Statistical Parametric Mapping.ResultsNo baseline differences between treatment groups were found (placebo/intervention: n = 25/25; age 66 ± 8/65 ± 7 years; female 44%/48%; MMSE 25 ± 3/25 ± 3). [18F]FDG-PET data were available for quantitative (placebo n = 19, intervention n = 18) and semiquantitative (placebo n = 20, intervention n = 22) analyses. At follow-up, no change within treatment groups and no statistically significant difference in change between treatment groups in CMRglc in any regions of interest were found by both quantitative and semiquantitative analyses. No treatment effect was found in the cerebellar gray matter using quantitative measures. The additional Statistical Parametric Mapping analyses did not yield consistent differences between treatment groups.DiscussionIn this exploratory trial, we found no robust effect of 24-week intervention with Souvenaid on synapse function measured by [18F]FDG-PET. Possible explanations include short duration of treatment.

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Section: Discussionmentioning

confidence: 98%

Exploring effects of Souvenaid on cerebral glucose metabolism in Alzheimer's disease

Scheltens

Briels

Yaqub

et al. 2019

A&D Transl Res & Clin Interv

Self Cite

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“…Despite several systematic reviews and meta-analyses of observational studies in recent years,6,9 no firm conclusions can be drawn. Intervention studies on diet modification and/or supplementation do not show an effect,10–13 with one exception 14. Most previous studies on diet and dementia had a short follow-up, typically less than 10 years where reverse causation may bias results as dietary behavior and nutrient intake may be altered during the long preclinical period of dementia 15…”

Section: Introductionmentioning

confidence: 99%

Association of Midlife Diet With Subsequent Risk for Dementia

Akbaraly

Singh‐Manoux

Dugravot

et al. 2019

JAMA

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Importance Observational studies suggest that diet is linked to cognitive health. However, the duration of follow-up in many studies is not sufficient to take into account the long preclinical phase of dementia and the evidence from intervention studies is not conclusive. Objectives To examine whether midlife diet is associated with subsequent risk of dementia. Design, Setting and Participants Population-based cohort study established in 1985-1888, with dietary intake assessment in 1991-1993, 1997-1999 and 2002-2004; follow-up for incident dementia until March 2017. Exposures Food frequency questionnaire to derive the Alternate Healthy Eating Index (AHEI), an 11-component diet quality score (range=0-110), with higher scores indicating a healthier diet. Main Outcome and Measures Incident dementia ascertained through linkage to electronic health records. Results Among 8225 (mean age 50.2 (SD, 6.1) years; 5686, 69.1% men) dementia-free participants in 1991-1993 a total of 344 cases of incident dementia were recorded over a median follow-up of 24.8 (IQR, 24.2 to 25.1) years. No significant difference in incidence rate (IR) of dementia was observed in tertiles of AHEI exposure in 1991-1993, 1997-1999 (median follow-up 19.1 years) and 2002-2004 (median follow-up 13.5 years). Compared with IR of dementia of 1.76 (95% CI, 1.47-2.12) per 1000 person-years in the worst tertile of AHEI (lowest tertile of diet quality) in 1991-1993, the absolute rate differences for the intermediate and the best tertiles were, respectively, 0.03 (95 % CI, -0.43 to 0.49) and 0.04 (95% CI, -0.42 to 0.51) per 1000 person-years. In 1997-1999, the absolute rate differences in the intermediate and the best AHEI tertiles compared to the worst tertile (IR=2.06 (95% CI, 1.62-2.61) per 1000 person-years) were respectively 0.14 (95 % CI, -0.58 to 0.86) and 0.14 (95% CI, -0.58 to 0.85) per 1000 person-years. In 2002-2004, these absolute rate differences with the worst AHEI tertile (IR=3.12 (95% CI, 2.49-3.92) per 1000 person-years) were respectively -0.61 (95 % CI, -1.56 to 0.33) and -0.73 (95% CI, -1.67 to 0.22) per 1000 person-years in the intermediate and best AHEI tertiles. In multivariate analysis, HRs of dementia per 10-point AHEI increment were not significant as assessed in 1991-1993 (0.97, 95% CI, 0.87-1.08)), in 1997-1999 (0.97, 95% CI, 0.83-1.12)), or in 2002-2004 (0.87, 95% CI, 0.75-1.00)). Conclusion In this long-term prospective cohort study, diet quality assessed in midlife was not significantly associated with subsequent risk of dementia.

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“…A recent study has supplemented for 2 years patients with precursor signs of Alzheimer's disease. The active ingredient was composed of omega-3 fatty acids, uridine, choline, phosphates and B vitamins but this supplementation had no effect on cognitive scores compared to the placebo (Soininen et al, 2017). Thus, there is currently no consensus on the effectiveness of a nutritional strategy to prevent or limit the progression of cognitive decline.…”

Section: Evidence Of Effective Prevention Strategiesmentioning

confidence: 99%

Aging, cognitive decline, apolipoprotein E and docosahexaenoic acid metabolism

Plourde

2018

OCL

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-In Canada, ∼17 millions of adults between 30-64 years old could benefit from a prevention strategy to lower the risk of Alzheimer's disease (AD). My group is working on a population that is particularly at risk of AD, the carriers of an epsilon 4 allele of apolipoprotein E (E4), a genetic risk. Around 20% of the population in industrial countries have this genetic risk but not all carriers will develop AD, suggesting that environmental factors modulate the clinical manifestation and risk of AD in the carriers. My group has discovered that the metabolism of docosahexaenoic acid (DHA) is disrupted during aging and in E4 carriers, a finding replicated in homozygous mice knocked-in for human E4 allele (hAPOE4). We recently showed that a diet containing DHA prevented behavioral deficits in hAPOE4 mice. Another group reported in E4 carriers that the ratio of arachidonic acid (ARA): DHA is disrupted in the plasma and constitute a preclinical marker of mild cognitive impairment/AD in E4 carriers. Using our kinetics approaches with uniformly labelled carbon 13 fatty acids, we showed that the kinetics of 13 C-DHA is modified by age and E4 carriage. The kinetics of 13 C-arachidonic acid was however not modified by age conversely to that of 13 C-eicosapentaenoic acid (EPA). We also reported that the synthesis of 13 C-DHA from 13 C-EPA started 2 h after the tracer intake in older adults conversely to 7 d in young men. Whether old men needs in DHA is higher or whether their ability to use it is lower remains to be established. These differences in the DHA and EPA metabolism seems, however related to physiological modifications occurring during aging and in E4 carriers and obscure the relationship between plasma DHA and EPA levels, dietary fatty fish intake and cognitive status.Keywords: docosahexaenoic acid / arachidonic acid / eicosapentaenoic acid / aging / cognitive decline / apolipoprotein E / kinetics Résumé -Vieillissement, déclin cognitif, apolipoprotéine E et métabolisme de l'acide docosahexaénoïque. Au Canada, 17 millions d'adultes âgés entre 30-64 ans pourraient bénéficier d'une intervention en prévention pour diminuer leur risque de développer la maladie d'Alzheimer (MA). L'un des groupes les plus à risque de développer la MA, les porteurs de l'allèle epsilon 4 de l'apolipoprotéine E (E4), est au centre des recherches menées par mon groupe. Environ 20 % de la population des pays industrialisés sont porteurs d'E4 mais ce ne sont pas tous les porteurs qui développeront la MA, ce qui suggère que des facteurs environnementaux puissent moduler l'expression clinique et le risque de la MA chez les porteurs. Nous avons découvert que le métabolisme de l'acide docosahexaénoïque (DHA) est débalancé pendant le vieillissement et chez les porteurs de l'E4. Ces découvertes ont été répliquées dans un modèle de souris transgénique dont l'apolipoprotein de souris a été remplacé par de l'E4 humaine (hAPOE4). Nous avons récemment montré qu'une diète riche en DHA prévenait les déficits comportementaux chez la souris hAPOE4. U...

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24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial

Cited by 192 publications

References 37 publications

Exploring effects of Souvenaid on cerebral glucose metabolism in Alzheimer's disease

Exploring effects of Souvenaid on cerebral glucose metabolism in Alzheimer's disease

Association of Midlife Diet With Subsequent Risk for Dementia

Aging, cognitive decline, apolipoprotein E and docosahexaenoic acid metabolism

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