Randomized Controlled Trial

. 2024 May 30;16(1):118.

doi: 10.1186/s13195-024-01468-x.

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-AD_mini randomized controlled trial

Charlotta Thunborg^#^{1

2

3}, Rui Wang^#^{1

4

5}, Anna Rosenberg^{1

6}, Shireen Sindi^{1

7}, Pia Andersen^{1

2}, Sandrine Andrieu^{8

9}, Laus M Broersen¹⁰, Nicola Coley^{8

9}, Celine Couderc⁸, Celine Z Duval^{11

12}, Gerd Faxen-Irving¹, Göran Hagman², Merja Hallikainen⁷, Krister Håkansson^{1

2

13}, Eija Kekkonen⁷, Jenni Lehtisalo^{7

14}, Nicholas Levak^{1

2}, Francesca Mangialasche¹, Johannes Pantel^{11

12}, Anders Rydström¹, Anna Stigsdotter-Neely^{15

16}, Anders Wimo¹, Tiia Ngandu¹⁴, Hilkka Soininen⁷, Tobias Hartmann^{11

17}, Alina Solomon^#^{1

6

7}, Miia Kivipelto^#^{18

19

20

21

22}

Affiliations

¹ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research QA32, Karolinska Institute, Karolinska Vägen 37 A, Solna, 171 64, Sweden.
² Theme Inflammation and Aging, Karolinska University Hospital, Karolinska Vägen 37 A, Solna, Stockholm, 171 64, Sweden.
³ Department of Caring Sciences, Faculty of Health and Occupational Studies, Gävle, 801 76, Sweden.
⁴ Department of Physical Activity and Health, the Swedish School of Sport and Health Sciences, Stockholm, SE-114 86, Sweden.
⁵ Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, 600 Highland Ave J5/1 Mezzanine, Madison, WI, 53792, USA.
⁶ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 8, Kuopio, 70210, Finland.
⁷ The Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, St Mary's Hospital, Norfolk Place, London, W2 1PG, UK.
⁸ Department of Clinical Epidemiology and Public Health, CHU de Toulouse, and Aging Research Team, CERPOP Inserm UMR 1295, Jules Guesde, Toulouse, 31000, France.
⁹ IHU HealthAge, Toulouse, 31059, France.
¹⁰ Danone Nutricia Research, Utrecht, Netherlands.
¹¹ German Institute for Dementia Prevention (DIDP), Saarland University, Homburg, 66424, Germany.
¹² Institute of General Practice, Goethe University Frankfurt a.M, Frankfurt, 60590, Germany.
¹³ Stockholm Gerontology Research Center, Tomtebodavägen 18a, Solna, 171 65, Sweden.
¹⁴ Population Health Unit, Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Mannerheimintie 166, P.O. Box 30, Helsinki, Finland.
¹⁵ Department of Social and Psychological Studies, Karlstad University, Karlstad, 651 88, Sweden.
¹⁶ Engineering Psychology, Luleå University of Technology, Luleå, 971 87, Sweden.
¹⁷ Department of Experimental Neurology, Medical Faculty, Saarland University, Homburg, 66424, Germany.
¹⁸ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research QA32, Karolinska Institute, Karolinska Vägen 37 A, Solna, 171 64, Sweden. miia.kivipelto@ki.se.
¹⁹ Theme Inflammation and Aging, Karolinska University Hospital, Karolinska Vägen 37 A, Solna, Stockholm, 171 64, Sweden. miia.kivipelto@ki.se.
²⁰ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 8, Kuopio, 70210, Finland. miia.kivipelto@ki.se.
²¹ The Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, St Mary's Hospital, Norfolk Place, London, W2 1PG, UK. miia.kivipelto@ki.se.
²² Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Yliopistonranta 8, Kuopio, 70210, Finland. miia.kivipelto@ki.se.

^# Contributed equally.

PMID: 38812047
PMCID: PMC11138035
DOI: 10.1186/s13195-024-01468-x

Randomized Controlled Trial

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-AD_mini randomized controlled trial

Charlotta Thunborg et al. Alzheimers Res Ther. 2024.

. 2024 May 30;16(1):118.

doi: 10.1186/s13195-024-01468-x.

Authors

Affiliations

¹ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research QA32, Karolinska Institute, Karolinska Vägen 37 A, Solna, 171 64, Sweden.
² Theme Inflammation and Aging, Karolinska University Hospital, Karolinska Vägen 37 A, Solna, Stockholm, 171 64, Sweden.
³ Department of Caring Sciences, Faculty of Health and Occupational Studies, Gävle, 801 76, Sweden.
⁴ Department of Physical Activity and Health, the Swedish School of Sport and Health Sciences, Stockholm, SE-114 86, Sweden.
⁵ Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, 600 Highland Ave J5/1 Mezzanine, Madison, WI, 53792, USA.
⁶ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 8, Kuopio, 70210, Finland.
⁷ The Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, St Mary's Hospital, Norfolk Place, London, W2 1PG, UK.
⁸ Department of Clinical Epidemiology and Public Health, CHU de Toulouse, and Aging Research Team, CERPOP Inserm UMR 1295, Jules Guesde, Toulouse, 31000, France.
⁹ IHU HealthAge, Toulouse, 31059, France.
¹⁰ Danone Nutricia Research, Utrecht, Netherlands.
¹¹ German Institute for Dementia Prevention (DIDP), Saarland University, Homburg, 66424, Germany.
¹² Institute of General Practice, Goethe University Frankfurt a.M, Frankfurt, 60590, Germany.
¹³ Stockholm Gerontology Research Center, Tomtebodavägen 18a, Solna, 171 65, Sweden.
¹⁴ Population Health Unit, Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Mannerheimintie 166, P.O. Box 30, Helsinki, Finland.
¹⁵ Department of Social and Psychological Studies, Karlstad University, Karlstad, 651 88, Sweden.
¹⁶ Engineering Psychology, Luleå University of Technology, Luleå, 971 87, Sweden.
¹⁷ Department of Experimental Neurology, Medical Faculty, Saarland University, Homburg, 66424, Germany.
¹⁸ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research QA32, Karolinska Institute, Karolinska Vägen 37 A, Solna, 171 64, Sweden. miia.kivipelto@ki.se.
¹⁹ Theme Inflammation and Aging, Karolinska University Hospital, Karolinska Vägen 37 A, Solna, Stockholm, 171 64, Sweden. miia.kivipelto@ki.se.
²⁰ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 8, Kuopio, 70210, Finland. miia.kivipelto@ki.se.
²¹ The Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, St Mary's Hospital, Norfolk Place, London, W2 1PG, UK. miia.kivipelto@ki.se.
²² Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Yliopistonranta 8, Kuopio, 70210, Finland. miia.kivipelto@ki.se.

^# Contributed equally.

PMID: 38812047
PMCID: PMC11138035
DOI: 10.1186/s13195-024-01468-x

Abstract

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.

Keywords: Adherence; Alzheimer’s disease; Lifestyle intervention; Medical food; Multimodal intervention; Prevention; Randomized controlled trial.

PubMed Disclaimer

Conflict of interest statement

Prof. Miia Kivipelto is the Editors-in-Chief of Alzheimer's Research & Therapy. Dr. Anna Rosenberg serves as Associate Editor for Alzheimer's Research & Therapy.

Figures

**Fig. 2**
Adherence to healthy lifestyle changes from baseline to month 6 in all randomized participants. When compared to the lifestyle intervention group, the lifestyle intervention + medical food group showed significant improvement in cardiovascular risk burden (P = 0.016), but no differences were observed in changes for healthy dietary intake (P = 0.533), physical activity (P = 0.215), cognitive and social activities (P = 0.726), or overall healthy lifestyles (P = 0.338)

See this image and copyright information in PMC

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Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-AD_mini randomized controlled trial

Affiliations

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-AD_mini randomized controlled trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical