Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial

Gazi Saadmaan¹, Maria Carolina Dalmasso^{2

3}, Alfredo Ramirez^{3

4

5

6

7}, Mikko Hiltunen⁸, Nina Kemppainen^{9

10}, Jenni Lehtisalo^{1

11}, Francesca Mangialasche¹², Tiia Ngandu^{11

12}, Juha Rinne^{9

10}, Hilkka Soininen¹, Ruth Stephen¹, Miia Kivipelto^{1

12

13

14}, Alina Solomon^{1

12

14}

Affiliations

¹ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
² Studies in Neuroscience and Complex Systems Unit (ENyS), CONICET-HEC-UNAJ, Florencio Varela, Argentina.
³ Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.
⁴ Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
⁵ German Center for Neurodegenerative Diseases, DZNE Bonn, Bonn, Germany.
⁶ Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas, USA.
⁷ Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
⁸ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
⁹ Turku PET Centre, University of Turku, Turku, Finland.
¹⁰ Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
¹¹ Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
¹² Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
¹³ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
¹⁴ Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK.

PMID: 38647197
PMCID: PMC11180864
DOI: 10.1002/alz.13843

Randomized Controlled Trial

Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial

Gazi Saadmaan et al. Alzheimers Dement. 2024 Jun.

. 2024 Jun;20(6):4345-4350.

doi: 10.1002/alz.13843. Epub 2024 Apr 22.

Authors

Affiliations

¹ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
² Studies in Neuroscience and Complex Systems Unit (ENyS), CONICET-HEC-UNAJ, Florencio Varela, Argentina.
³ Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany.
⁴ Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany.
⁵ German Center for Neurodegenerative Diseases, DZNE Bonn, Bonn, Germany.
⁶ Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas, USA.
⁷ Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
⁸ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
⁹ Turku PET Centre, University of Turku, Turku, Finland.
¹⁰ Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
¹¹ Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
¹² Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
¹³ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
¹⁴ Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, UK.

PMID: 38647197
PMCID: PMC11180864
DOI: 10.1002/alz.13843

Abstract

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.

Keywords: APOE4; Alzheimer's disease; clinical trial; dementia; genetic risk score; neuroimaging biomarker.

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Conflict of interest statement

The authors report no conflicts of Interest. Author disclosures are available in the Supporting Information.

References

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Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial

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Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial

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Abstract

Conflict of interest statement

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