Review

. 2021 Oct 11;13(1):169.

doi: 10.1186/s13195-021-00895-4.

Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6

Janice M Ranson^{1

2}, Timothy Rittman^{2

3}, Shabina Hayat⁴, Carol Brayne⁴, Frank Jessen⁵, Kaj Blennow⁶, Cornelia van Duijn⁷, Frederik Barkhof^{8

9}, Eugene Tang^{2

10}, Catherine J Mummery^{2

11}, Blossom C M Stephan¹², Daniele Altomare^{13

14}, Giovanni B Frisoni^{13

14}, Federica Ribaldi^{13

14

15

16}, José Luis Molinuevo¹⁷, Philip Scheltens^{18

19}, David J Llewellyn^{20

21

22

23}; European Task Force for Brain Health Services

Collaborators, Affiliations

Collaborators

European Task Force for Brain Health Services:
Marc Abramowicz, Daniele Altomare, Frederik Barkhof, Marcelo Berthier, Melanie Bieler, Kaj Blennow, Carol Brayne, Andrea Brioschi, Emmanuel Carrera, Gael Chételat, Chantal Csajka, Jean-François Demonet, Alessandra Dodich, Bruno Dubois, Giovanni B Frisoni, Valentina Garibotto, Jean Georges, Samia Hurst, Frank Jessen, Miia Kivipelto, David J Llewellyn, Laura McWhirter, Richard Milne, Carolina Minguillón, Carlo Miniussi, José Luis Molinuevo, Peter M Nilsson, Janice M Ranson, Federica Ribaldi, Craig Ritchie, Philip Scheltens, Alina Solomon, Wiesje van der Flier, Cornelia van Duijn, Bruno Vellas, Leonie Visser

Affiliations

¹ College of Medicine and Health, University of Exeter, Exeter, UK.
² Deep Dementia Phenotyping (DEMON) Network, Exeter, UK.
³ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁴ Department of Public Health and Primary Care, Cambridge Public Health, University of Cambridge, Cambridge, UK.
⁵ Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁷ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁸ Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
⁹ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
¹⁰ Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
¹¹ Dementia Research Centre, Institute of Neurology, University College London, and National Hospital for Neurology and Neurosurgery, University College London Hospital, London, UK.
¹² Institute of Mental Health, Division of Psychiatry and Applied Psychology, School of Medicine, Nottingham University, Nottingham, UK.
¹³ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
¹⁴ Memory Clinic, Geneva University Hospitals, Geneva, Switzerland.
¹⁵ Laboratory of Alzheimer's Neuroimaging and Epidemiology (LANE), Saint John of God Clinical Research Centre, Brescia, Italy.
¹⁶ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹⁷ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
¹⁸ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁹ Life Science Partners, Amsterdam, The Netherlands.
²⁰ College of Medicine and Health, University of Exeter, Exeter, UK. david.llewellyn@exeter.ac.uk.
²¹ Deep Dementia Phenotyping (DEMON) Network, Exeter, UK. david.llewellyn@exeter.ac.uk.
²² Alan Turing Institute, London, UK. david.llewellyn@exeter.ac.uk.
²³ 2.04 College House, St Luke's Campus, University of Exeter Medical School, Exeter, EX1 2 LU, UK. david.llewellyn@exeter.ac.uk.

PMID: 34635138
PMCID: PMC8507172
DOI: 10.1186/s13195-021-00895-4

Review

Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6

Janice M Ranson et al. Alzheimers Res Ther. 2021.

. 2021 Oct 11;13(1):169.

doi: 10.1186/s13195-021-00895-4.

Authors

Collaborators

European Task Force for Brain Health Services:
Marc Abramowicz, Daniele Altomare, Frederik Barkhof, Marcelo Berthier, Melanie Bieler, Kaj Blennow, Carol Brayne, Andrea Brioschi, Emmanuel Carrera, Gael Chételat, Chantal Csajka, Jean-François Demonet, Alessandra Dodich, Bruno Dubois, Giovanni B Frisoni, Valentina Garibotto, Jean Georges, Samia Hurst, Frank Jessen, Miia Kivipelto, David J Llewellyn, Laura McWhirter, Richard Milne, Carolina Minguillón, Carlo Miniussi, José Luis Molinuevo, Peter M Nilsson, Janice M Ranson, Federica Ribaldi, Craig Ritchie, Philip Scheltens, Alina Solomon, Wiesje van der Flier, Cornelia van Duijn, Bruno Vellas, Leonie Visser

Affiliations

¹ College of Medicine and Health, University of Exeter, Exeter, UK.
² Deep Dementia Phenotyping (DEMON) Network, Exeter, UK.
³ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
⁴ Department of Public Health and Primary Care, Cambridge Public Health, University of Cambridge, Cambridge, UK.
⁵ Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, Cologne, Germany.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁷ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁸ Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
⁹ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
¹⁰ Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
¹¹ Dementia Research Centre, Institute of Neurology, University College London, and National Hospital for Neurology and Neurosurgery, University College London Hospital, London, UK.
¹² Institute of Mental Health, Division of Psychiatry and Applied Psychology, School of Medicine, Nottingham University, Nottingham, UK.
¹³ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
¹⁴ Memory Clinic, Geneva University Hospitals, Geneva, Switzerland.
¹⁵ Laboratory of Alzheimer's Neuroimaging and Epidemiology (LANE), Saint John of God Clinical Research Centre, Brescia, Italy.
¹⁶ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹⁷ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
¹⁸ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁹ Life Science Partners, Amsterdam, The Netherlands.
²⁰ College of Medicine and Health, University of Exeter, Exeter, UK. david.llewellyn@exeter.ac.uk.
²¹ Deep Dementia Phenotyping (DEMON) Network, Exeter, UK. david.llewellyn@exeter.ac.uk.
²² Alan Turing Institute, London, UK. david.llewellyn@exeter.ac.uk.
²³ 2.04 College House, St Luke's Campus, University of Exeter Medical School, Exeter, EX1 2 LU, UK. david.llewellyn@exeter.ac.uk.

PMID: 34635138
PMCID: PMC8507172
DOI: 10.1186/s13195-021-00895-4

Abstract

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.

Keywords: Aging; Alzheimer’s disease; Brain health services; Dementia; Prevention; Public health; Risk factors; Risk profiling.

PubMed Disclaimer

Conflict of interest statement

GBF reports grants from Alzheimer Forum Suisse, Académie Suisse des Sciences Médicales, Avid Radiopharmaceuticals, Biogen, GE International, Guerbert, Association Suisse pour la Recherche sur l’Alzheimer, IXICO, Merz Pharma, Nestlé, Novartis, Piramal, Roche, Siemens, Teva Pharmaceutical Industries, Vifor Pharma, and Alzheimer’s Association; he has received personal fees from AstraZeneca, Avid Radiopharmaceuticals, Elan Pharmaceuticals, GE International, Lundbeck, Pfizer, and TauRx Therapeutics.

KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program.

JLM is currently a full time employee of Lundbeck and has previously served as a consultant or at advisory boards for the following for-profit companies, or has given lectures in symposia sponsored by the following for-profit companies: Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, ProMIS Neurosciences.

All other authors declare that they have no competing interests.

Figures

**Fig. 1**
Timeline of the discovery of frequent and rare variants in Alzheimer’s disease. Frequent/common variants discovered in GWAS are shown above the horizontal date axis, and rare variants discovered using sequencing and arrays are shown below the date axis

**Fig. 2**
Proposed workflow for dementia risk profiling in BHSs

See this image and copyright information in PMC

References

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Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6

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Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6

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Conflict of interest statement

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