Informing cognitively healthy research participants of modifiable dementia risk factors: Ethical implications

Abstract

Research has shown that up to 40% of dementia incidence can be accounted for by 12 modifiable lifestyle risk factors. However, the predictive value of these risks factors at an individual level remains uncertain. Ethical considerations that are typically invoked with respect to the disclosure of individual research results—beneficence and non-maleficence, respect for autonomy, and justice—do not provide conclusive justification for, or against, disclosing modifiable risk factors for future dementia to cognitively unimpaired research participants. We argue for a different approach to evaluating the disclosure of individual-level modifiable risk factors for dementia. Rather than focusing on individual-level disease prediction and prevention, we suggest that disclosure should be evaluated based on the impact of behavioral and lifestyle changes on current brain health.

Keywords

Alzheimer's disease brain health dementia modifiable research ethics research participants risk factors

Introduction

Dementia is a global epidemic that presents profound challenges to individuals, families, health care systems, and societies throughout the world. By 2050, the number of people living with dementia is expected to reach 139 million, and the associated costs to surpass $2.8 trillion by 2030.¹ Evidence suggests that up to 40% of worldwide dementia can be accounted for by 12 modifiable lifestyle risk factors, many of which begin to impact in mid-life, e.g., alcohol consumption, obesity, and hypertension, and which, therefore, could be prevented or reduced.^2,3 Pathophysiological processes underlying Alzheimer's disease (AD), the most common cause of dementia, may be present decades before the onset of these clinical symptoms.⁴

The term ‘Alzheimer's disease’ has been variously used to refer to (1) a particular pathophysiological disease process requiring the presence of specific biomarkers, which may or may not precede clinical symptoms, (2) a clinical syndrome characterized by progressive cognitive and behavioral impairment, which is probabilistically linked to the presence of specific biomarkers. Conversely, ‘dementia’ refers to an age-related clinical syndrome characterized by progressive memory and cognitive decline, of which Alzheimer's disease is one potential cause, and for which biomarkers are neither necessary nor sufficient for a diagnosis. There is disagreement over whether (1) or (2) is the most appropriate definition for Alzheimer's disease; for an overview, see Daly et al.⁵ In this paper, we will refer primarily to (2), though distinguish this from (1) where appropriate.

Efforts to reduce the scale and impact of dementia have led to a growing emphasis on brain health, a holistic state and set of processes that can be actively promoted through lifestyle behaviors.^2,6 It is increasingly recognized that the combination of two broad approaches is required to meet the challenge posed by the dementia epidemic.⁷ On the one hand, there is the whole-population approach to dementia prevention, which focuses on interventions that aim to reduce everyone's risk across society, regardless of individual risk status for dementia. The rationale for this approach is that many of the risk factors for dementia e.g., obesity and physical inactivity, poor diet, high blood pressure, smoking, low education and lack of cognitive stimulation, social isolation and loneliness, are highly prevalent, and to reduce the absolute burden of disease, scalable interventions that target these risks by efficiently applying available resources to a large number of people are required.⁷ Moreover, it is well established that dementia follows a social economic gradient, and, therefore, culturally-informed societal interventions that tackle the root of inequities are required to reduce its prevalence for all across societies.⁷

On the other hand, the at-risk individuals approach to prevention seeks to identify individuals at highest risk for developing dementia, in order to deliver focused risk reduction and preventative interventions to high-risk groups. The later approach is highly targeted and research intensive, and promises to deliver biomarkers of incipient dementia that can be used for future population-level prevention efforts. Examples of this approach are international multi-site and longitudinal programs, such as the PREVENT Dementia Programme.⁸ These programs collect deep phenotyping data, including brain structure and function via magnetic resonance imaging, amyloid-β load through positron emission tomography, clinical and cognitive data, lifestyle information, etc., from at-risk mid-life individuals, who are cognitively healthy at enrolment, and follow them up longitudinally. Such research programs aim to provide essential knowledge on novel, early and sensitive biomarkers of AD neurodegeneration, risk modification intervention targets for early prevention, and tractable mechanisms for targeting therapeutics and designing future clinical trials.^9,10 The mid-life age group is of particular importance to this prevention approach, because it presents a critical and unique window for disease-course altering interventions, before the manifestation of substantial brain damage.

Accumulating studies of cognitively unimpaired middle-aged individuals are showing that modifiable risk factors for late-life dementia (as assessed by aggregate dementia scales, such as the Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score),¹¹ are associated with worse cognition (e.g., poorer visual recognition,¹⁰ lower episodic and relational memory¹²) and declining brain structure (e.g., lower hippocampal volume,¹⁰ thinner cortex, larger hippocampal fissure¹³) an estimated 23 years prior to dementia onset. Conversely, stimulating lifestyle activities are associated with better cognition (e.g., episodic and relational memory) in at-risk mid-life populations, and may protect against the risk of sporadic late-onset dementia, such as for those with a family history of AD.¹⁴ A recent study found that inherited AD risk (i.e., Apolipoprotein E [APOE] ε4 genotype) modulated the association between sex, lifestyle factors and cognition: APOE ε4 + females showed a significant association between higher occupational attainment and stronger episodic and relational memory.¹² These findings suggest that modifiable lifestyle activities can offset cognitive decrements due to inherited AD risk in mid-life, and support the targeting of modifiable lifestyle activities for the early prevention of AD.

Deep phenotyping studies like the ones described above are designed to provide group-level evidence of the impact of risk-factors but can also generate individual-level information about brain and behavior that may be relevant to research participants. Research has shown that 9 out of 10 people want to know their risk of brain disease,¹⁵ and that once individuals know their own risk of AD, they adopt health behaviors faster.¹⁶ However, current clinical guidelines recommend against disclosing individual-level information about non-modifiable risk factors (e.g., APOE ε4 carrier status, amyloid-β in cerebrospinal fluid) to cognitively unimpaired individuals, due to the low predictive value of these risk factors for future dementia.¹⁵ By contrast, disclosing information about modifiable risk factors to research participants (e.g., those captured in dementia risk scores like CAIDE) has not been discussed in previous recommendations,¹⁷ despite recent studies showing that these factors are strongly associated with reduced brain health in mid-life.^10,12,13

Modifiable risk factors are critically different from non-modifiable factors, insofar as they are actionable. Studies show that people want information more when they believe it will be useful in guiding their actions, and that actionability is the number one motive that drives people to seek health information.¹⁸ Here, we argue that disclosing research-derived modifiable risk information can promote current brain health, independent of its individual-level predictive value for future dementia, and thus, ought to be made available to research participants.

Current ethical guidance

Much of the current ethical guidance concerning the disclosure of individual research results has arisen in the context of genetics research. Historically, three criteria have been used to determine whether disclosure of individual research results is required: i) analytical validity (the results are scientifically valid and confirmed); ii) clinical significance (they have significant implications for a participant's health); iii) clinical ‘actionability’ (a course of action to ameliorate or change the clinical course of the disease is readily available).^19,20 These criteria have typically been justified based on the so-called ‘duty to warn’, as well as the duty to avoid causing harm to research participants. Individual research results describing modifiable risk factors for dementia are unlikely to meet these conditions. While these results are scientifically valid, their predictive value at the individual level (i.e., the extent to which modifying a particular behavioral or lifestyle factor will reduce individual risk of dementia) remains uncertain.² Moreover, the lack of established preventive interventions (i.e., the clinical ‘actionability’ of the results) for dementia diminishes the requirement to make research results available according to standard ethics guidelines.

Even when individual research results do not satisfy the above criteria, disclosure may nevertheless be permissible based on considerations of beneficence and non-maleficence, respect for participant autonomy, and justice. However, these same considerations have also been used to argue against disclosure; for an overview of this debate, see Downey et al.²¹ As we argue below, considerations of beneficence and non-maleficence, respect for autonomy, and justice do not provide a conclusive case in favor of, or against, disclosing individual-level risk information about modifiable risk factors for dementia. However, if we reframe this information as concerning current brain health rather than future dementia risk, the case for disclosure is much more compelling.

Ethical considerations concerning disclosure of individual research results

Beneficence/non-maleficence

Beneficence emphasizes the importance of promoting and safeguarding the well-being of participants, while non-maleficence emphasizes the importance of minimizing possible harms to participants resulting from the conduct of research. The benefits of disclosing modifiable risk factors can be framed in terms of potential impact on dementia in later life.¹⁶ Early and accurate information about modifiable risk may motivate participants to seek treatment for risk factors (e.g., for hypertension), adopt health behaviors faster, or seek further education and support services to help reduce their risk. However, as described above, the extent to which modifying behavior or lifestyle factors will reduce individual-specific risk of dementia remains uncertain.

It can also be argued that information about modifiable risk factors might have ‘personal utility’ to participants,²² independently of any impact on dementia risk. These benefits include arranging financial affairs, advance care planning, preparing family members, and enrolling in research. For example, knowledge of risk status might result in a participant altruistically enrolling in further research, from which they derive personal satisfaction independent of any health benefits. Conversely, others have argued that the beneficence obligation of researchers (particularly non-clinician researchers), does not extend to offering results with personal utility.²³

A common concern relating to disclosure of dementia risk information to cognitively unimpaired individuals is psycho-social harm.²⁴ Studies have shown that for a significant portion of the population (26%–39%), dementia is the most feared medical diagnosis, surpassing even cancer.²⁵ As a result, there is concern that risk disclosure can cause adverse psychological effects (e.g., anxiety, depression).^26,27 Recent findings even show an increased risk of suicide attempt in individuals who received a recent diagnosis of mild cognitive impairment or dementia.²⁸

Yet, the disclosure of dementia risk, especially modifiable risk, is likely very different from a diagnosis of early dementia or AD. This is supported by data showing that the risk of psychological harm from the disclosure of non-modifiable risk information is low, and that the risk of potential harm dissipates over time.^16,22,26 Research does suggest, however, that participant concerns about stigma or discrimination may be justified, and that the process of disclosing one's risk to others can be a significant source of anxiety.¹⁶

Furthermore, studies have shown that knowledge of dementia risk can lead to altered perceptions or expectations about oneself (e.g., so-called ‘hypervigilance’), which negatively influences performance (e.g., poorer performance on objective and self-assessment memory tasks), and can lead to avoidance of behaviors that protect against dementia (e.g., social integration).²⁹ Finally, routine communication of risk may result in excessive testing and unnecessary treatment of age-related cognitive changes,³⁰ which could impact on insurance or employment status, and resource allocation throughout the healthcare system.

Respect for autonomy

A further consideration in favor of disclosing modifiable risk factors to participants is respect for autonomy, which calls for recognition of an individual's capacity to rationally determine and pursue their own ends. By providing participants with information that they can incorporate into future decision-making, disclosing individual research results is argued to promote participant autonomy. Withholding information that might be used in decision-making—even with the aim of protecting participants from harm—may violate autonomy because it interferes with a participant's ability to self-determine,³¹ particularly when individuals request research results.

Conversely, some have argued that disclosing information about dementia risk does not promote participant autonomy. Insofar as these risk factors lack predictive value, they do not convey any meaningful information on which to base future decision-making.²⁷ Moreover, if participants misinterpret these results (i.e., if participants form false beliefs about their level of risk), disclosing them potentially undermines their ability to act according to their values. While the empirical literature on feeding back dementia risk information to cognitively unimpaired participants is limited, there is evidence that participants can understand the prognostic uncertainty of inherited dementia risk.¹⁶ This argues against a default assumption that participants will misinterpret risk information, or that they are incapable of rationally incorporating information of limited predictive value into their decision-making, especially if adequate support and guidance is provided.

Justice

While typically receiving less attention than considerations of beneficence and respect for autonomy, the feedback of individual research results alsoraises justice considerations. Justice requires that there should be fairness in the distribution of the benefits and burdens of research. With respect to disclosing individual research results, this requires that results are made available in a consistent way. The fact that certain individuals or groups may be more difficult to engage, or require greater resources (e.g., follow-up) to ensure their understanding of results, is not an acceptable basis for withholding results. An obvious obstacle here is cost: larger research studies may simply have more resources available for follow-up than smaller studies, meaning that participants in a study with a larger budget may be more likely to receive their individual-level results than those participating in a smaller study. Further, making information about modifiable risk available to research participants does not mean that all participants will be equally able to act on this information, as various forms of social and structural inequality (e.g., socioeconomic, environmental, health) may act as barriers to individuals modifying lifestyle factors. These barriers are not in themselves a reason to withhold potentially useful health information, but they raise important concerns about the appropriate role of individual-level risk information in wider efforts to reduce dementia risk at a population level.^5,7,32,33

Focus on optimizing current brain health

As the above discussion demonstrates, considerations of beneficence and non-maleficence, respect for autonomy, and justice do not provide conclusive justification for, or against, disclosing individual-level risk information, including modifiable risk, for future dementia to cognitively unimpaired research participants.

Therefore, we argue for a different approach to evaluating the disclosure of individual-level modifiable risk factors for AD. Rather than focusing on individual-level disease prediction and prevention, we suggest that the permissibility of disclosure be evaluated based on the potential impact of behavioral and lifestyle changes on current brain health. This aligns with a broader trend in dementia research towards a holistic approach to understanding and treating AD. Since the 1990s, the majority of research into treatments for AD has been based on the hypothesis that the disease is related to the accumulation of proteins in the brain (e.g., amyloid and tau), which in turn impairs cognitive function. Yet, while several drugs have been developed that successfully remove these proteins, they have not led to significant improvement in clinical outcomes,³⁴ leading to questions over whether the protein-reduction strategy is the best way to treat AD.⁵ Consequently, there has been an increased emphasis on modifying lifestyle factors for dementia risk reduction and preventative interventions.

The impact of lifestyle factors on any individual's likelihood of developing dementia is uncertain.² Nevertheless, the disclosure of individual risk information is useful for maximizing brain health throughout the lifespan. For example, even if a middle-aged individual who shows high modifiable risk of future dementia (e.g., based on aggregate dementia risk scores, such as the CAIDE score excluding APOE ε4 status, or scores of lifestyle activities such as the Lifetime of Experiences Questionnaire,³⁵ that may indicate social isolation, physical inactivity, or lack of intellectual stimulation) never develops dementia, they can benefit from adapting a healthier lifestyle in the present. Research has found that more frequent engagement in physically, socially and intellectually stimulating activities is associated with stronger episodic and relational memory in mid-life individuals with a family history of AD,¹⁴ and higher occupational attainment is associated with episodic and relational memory in females who carried the APOE ε4 allele.¹²

The focus on modifiable lifestyle factors for current brain health provides a clear justification for disclosure that is aligned with considerations of beneficence, respect for participant autonomy, and justice. The benefits of individual-level disclosure are not contingent on a reduction in dementia likelihood, and the likelihood of psychosocial harms is mitigated by the fact that individual research results are not framed as the presence of disease, or as deterministically leading to the development of dementia. Moreover, while these results are not necessarily predictive of future disease, they convey meaningful information on which a participant can base decision-making about their brain health. And because they are reasonably simple to convey, additional costs associated with feedback are not likely to restrict feedback only to large studies. Indeed, this might provide underrepresented groups access to information they wouldn’t otherwise receive; insofar as this is an enticement to participate, this might help to attract otherwise underserved participants to research.

Focusing on the impact of risk disclosure on brain health is also consistent with a more participant-centric model of research. Providing individual-level results acknowledges a participant's contribution to research and has been argued to improve transparency and trust in the research enterprise,¹⁹ which in turn might lead to increased enrolment, and promotion of long-term relationships with research participants. This approach is particularly valuable for establishing more inclusive research with underrepresented groups, for whom relationships of trust with the biomedical community are currently lacking.

When individual research results are returned, the process of communicating them to participants must strive to promote understanding of the meaning, application, and limitations of this information. This requires training of staff on how to deliver this feedback so that the information is given in a clear and accurate way. Studies show that individuals vary greatly in extent to which they desire health information.³⁶ Therefore, a transparent strategy for communicating results, e.g., via prior discussion during the study consent process, should be part of the research protocol, including what support and guidance will be provided to participants. Participants may need to go through a separate informed consent at study conclusion, prior to receiving results, to ensure that they have not changed their mind about disclosure, and to inform them about new or unexpected findings that were not discussed in the initial informed consent.

While we have argued for the benefits of making individual-level risk information available to research participants, it is important that disclosure of individual-level risk not be construed as a form of ‘victim blaming’.³⁷ Similarly, disclosure should not overemphasize the impact of individual behavior change on dementia risk, nor under-emphasize the importance of structural factors that may not only impede risk-reducing lifestyle changes (e.g., food insecurity may make it difficult to adopt a healthier diet), but also increase dementia risk (e.g., living in a dense urban environment may increase exposure to pollution).^7,32,33,38 The whole-population approaches mentioned above aims to circumvent these structural barriers, and while an in-depth discussion of these is outside the scope of this paper, we emphasize the value of combining the ‘at-risk groups’ and ‘whole-population’ approaches for addressing the scale and impact of dementia across the globe.^7,38

Conclusion

In summary, when viewed from the perspective of disease prediction and prevention, it is difficult to assess whether making individual-level, modifiable risk information available to participants is ethically justified. This is due in large part to the fact that the impact of lifestyle factors on dementia risk at the individual level remains uncertain. By contrast, when viewed from the broader perspective of promoting current brain health, making this same information available is more clearly justified. Thus, our argument is primarily about how risk information is framed and communicated to participants, should they choose to receive it. At the same time, while disclosing modifiable risk information might lead to the adoption of lifestyle behaviors conducive to brain health, it is important that individual-level brain health promotion be seen as complementary rather than opposed to population-level approaches.

Footnotes

Acknowledgments

The authors have no acknowledgments to report.

ORCID iD

Lorina Naci

Author contributions

Mackenzie Graham (Conceptualization; Writing – original draft; Writing – review & editing); Martin Rossor (Writing – review & editing); Brian Lawlor (Writing – review & editing); Lorina Naci, PhD (Conceptualization; Funding acquisition; Project administration; Resources; Writing – original draft; Writing – review & editing).

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: L.N. was funded by a L’Oréal-UNESCO for Women In Science International Rising Talent Award, the Welcome Trust Institutional Strategic Support grant, and the Global Brain Health Institute Project Grant. M.G. was funded by the Wellcome Trust [203132/Z/16/Z].

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

World Health Organization. Global status report on the public health response to dementia. Geneva: World Health Organization, 2021.

Livingston

Huntley

Sommerlad

, et al. Dementia prevention, intervention, and care: 2020 report of the lancet commission. Lancet 2020; 396: 413–446.

Barnes

Yaffe

. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol 2011; 10: 819–828.

Sperling

Aisen

Beckett

, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the national institute on aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 280–292.

Daly

Keuck

. Alzheimer’s disease: Engaging with an unstable category. In: Schramme

Walker

(eds) Handbook of the Philosophy of Medicine, 2^nd Edition. Dordrecht: Springer Nature B.V., 2024. https://doi.org/10.1007/978-94-017-8706-2_113-1

Chen

Demnitz

Yamamoto

, et al. Defining brain health: a concept analysis. Int J Geriatr Psychiatry 2021; 37: 1–13.

Walsh

Govia

Peters

, et al.

What would a population-level approach to dementia risk reduction look like, and how would it work?

Alzheimers Dement 2023; 19: 3203–3209.

Ritchie

. The PREVENT study: a prospective cohort study to identify mid-life biomarkers of late-onset Alzheimer's disease. BMJ Open 2012; 2: e001893.

Ritchie

Waymont

JMJ

Pennington

, et al. The Scottish brain health service model: rationale and scientific basis for a national care pathway of brain health services in Scotland. J Prev Alzheimers Dis 2022; 9: 348–358.

10.

Ritchie

Carrière

, et al. The midlife cognitive profiles of adults at high risk of late-onset Alzheimer’s disease: the PREVENT study. Alzheimers Dement 2017; 13: 1089–1097.

11.

Kivipelto

Ngandu

Laatikainen

, et al. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol 2006; 5: 735–741.

12.

Deng

Ritchie

, et al. Sex differences in the associations between risk for late-life AD, protective lifestyle factors and cognition in mid-life. Alzheimers Dement 2023; 19: e074791.

13.

Dounavi

Newton

Jenkins

, et al. Macrostructural brain alterations at midlife are connected to cardiovascular and not inherited risk of future dementia: the PREVENT-dementia study. J Neurol 2022; 269: 4299–4309.

14.

Heneghan

Deng

Wells

, et al. Modifiable lifestyle activities affect cognition in cognitively healthy middle-aged individuals at risk for late-life Alzheimer's disease. J Alzheimers Dis 2023; 91: 833–846.

15.

Carver

Fredheim

NAG

Mowinckel

, et al. People's interest in brain health testing: findings from an international, online cross-sectional survey. Front Public Health 2022; 10: 998302.

16.

Largent

Bhardwaj

Abera

, et al. Disclosing genetic risk of Alzheimer’s disease to cognitively unimpaired older adults: findings from the study of knowledge and reactions to APOE testing (SOKRATES II). J Alzheimers Dis 2021; 84: 1015–1028.

17.

Dubois

Villain

Frisoni

, et al. Clinical diagnosis of Alzheimer's disease: recommendations of the international working group. Lancet Neurol 2021; 20: 484–496.

18.

Kelly

Sharot

. Individual differences in information-seeking. Nat Commun 2021; 12: 7062.

19.

National Bioethics Advisory Commission (NBAC). Research involving human biological materials: Ethical issues and policy guidance: Report and recommendations of the National Bioethics Advisory Commission, vol. 1. Rockville, MD: NBAC, 1999.

20.

Wolf

Crock

Van Ness

, et al. Managing incidental findings and research results in genomic research involving biobanks and archived datasets. Genet Med 2012; 14: 361–384.

21.

National Academies of Sciences, Engineering and Medicine. Downey

Busta

Mancher

, et al. (eds). Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington (DC): National Academies Press, 2018.

22.

Erickson

Chin

Johnson

, et al. Disclosure of preclinical Alzheimer’s disease biomarker results in research and clinical settings: why, how, and what we still need to know. Alzheimers Dement 2021; 13: e12150.

23.

Clayton

McGuire

. The legal risks of returning results of genomics research. Genet Med 2012; 14: 473–477.

24.

Graham

Farina

Ritchie

, et al. Fear of dementia and public sharing of research results. Camb Q Healthc Ethics 2022; 31: 498–505.

25.

Kessler

Bowen

Baer

, et al. Dementia worry: a psychological examination of an unexplored phenomenon. Eur J Ageing 2012; 9: 275–284.

26.

de Wilde

van Buchem

Otten

RHJ

, et al. Disclosure of amyloid positron emission tomography results to individuals without dementia: a systematic review. Alzheimers Res Ther 2018; 10: 72.

27.

Bunnik

Smedinga

Milne

, et al. Ethical frameworks for disclosure of Alzheimer’s disease biomarkers to research participants: conflicting norms and a nuanced policy. Ethics Hum Res 2022; 44: 2–13.

28.

Günak

Barnes

Yaffe

, et al. Risk of suicide attempt in patients with recent diagnosis of mild cognitive impairment or dementia. JAMA Psychiatry 2021; 78: 659–666.

29.

Bemelmans

Tromp

Bunnik

, et al. Psychological, behavioral and social effects of disclosing Alzheimer's disease biomarkers to research participants: a systematic review. Alzheimers Res Ther 2016; 8: 46.

30.

Fox

Lafortune

Boustani

, et al. The pros and cons of early diagnosis in dementia. Br J Gen Pract 2013; 65: e510–e512.

31.

Shalowitz

Miller

. Disclosing individual results of clinical research: implications of respect for participants. JAMA 2005; 294: 737–740.

32.

Walsh

Govia

Wallace

, et al. A whole population approach is required for dementia risk reduction. Lancet Health Longev 2022; 3: e6–e8.

33.

Eggink

Moll van Charante

van Gool

, et al. A population perspective on prevention of dementia. J Clin Med 2019; 8: 834.

34.

Ebell

Barry

Baduni

, et al. Clinically important benefits and harms of monoclonal antibodies targeting amyloid for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Ann Fam Med 2024; 22: 50–62.

35.

Valenzuela

Sachdev

. Assessment of complex mental activity across the lifespan: development of the lifetime of experiences questionnaire (LEQ). Psychol Med 2007; 37: 1015–1025.

36.

Sharot

Sunstein

. How people decide what they want to know. Nat Hum Behav 2020; 4: 14–19.

37.

Horstkotter

Deckers

Kohler

. Primary prevention of dementia: an ethical review. J Alzheimers Dis 2021; 79: 467–476.

38.

Daly

. The iceberg of dementia risk: empirical and conceptual arguments in favour of structural interventions for brain health. Cereb Circ Cogn Behav 2024; 6: 100193.