Amyloid PET disclosure in subjective cognitive decline: Patient experiences over time

1. BACKGROUND

Alzheimer's disease (AD) is a neurodegenerative disease, characterized by the accumulation of amyloid and tau, ultimately leading to dementia. ¹ With advanced diagnostic tests, such as amyloid positron emission tomography (PET), AD‐related pathology can be detected in early stages of the disease, before the onset of dementia. ² Individuals with subjective cognitive decline (SCD) present at memory clinics with cognitive complaints, yet do not show deficits on neuropsychological testing. ³ Because prognosis is uncertain and there is no available treatment for individuals with SCD, clinicians are reluctant to assess AD‐biomarker status, as they worry that such information might do more harm than good. ⁴ , ⁵ Nonetheless, a substantial number of individuals with SCD visit the memory clinic, often with a high need for information about their risk of developing dementia. ⁶ , ⁷ , ⁸ Meanwhile, memory clinic professionals indicate a need for tools or training in communicating about uncertainty and dementia risk. ⁵ Recommendations for assessment and disclosure of AD biomarkers in cognitively unimpaired individuals exist, but are largely based on expert opinion and/or are based on a clinical trial setting. ⁹ , ¹⁰ , ¹¹ , ¹²

Previous studies investigating the impact of sharing results of AD‐biomarker testing with cognitively unimpaired individuals (mostly in a trial setting) showed disclosure to be sufficiently understood, emotionally safe, and to allow individuals to take preventive actions. ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ The latter two are patient‐reported outcomes (PROs), that is, any report of patients’ view of their health status. ²¹ Patient‐reported experiences (PREs) are patients’ experiences of health care, such as their satisfaction with the consultation and the information received. ²¹ The decision to learn one's amyloid status is very personal, as pros and cons do not clearly outweigh each other. ²² For example, an individual can experience unpleasant feelings of uncertainty about the future as a consequence of learning their positive amyloid status (PRO), while at the same time still valuing the information provided (PRE). Thus far, PREs have hardly been a research topic of interest in this context, and therefore it is unknown whether disclosure of AD‐biomarker results actually addresses the individual's need for information. ²¹ , ²³ This is of importance, as the decision to learn one's amyloid status cannot be undone once the information is disclosed. In this light, it is important to know how people reflect on learning their amyloid status after some time, as this might differ from their immediate response. ²⁴

We therefore set out to study both outcomes and experiences of amyloid PET disclosure in individuals with SCD from a memory‐clinic cohort, immediately after disclosure and 6 months later. In doing so, we also considered the potential influence of amyloid status (positive vs. negative). As disclosure consultations have taken place both face to face and by phone, we also explored consultation modality as a factor associated with outcomes and experiences.

2. METHODS

3. RESULTS

4. DISCUSSION

Individuals with SCD valued amyloid PET disclosure positively, both immediately after and 6 months later. They were satisfied with the consultation and experienced low levels of regret about the decision to receive their amyloid PET scan result, regardless of whether the result was positive or negative. Amyloid‐positive individuals reported a higher information need after 6 months compared to those testing negative; they, in particular, wanted information about drug research or advice on what can be done to slow disease progression. In terms of emotional impact, we did not observe an increase in negative emotions. After 6 months, amyloid‐positive individuals reported more often to have recorded their wishes for the future.

Previous studies, often conducted in a trial setting, showed that disclosing AD‐biomarker results to cognitively unimpaired individuals is sufficiently understood, emotionally safe, and allows individuals to take preventive actions. ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ We expand on these findings by studying a memory‐clinic cohort of individuals with SCD and additionally looking into their experiences with the amyloid PET disclosure process over a 6‐month period. Some participants, more frequently those A+, wished for more information, for example, on the development of drug research and advice on what can be done to slow disease progression. Although some still had questions, participants experienced low levels of regret about the decision to receive their amyloid PET scan result. Participants valued receiving information about their own health status (A+ and A‐) and the possibility to act (A+), along with feelings of certainty and relief (A−). Amyloid‐positive participants took the importance of timing (e.g., does this information come at the right point in time), and irreversibility (e.g., knowing this information cannot be undone) into consideration. This illustrates the importance of a shared decision‐making process before embarking on diagnostic testing in memory clinic practice, as emphasized in disclosure recommendations. ⁹ , ¹⁰ , ¹¹ , ¹² , ³⁹

We found that most individuals with SCD sufficiently understood that amyloid is a protein in the brain, the presence of which can be visualized with an amyloid PET scan, indicating an increased risk of developing AD dementia. Previous studies investigating understanding of AD‐biomarker results in cognitively unimpaired individuals also found sufficient understanding in most participants. ¹⁸ , ¹⁹ In all three studies, some participants expressed a desire for information about the amount of amyloid detected. The approval of quantification of amyloid PET, that is, Centiloids, ⁴⁰ for clinical practice is relevant in this context. A few participants considered the presence of amyloid to indicate already having AD or dementia. The question of whether AD can be diagnosed based on biomarker evidence in the absence of clinical symptoms, and second, whether SCD would count as symptomatic or asymptomatic is an ongoing and sometimes heated debate in the field. ⁴¹ , ⁴² , ⁴³ This lack of clarity and degree of uncertainty can easily confuse patients, making it important that clinicians carefully explain what has been found, and what can be learned from this, including the uncertainty surrounding this finding. Furthermore, the interchangeable use of “Alzheimer's disease” and “dementia” is an acknowledged misconception that must be actively addressed when disclosing AD biomarkers, especially in pre‐dementia stages. ⁴⁴ , ⁴⁵ In addition to post‐disclosure, these topics are important to address during pre‐testing counseling. ⁹ , ¹⁰ , ¹¹ , ¹² The use of (risk) communication strategies, such as using a visualization of the AD continuum or using the teach‐back method, could support clinicians in these challenges. ⁴⁶ , ⁴⁷

In terms of PROs, we investigated the emotional impact and behavioral (intentions to) change. In line with previous studies, we found that disclosure of AD‐biomarker results did not significantly increase negative affect, uncertainty, or anxiety. ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ²⁰ We add to the literature by also looking into positive affect. This was highest in the week surrounding the disclosure consultation compared to 6 months thereafter, independent of amyloid status. The positive affect scale included items such as “interested,” “attentive,” and “excited.” It could be that the prospect of receiving the amyloid PET scan result or more in general the anticipated hospital visit to contribute to science induced these feelings. We did not see differences in any of the measured emotions between amyloid groups. This fits with the notion that a well‐considered decision made in a context in which there is no clear right or wrong can limit the emotional impact, regardless of the result. ⁴⁸ With regard to behavioral (intentions to) change, we found that immediately after disclosure, A+ participants were more inclined to review and possibly amend insurance policies and after 6 months, more frequently reported to have recorded their wishes for the future. These findings are largely in line with earlier findings that A+ participants were more likely to change their lifestyle and/or future plans. ¹⁶ , ¹⁸

Our study has some limitations. First, our sample was relatively highly educated, thereby limiting generalizability. Although participants initially were referred to the memory clinic, they all participated in the SCIENCe study, and as such were highly motivated to increase knowledge about the brain and AD. Indeed, they reported a high information need about their health status and it is likely that their prior knowledge about AD, its diagnostics, and brain health was above average. Special attention is warranted to ensure applicability for groups who are underrepresented in our study, such as individuals who are not of White European descent or have different levels of education. Their experiences and outcomes might differ and this could lead to additional implications for clinical practice. Nonetheless, our sample presented at a memory clinic and wanted to hear their results. In that way, our findings have immediate relevance for a memory clinics setting, in which individuals present at increasingly early stages, and increasingly demand to know their dementia risk or biomarker status. ⁴⁹ Strengths of our study are that our sample is a memory‐clinic cohort, thus mimicking clinical practice more closely than previous studies in trial settings. With an ever‐increasing number of studies confirming the association between amyloid and cognitive decline in pre‐symptomatic stages, ⁵⁰ , ⁵¹ , ⁵² the number of trials targeting the pre‐symptomatic phase of AD is expected to increase. ⁵³ Individuals presenting with SCD at a memory clinic form an important target population for such studies. We evaluated a broad range of both PROs and PREs, with relatively long follow‐up of 6 months. As such our study provides important information on the patient perspective regarding early disclosure of amyloid status.

Future studies should replicate our findings regarding consultation modality, as the COVID‐19 pandemic might have made participants more understanding of consultations not taking place face to face. One former study also showed virtual disclosure to be safe and feasible. ⁵⁴ In addition, our next step would be to further develop supporting tools in the context of SCD that can be easily incorporated in clinical practice. Clinicians, researchers, and individuals with lived experience call for an improvement of communication about AD by means of education and communication tools. ⁵ , ⁴⁵ , ⁵⁵ The lack of implementation of current communication recommendations in memory clinic practice might not only be due to contextual issues, but also because of their form, that is, large amounts of written text. Based on our findings, we suggest (1) a conversation guide to shared decision making on the assessment of AD biomarkers in the context of SCD, containing the pros and cons of knowledge of biomarker results (e.g., possibility to act, feelings of relief, timing, and irreversibility), (2) a question prompt list to fill out at home and bring to the consultation, consisting of the information needs mentioned by individuals with SCD, and (3) a results page the individual with SCD can take home, including a visualization of the AD continuum and space for the neurologist to write personalized notes. ⁵⁶ , ⁵⁷ , ⁵⁸ To foster accessibility, we developed and gathered prototype tools on www.ADappt.health, a web‐based toolkit for communication support in the memory clinic. ⁵⁷ Future studies should assess the implementation and effectiveness of the use of such tools in clinical practice.

5. CONCLUSION

In conclusion, participants with SCD positively valued amyloid PET disclosure, independent of amyloid status. Importantly, participants experienced low levels of regret about the decision to receive their amyloid PET scan result, irrespective of the actual result. A+ individuals more frequently reported unmet information needs after 6 months, confirming that patients in a memory clinic setting want more, rather than less, information. Sharing results of AD‐biomarker testing with research participants with SCD is emotionally safe and allows them to take actions.

CONFLICT OF INTEREST STATEMENT

H.H., T.R., A.F., E.G., M.L., J.S., C.T., D.V., and E.S. report no financial disclosures or conflicts of interest. A.H. is advisor to the Brain Research Center. Research programs of A.H. have been funded by ZonMW and Alzheimer Nederland. All funding is paid to her institution. L.N.C.V. has been an invited speaker at Schwabe Group, fees were paid to her institution. Research programs of W.F. have been funded by ZonMW, NWO, EU‐JPND, EU‐IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes‐Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc., Novartis‐NL, Life‐MI, AVID, Roche BV, Fujifilm, Eisai, Combinostics. W.F. holds the Pasman chair. W.F. is recipient of ABOARD, which is a public–private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP‐allowance; #LSHM20106). W.F. is recipient of TAP‐dementia (www.tap‐dementia.nl), receiving funding from ZonMw (#10510032120003). TAP‐dementia receives co‐financing from Avid Radiopharmaceuticals and Amprion. All funding is paid to her institution. W.F. has been an invited speaker at Biogen MA Inc., Danone, Eisai, WebMD Neurology (Medscape), NovoNordisk, Springer Healthcare, and European Brain Council. All funding is paid to her institution. W.F. is consultant to Oxford Health Policy Forum CIC, Roche, Biogen MA Inc., and Eisai. All funding is paid to her institution. W.F. participated on advisory boards of Biogen MA Inc., Roche, and Eli Lilly. W.F. is a member of the steering committee of EVOKE/EVOKE+ (NovoNordisk). All funding is paid to her institution. W.F. is a member of the steering committee of PAVE, and Think Brain Health. W.F. was associate editor of Alzheimer, Research & Therapy in 2020/2021. W.F. is associate editor at Brain. Author disclosures are available in the supporting information.

CONSENT STATEMENT

All participants provided informed consent.

Supporting information

Hendriksen HMA, de Rijke TJ, Fruijtier A, et al. Amyloid PET disclosure in subjective cognitive decline: Patient experiences over time. Alzheimer's Dement. 2024;20:6556–6565. 10.1002/alz.14148