Impact of sharing Alzheimer's disease biomarkers with individuals without dementia: A systematic review and meta‐analysis of empirical data

We conducted a systematic literature review and meta‐analysis of empirical evidence on expected and experienced implications of sharing Alzheimer's disease (AD) biomarker results with individuals without dementia.

Discussion: Interest in AD biomarker testing was high and sharing their results did not cause psychological harm.

K E Y W O R D S
Alzheimer's disease, amyloid, biomarkers, diagnosis, disclosure, ethics, preclinical, prodromal, risk, tau

Highlights
• Most personal stakeholders expressed interest in Alzheimer's disease biomarker assessment.
• Personal motivations included gaining insight, improving lifestyle, or preparing for the future.
• There was no short-term psychological impact of sharing biomarker status, implying it can be safe.
• Most professional stakeholders valued biomarker testing, believing the benefits outweigh the risk.
• Harmonized guidelines on biomarker testing and sharing results are required.

BACKGROUND
[3] Decades of fundamental research and technological innovations have enabled in vivo detection of these protein changes in cerebrospinal fluid (CSF) and using positron emission tomography (PET) scans.This has led to a shift toward a biological definition of AD, by characterizing individuals based on the presence of AD-associated pathology.The "ATN" (amyloid/tau/neurodegeneration) research framework denotes AD as the combination of abnormal amyloid and abnormal tau, meaning persons with this profile have the disease, even if they don't fulfill criteria for dementia (yet). 4While the construct was introduced for research purposes, the approval of disease-modifying therapies, 5,6 increase of prognostic accuracy, [7][8][9] and advancements in blood-based biomarkers [10][11][12][13] suggest biomarker testing may move into clinical practice to improve diagnostic accuracy, and therapeutic decision making. 14 the same time, this has fueled a heated and ongoing debate in the field.When patients without substantial cognitive deficits visit a memory clinic, is it ethically acceptable to conduct AD biomarker assessments and communicate the outcome?[23] Previous reviews indicate that disclosing amyloid PET results does not pose immediate psychological harm to asymptomatic research partici-pants, but little is known about social and behavioral implications and the impact in cognitively impaired populations. 24,25 address these issues, we recently conducted a systematic review of theoretical data, and identified 26 diverse and contradictory considerations related to a clinical, personal, and societal context. 26A next step is to examine how these, and perhaps other, aspects are perceived by stakeholders, including the general public, patients, families, and health-care professionals.In this study, we therefore aimed to provide an overview of empirical data on expected and experienced implications of sharing AD biomarker results with individuals who do not have dementia (yet).

METHODS
A systematic literature search was conducted (by J.C.F.K. and J.v.d.S.) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement guidelines. 27Our query combined synonyms and spelling variations on the terms "Alzheimer's" AND "disclos*" OR "diagnos*" AND "predementia" AND "biomarkers," using controlled standardized keywords as well as free text terms (Material S1 in supporting information).We searched PubMed, Embase, APA PsycInfo, and Web of Science Core Collection from inception up to November 10, 2021.Additional records were identified through other sources, for example, reference lists.
To be included, publications had to present empirical data (quantitative or qualitative) on expected or experienced implications of disclosing amyloid and/or tau results to cognitively normal (CN) individuals or those with subjective cognitive decline (SCD) or mild cognitive impairment (MCI; corresponding to clinical stages 1-3 in the ATN framework). 28Data could be collected from any perspective, including patients, family members, clinicians, and so forth.The scope was limited to scientific articles written in English for which the full text was available (no editorials, commentaries, conference proceedings or [sections of] books).Studies on later stages and other types of dementia or neurodegenerative diseases were not included, as well as those primarily focused on trial design or genetic risk.
Two authors (J.v.d.S. and W.M.v.d.F.) independently screened all titles and abstracts.Articles marked as potentially relevant were assessed for eligibility based on full text.In case of discrepancy, arguments for inclusion and exclusion were discussed while re-examining the contents and criteria.In all cases consensus was reached.
Included articles were grouped according to design (qualitative, quantitative), study population, and timing (i.e., expectations before or experiences after disclosure).Content was analyzed inductively, by identifying and categorizing main findings.We summarized the results narratively by the most common themes emerging from the data.
Studies reporting sufficient quantitative data on the psychological impact of biomarker disclosure were included in a meta-analysis.
From these we extracted pre-and post-disclosure measurements and calculated standardized mean differences in test scores of anxiety, depression, stress, or suicidality.A random-effects model was used to synthesize effect sizes.In case of multiple follow-up assessments within a single study, we selected the measurement closest to 3 months after disclosure, as this was the most common follow-up time across publications.Two corresponding authors of studies included in the meta-analysis were contacted for additional information, and both responded.Risk of bias was assessed by two authors (J.v.d.S. and C.G.) independently using the Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I) tool (Material S2 in supporting information). 29

RESULTS
The flow diagram in Figure 1 shows that our database search, complemented with additional records identified through other sources, and after removing duplicates, yielded 8046 records.Two reviewers independently screened all titles and abstracts, by consensus excluding 7853 for not addressing the topic of interest.Subsequently, 193 full-text records were examined for eligibility.After applying selection criteria, we included 35 articles.

Personal stakeholders' perspective: expectations
[62] Authors reported on (hypothetical) interest, comprehension, and implications regarding various types of biomarker testing in individuals without dementia.[62]

Interest
1][62] A randomized controlled survey among 219 CN research participants, who had undergone blinded biomarker assessments, found that 95% wanted to learn their results. 36When posed as a hypothetical scenario, 72% to 75% CN research participants expected they would want to take a test, 34,44 versus 80% to 81% of (mostly) CN at-risk individuals involved with an AD prevention registry. 33,40Similarly, most or all research participants with MCI in two semi-structured interview studies opted to receive their predetermined amyloid status. 60,62Three studies in (mostly) CN populations found that a family history and/or high perceived susceptibility predisposed for a higher desire for testing, 33,36,40 yet in one, a survey among 164 at-risk participants, having an affected parent was inversely related 40 and according to a fourth study among 874 community-dwelling older adults self-rated risk was irrelevant. 44"Extreme interest" was lower in a survey among members of the general population (55.1% vs. 12.5%). 36Likewise, qualitative studies found the majority of individuals were open to predictive testing. 50,51,56,57,60,61

Comprehension
Seven studies reported on personal stakeholders' knowledge and comprehension of biomarker tests and results. 33,36,40,56,57,60,62In a randomized controlled survey among 219 CN research participants interest decreased after an educational intervention on benefits and limitations, except in participants with high subjective risk, family history, and low attendance to research meetings. 36Another study among 164 (mostly) CN at-risk participants found desire to learn test results was not associated with factual knowledge about amyloid brain imaging. 40In a survey among 4036 visitors of a prevention website 33% of respondents did not recognize that elevated biomarkers (CSF and amyloid PET) in a mildly symptomatic person reflected "either increased risk for or presence of AD." 33 Qualitative studies provided more insight.According to focus groups with mainly CN research participants, interpretation of biomarker status was shaped by family history. 56,57In two interview studies, patients with MCI demonstrated adequate understanding, 62 but were sometimes confused by the use of contra-intuitive terminology, mistakenly believing that a "negative" result would be the "unfavorable scenario" and vice versa. 60

Implications
[62] In quantitative and qualitative studies most frequently anticipated positive implications among all groups included preparing for cognitive decline by arranging medical, financial, legal, and personal affairs; 33,36,40,44,50,51,57,[60][61][62] adopting a healthier lifestyle to reduce risk; 33,36,50,51,56,57,61 obtaining early access to care or medication; 40,50,51,56,57 contributing to research; 36,40,51,62 and revising life plans and priorities to enjoy the time left. 33,40,50,51,56,57,60,611][62] Those more sceptic doubted the clinical validity, the prognostic certainty, and the medical utility. 40,50,51,56,61A lack of need or benefit was only reported by studies among (caregivers or family members of) patients with MCI. 50,51,621][62] Qualitative research among patients with MCI and their caregivers or family members also reported worry about consequences for their loved ones. 51,56,601][62] They found 10% to 12% of individuals involved with a prevention registry reported expected thoughts of ending one's life, 33,40 compared to 6% in AD research participants, 34 and <0.01%among those whose biomarkers had been measured but not communicated. 36Focus groups with participants from Germany and Israel found cultural variation in openness to discussing assisted dying. 50st CN individuals would share the presence of AD biomarker evidence with their spouse, but only half with their friends, 33 and few anticipated feeling comfortable disclosing their risk to their employer or health insurance company. 36Informing others was perceived both as a benefit and liability. 56,57,60,61Although being monitored by physicians and loved ones was appreciated, it was also feared to turn into surveillance or second-guessing, loss of social and professional status, or the freedom to drive a car. 56,57,60,61Indeed, a vignette-based randomized controlled trial among members of the general population suggested the stigma of dementia spills over into preclinical AD, irrespective of treatment availability. 46

Motivation
Three studies addressed personal stakeholders' motivation to be informed of biomarker status. 41,52,53Despite differences in design, results suggest that individuals at (perceived) risk were primarily driven by the wish to confirm or assuage subjective memory concerns.A questionnaire among 4327 CN participants identified altruism/contributing to research as the most important reasons.However those who (unknowingly) had elevated amyloid scored higher on motivations of perceived risk, and this association was mediated by perceived cognitive problems. 41Similarly, family members of CN participants with at least one first-degree relative with AD were mostly interested in learning their relatives' predisposition, either to be reassured or make plans accordingly. 53In addition, semi-structured interviews with patient-caregiver dyads in various (pre)dementia stages showed the majority was compelled by wanting to receive a definite (etiological) diagnosis, learn more about the condition, and follow their physician's recommendation to undergo the scan, while reasons for opting out of testing included costs, insurance coverage, or lack of benefits. 52

Comprehension
64 When sharing amyloid status after pre-disclosure education, most CN participants and most family members understood that elevated levels implied "an increased but uncertain risk of developing AD dementia," although their understanding of the probability varied considerably and some requested information on the degree of amyloid elevation.53,54,64 Half of those with normal readings and the majority of family members knew their chances were decreased.53,54 Yet overall, some participants felt the information was ambiguous or insufficient. 49,53,54Patients with MCI who tested positive could not recall the exact message after disclosure, like their amyloid-negative peers did, although they were able convey the essence in their own words.59 A few (mostly less involved) family members misinterpreted the results, and some patients with MCI were confused by the terminology, struggling with the notion that a "positive" outcome was "bad."59

Implications
3][54]59,63 Seven of these presented quantitative data.In the largest study, 1705 CN and pre-scan educated participants were informed of their results according to a specified protocol, and psychologically assessed before, at, and after disclosure. 37dividuals with elevated amyloid levels (n = 1167) were no more likely to experience short-term negative psychological consequences than those with normal results (n = 538).However, the positive group did have increased concern about AD, whereas the negative reported a slight improvement in future time perspective.One study among 97 CN participants found distress was slightly higher in the elevated group, 32 while another with 42 participants with SCD reported higher distress in those with normal results, 48 both associated with baseline levels of anxiety or depression.Research with 24 patients with MCI measured more variability in anxiety from day to day in those with elevated results compared to those with normal scan outcomes. 38None of the other studies found sustained effects or significant differences between groups or over time.
Five studies provided sufficient data on pre-and post-disclosure measurements of anxiety, depression, stress, or suicidality to be included in a meta-analysis.These assessed CN participants, 32,37 those with subjective decline, 48,49 or MCI/mild AD, 47 with follow-up times  2).These forest plots further show this is consistent across outcomes and studies.Thus, our synthesis of results across quantitative studies indicates that disclosure does not infer short-term psychological harm.
[55] The majority of participants were reassured, relieved, or happy upon receiving normal test outcomes, 49,[52][53][54][55]59 although in patients with MCI this was sometimes tempered by not having an explanation for concerns or symptoms.52,54,59 CN individuals tended to reinterpret previous "memory lapses" as normal aging, 53,54 those with MCI resumed previously suspended "normal" activities and plans. 59 Coversely, upon learning amyloid levels were elevated, participants felt sadness, worry, or despair, 49,[52][53][54]59 although they also indicated they appreciated knowing the cause of the cognitive complaints, having more certainty, and better follow-up and monitoring of health and symptoms.49,52,54,59 Compared to those with normal biomarkers, they were more likely to make lifestyle changes to improve physical and cognitive health; 49,54 adapt future plans, including practical, medical, financial, and legal affairs; 49,[52][53][54]59,63 and reevaluate priorities to enjoy time left and optimize quality of life.[53][54][55]59 One interview study among CN participants found that two thirds of interviewees with elevated amyloid reported not thinking of physicianassisted death, several were ambivalent, and approximately one in five stated pursuing this upon deterioration.Proportions were roughly equivalent in those with negative results, when asked to consider being positive.63 Some participants with SCD were satisfied with the level or social support, 49 and patient with MCI experienced improved relationships, due to more openness and understanding. 59 Other described uncertainties about the future and becoming aware or paranoid of cognitive slips.54,59 Family members acknowledged watching them more closely, 53 to the point where patients with MCI felt that monitoring turned into patronizing attitudes.59 In addition, participants struggled to decide whom to confide in, as well as why and how to tell others about their test results, for fear of negative reactions, losing control of the information, and worries about stigma and discrimination.55,59 As such, amyloid imaging was considered different from other medical tests, 53,54 partially because of the unique relationship to their identity as perceived by themselves and others. 54 Even o, upon reflection most interviewees stated they would make the same decision again, 52,59 but cautioned others to reflect on their desire and capacity to learn such sensitive information about themselves.53

Attitudes
Regarding the quantitative data, three studies among European health professionals found that 58% to 88% believed the benefits outweighed the risks of detecting AD in patients with MCI. 31,39,42In addition, a survey among 26 European physicians found that 12% often observed harm.Furthermore, 92% rarely or never learned their patients regretted being informed. 39One survey on attitudes regarding predementia biomarker testing in the United States reported that, compared to patient stakeholders, clinicians placed more value on the harm of false positive results, but judged it less important to test asymptomatic individuals. 30 contrast, qualitative data from an interview study among 15 Dutch physicians led to the conclusion that a predementia biomarker diagnosis did not fit with their views on good care, regardless of the absence or presence of symptoms, for lack of medical utility. 58

Practices
Data on current practices were quantitative and mostly from European studies. 31,35,39,42,43,45A survey among 110 physicians from 42 centers found that 92% had access to CSF and 51% to amyloid PET testing. 35wever, another questionnaire revealed that <25% of clinicians routinely performed lumbar punctures or amyloid imaging. 31Practices on disclosure and terminology differed.According to two other studies, in the case of abnormal results nearly all Belgian clinicians disclosed a diagnosis of AD to patients with MCI, 39 whereas 88% of German physicians communicated an increased risk for dementia to patients with MCI and 53% to persons with SCD. 43 a survey among 159 Alzheimer's Disease Neuroimaging Initiative investigators from the United States, most never returned amyloid PET results to research participants with MCI (90%) or CN subjects (94%), although after the US Food and Drug Administration's approval of florbetapir the majority would return them to those with MCI (73%) or even CN individuals (58%) upon request.45 Reasons for performing biomarker testing included increasing diagnostic certainty, providing counseling, starting medical intervention, facilitating follow-up planning, and selecting research participants.31 Barriers were lack of: validity, standards, time, confidence, clinical utility, knowledge about the impact on patients and relatives, as well as cost, risk, and burden of the procedures.30,31,42,45,58 In addition, practices on counseling, disclosure, referral to support groups, and advice on preventive strategies, as well as information on driving and advance care planning varied across countries and between centers, 35,42,43 illustrating room for developing, harmonizing, and educating testing standards and disclosure protocols.43,45

DISCUSSION
In our systematic review of the impact of sharing AD biomarker results with individuals who do not have dementia, from different stakeholders and perspectives, we found that the vast majority of individuals was interested in biomarker testing, learning their results was well tolerated, and this information was perceived as actionable.Although most professional stakeholders valued biomarker assessments, their attitudes and practices varied considerably, illustrating the importance of developing guidelines and recommendations for how to incorporate biomarker testing in diagnostic work-up.
Upon comparing these results to our previous systematic review of theoretical data on this topic, from which we synthesized 26 diverse and opposing considerations, related to a clinical, personal, or societal context, we noticed three things.First, the empirical studies almost exclusively addressed clinical and personal implications; only one examined a societal consequence, that is, how biomarker results affect the stigma related to AD. 46 Second, authors of theoretical literature tended to focus on risks, whereas participants of empirical studies were prone to highlight benefits.Third, patients and relatives identified new nuances and concepts, which were not addressed as extensively in theoretical literature, including the influence of subjective risk and family history; the dynamic among monitoring, vigilance, and paranoia; and the impact on quality of life.These findings identify gaps in knowledge and starting points for future research.We believe the discrepancies should not be interpreted as contradictory but rather as complementary, as they capture different aspects: the theoretical data are more reflective of ethical acceptability in general, while empirical data are closer to social acceptance, and both are relevant. 65It is important to consider how both perspectives can be integrated in a comprehensive moral evaluation. 66,67ong personal stakeholders, interest in biomarker information was high.Nearly all (80%-94%) participants who had been tested in a research setting wished to receive their results, 36,60,62 the vast majority (72%-81%) of persons involved with AD studies would hypothetically want to learn their biomarker status, 33,34,40,44,51,56,57,61 while diverse samples more representative of the general population were about evenly split pro and con. 36,509][70] Interestingly, several surveys in our review found associations with subjective risk and a family history, 33,36,40 but in one, having an affected parent actually lowered desire for biomarker assessment, 40 and in another no relation with perceived susceptibility was found. 44An explanation for these contradictory findings could be that persons with substantial concerns about their cognitive health may be a self-selected target population for biomarker assessment in pursuit of insight and control of their future.
However, similar to pre-symptomatic testing for pathogenic mutations of AD, 71,72 for some a high likelihood and more caregiving experience may deter them from wanting to be confronted with their disposition for an incurable and fatal disease.
One of the main concerns of sharing biomarker results with individuals who do not have substantial symptoms is the emotional burden of knowing one's status. 73,74Our meta-analysis found that in a protocol with pre-scan education the short-term psychological impact of disclosure was not significant when considering all participants, nor when examining those with positive or negative biomarker separately.This supports the emerging consensus that the psychological risk of sharing biomarker results to individuals without dementia does not reach the threshold for clinical concern. 75Some studies in our review reported a (trend toward) more variability, 38 or a slight increase in distress, anxiety, or depression, 32,47,48 in all subjects or either subgroup, even exclusively in those with normal biomarkers. 47,48In addition, qualitative data indicate that while "clean" scans generally evoked reactions of relief or reassurance, lack of an explanation for concern also gave disappointment or frustration, and although evidence of AD pathology typically led to stress or anxiety, it provided insight and clarity too.
These ambivalent responses to both "good" and "bad" news suggest that the degree of concerns and symptoms (including those too subtle to be picked up by neuropsychological tests) shapes the expectations of individuals and their families, which may in turn modify their reactions to the test outcomes.This hypothesis is supported by recent findings that when scan results confirm care partners' suspicions of elevated amyloid, they tend to report relief and gratitude rather than distress. 76re personal and contextual factors may influence the nature of responses, which emphasizes the importance of pre-test counseling and psychological screening. 77other matter of extensive debate is the actionability of sharing biomarker data, in terms of personal utility. 78Several of the included studies in CN participants or individuals with SCD reported that those with elevated amyloid were more likely to actually make changes to their lifestyle, by adjusting their diet, exercising more, challenging their minds, or considering trial participation, to remain cognitively healthy and to delay or prevent cognitive symptoms. 49,53,54In addition, they were more likely to actually prepare for the future, by changing financial, legal, and medical plans, as well as their living arrangements.Last, they were more likely to actually improve quality of life, by adapting their use of leisure time. 53,54This is consistent with research showing that disclosing genetic risk information to asymptomatic individuals is associated with changes in health behaviors and preparations for cognitive decline. 69,79,80However, although some participants reported sharing their biomarker status with their significant others improved relationships and social support, others struggled to decide whom to confide in and mentioned patronizing, stigmatizing, and discriminating attitudes. 55,59More research is needed into these social aspects, the dynamics between benign and adverse implications, and their development in the longer term.
We found that the majority of professional stakeholders value biomarker testing, believing the benefits outweighed the risks. 31,39,42wever, as most studies examined attitudes and practices in European health-care professionals, and the majority involved patients with MCI, these findings may not be representative for all clinicians and populations.In addition, regional and conceptual variations were found.
Differences in opinions on what abnormal biomarkers implied for individuals were strongly related to the desirability of testing and the communication of results.Dutch physicians believed such outcomes indicated an uncertain prospect, rather than the definite presence of a disease. 58Whereas Belgian clinicians shared a diagnosis of AD, 39 German physicians disclosed an increased risk for dementia. 43These inconsistencies may compound existing misconceptions in society. 81,82ttle is known about the implications of various framings, although one study reported not the label, but the prognosis, contributed to stigma and discrimination. 835][86] The advance of disease-modifying treatments will further increase medical utility. 5,6tably, empirical data on stakeholders' interest in learning their biomarker status were mostly based on CN research engaging individuals or members of the general public, while results on their experiences tended to include more patients with SCD or MCI, and findings on professional stakeholders' attitudes and practices mostly surveyed dementia specialists.This suggests a gap in data, as these are differ- More research is needed to assess the motivation for and impact of biomarker testing in various cognitive stages and different settings.
Previous research suggests that individuals come to memory clinics with specific motivations, which are not always stated and may differ from those of their caregivers. 87As the evaluation of the risk and benefits is specific to the individual and their situation, this merits shared decision making and a personalized approach.

Strengths and limitations
We supplemented our systematic review with a meta-analysis of several studies evaluating the impact of sharing biomarker results with persons who do not have dementia.Another strength is our extensive search strategy, which enabled us to synthesize data from both the personal and professional perspective, providing a comprehensive overview.We incorporated both quantitative and qualitative studies, which conveyed complementary information.In addition, there are some limitations which should be addressed in future research.First, there was considerable heterogeneity among study designs and quality, which complicated comparison of results.Some were based on small and specific populations.The concept of biomarker testing had diverse operationalizations, such as a hypothetical assessment, a combination of both biological and genetic markers, or amyloid PET imaging alone.Populations consisted of CN individuals or those with SCD or MCI and their relatives, and most were research participants rather than clinical patients, for whom biomarker testing might be most relevant.Due to the limited body of data and the variety in methods used for analysis in the included studies, it was not always possible to distinguish between these groups in our synthesis.Second, as few studies were available for meta-analysis and follow-up was relatively short, careful interpretation of the overall results is warranted and the long-term impact remains to be assessed.Third, the vast majority of studies included US and European participants, predominantly White and well educated.In most studies, individuals were psychologically screened and those with elevated levels of anxiety, depression at baseline, or a history of suicidal ideation were excluded.Several publications reported on different aspects of a single study or included participants from the same cohorts.These limitations severely constrain generalizability.There is a lack of research into people with more socioeconomic, ethnic, and racial diversity as well as those with lower psychological resources.Future research should be more inclusive, involve larger sample sizes, and include patient-centered outcomes in more biologically oriented studies, whether trials or biomarker validation.

CONCLUSION
In conclusion, biomarker testing in individuals who do not have dementia is a topic of ethical debate.Based on the available empirical data on the impact of sharing results, our systematic review and metaanalysis found that interest among personal stakeholders is high, and sharing test results does not cause significant short-term psychological harm and offers actionability.Although most health-care professionals value biomarker testing, attitudes and practices varied considerably.
Development and harmonization of testing guidelines and communication protocols are required, particularly in view of the imminent advancements in disease-modifying therapies.

ACKNOWLEDGMENTS
: There is a need of developing guidelines and recommendations for how to incorporate biomarker testing and sharing results in diagnostic workup, particularly considering the imminent advancements in disease-modifying treatment.

ranging from 6 F I G U R E 2
weeks to 1.5 years.Meta-analysis of the standardized mean outcome difference (pre-disclosure vs. 3 months post-disclosure) revealed no significant psychological impact when considering all par-Forest plots of the psychological impact of sharing AD biomarkers results with individuals who do not have dementia.Forest plots of the short-term psychological impact of sharing AD biomarker results with individuals who do not have dementia, before versus 3 months after disclosure, are shown using a random effects model, considering all participants (random-effect estimate = 0.10, SE = 0.23, P = 0.65), only biomarker-negative individuals (left plot, magenta: random-effect estimate = 0.19, SE = 0.32, P = 0.55) and only biomarker-positive individuals (right plot, magenta: random-effect estimate = 0.01, SE = 0.33, P = 0.97).AD, Alzheimer's disease; BAI, Beck Anxiety Index; BDI-II, Beck Depression Inventory-II; CES-D, Center for Epidemiologic Studies Depression; CSSRS, Columbia Suicide Severity Rating Scale; DASS, Depression; Anxiety, and Stress Scale; GDS, Geriatric Depression Scale; HADS, Hospital Anxiety and Depression Scales; SE, standard error; SMD, Standardised Mean Difference; STAI, State-Trait Anxiety Inventory.ticipants (random-effect estimate = 0.10, standard error [SE] = 0.23, P = 0.65), nor when considering individuals with negative biomarkers (estimate = 0.19, SE = 0.32, P = 0.55), or positive biomarkers (estimate = 0.01, SE = 0.33, P = 0.97) separately (see Figure ent situations.Implications of receiving amyloid and/or tau test results may differ depending on individuals' cognition (i.e., CN, SCD, or MCI), and the context in which this information is shared (i.e., as part of trial participation or in the memory clinic).Currently, the absence or presence of cognitive impairment determines whether disclosure of test results is only recommended in research settings or also permissible in clinical practice, although this may change once a preclinical diagnosis of AD becomes medically actionable.Still, our findings suggest subjective concerns and symptoms affect patients' anticipation of the results and thus the emotional impact of learning them, as elevated biomarkers may confirm or explain suspicions, while those without worries or unaware of signs may be less prepared to receive "bad news."Especially for the latter, pre-test screening, counseling, and education (on topics including uncertainty, stigma, and discrimination) are important.Conversely, to patients with MCI, biomarker results provide information on the underlying condition of a syndrome that has already been diagnosed, whereas negative biomarkers may create frustration over lack of insight into the cause.Furthermore, disclosure in a symptomatic phase may leave less time and opportunity to benefit from diseasemodifying therapies, adopt a risk-reducing lifestyle, arrange personal affairs, and advance life plans, whereas the risk of for medicalization, stigmatization, and discrimination may be bigger in a preclinical stage.
Publications on personal stakeholders' experiences after learning biomarker results.Publications on professional stakeholders' attitudes and practices regarding biomarker testing.
TA B L E 2Abbreviations: A4, Anti-Amyloid Treatment in Asymptomatic AD; ADRC, Alzheimer's Disease Research Center; APEX, Alzheimer's Prevention through Exercise; APOE, apolipoprotein E; CN, cognitively normal; BAI, Beck Anxiety Index; BDI-II, Beck Depression Inventory-II; BioAdaptAD, Biomarker-Based Adaptive Development in Alzheimer's Disease; CAADS, Concerns About Alzheimer's Disease Scale; CES-D, Center for Epidemiologic Studies Depression; CSSRS, Columbia Suicide Severity Rating Scale; DASS, Depression; Anxiety, and Stress Scale; EMA, ecological momentary assessment; FTPS, Future Time Perspective Scale; GDS, Geriatric Depression Scale; HADS, Hospital Anxiety and Depression Scales; IES, Impact of Events Scale; IES-R, Impact of Events Scale Revised; IGT-AD, Impact of Genetic Testing for Alzheimer's Disease; LEARN, Longitudinal Evaluation of Amyloid Risk and Neurodegeneration; MAC-Q, Memory Assessment Clinic questionnaire; MCI, mild cognitive impairment; PET, positron emission tomography; PHQ, Patient Health Questionnaire; REVEAL-SCAN, Risk Evaluation and Education of Alzheimer's Disease: The Study of Communicating Amyloid Neuroimaging; SCD, subjective cognitive decline; SOKRATES (I), Study of Knowledge and Reactions to Amyloid Testing; SOKRATES II, Study of Knowledge and Reactions to APOE Testing; STAI, State-Trait Anxiety Inventory; US, United States; VPAI, Views and Perceptions of Amyloid Imaging questionnaire.TA B L E 3 Abbreviations: AAN, American Acedemy of Neurology; AD, Alzheimer's disease; ADNI, Alzheimer's Disease Neuroimaging Initiative; BeDeCo, Belgian Dementia Council; CN, cognitively normal; CSF, cerebrospinal fluid; EADC, European Alzheimer's Disease Consortium; EAN, European Academy of Neurology; EU, European Union; FDA, Food and Drug Administration; MCI, mild cognitive impairment; MOPEAD, Models of Patient Engagement for Alzheimer's Disease; PET, positron emission tomography; SCD, subjective cognitive decline; US, United States.
Research of Alzheimer CenterAmsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience.Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam.The clinical database structure was developed with funding from Stichting Dioraphte.The chair of Dr. Van der Flier is supported by the Pasman stichting.Jetske van der Schaar is appointed at ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106).More than 30 partners participate in ABOARD.ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds.Yolande Pijnenburg is recipient of YOD-MOLECULAR (NWO #KICH1.GZ02.20.004).