Attitudes,Motivations,and Barriers to Pre-Symptomatic Alzheimer’s Disease Screening: Development and Validation of the ‘Perceptions regarding pRE-symptomatic Alzheimer’s Disease Screening’ (PRE-ADS) Questionnaire

Abstract

Background:

Pre-symptomatic screening methods for detecting a higher risk of Alzheimer’s disease (AD) are gaining popularity; thus, more people are seeking these tests. However, to date, not much is known about the attitudes toward pre-symptomatic AD screening.

Objective:

The goal of this study is to examine the psychometric properties of a tool for assessing the attitudes, barriers, and motivations to pre-symptomatic AD screening.

Methods:

This is a cross-sectional study performed on 208 Greek participants (189 students and 19 caregivers) provided with an online questionnaire. Psychometric properties were assessed through the examination of its construct validity (principal component analysis) and internal consistency.

Results:

Exploratory factor analysis revealed the presence of four factors. The first factor is labeled as “Perceived harms of testing” (10 items), the second “Acceptance of testing” (5 items), the third “Perceived benefits of testing” (6 items), and the fourth factor “Need for knowledge” (4 items). The reliability (internal consistency) of each factor separately was acceptable to good (0.70–0.87) while the internal consistency of the overall questionnaire (25 items) was good (Cronbach’s α=0.82).

Conclusion:

PRE-ADS is a valid questionnaire that might help in the research of peoples’ attitudes related to the pros and cons of pre-symptomatic screening for AD, and the development of effective counseling programs and prevention strategies. However, future research is required in the target population.

Keywords

Alzheimer’s disease attitudes benefits perceived harms pre-symptomatic testing psychometrics screening screening acceptance validation

INTRODUCTION

Genetic susceptibility tests for various medical conditions are gaining increasing attention across health care, research, and direct-to-consumer settings [1]. The increasing availability of reliable genetic tests at lower prices as opposed to years ago has made them accessible and welcomed in clinical practice [2]. A considerable number of studies have also been carried out in an attempt to unwrap biomarkers (genomics and proteomics) that may be typical indicators for preclinical (before symptoms occur) disease screening and predictive prognosis [3]. Specifically, in dementia, the new screening methods—gene discoveries and the identification of biomarkers—in individuals without symptoms have increased the early detection of some types of the disease [3, 4]. Nowadays, there is a combination of biomarkers in Alzheimer’s disease (AD), which is the most common type of dementia, such as the non-invasive neuroimaging, cerebrospinal fluid (Aβ_1-42, Aβ_1-40, tau, and phospho-tau), and genetic evidence of AD in the in vivo antemortem brain [5]. These can be detected in asymptomatic people seeking AD screening (AD pre-symptomatic screening) or people who are in the preclinical stage of AD, when cognitive impairments are largely undetectable [5].

Late-onset AD (LOAD) is the most common form of AD and typically occurs after the age of 65, in contrast with early onset AD (EOAD) which is relatively rare, accounting for less than 5% of AD cases, that manifests before the age of 65. Mutations in the amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes can lead to a fully penetrant autosomal dominant form of EOAD, whereas the penetrance of mutations in presenilin-2 (PSEN2) gene is estimated to be around 95% [6]. The apolipoprotein E (APOE) gene, specifically the APOE ɛ4 allele, is associated with an increased risk of developing LOAD. Individuals with one copy of the apolipoprotein APOE ɛ4 allele have a three-to four-fold increase in the risk of developing LOAD. The risk is often higher in individuals who have two copies of the APOE ɛ4 allele [6, 7]. However, parent-offspring concordance in EOAD was estimated to be < 10%, indicating that full penetrant dominant alleles are not the sole players in EOAD, as well as the APOE ɛ4 allele is neither a necessary nor sufficient predictor of the disease. The effect of APOE ɛ4 accounts for only 27.3% of the estimated heritability of 58–79%, and the association between APOE ɛ4 allele and AD has been shown to vary by race and ethnicity [8, 9].

All these early genetic tests are gaining traction and, in the future, may be approachable for a considerable population of asymptomatic people outside of the research environment [10]. In addition to that, there is a significant public interest in preclinical testing [11]. Although people have some medical and technological knowledge of pre-symptomatic testing procedures, sociologically and psychologically they are not prepared. Ethical, legal, practical, and also financial questions for people and the global community are rising. In particular, individuals all over the modern world will face a dilemma: Should they proceed with testing? Would they want to know if they pertain to the higher-risk population for this disease which is characterized by few treatments? [4]. On one hand, the participation in such a process and the disclosure of the AD screening results by counseling experts can help raise awareness about AD. Specifically, the disclosure of the results by an expert would prevent unreasonable decisions based on misinterpretations of technical terms. Instead, it would enhance the genetic literacy and improve the conformity with health-screening methods. Research demonstrates that participating in biomarkers screening methods and in the disclosure process could promote proactive prevention strategies for AD such as healthier lifestyle and wellness changes (physical exercise, diet, vitamins, cognitive stimulation, stop smoking) [12 –16]. Furthermore, it can probably provide access to the knowledge necessary to decide whether or not to participate in advanced, pharmaceutical treatments to prevent disease and to develop plans for the future [17]. The knowledge and the proper evaluation of the screening results can support families by decreasing potential psychological morbidity, changing to more positive attitudes in taking a pre-symptomatic AD screening, decreasing fear and stigma for this kind of procedure, and encouraging long-term health insurance, which is particularly relevant for the long-term nature of AD [18]. Thus, a pre-symptomatic screening can be a first step for improving personalized care and establishing prevention measures.

On the other hand, many individuals struggle to understand testing information and its implications for their health. When receiving testing results, sometimes they experience unnecessary anxiety and psychological distress, or proceed with decisions about their health based on insufficient information that often result in increased healthcare costs [17]. A number of risks factors for such testing needs to be considered, including psychological implications (i.e., the appearance of depression, suicide intention), impact on insurance and employment, and the understanding of the test’s limitations [2, 19].

The broad use of genetic and biomarker testing does not reflect heightened knowledge and awareness of the risk of developing AD in the general public. This fact prompted the need for a clear and understandable information and participation in educational activities [16 , 20–25]. Nonetheless, communicating about AD risk is composite, especially on how to communicate optimally the risk and what to tell on an individual level—the actual risk—due to the fact that the worried individuals have not yet been cognitively impaired. Ideally, AD risk communication strategies should maximize the possible benefits of knowing the actual risk and minimize potential harms [26].

Appraising the perspectives of individuals who are likely to seek pre-symptomatic testing for AD, as well as understanding of public preferences and differences are crucial for better development of screening programs, effective counseling, and supportive interventions [19 , 28]. By addressing potential motivations and barriers of asymptomatic individuals seeking AD screening, healthcare providers and policymakers can be better prepared to anticipate and address the questions and consequences that may arise from this rapidly growing practice [11, 21]. In addition, exploring acceptability can broadly highlight critical ethical, legal, and social issues relevant to the development of new programs for screening and reveal how informed choice, confidentiality, and respect for autonomy might be ensured [28].

In literature, there are many studies that have examined the public acceptance, attitudes, and the most common factors influencing intentions to take a genetic and/or a pre-symptomatic biomarker testing for the risk of dementia and AD [11 , 28–31] and also other studies that have focused on older people and patients’ preferences and perceptions on dementia or AD screening in primary care [16 , 20–25]. Besides, other studies have also analyzed caregivers’ attitudes about dementia and AD screening [32 –34], or the acceptance, people’s intentions, beliefs, and anticipated behavior of asymptomatic individuals who reported a family history of dementia and AD [17 , 36]. However, it remains unclear what the specific factors are that promote or reduce AD pre-symptomatic screening acceptance in these caregiver groups, and so further research is required. In addition, little is known about the preferred way of communicating these results and the type of support these people wish to receive.

Furthermore, a variety of studies have developed scales to measure attitudes, the need for knowledge, benefits, and barriers in obtaining AD screening [4 , 38]. Most of these studies use self-administered survey questionnaires or a structured interview guide developed for the purpose of studies and focusing on a specific population. The most widely used scale is the “Perceptions Regarding Investigational Screening for Memory in Primary Care” (PRISM-PC) Questionnaire [39] that has been developed to capture patients’ and caregivers’ attitudes about dementia screening in primary care. Also, Galvin et al. (2006) [40] developed and validated a questionnaire to explore psychosocial determinants of screening for cognitive dysfunctions and AD in older adults. This scale measures knowledge about AD, self-efficacy, and perceived susceptibility, severity, pros, and cons of dementia screening [40, 41]. The modified Dementia Screening and Perceived Harms (mSAPH) questionnaire, a modified version of PRISM-PC, has also been used for measuring acceptability and attitudes toward dementia screening in primary care patients [42]. Including the above, many of the questionnaires were based on the Health Belief Model (HBM), a theoretical model that attempts to explain and predict the reasons why some individuals practice preventive health behavior, to develop their hypotheses and factors predicting interest in AD testing [43]. All these scales are usable; however, they lack validation of different samples, and none of them focus on the need for knowledge and support that people would like to have prior, during, and after announcing the results of testing. For example, in the population of Greece, there are currently no validated questionnaires on attitudes to the screening of AD in asymptomatic people, although AD is a significant health problem in this population.

Therefore, the purpose of this current study was to develop and examine the psychometric properties of an online questionnaire about attitudes toward pre-symptomatic AD screening and the need of people for knowledge and support. Specifically, in this study, a quantitative scale was developed to assess: 1) perceptions, attitudes, and acceptance of pre-symptomatic screening for AD, 2) motivations and barriers for seeking such screening, and 3) the need for knowledge and the rationale for disclosure of potential AD risk. The results of this study will be used in a more extensive research project to investigate and evaluate attitudes toward AD biomarkers screening and genetic testing of asymptomatic people with a family history of AD including psychological and demographic predictors of test intentions. These results may help design a well-structured and efficient genetic counseling program that will be applied in clinical practice and further research studies.

METHODS

Study design

This is a quantitative cross-sectional study to assess the attitudes, barriers, and motivations to pre-symptomatic AD screening.

Developing the “Perceptions regarding pRE-symptomatic Alzheimer’s Disease Screening” (PRE-ADS) Questionnaire

The content of this scale was based on 1) the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) Questionnaire [35], which is based on the value expectancy theory of the HBM [40], 2) a review of the literature of attitudinal previous study on pre-symptomatic AD screening and genetic counseling, and 3) a board of clinical expert opinions regarding the main research questions of a larger project in genetic counseling, placed in the Greek Association of Alzheimer Disease and Related Disorders (GAADRD) Journal.

According to its developer, the PRISM-PC questionnaire is composed of two separate sub-scales, namely, the patient’s acceptance of the dementia screening scale and the patient’s perceived barriers and motivations for the dementia screening scale, and it has been used in the primary care setting. Particularly, the PRISM-PC questionnaire consists of 50 items, with 12 of them capturing self-reported sociodemographic data and information concerning a participant’s experience with or without exposure to AD, and 38 items measuring the participant’s attitudes toward the acceptability and pros and cons of dementia screening [22, 39]. It consists of five domains, while the internal consistency of all subscale scores and the total acceptance score, using Cronbach’s alpha coefficient, range from 0.58–0.85: acceptance: 0.89; benefits: 0.79; stigma: 0.74; insurance/independence: 0.72; suffering/emotional: 0.58. Each item is rated on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”, with higher scores indicating stronger agreement. Domain scores were calculated for dementia screening acceptance, benefit, stigma, loss of independence, and suffering.

The PRISM-PC questionnaire was mainly ground on the HBM theory [43], which has been used to better understand people’s perceptions about testing and screening for asymptomatic diseases and their reluctance to engage in preventive health behavior. This model serves as the conceptual basis for items related to knowledge and beliefs about dementia, AD, memory loss in older people, and the availability and accessibility to screening tests for cognitive decline and other medical conditions. The components of the HBM are based on four main concepts: the attitudes toward disease susceptibility and severity, and the perceived motivations and harm of taking a specific health action (see [43, 44] for more information). The HBM recommends that somebody must believe that the benefits of preventable actions is more than the costs. Thus, barriers are most consistently found to have an impact on behavior, followed closely by the benefits and the susceptibilities [40].

In the current study, the PRISM-PC Questionnaire was revised and renewed by adding and excluding questions in order to meet the main goal of this study. Thus, from the 38 items of PRISM-PC, 21 were excluded due to cultural, social, and health insurance differences in Greek society and difficulties in responses by Greek participants (e.g., “If I had AD, I would not be able to get health insurance”, “I would not be able to get life insurance”, “I would lose my home”, “I would lose my driver’s license and other privileges”). On the other hand, 17 items were kept (acceptance items: 1, 3, 4, 5; benefits items: 1, 2, 3, 4, 5, 7, 8; stigma items: 1, 6; suffering/emotional: 1, 2, 3, 4). Additionally, due to the 5th factor’s low internal consistency (α=0.58) of PRISM-PC, the four items that constitute it were replaced by similar sentences (“My family will suffer from the additional costs of my care”; “My family will suffer emotionally”; “I feel that I would be overwhelmed by mental pain”; “I feel that I would be overwhelmed by intense anxiety”).

Moreover, 16 new items based on HBM, and the investigators’ research questions were added in order to focus on the main goal and the primary hypothesis.

The final items of the questionnaire were 37 in the main section of the questionnaire (plus 22 demographic questions in the introduction section), and each item was scored on a 5-point Likert scale with potential responses of strongly agree, agree, do not know, disagree, and strongly disagree (1 = strongly disagree to 5 = strongly agree). The higher the score, the stronger the agreement indicating with the acceptance of pre-symptomatic testing for AD, motivation for seeking such testing, and higher the need for knowledge on AD risk. Finally, for the purpose of the current study, we added in the introductory part of the questionnaire, sociodemographic questions (age, gender, marital status, educational level, working status and residence (6 items), health status questions (3 items), concerns about getting AD (1 item), beliefs about the treatment of AD (1 item) and information regarding participant’s prior experience with AD (11 items) (Supplementary Material).

The method of forward-backward translation [45] was followed for the remaining 17 items of the PRISM-PC Questionnaire into Greek. In more detail, two Greek experts in the field translated the original English versions into Greek separately. Then, a bilingual English teacher who works with people with dementia carried out the back translation from English to Greek. A comparison of the originally translated and the back-translated Greek versions were performed for consistency, relevance, and meaning of the content.

Before administering the scale, the pre-final version of the questionnaire was evaluated by five adults (3 caregivers and 2 experts in dementia) to discern any potential difficulties in understanding or any objections they might have concerning the text and the content. As a result, the final Greek questionnaire, namely PRE-ADS, was ready without any other objections.

Study procedure

The study was conducted from April 2021 to June 2021 in Greece. University students and caregivers completed the survey online using an active link for one month via Google Forms. The online method was used due to the restriction measures of the COVID-19 pandemic, as well as its ability to collect data with greater ease and faster speed compared to traditional methods [46]. Before starting with the questionnaire, all participants were informed about the purpose of the study and gave their consent to continue with this procedure. The mean administration time for the questionnaire ranged from 15–20 min.

Settings and participants

The sample of this study comprised a convenient sample of university students and caregivers, due to practical restraints (easy to reach, contact, and available to participate) [47]. The questionnaire was sent randomly via email to 200 students from both the School of Psychology and the School of Medicine of Aristotle University of Thessaloniki, who attended the courses related to dementia and where two of the authors (D.M. and M.T.) were tutors. Furthermore, to get access to caregivers’ data, one of the authors (M.T.), sent the link of the survey via email to caregivers, inviting them to participate as members of GAADRD day centers. The organization uses the members’ mailing list for communication purposes, and all members have agreed to be contacted. The main eligibility criteria for including participants were to be aged 18 years and older and Greek as a native language. Two hundred eight (208) people enrolled in this cross-sectional study (189 students -81.3%) and 19 caregivers of people with dementia. Most of the participants were female (93.3%), ranging from 18–40 years old (93.8%), single (59.3%), living in urban areas of Greece (76.1%), and highly educated (13 or more years of education; 96.6%). Table 1 describes the demographical characteristics of participants.

Table 1

Demographical characteristics of participants

		n	%
Gender	Male	14	6.7
	Female	195	93.5
Age (y)	20–30	185	88.5
	31–40	11	5.3
	41–50	7	3.3
	51–60	3	1.4
	61–70	3	1.4
	71–80	0	0
	81–90	0	0
Education	Ph.D./Post-doc	3	1.4
	Post graduate studies	17	8.1
	Graduates studies	182	87.1
	Higher education	7	3.3
	Primary school	0	0
	Without education	0	0
Marital status	Married	10	4.8
	Unmarried	124	59.3
	Divorced	5	2.4
	Widowed	1	0.5
	In relationship	69	33
Working status	Public sector employee	14	6.7
	Private employee	10	4.8
	Freelancer	8	3.8
	Seasonal employee	1	0.5
	Unemployed	5	2.4
	Student	170	81.3
	Retired	1	0.5
Residence	Thessaloniki	68	32.5
	Athens	47	22.5
	In another big city in Greece	44	21.1
	Village/ Province of Greece/	34	16.3
	Island	10	4.8
	Abroad	6	2.9
Do you have a family history of AD?	Yes	78	37.3
	No	131	62.7
Are you a caregiver of a person with AD?	Yes	19	9.1
	No	189	90.9

Ethical considerations

The study protocol was accepted by the Scientific and Ethics Committee of the GAADRD (Scientific Committee Approved Meeting Number: 65/06-02-2021). The development of the protocol of this survey followed the ethical standards outlined in the Declaration of Helsinki. Furthermore, Greek Law of Data Protection was respected through the anonymity and confidentiality of the data and according to the General Data Protection Regulation (EU) 2016/679 of the European Parliament. All participants took part voluntarily in the study. Informed consent was provided before the beginning of the survey, which included details on the main goals of the study.

Statistical analysis

The statistical analysis was carried out using SPSS V 27.0 (IBMCorp, Armonk, NY, USA). Prior to conducting the analyses, 16 items were reverse scored so that the higher score indicated stronger agreement.

The following psychometric properties were evaluated: 1) Structural validity of the PRE-ADS was examined by using the exploratory factor analysis (EFA), and 2) internal consistency of its subscales was assessed using Cronbach’s alpha coefficient (the minimum acceptable value is 0.7). Principal component analysis (PCA) was used to extract factors to test the factor structure of the questionnaire in order to explore structural validity. The following criteria to extract the factor components were taken into consideration: the eigenvalues, an index that estimates the amount of variance explained by each factor (minimum of 1), the scree plot (Cattell’s test), which depicts different observable components, the Kaiser-Meyer-Olkin that measures sample adequacy (minimum acceptable value is 0.50) and Bartlett’s test of sphericity. Factor patterns were rotated using Varimax rotation. The number of factors kept was determined based on the combination of the scree plot and eigenvalues result as well as clinical judgment.

RESULTS

Structural validity of the PRE-ADS

Factor loadings of the items were kept if they were≥0.40. The Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy was high with a value of 0.74, which indicates that the sampling is adequate, and the scale has good internal consistency without too much item redundancy. Bartlett’s test of sphericity was significant, χ²(208)=3199.041, p < 0.001. This shows that EFA is suitable.

The initial analysis with the 37 items revealed a ten-factor solution. We excluded two items because they had low loadings (<0.40). Particularly, the eigenvalues of the first ten factors were: 5.48, 5.34, 2.69, 2.14, 1.79, 1.73, 1.34, 1.30, 1.27, and 1.14, showing that the eigenvalues leveled off after five or six factors. We took into consideration the scree plot suggesting the existence of five or six factors. Clinical judgment suggested that the five-factor solution was sensible, and then the analysis was rerun for five factors solution. We found that 5 items had loadings under 0.40, and thus, these questions were excluded. After this step, the screen plot suggested the existence of four factors, accounting for 63.4% of the total variance. After checking the commonalities, five items were found to have low values (0.19, 0.11, 0.29, 0.24, 0.25) and thus were excluded.

We repeated the four-factor analysis, and the final solution revealed that ten items loaded on the first factor, five items on the second factor, six items on the third factor, and four items on the fourth factor. The first factor was labeled as “Perceived harms of testing” since the ten items loaded on this factor are related to the emotional and financial suffering of the family (items 9, 10, 15, 16), the sense of stigma (items 18, 21), and individuals’ psychological effects such as the appearance of depression, distress, and anxiety symptoms (items 11, 12, 19, 20). The second factor was labeled as “Acceptance of testing” because the five items referred to the preference to be informed about the higher risk (item 1) and the willingness to be screened for AD on a regular basis by using different screening methods (items 2, 3, 4, 5). The third factor, labeled as “Perceived benefits of testing”, includes six items that refer to the increased motivation to have a healthier lifestyle, change behaviors, and improve quality of life as well as the sense that there is more time for future planning (items 13, 22, 25). Also, there are perceived benefits for the family as there will be more time for an overall discussion about the care and financial requirements and a better chance to plan the health care services (items 17, 23, 24). The fourth factor reflected the “Need for knowledge”, including four items referring to the need/motivation to obtain more information on testing, prevention measures, and the new developments in AD treatment (items 6 and 14). This factor also includes the desire to have a counseling session with a health professional or expert in the field to receive more informed advice for the higher risk and to discuss feelings and thoughts (items 7 and 8). Table 2 displays the pattern coefficients for all the final 25 items. For each factor, a higher score on the 5-point Likert scale means higher levels of acceptance, perceived benefits, needs for knowledge, and lower levels of perceived harms. Ten of these items had to be reverse scored (9, 10, 11, 12, 15, 16, 18, 19, 20, 21).

Table 2

Exploratory factor analysis of PRE-ADS questionnaire (4 factors)

Items	Mean (SD)	Cronbach’s α if item deleted	Factor 1	Factor 2	Factor 3	Factor 4
19. I would be depressed*.	2.35 (0.88)	0.784	0.776
11. I feel that I would be overwhelmed by mental pain.	2.37 (0.96)	0.787	0.752
16. My family would suffer emotionally*.	2.08 (0.85)	0.785	0.701
18. I think that others will treat me in a different way*.	2.40 (0.94)	0.788	0.692
20. I would be anxious*.	1.95 (0.68)	0.790	0.656
15. My family would suffer financially*.	2.83 (0.99)	0.787	0.650
12. I feel that I would be overwhelmed by intense anxiety.	1.96 (0.76)	0.789	0.627
9. My family will suffer from the additional costs of my care.	2.46 (0.97)	0.790	0.597
10. My family will suffer emotionally.	1.83 (0.82)	0.787	0.586
21. I would give up on life.	3.85 (0.88)	0.798	0.548
4. I would like to be tested for the presence of AD on a regular basis with pictures of my head or brain (CT-scan or MRI).	2.99 (1.03)	0.789		0.815
5. I would like to be tested for the presence of AD on a regular basis with the use of biomarkers in cerebrospinal fluid (Aβ amyloid, t-protein)*.	3.13 (0.99)	0.789		0.784
3. I would like to get a genetic testing with blood sample in order to find if I am in a higher risk for AD.	2.35 (0.93)	0.786		0.764
2. I would like to be tested for the presence of AD on a regular basis with a short questionnaire.	2.45 (1.03)	0.788		0.732
1. I would like to know if I am at higher risk than others for developing Alzheimer’s disease.	2.02 (0.96)	0.790		0.657
23. I would have more time to talk with my family about my health care.	2.08 (0.73)	0.792			0.731
24. I would have more time to talk with my family about my finances.	2.02 (0.64)	0.793			0.725
17. My family would have a better chance to take care of me.	2.09 (0.73)	0.791			0.651
25. I would be motivated to have a healthier lifestyle (physical exercise, diet, vitamins, cognitive stimulation, stop smoking).	1.75 (0.78)	0.793			0.585
13. I would improve my quality of life*.	1.83 (0.85)	0.798			0.581
22. I would have more time to plan my future.	2.67 (0.84)	0.796			0.570
7. I would like to discuss it further and to get advice from a doctor or another health professional expert in this field*.	1.40 (0.58)	0.790				0.751
6. In order to decide to be tested for the presence of AD, I would need more information and details*.	1.60 (0.70)	0.792				0.612
14. I will be motivated to stay abreast of new developments in AD treatment and prevention*.	1.49 (0.59)	0.787				0.561
8. I would like to meet a health professional, expert on genetics, in order to discuss my feelings and my thoughts*.	1.41 (0.64)	0.787				0.553
Eigen value			5.48	5.34	2.69	2.14
Variance explained			13.71	13.35	6.73	5.37
Cronbach α			0.87	0.86	0.76	0.70

*Each statement begins with the “If I was informed that I am in a higher risk of AD... . With * are highlighted the new items versus those taken form the PRISM-PC questionnaire.

The internal consistency of the PRE-ADS

The degree of the interrelatedness among test items is called internal consistency. Cronbach’s alpha coefficient for the total PRE-ADS was good (Cronbach’s α=0.82), suggesting very satisfactory internal consistency. That means that each item is correlated positively with the sum of the other items of the scale and significantly (all p < 0.0001). However, the total questionnaire’s α presupposes a second-order factor of PRE-ADS, something which was not examined in this exploratory study.

Internal consistency of each factor separately was satisfactory to very satisfactory (0.70–0.87). Specifically, the reliability of “Perceived harms of testing” (factor 1) was α=0.87 (good reliability). Regarding the “Acceptance of testing” (factor 2) was α=0.85, “Perceived benefits of testing” (factor 3) was α=0.76 (acceptable reliability) and for the factor “Need for knowledge” (factor 4) was α=0.70 (acceptable reliability).

DISCUSSION

In the current cross-sectional study, a scale for capturing the attitudes of people about pre-symptomatic AD screening, based on PRISM-PC, was developed and validated for the Greek population by exploring its psychometric properties. The current article describes the conceptual basis for developing a questionnaire designed to understand attitudes and positive and negative factors that may influence an asymptomatic individual’s intention to obtain a test for the risk of early- and late-onset AD. The Greek PRE-ADS questionnaire was found to have high internal consistency and structural validity and is easy to administer (less than 15 min), and therefore shorter than the PRISM-PC Questionnaire (30 min administration). The psychometric properties of PRE-ADS compared well with the psychometric properties of PRISM-PC (α=0.58–0.85) and with other similar scales including Galvin et al. [40] (α=0.62–0.92) and Holsinger et al. [42] (α=0.81) [40, 42]. This tool was a helpful tool for assessing perceptions toward pre-symptomatic screening for AD in older adults and caregivers of people with AD.

The final version of the PRE-ADS scale was composed of 25 items that loaded on 4 factors. The first factor “Perceived harms of testing” consisted of items such as “concerning the family”, “stigmatization”, “perceived threat”, “anxiety”, and “depression feelings” of testing that were among the most common questions included in similar scales measuring attitudes, perceptions, and pros and cons of AD screening [17 , 42]. The internal consistency of this factor (a = 0.87) was higher compared to the internal consistency of the “barriers factor” of Christensen et al. [17] (α=0.81), Roberts [37] (α=0.73), Boustani et al. [39] (α=0.74–0.58), Galvin et al. [40] (α=0.70), and Holsinger et al. [42] (α=0.73–0.70). Finally, among these barriers, psychological traits such as anxiety and depression are hypothesized to influence and impact belief systems and they are considered to be predisposing factors for asking a pre-symptomatic biomarker test for a disease. Differences in personality traits may be significant determinants of an individual’s perceived psychological health and the intention to seek screening for a disorder with cognitive declines [40].

The second factor “Acceptance of testing” included similar items with the “Acceptance of dementia screening” domain of the PRISM-PC Questionnaire, also having similar internal consistency (α=0.89) with our scale. However, PRE-ADS included one more item about the desire to be tested with biomarkers in cerebrospinal fluid, which is a common method in AD screening [5], and it was also included in the survey of Caselli et al. [11] and Gooblar et al. (2015) [30]. Additionally, the question of the willingness to know if he/she is at higher risk than others to develop AD is part of most scales in this field [11 , 42].

In the third factor “Perceived benefits of testing”, is an item describing the need of family to be prepared for the potential development of the disease, which is included in other scales like the PRISM-PC Questionnaire and survey instrument of Gooblar et al. [30]. The items referring to the motivation for changes in the quality of life are also highlighted by other studies [11 , 42], with a favorably compared internal consistency for this factor of benefits such as α=0.80 [37], α=0.79 [39], α=0.70 [40], and α=74 [42]. The four items of the fourth factor “Need for knowledge” were developed by the investigators, and according to the main goals of this research, there were no previous scales that focused on the need for knowledge and support that people wish to have before, during and after the pre-symptomatic testing. Only the questionnaire of Gooblar et al. [30] referred to the need of counseling in the disclosure process of higher risk for AD to people at risk, and Christensen et al. [17] included a question about the motivation to stay abreast of new developments in AD treatment and prevention.

Further research within the field suggests that people with an immediate blood relative with AD express higher levels of interest regarding early screening for AD [4]. On the other hand, people who genetically have higher possibilities of developing the disease reveal lower interest in a more detailed screening [33]. The results of our questionnaire can analyze these differences due to the additional questions regarding participant’s prior experience with AD that have been added in the introductory part and focusing on collecting data about caregivers and the impact of family history on relatives (Supplementary Material). Also, results from previous studies have underlined essential factors that need to be measured such as the reason for being a caregiver and the type of relationship between caregiver and their loved one (e.g., being a spouse or an adult child) [32]. The introductory section of PRE-ADS scale included such questions and can reach differences between relatives who are caregivers and non-caregivers. However, additional research needs to be done by using this scale in these different populations.

There are psychological (i.e., the appearance of depression, suicide intention), insurance, employment, and ethical implications of predictive biomarker testing in asymptomatic healthy individuals at risk for developing AD [2, 19]. Findings have shown that the possibility of dealing with these implications appeared to be a significant reason for seeking pre-symptomatic screening [4 , 48]. In addition, gaining information that would allow the prevention of future AD such as information about clinical prevention trials [38] and non-pharmacological strategies, including healthier lifestyle/behavioral changes and wellness changes (physical exercise, diet, vitamins, cognitive stimulation, stop smoking), can also increase the intension to seek pre-symptomatic testing [48]. There are also data that highlighted multiple barriers for being tested, and these barriers cause the people’s refusal to proceed with a screening test [32, 48]. Both perceived benefits and costs impact people’s decision to accept AD screening in a pre-symptomatic stage. Future studies should therefore measure the advantages and disadvantages of pre-symptomatic screening in different settings.

Moreover, according to study results, a predictive test could not only benefit medical research, but it could also transform political and legal landscapes by developing a large constituency of asymptomatic, diagnosed adults [31]. Thus, there is an increased need of developing the best way to inform people about the screening process and disclose a higher risk for AD by informing participants accurately and honestly while looking at the possible impact, especially in the context of future individualized risk profiling [31]. Collecting data in this field may contribute to the current improvement of general screening methods and the use of the current questionnaire may support this initiative.

This is the first study that created a questionnaire for measuring the attitudes of Greek people toward pre-symptomatic screening for AD. PRE-ADS can play a significant role in the research context providing information for and the implementation of genetic counseling in healthcare. Capturing data via this questionnaire might help health service researchers in AD to better understand better peoples’ perspectives related to the pros and cons of AD screening. By targeting these barriers, we could potentially facilitate the development of an individualized counseling program and tailor our counseling and educational interventions for caregivers and relatives [19]. The development of these health services potentially seems to play a critical role in helping participants make informed decisions about whether to proceed with genetic testing or participate in a therapeutic intervention such as clinical trial. They can discuss and weigh the potential benefits and risks of participating in these processes, and they can also explore their personal values and beliefs, as well as their social, emotional, and financial needs and concerns [49]. Conclusively, PRE-ADS is a valid tool, which strengths comprise a practical length and ease of administration.

Limitations and future research

This study has some limitations, as the PRE-ADS scale is a self-report questionnaire. Furthermore, our sample was comprised mostly of students, which is not a representative sample of the general population because they are young and highly educated, they are easy to contact and reach, available and willing to participate. In this case, the higher education levels can influence the understanding of the test. Thus, the generalization of the results is limited. Additional research should include a target group of the general public and a test-retest design. Moreover, the questionnaire was tailored towards the Greek society, and its health, social, insurance system, thus limiting the generalizability to other countries with different systems.

Also, in this study we did not conduct confirmatory factor analysis, which, however, is necessary in the next steps of the PRE-ADS administration.

Furthermore, convergent validity testing should be conducted between the PRE-ADS scale and other similar scales measuring attitudes towards screening for AD (such as the Questionnaire of Galvin et al., 2006) [40], benefits and limitations of the disclosure of a higher risk for AD (such as Questionnaire of Gooblar et al., 2015) [30], and barriers and motivations in order to follow an AD screening (such as PRISM-PC Questionnaire of M. Boustani et al., 2008) [39]; however, this was beyond the scope of the current study.

Lastly, another future direction of this study is to share the PRE-ADS questionnaire to participants, including scales that measure the knowledge about AD, risk, and genetics, such as the Dementia Knowledge Assessment Tool [50] and the Dementia Attitudes Scale [51], and to compare their AD literacy with the acceptance of pre-symptomatic AD screening.

Footnotes

ACKNOWLEDGMENTS

Permission was given by the developer of the PRISM-PC Questionnaire, Dr. M.A. Boustani, before the start of this study.

The authors would like to thank Dr. Birgit Teichmann from Network Aging Research, Heidelberg University for her significant contribution in the preparation of the manuscript and for invaluable comments to develop further the paper. We would like also to thank Ms. Taisiya Baysalova from the same research institute, for her support in the improvements of the language.

FUNDING

The authors have no funding to report.

CONFLICT OF INTEREST

The authors have no conflict of interest to report.

DATA AVAILABILITY STATEMENT

The data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

The supplementary material is available in the electronic version of this article: .

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