Neurol Ther (2022) 11:1183–1192 https://doi.org/10.1007/s40120-022-00367-3 ORIGINAL RESEARCH Awareness of Diagnosis in Persons with Early-Stage Alzheimer’s Disease: An Observational Study in Spain Alberto Villarejo-Galende . Elena Garcı́a-Arcelay . Gerard Piñol-Ripoll . Antonio del Olmo-Rodrı́guez . Félix Viñuela . Mercè Boada . Emilio Franco-Macı́as . Almudena Ibañez de la Peña . Mario Riverol . Albert Puig-Pijoan . Pedro Abizanda-Soler . Rafael Arroyo . Miquel Baquero-Toledo . Inmaculada Feria-Vilar . Mircea Balasa . Ángel Berbel . Eloy Rodrı́guez-Rodrı́guez . Alba Vieira-Campos . Guillermo Garcı́a-Ribas . Silvia Rodrigo-Herrero . Albert Lleó . Jorge Maurino Received: April 24, 2022 / Accepted: May 13, 2022 / Published online: June 1, 2022 Ó The Author(s) 2022 ABSTRACT assessed awareness of diagnosis among people with early-stage AD and its impact on different Introduction: Limited information is available person-centered outcome measures. on people’s experiences of living with Alzhei- Methods: We conducted an observational, mer’s disease (AD) at earlier stages. This study cross-sectional study in 21 memory clinics in A. Villarejo-Galende E. Franco-Macı́as Department of Neurology, Hospital Universitario 12 Dementia Unit, Department of Neurology, Hospital de Octubre, Instituto de Investigación Hospital 12 Universitario Virgen del Rocı́o, Instituto de de Octubre (I?12), CIBERNED, Madrid, Spain Biomedicina de Sevilla (IBiS), Sevilla, Spain E. Garcı́a-Arcelay  J. Maurino (&) A. I. de la Peña Medical Department, Roche Farma, Ribera del Loira Centro de Investigación de Parkinson, Policlı́nica 50, 28042 Madrid, Spain Guipúzcoa, San Sebastián, Spain e-mail: jorge.maurino@roche.com M. Riverol G. Piñol-Ripoll Department of Neurology, Clı́nica Universidad de Unitat Trastorns Cognitius, Hospital Universitari de Navarra, Pamplona, Spain Santa Maria, Institut de Recerca Biomèdica de Lleida (IRBLLeida), Lleida, Spain A. Puig-Pijoan Cognitive Impairment and Movement Disorders A. del Olmo-Rodrı́guez Unit, Department of Neurology, Hospital Del Mar Department of Neurology, Hospital Universitario Medical Research Institute (IMIM), Barcelona, Spain Dr. Peset, Valencia, Spain P. Abizanda-Soler F. Viñuela Department of Geriatrics, Complejo Hospitalario Instituto Neurológico Andaluz, Hospital Victoria Universitario de Albacete, Albacete, Spain Eugenia, Unidad de Deterioro Cognitivo, Hospital Universitario Virgen Macarena, Sevilla, Spain R. Arroyo Department of Neurology, Hospital Universitario M. Boada Quirónsalud, Madrid, Spain Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, CIBERNED, Barcelona, Spain 1184 Neurol Ther (2022) 11:1183–1192 Spain. Persons aged 50–90 years, diagnosed with Conclusions: Awareness of diagnosis was a prodromal or mild AD (NIA/AA criteria), a Mini common phenomenon in persons with early- Mental State Examination (MMSE) score C 22, stage AD negatively impacting their quality of and a Clinical Dementia Rating-Global score life. Understanding illness representations in (CDR-GS) of 0.5 or 1.0 were recruited. The earlier stages may facilitate implementing opti- Representations and Adjustment to Dementia mized care that supports improved quality of Index (RADIX) was used to assess participants’ life and well-being. beliefs about their condition and its consequences. Keywords: Alzheimer’s disease; Awareness; Results: A total of 149 persons with early-stage Illness representation; Well-being; Quality of AD were studied. Mean (SD) age was 72.3 (7.0) life; Diagnosis years and 50.3% were female. Mean duration of AD was 1.4 (1.8) years. Mean MMSE score was Key Summary Points 24.6 (2.1) and 87.2% had a CDR-GS score of 0.5. Most participants (n = 84, 57.5%) used a Awareness of the condition and its descriptive term related to specific AD symp- diagnosis among persons with early-stage toms (e.g., memory difficulties) when asked Alzheimer’s disease has been little what they called their condition. Participants explored. aware of their diagnosis using the term AD (n = 66, 45.2%) were younger, had more Awareness of Alzheimer’s disease diagnosis depressive symptoms, and poorer life satisfac- was a common phenomenon in persons tion and quality of life compared to those in early stages negatively impacting their without awareness of their specific diagnosis. quality of life. Practical and emotional consequences RADIX The identification of persons with scores showed a significant negative correlation awareness of their diagnosis, especially in with Quality of Life in Alzheimer’s Disease score the early stages of the disease, should be a (rho = - 0.389 and - 0.413, respectively; goal to implement individualized p \ 0.0001). Years of education was the only strategies to preserve quality of life. predictor of awareness of AD diagnosis [OR = 1.04 (95% CI 1.00–1.08); p = 0.029]. M. Baquero-Toledo A. Vieira-Campos Department of Neurology, Hospital Universitari i Department of Neurology, Hospital Universitario de Politècnic La Fe, Institut d’Investigació Sanitaria La La Princesa, Madrid, Spain Fe, Valencia, Spain I. Feria-Vilar G. Garcı́a-Ribas Department of Neurology, Complejo Hospitalario Department of Neurology, Hospital Universitario Universitario de Albacete, Albacete, Spain Ramón y Cajal, Madrid, Spain M. Balasa S. Rodrigo-Herrero Alzheimer’s Disease and Other Cognitive Disorders Department of Neurology, Hospital Universitario Unit, Hospital Clı́nic, Institut d’Investigacions Juan Ramón Jiménez, Huelva, Spain Biomèdiques August Pi I Sunyer (IDIBAPS), A. Lleó Barcelona, Spain Memory Unit, Department of Neurology, Hospital Á. Berbel de La Santa Creu i Sant Pau, Biomedical Research Department of Neurology, Hospital Central de la Institute Sant Pau, Universitat Autònoma de Cruz Roja, Madrid, Spain Barcelona, Barcelona, Spain E. Rodrı́guez-Rodrı́guez Department of Neurology, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain Neurol Ther (2022) 11:1183–1192 1185 INTRODUCTION up visits between February and June 2021. This study was approved by the research review Alzheimer’s disease (AD) is the most common board of Hospital de la Santa Creu i Sant Pau, type of dementia and its prevalence continues Barcelona, Spain (reference number EC/20/396/ to increase mainly because of population 6186 [OBS]), and performed in accordance with growth and ageing [1]. Impaired awareness of the 1964 Helsinki Declaration and its later cognitive and functional deficits or anosognosia amendments. According to Spanish legislation is a common phenomenon in persons with AD (Orden SAS/3470/2009), non-interventional with a prevalence ranging from 21% to 81% studies require approval by a single ethics [2, 3]. Low awareness predicts progression to committee and this approval applies to all par- dementia in both subjects with normal cogni- ticipating centers. All participants provided tion and persons with mild cognitive impair- written informed consent. ment by an average of 3 years [4, 5]. The impact of anosognosia on AD persons Outcome Measures and their caregivers has been extensively stud- ied, but awareness of the condition and its The RADIX is a brief, self-report instrument diagnosis has only recently begun to be validated in people with mild to moderate explored [2, 3, 6–12]. Quinn et al. developed the dementia to assess their understanding of the Representations and Adjustment to Dementia condition and its consequences in five compo- Index (RADIX), a specific instrument to assess nents: identity, cause, disease course over time people’s beliefs about dementia and their (timeline), possibilities for controlling the dis- impact on subsequent adjustment [13]. In a ease, and practical and emotional consequences sample of 917 persons with mild-to-moderate [13]. A nine-question screening checklist is dementia in the UK, those with awareness of included to screen out those who did not their condition reported a higher rate of identify any difficulties or changes. Identity and depression and lower indices of well-being and cause are open questions to capture the per- psychological resources [12]. spective of the person with dementia. A list of AD care should focus on person-centered options of possible causes is offered to the outcomes [14, 15]. Maintaining autonomy and respondent including ageing, changes within quality of life based on persons’ preferences and the brain, disease or physical condition, hered- beliefs is essential, especially in the early stage itary condition, lifestyle events, or don’t know. of the disease when decision-making capacity is Questions on timeline and control are single less impaired [14–16]. The aim of this study was items rated on a four-point scale. For practical to assess awareness of diagnosis among persons and emotional consequences, responses to the with early-stage AD and its impact on different questions are rated on a four-point scale (from psychological and behavioral dimensions. strongly disagree to strongly agree) and can be summed to give an overall score and then divided by 4 and 5 to give the mean score, METHODS respectively. Higher scores indicate greater negative consequences. This questionnaire was This is an observational, cross-sectional study developed in English and is available at https:// conducted at 21 hospital-based memory clinics. medicine.exeter.ac.uk/reach/publications/. In Key eligibility criteria included age between 50 this study, a Spanish version was used after and 90 years old, a diagnosis of prodromal or previous forward/backward translations. mild AD (National Institute on Aging/Alzhei- The Quality of Life in Alzheimer’s Disease mer’s Association criteria), a Mini Mental State (QoL-AD), Functional Activities Questionnaire Examination (MMSE) score C 22, and a Clinical (FAQ), Beck Depression Inventory-Fast Screen Dementia Rating-Global score (CDR-GS) of 0.5 (BDI-FS), Beck Hopelessness Scale (BHS), Satis- or 1.0 [17, 18]. Participants were consecutively faction With Life Scale (SWLS), and General recruited in the context of their regular follow- 1186 Neurol Ther (2022) 11:1183–1192 Self-Efficacy Scale (GSES) were used to gather Definitions information on quality of life, functioning, mood, feelings of hopelessness, life satisfaction, Awareness of diagnosis was defined when par- and self-efficacy, respectively [19–24]. Cogni- ticipants used a diagnostic term or descriptive tion was assessed using the Alzheimer Disease terms with specific symptoms to refer to the Assessment Scale-Cognitive (ADAS-Cog13) [25]. diagnosis of their illness (RADIX diagnosis item) The QoL-AD is a 13-item self-report question- [13]. Awareness of AD diagnosis was defined naire designed to assess quality of life of persons when participants specifically used the word with a diagnosis of AD [19]. Each item is rated Alzheimer to refer to the diagnosis of their using a four-point scale ranging from 1 (poor) to condition. Participants who were able to give 4 (excellent). Higher scores indicate better the diagnosis using the term AD and considered quality of life. The FAQ is a 10-item, informant- that their condition was going to worsen over based instrument to measure activities of daily time were classified as high awareness group living in elderly people [20]. Each item is rated (RADIX diagnosis and timeline items) [12, 13]. using a four-point scale ranging from 0 (normal) to 3 (dependent). A cutoff C 6 indicates func- Statistical Analysis tional impairment. The BDI-FS is self-report seven-item questionnaire assessed on a four- Logistic regression was used to explore predic- point scale (no symptoms to severe symptoms) tors of AD awareness using sociodemographic, [21]. Total score ranges from 0 to 21 with a clinical, cognitive, and psychological/behav- cutoff C 4 indicating the presence of depressive ioral characteristics. Variables with a statistical symptoms. The BHS is a 20-item self-report relationship to awareness and a p value of less inventory to measure three major components than 0.2 were candidates for the model. Step- of hopelessness: feelings about the future, loss wise automatic variable selection method was of motivation, and future expectations [22]. applied in model building. Correlations Each optimistic response is scored as 0 and each between RADIX components and quality of life pessimistic response is scored as 1. Total score were also analyzed. ranges from 0 to 20 with higher values indi- cating higher levels of hopelessness. A cut- off C 9 indicates moderate-to-severe RESULTS hopelessness and identifies a high-risk group for potential suicide [26]. Participants indicated A total of 149 persons with early-stage AD were how much they agree or disagree with each of studied. Mean (SD) age was 72.3 (7.0) years and the five items of the SWLS using a seven-point 50.3% were female. Mean duration of AD was scale that ranges from 1 (strongly disagree) to 7 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1) (strongly agree) [23]. A cutoff score C 25 indi- and 87.2% had a CDR-GS score of 0.5. cates that respondents are satisfied or extremely Sociodemographic and clinical characteristics satisfied with their life. The GSES is a 10-item are shown in Table 1. self-report instrument to assess whether a per- Only three persons (2%) did not complete son believes he or she can perform novel or any of the RADIX screening items. Most par- difficult tasks or cope with adversity in different ticipants (n = 84, 57.5%) used a descriptive term domains of functioning [24]. Each item is rated related to specific AD symptoms (e.g., memory using a four-point scale ranging from 1 (not at difficulties) when asked what they called their all true) to 4 (exactly true). Higher scores indi- condition. Don’t know (22.7%), ageing (21.4%), cate higher levels of an optimistic self-belief. brain changes (20.7%), and hereditary condi- tion (15.6%) were the most common reported causes. Illness representations according to RADIX responses are shown in Table 2. Neurol Ther (2022) 11:1183–1192 1187 Table 1 Sociodemographic and clinical characteristics of Table 2 Illness representations according to RADIX the participants responses (N = 146) N = 149 Categories N (%) Age, years, mean (SD) 72.3 (7.0) Identity Sex, female, n (%) 75 (50.3) Descriptive term using specific symptoms 84 (57.5) Years of education, mean (SD) 13.1 (9.9) Diagnostic term 46 (31.5) Time since diagnosis, years, mean (SD) 1.4 (1.8) Don’t know 10 (6.8) CDR-GS score of 0.5, n (%) 130 (87.2) Unclassifiable 6 (4.1) MMSE score, mean (SD) 24.6 (2.1) Diagnosis ADAS-Cog13 score, mean (SD) 24.4 (5.2) Diagnostic term 83 (45.2) QoL-AD score, mean (SD) 37.9 (4.5) Descriptive term using specific symptoms 33 (22.6) FAQ score, mean (SD) 5.9 (6.2) Don’t know 27 (18.5) FAQ score C 6, n (%) 57 (38.2) Unclassifiable 3 (2.0) SWLS score, mean (SD) 27.5 (5.7) Cause SWLS score C 25, n (%) 120 (80.5) Don’t know 35 (22.7) GSES score, mean (SD) 29.9 (6.3) Ageing 33 (21.4) BDI-FS score, mean (SD) 2.1 (2.2) Brain changes 32 (20.7) BDI-FS score C 4, n (%) 33 (22.1) Hereditary 24 (15.6) BHS score, mean (SD) 10.7 (2.4) Lifestyle 18 (11.7) BHS score C 9, n (%) 124 (83.2) Illness or physical problem 5 (3.2) ADAS-Cog Alzheimer Disease Assessment Scale-Cognitive, Unclassifiable 7 (4.5) BDI-FS Beck Depression-Fast Screen, BHS Beck Hope- Evolution lessness Scale, CDR-GS Clinical Dementia Rating-Global Score, FAQ Functional Activities Questionnaire, GSES Get worse 71 (48.6) Global Self-Efficacy Scale, MMSE Mini Mental State Stay the same as it is now 31 (21.2) Examination, QoL-AD Quality of Life in Alzheimer’s Disease, SD standard deviation, SWLS Satisfaction With Get better 26 (17.8) Life Scale Don’t know 18 (12.3) Practical consequences, mean (SD) 1.8 (0.6) Emotional consequences, mean (SD) 2.2 (0.8) In total 116 (79.4%) participants were aware of their condition (Table 2) and 66 (45.2%) used RADIX Representations and Adjustment to Dementia the term AD when asked if they knew their Index, SD standard deviation specific diagnosis (Table 3). These persons were younger, had more depressive symptoms, and poorer life satisfaction and quality of life com- pared to those without awareness of their logistic regression approach was used to explore specific diagnosis (Table 3). predictors of awareness among these partici- Nineteen (13%) participants were able to pants. Years of education was the only predictor give the AD diagnosis and considered that their of high awareness of AD diagnosis [OR = 1.04 condition was going to worsen over time. A (95% CI 1.00–1.08); p = 0.02] (Table 4). 1188 Neurol Ther (2022) 11:1183–1192 Table 3 Description of participants according to aware- Table 3 continued ness of AD diagnosis AD No AD p value AD No AD p value awareness awareness awareness awareness N = 66 N = 80 N = 66 N = 80 Practical 1.9 (0.6) 1.7 (0.6) 0.037 Age, years, mean 70.2 (6.6) 73.8 (6.9) 0.001 consequences (SD) score, mean (SD) Sex, female, n (%) 34 (51.5) 40 (50.0) 0.869 AD Alzheimer’s disease, ADAS-Cog Alzheimer’s Disease Years of education, 13.9 (11.5) 12.6 (8.5) 0.446 Assessment Scale-Cognitive, BDI-FS Beck Depression-Fast mean (SD) Screen, BHS Beck Hopelessness Scale, CDR-GS Clinical Disease duration, 1.3 (1.8) 1.3 (1.6) 0.861 Dementia Rating-Global Score, FAQ Functional Activities Questionnaire, GSES Global Self-Efficacy Scale, MMSE years, mean (SD) Mini Mental State Examination, QoL-AD Quality of Life CDR-GS score of 61 (92.4) 67 (83.7) 0.134 in Alzheimer’s Disease, SD standard deviation, SWLS 0.5, n (%) Satisfaction With Life Scale MMSE score, mean 24.8 (2.2) 24.5 (2.0) 0.369 (SD) ADAS-Cog13 24.2 (5.8) 24.4 (4.8) 0.792 score, mean (SD) Practical and emotional consequences RADIX scores showed a significant negative QoL-AD score, 36.6 (4.5) 38.8 (4.1) 0.002 correlation with QoL-AD score (rho = - 0.389 mean (SD) and - 0.413, respectively; p \ 0.0001). FAQ score, mean 4.9 (5.1) 6.5 (5.0) 0.104 (SD) DISCUSSION SWLS score, mean 26.4 (6.3) 28.6 (4.9) 0.015 (SD) The impact of impaired awareness on persons with AD and their caregivers has been exten- GSES score, mean 29.5 (6.3) 30.6 (6.3) 0.307 sively studied [2, 6–8, 27, 28]. Anosognosia was (SD) associated with poor autonomy, greater fre- BDI-FS score, mean 2.7 (2.6) 1.5 (1.7) 0.001 quency and severity of behavioral symptoms, (SD) lower treatment adherence, greater caregiver BDI-FS score C 4, 22 (33.3) 11 (13.7) 0.009 n (%) Table 4 Predictors of awareness using logistic regression BHS score, mean 11.1 (2.7) 10.4 (2.2) 0.086 analysis (SD) OR 95% CI p value Emotional 2.4 (0.8) 2.0 (0.7) 0.003 Age 0.94 0.88–1.01 0.103 consequences Years of education 1.04 1.00–1.08 0.029 score, mean (SD) BDI-FS score 1.14 0.95–1.38 0.156 BDI-FS score C 4 2.26 0.81–6.32 0.118 BDI-FS Beck Depression-Fast Screen, CI confidence interval, OR odds ratio Neurol Ther (2022) 11:1183–1192 1189 burden, and discrepancy in perception of qual- informed about their AD diagnosis, which has ity of life between people with AD and their been associated with a better quality of life caregivers [2, 27, 28]. [15, 30]. However, having a better awareness of Different studies have shown that persons AD diagnosis correlates with more depressive with AD are still able to describe their problems, symptoms and poorer quality of life [12]. In our experiences, and preferences at different stages study, a negative hope for the future, one of the of the disease [10, 14, 15]. In a qualitative and most important factors for suicide, was also quantitative study with mild and moderate AD highly prevalent [26]. Therefore, identifying persons, Trindade et al. found that awareness of and understanding persons’ representations of condition was more preserved than awareness AD from the onset of the disease may be of specific functional deficits [10]. Mayelle et al. essential for early implementation of individu- using the Awareness of Self and Disease Assess- alized interventions to enable well-being and ment scale found that awareness in AD is maintenance of independence where possible. heterogeneous and can fluctuate over time with Our study has some limitations that deserve three different patterns (deficit, stability, or mention. First, the aim of this study was to improvement) [11]. However, little is known assess awareness of condition and its associated about the impact of having awareness of diag- factors using a comprehensive battery of self- nosis, especially at earlier stages of the disease. report measurements. Traditionally, self-report In our study, awareness of diagnosis was a measures have been considered insensitive in common phenomenon with 45% of persons this disease [31]. The discrepancy between per- being able to use the term AD in a population sons’ and caregivers’ scores on quality of life with a mean disease duration of 1.4 years. and other symptom dimensions begins even Awareness was associated with the presence of with very mild cognitive impairment. Second, depressive symptoms, poor life satisfaction, and although the RADIX is a useful and validated quality of life. tool to understand dementia representations, Similar findings were found in a recent sys- the use of open questions and the listing of tematic review in persons with mild to moder- options for possible causes in this questionnaire ate AD by Azocar et al. [28]. Most studies can be challenging for respondents and the showed a negative association between reliability of their subjective assessments impaired awareness and depression and anxiety [12, 13]. Third, given the cross-sectional design (Pearson correlations ranging from 0.3 to 0.7). of the study, we have no information about The IDEAL (Improving the experience of participants’ potential changes in their levels of Dementia and Enhancing Active Life) study awareness over time [9, 11]. Finally, this study investigated illness representations using the did not collect whether the participants had RADIX questionnaire in a population with received any information on the disease and its mild-to-moderate dementia in the UK [12]. The long-term prognosis. Therefore, we cannot rule participants (11.2%) categorized by high out that a greater awareness of the diagnosis awareness of their dementia diagnosis and may reflect a better provision of information. knowledge of its causes and prognosis reported a higher rate of depressive symptoms and lower satisfaction with life, optimism, self-efficacy CONCLUSIONS and self-esteem [12]. Younger age and depressed mood were stronger predictors of this awareness Awareness of diagnosis was a common phe- group than the level of cognitive or functional nomenon in persons with early-stage AD and impairment [12]. In our study, the only pre- negatively impacted their quality of life and dictor of awareness of AD was years of well-being. Awareness of diagnosis could be a education. signal to identify early in order to implement Persons’ beliefs and expectations about an specific strategies to prevent depression and illness determine their emotional reactions and preserve quality of life. The approach to such coping responses [29]. Persons prefer to be actions must be based on a holistic view of the 1190 Neurol Ther (2022) 11:1183–1192 person and their environment and must be Eisai, Servier, and Schwabe Pharma; funding treated in a multidisciplinary way. sources with Life Molecular Imaging, Bioiberica, and Schwabe; and grants from CIBERNED, EU/ EFPIA, Instituto de Salud Carlos III (ISCIII), ACKNOWLEDGEMENTS Fundación La Caixa, and Grı́fols. Rafael Arroyo discloses being an advisory board participant and receiving speaking fees from Almirall, Funding. This study was funded by the Bayer, Biogen, Merck, Novartis, Roche, Sanofi, Medical Department of Roche Farma Spain and Teva. Albert Lleó discloses honoraria from a (ML42346). The sponsor also funded the jour- consulting/advisory role with Grifols, Fujirebio- nal’s Rapid Service fee. Europe, Novartis, Roche, Otsuka, Nutricia, Zambón, Biogen, Lilly, and KRKA. Co-author of Authorship. All named authors meet the a patent on markers of synaptopathy in neu- International Committee of Medical Journal rodegenerative diseases (EP18382175.0, PCT/ Editors (ICMJE) criteria for authorship for this EP2019/056535). Elena Garcı́a-Arcelay and article, take responsibility for the integrity of Jorge Maurino are employees of Roche Farma the work as a whole, and have given their Spain. Gerard Piñol-Ripoll, Félix Viñuela, approval for this version to be published. Almudena Ibañez de la Peña, Mario Riverol, Albert Puig-Pijoan, Pedro Abizanda-Soler, Author Contributions. All authors made a Miquel Baquero-Toledo, Inmaculada Feria-Vilar, significant contribution to the work reported, Mircea Balasa, Ángel Berbel, Eloy Rodrı́guez- whether in study conception, design, execu- Rodrı́guez, Alba Vieira-Campos, Guillermo tion, acquisition of data, analysis and interpre- Garcı́a-Ribas, and Silvia Rodrigo-Herrero declare tation, or in all these areas; all took part in no competing interests. drafting, revising or critically reviewing the article; all gave final approval of the version to Compliance with Ethics Guidelines. This be published; all have agreed on the journal to study was approved by the research review which the article has been submitted; and all board of Hospital de la Santa Creu i Sant Pau, agree to be accountable for all aspects of the Barcelona, Spain (reference number EC/20/396/ work. 6186 [OBS]), and performed in accordance with the 1964 Helsinki Declaration and its later Disclosures. This study was funded by the amendments. According to Spanish legislation Medical Department of Roche Farma Spain (Orden SAS/3470/2009), non-interventional (ML42346). The funder had no role in study studies require approval by a single ethics design, data collection and analysis, decision to committee and this approval applies to all par- publish, or preparation of the manuscript. ticipating centers. Participants provided written Alberto Villarejo-Galindo discloses honoraria informed consent. from a consulting/advisory role with KRKA, Kern Pharma, Exeltis, Esteve, Roche, AbbVie, Data Availability. Qualified researchers Schwabe, Neuraxpharm, Nutricia, and Alter. may request access to individual patient-level Antonio del Olmo-Rodrı́guez discloses hono- data through the corresponding author. The raria from a consulting/advisory role with Alter, datasets generated during the analysis of the Biocross, Biogen, KRKA, Esteve, Schwabe, study are available from the corresponding Nutricia, and Lilly. Emilio Franco-Macı́as dis- author on reasonable request. closes honoraria from a consulting/advisory role with Kern Pharma, Esteve, Roche, and Open Access. This article is licensed under a Neuraxpharm. Mercè Boada discloses honoraria Creative Commons Attribution-NonCommer- from a consulting/advisory role with Grifols, cial 4.0 International License, which permits Araclon Biotech, Roche, Lilly, Merck, Biogen, any non-commercial use, sharing, adaptation, Zambon, Novo-Nordisk, Bioiberica, Biogen, distribution and reproduction in any medium Neurol Ther (2022) 11:1183–1192 1191 or format, as long as you give appropriate credit 8. Conde-Sala JL, Turró-Garriga O, Piñán-Hernández to the original author(s) and the source, provide S, et al. Effects of anosognosia and neuropsychiatric symptoms on the quality of life of patients with a link to the Creative Commons licence, and Alzheimer’s disease: a 24-month follow-up study. indicate if changes were made. The images or Int J Geriatr Psychiatry. 2016;31:109–19. other third party material in this article are included in the article’s Creative Commons 9. Jacus JP, Mayelle A, Voltzenlogel V, et al. Modelling awareness in Alzheimer’s disease. J Alzheimers Dis. licence, unless indicated otherwise in a credit 2020;76:89–95. line to the material. If material is not included in the article’s Creative Commons licence and 10. Trindade PGE, Santos RL, Johannessen A, Neto JPS, your intended use is not permitted by statutory Dourado MCN. Awareness of functional status: people with Alzheimer’s disease abilities to self-re- regulation or exceeds the permitted use, you port impairment in activities of daily living. will need to obtain permission directly from the J Alzheimers Dis Rep. 2020;4:405–15. copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by- 11. Mayelle A, Hazebrouck C, El Haj M, et al. Awareness for people with Alzheimer’s disease: profiles and nc/4.0/. weekly trajectories. Front Aging Neurosci. 2022;13: 781426. 12. Alexander CM, Martyr A, Gamble LD, et al. Does REFERENCES awareness of condition help people with mild-to- moderate dementia to live well? Findings from the IDEAL programme. BMC Geriatr. 2021;21:511. 1. GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 13. Quinn C, Morris RG, Clare L. Beliefs about 2019 and forecasted prevalence in 2050: an analysis dementia: development and validation of the rep- for the Global Burden of Disease Study 2019. Lancet resentations and adjustment to dementia index Public Health. 2022;7:105–25. (RADIX). Am J Geriatr Psychiatry. 2018;26:680–9. 2. Cacciamani F, Houot M, Gagliardi G, et al. Aware- 14. DiBenedetti DB, Slota C, Wronski SL, et al. Assess- ness of cognitive decline in patients with Alzhei- ing what matters most to patients with or at risk for mer’s disease: a systematic review and meta- Alzheimer’s and care partners: a qualitative study analysis. Front Aging Neurosci. 2021;13: 697234. evaluating symptoms, impacts, and outcomes. Alz- heimers Res Ther. 2020;12:90. 3. Alexander CM, Martyr A, Savage SA, Morris RG, Clare L. Measuring awareness in people with 15. Wehrmann H, Michalowsky B, Lepper S, Mohr W, dementia: results of a systematic scoping review. Raedke A, Hoffmann W. Priorities and preferences J Geriatr Psychiatry Neurol. 2021;34:335–48. of people living with dementia or cognitive impairment - a systematic review. Patient Prefer 4. Munro CE, Donovan NJ, Amariglio RE, et al. The Adherence. 2021;15:2793–807. impact of awareness of and concern about memory performance on the prediction of progression from 16. Lamont RA, Nelis SM, Quinn C, et al. Psychological mild cognitive impairment to Alzheimer disease predictors of ‘‘living well’’ with dementia: findings dementia. Am J Geriatr Psychiatry. 2018;26: from the IDEAL study. Aging Ment Health. 2020;24: 896–904. 956–64. 5. Hanseeuw BJ, Scott MR, Sikkes SAM, et al. Evolution 17. Folstein MF, Folstein SE, McHugh PR. ‘‘Mini-mental of anosognosia in Alzheimer’s disease and its rela- state’’. A practical method for grading the cognitive tionship to amyloid. Ann Neurol. 2020;87:267–80. state of patients for the clinician. J Psychiatr Res. 1975;12:189–98. 6. Mak E, Chin R, Ng LT, Yeo D, Hameed S. Clinical associations of anosognosia in mild cognitive 18. Berg L. Clinical dementia rating (CDR). Psy- impairment and Alzheimer’s disease. Int J Geriatr chopharmacol Bull. 1988;24:637–9. Psychiatry. 2015;30:1207–14. 19. Logsdon RG, Gibbons LE, McCurry SM, Teri L. 7. Yoon B, Shim YS, Hong YJ, et al. Anosognosia and Assessing quality of life in older adults with cogni- its relation to psychiatric symptoms in early-onset tive impairment. Psychosom Med. 2002;64:510–9. Alzheimer disease. J Geriatr Psychiatry Neurol. 2017;30:170–7. 20. Marshall GA, Zoller AS, Lorius N, et al. Functional activities questionnaire items that best discriminate 1192 Neurol Ther (2022) 11:1183–1192 and predict progression from clinically normal to beck hopelessness scale? A meta-analysis. Psychol mild cognitive impairment. Curr Alzheimer Res. Med. 2007;37:769–78. 2015;12:493–502. 27. Conde-Sala JL, Reñé-Ramı́rez R, Turró-Garriga O, 21. Elben S, Dimenshteyn K, Trenado C, et al. Screen et al. Clinical differences in patients with Alzhei- fast, screen faster: a pilot study to screen for mer’s disease according to the presence or absence depressive symptoms using the beck depression of anosognosia: implications for perceived quality inventory fast screen in parkinson’s disease with of life. J Alzheimers Dis. 2013;33:1105–16. mild cognitive impairment. Front Neurol. 2021;12: 640137. 28. Azocar I, Livingston G, Huntley J. The association between impaired awareness and depression, anxi- 22. Dyce JA. Factor structure of the Beck hopelessness ety, and apathy in mild to moderate Alzheimer’s scale. J Clin Psychol. 1996;52:555–8. disease: a systematic review. Front Psychiatry. 2021;12: 633081. 23. Pavot W, Diener E, Colvin CR, Sandvik E. Further validation of the Satisfaction with Life Scale: evi- 29. Diefenbach MA, Leventhal H. The common-sense dence for the cross-method convergence of well- model of illness representation: theoretical and being measures. J Pers Assess. 1991;57:149–61. practical considerations. J Soc Distress Homeless. 1996;5:11–38. 24. Schwarzer R, Jerusalem M. Generalized Self-Efficacy scale. In: Weinman J, Wright S, Johnston M, edi- 30. Mate KE, Pond CD, Magin PJ, Goode SM, McElduff tors. Measures in health psychology: A user’s port- P, Stocks NP. Diagnosis and disclosure of a memory folio. Causal and control beliefs. Windsor: NFER- problem is associated with quality of life in com- NELSON; 1995. p. 35–37. munity based older Australians with dementia. Int Psychogeriatr. 2012;24:1962–71. 25. Mohs RC, Knopman D, Petersen RC, et al. Devel- opment of cognitive instruments for use in clinical 31. Hongisto K, Väätäinen S, Martikainen J, et al. Self- trials of antidementia drugs: additions to the Alz- rated and caregiver-rated quality of life in Alzhei- heimer’s Disease Assessment Scale that broaden its mer disease with a focus on evolving patient ability scope. The Alzheimer’s Disease Cooperative Study. to respond to questionnaires: 5-year prospective Alzheimer Dis Assoc Disord. 1997;11(Suppl 2): ALSOVA cohort study. Am J Geriatr Psychiatry. S13–21. 2015;23:1280–9. 26. McMillan D, Gilbody S, Beresford E, Neilly L. Can we predict suicide and non-fatal self-harm with the