Concepts and objects of awareness in Alzheimer ’ s disease : an updated systematic review

Objectives: To compare and discuss the objects of awareness in Alzheimer’s disease (AD): awareness of cognitive deficits, of functional activities, of social-emotional functioning and behavioral impairment. Methods: A search in the PsycINFo, Pilots, PubMed/Medline and ISI electronic databases according to Prisma methodology was performed. We included studies about awareness in people with AD published between 2010 and 2015, with the combination of keywords: “Alzheimer AND awareness of deficits”, “Alzheimer AND anosognosia”, “Alzheimer AND insight”, “dementia AND awareness of deficits”, “dementia AND anosognosia”, “dementia AND insight”. The articles were categorized according to the specific object of awareness. Results: Seven hundred and ten records were identified and, after application of the exclusion criteria, 191 studies were retrieved for potential use. After excluding the duplicates, 46 studies were included. Most studies assessed the cognitive domain of awareness, followed by the functional, social-emotional, and behavioral impairment domains. Memory deficits were not sufficient to explain impaired awareness in AD. Longitudinal studies did not find discrepancies between patients and caregivers’ reports, indicating that awareness is not related to cognition. Conflicting findings were observed, including the relation between awareness, mood, severity of disease, and personal characteristics. Conclusions: The studies show lack of conceptual consensus and significant methodological differences. The inclusion of samples without differentiation of dementia etiology is associated to symptomatic differences, which affect awareness domains. Awareness in AD is a complex and multidimensional construct. Different objects elicit different levels of awareness.


INTRODUCTION
Empirical research has recently focused on exploring awareness in people with dementia (PwD) 1,2 .Awareness is the recognition of changes caused by the deficits related to the disease process.It includes three dimensions: the ability to recognize a specific deficit, the emotional response to the difficulties and the ability to understand the impact of the impairment in the functional activities 3,4 .This construct integrates biological, psychological and social levels and is not simply as a symptom of illness 3 .
Awareness may be considered a relational concept.It can only be expressed in its relation to something, such as to the pathological state or non-morbid experience 5 .Three main factors determine clinical phenomena of awareness: the underlying concept selected by the clinician/researcher, the measure used to elicit it, and the specific object of awareness chosen 6,7 .These factors may be particularly variable in dementia research.
The objects of awareness may range from physical attributes of the environment or internal states to factors of one's own functioning or situation, external events, mental representations and aspects of self 8 .Therefore, awareness cannot be isolated from its object.This complexity is captured because different 'objects' will determine different kinds of judgments 6 .
Impaired awareness is a complex and multidimensional phenomenon, commonly reported as a clinical feature of dementia, and can range from mild to severe stages 2 .Studies focusing on clinical correlates and predictors of unawareness have produced inconclusive findings.Probably, the several conceptual models of awareness and methodological differences, such as heterogeneity of sample and level of disease severity may explain these uncertain findings 9 .
It is essential to understand the differences between each object of awareness and of their specific traits, as it may be helpful for the improvement of strategies focused on the manage-ment of PwD 1,6,10 .In this context, this systematic review is aimed at exploring the different objects of awareness in Alzheimer's disease (AD).We consider that different objects of awareness raise different phenomena.Our primary goal is to systemize the results of the researches involving awareness according to each specific object.We proposed to discuss the concepts and domains used to evaluate types of awareness, such as awareness of cognitive deficits, of social-emotional status and behavioral impairment and awareness of functional activities.

METHODS
This systematic review is according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 11 .The search for literature was undertaken on April 5 th , 2015, using PsycINFo, Pilots, PubMed/Medline and ISI electronic databases.The search keywords included "Alzheimer", "dementia", "awareness of deficits", "insight" and "anosognosia" in the following combinations: "Alzheimer AND awareness of deficits", "Alzheimer AND anosognosia", "Alzheimer AND insight", "dementia AND awareness of deficits", "dementia AND anosognosia", "dementia AND insight".
Inclusion criteria were: (1) original cross-sectional or longitudinal quantitative researches, (2) studies on participants with AD diagnosis, (3) reports written in English or Portuguese and (4) publications from January 2010 to April 2015.The exclusion criteria were: (1) opinion papers or reviews, (2) participants with pre-clinical dementia conditions, other dementia or clinical pathologies and psychiatric comorbidities, (3) other impairments not related to awareness, (4) studies focused only on pharmacologically interventions or rehabilitation issues and (5) studies without full text.
Two authors (RLS and MLN) independently screened titles and abstracts to identify eligible papers.When the information was not enough to identify the inclusion and/or exclusion criteria, we retrieved the full text paper.We excluded all studies that clearly did not meet all inclusion criteria or that met at least one of the exclusion criteria.Afterwards, two authors (RLS and MCND) independently reviewed the full publications of the remaining papers and held consensus meetings to discuss any disagreement and to reach a consensus about inclusion.When necessary, a third co-author of this paper (MFBS) clarified study eligibility.

RESULTS
Initially, 710 records were identified through database searching: 13 in PsycINFo, 1 in Pilots, 247 in PubMed/Medline and 449 in ISI.The 191 studies that remained after application of the exclusion criteria were retrieved for potential use and the information of the full-text version of each study was evaluated.Cross-referencing of reference lists of all selected papers was undertaken.After duplicates were removed, the total number of studies was reduced to 46.The flow diagram about the different phases of the systematic review is shown in Figure 1.
Awareness was defined as the capability of an individual to accurately evaluate and report about his abilities and limitations 12 .Awareness of disease was defined as the ability to perceive changes in oneself and/or in functional activities caused by deficits associated with the disease process 45 .Self-awareness referred to the capacity to reflect upon and identify with one's own abilities, attitudes and behavior 33 .Self-appraisal was related to impaired awareness of one's own abilities 35 .Cognitive insight was defined as a PwD current capacity to evaluate his or her anomalous experiences and atypical interpretations of events 38 .Metacognition was the knowledge about cognition, including the ability to think about one's own basic cognitive abilities (such as episodic memory or executive functions) 41 .It was also defined as a process by which we understand and alter our own thinking 39 .Some concepts were used to define impairment in awareness, which may range from general to specific impairments, such as anosognosia of memory.Thus, loss of insight was defined as a lack of awareness of mental symptoms, which could be either frank denial or unconcern about consequences 37 .Meanwhile, Anosognosia was defined as an inability of patients to appreciate or recognize their own deficits in sensory, perceptual, motor, behavioral, or cognitive functioning 32 .In a strict sense, it referred to inability to recognize deficits or realize their extent 29 .Reduced awareness about cognitive deficits or illness, was also termed anosognosia, and ranges from the diagnosis and the condition itself to reduced awareness of deficits in specific abilities 49 .Moreover, unawareness of deficits was defined as inability to recognize the presence or appreciate the severity of deficits in sensory, perceptual, motor, affective, or cognitive functioning 42 .

DISCUSSION
The different concepts highlight the lack of clear definitions to its boundaries.They are problematic because they contribute to the variability and inconsistency of findings in the area.The conceptual heterogeneity used to define the awareness phenomenon is caused both by the researcher's theoretical perspectives and by the dementia studies from different fields such as Psychology, Psychiatry and Neurology 6 .Therefore, different perspectives coexist when referring to awareness, and it may explain the use of multiple terms for its definition.The concepts are often nonspecific and do not, consider the possible particularities of each terminology.There were degrees of awareness across the cognitive domain.Questionnaires of discrepancy between PwD and caregivers reports were especially sensitive for recent memory, followed by functional activities, apathy and attention 29 .The association of cognitive deficits with both unawareness of memory and behavior problems domains indicated that cognition may be a basis for self-insight and self-awareness.Thus, cognitive deficits may lead to global unawareness 42 .
A negative association between awareness and Mini-Mental State Examination (MMSE) suggested that awareness increased as global cognitive functions declined.This finding supported the view that low awareness was related to advanced disease stages 30 .Conversely, a longitudinal assessment of a group of PwD (Alzheimer's disease, vascular dementia and mixed dementia) presented that initial discrepancies were moderate in relation to memory.Surprisingly, there were no changes in discrepancy scores over time.PwD stability in awareness was observed, although the dementia symptoms and the cognitive impairment increase in the context of no change in psychological or social well-being 13 .
Another longitudinal research described that impaired awareness of disease was associated to cognitive and functional deficits at baseline 45 .However, in the second evaluation, awareness remained stable in a proportion of PwD and was followed by a relative decline, which is not only due to the cognitive impairment.Thus, deficits in awareness and cognition seem to be relatively independent, because mild PwD unawareness is mainly manifested by poor recognition on changes in functional activities 1 .
Van Vliet et al. 12 concluded that memory deficits are unlikely to explain impaired awareness, as mild PwD can display impaired awareness and PwD with severely disturbed memory retention and consolidation may still have intact awareness.Clinically, unawareness of memory deficit among people with AD was associated with lower scores on the MMSE and higher scores on the Cornell Scale for Depression in Dementia.So, depression may occur among people with higher levels of awareness as an emotional response to cognitive declines 42 .Awareness of cognitive deficits had association with general neuropsychological variables 15 .There were strongest associations with memory, but small significant correlations were also observed for attention, language and executive function.This finding suggested that memory was not the only cognitive domain influencing memory awareness 54 .An important aspect is that unawareness of memory deficit may be understood as an initiator of other behavioral abnormalities contributing to professional caregivers' burden 27 .
Interestingly, unawareness of memory deficit in AD subjects is an early symptom of their memory disorder, even in mild cognitive impairment (MCI).Thus, unawareness might be considered as a specific marker of the transition from MCI to AD.It is important to note that unawareness for memory deficit may be easily identified in standard clinical setting and used to evaluate the role of unawareness in predicting conversion from MCI to AD 51 .
A study 47 investigated the eventual existence of relationship between awareness and Clinical Competence (CC) in mild to moderate AD.A great proportion of PwD were unaware of cognitive, functional and behavioral deficits, with an increase of severity and prevalence of awareness along the progression of disease.Even people with very mild dementia and great awareness showed substantial deficits in CC.We can assume that deficits in executive function, memory and language may refer to the association between capacity and awareness, suggesting that these two constructs may be differently impaired in PwD 47 .
On self-evaluating their predictions, people with AD were generally less accurate in evaluating the level of their cognitive abilities than healthy older adults, significantly overestimating their performance on the pretest 19,53,55 .However, immediately after taking the test, people with AD were able to successfully modify their predictions based on task experience, demonstrating self-monitoring memory abilities 53,55 .Those AD participants who continued to exhibit poorer post experience prediction accuracy also tended to more significantly underestimate the frequency of everyday memory difficulties, when compared to caregivers report 55 .The association of the self-evaluating of actual performance with fluency and visuospatial abilities may reinforce the notion that unawareness is in part a neurocognitive deficit.The frontal lobes may be responsible for important processes in awareness, such as evaluating beliefs, monitoring errors or comparing current with past performance 50 .Thus, participants with mild AD were able to use confidence judgments to track the accuracy of their responses on a recollection test.Confidence-accuracy relationship was not impaired in the early stages of AD as PwD have relatively preserved metacognitive monitoring abilities on episodic memory tests, at least when the task was relatively well constrained 41 .
Quality of life (QoL) is considered an indicator of the effectiveness of both psychosocial and pharmacological interventions.Studies suggested an association between unawareness and QoL.The discrepancy between self-report/caregiver reports showed that higher levels of unawareness led PwD to have a more positive view of their QoL, despite their general deterioration 23 .This lack of awareness regarding their actual status suggests that PwD perceptions correspond to a mental image of themselves prior to their deterioration.In addition, Clare et al. 20 endorse that two domains of awareness -evaluative judgments of memory function and evaluative judgments of functional abilities -show small to medium correlations with self-reported QoL-AD, with higher levels of awareness related to lower QoL.
Awareness of social-emotional functioning elicits quite complex judgments.It occurs because PwD are not asked about a loss or impairment of 'function' as in the case of the memory or activities items; in fact, they are asked about their behaviors, personality, and views of themselves and their perspectives 19 .The judgments entailed in awareness of social-emotional functioning included wider-based judgments and perspectives.It is not surprising that higher levels of differences between subjects and carers were obtained, both in over-and under-estimations 19 .
Unawareness of social-emotional functioning was related to poorer cognitive performance, suggesting a relationship between dementia severity and degree of awareness in this domain 19 .In addition, loss of awareness of social-emotional skills was associated with the presentation and severity of behavioral and psychiatric disturbance in people with AD 17 .A significant relationship between self-reported QoL and the level of awareness in the three areas of social-emotional functioning (emotional recognition and empathy, social relationships and prosocial behavior) was also observed 17 .
In an assessment of a group of people with AD at three moments over approximately 20 months, discrepancies were initially least pronounced in relation to social-emotional functioning, with no changes over time 26 .Concerning emotional reactivity, non-conscious processing of emotion might extend to more complex feelings and attributions, such as frustration/disappointment after task failure and satisfaction after task success.However, there was dissociation between impaired performance judgment and preserved emotional reactivity to failure in AD 49 .
The phenomenon of unawareness affects not only deficits in cognition and daily functioning, but it can also manifest itself as non-recognition of affective symptoms.For example, PwD may be unaware of their depressive symptoms or anxiety in the sense of an ''affective'' unawareness 24 .Depression and unawareness were inversely correlated LITERATURE REVIEW J Bras Psiquiatr.2016;65(1):99-109.

Concepts and objects of awareness
among PwD, as unawareness was associated with a more positive self-appraisal among them and its presence increased with the progression of AD 22 .
We found only one study of awareness in young onset dementia.Longitudinally, people with young onset AD presented higher levels of awareness compared with late onset AD.A possible explanation was related to the higher levels of environmental demands faced daily by younger people, which may improve awareness of their limitations.Thereby, higher levels of awareness were associated with a higher risk of depressive symptoms and intact awareness was associated with depressive symptoms, an effect more pronounced in young onset compared with late onset dementia 12 .It is necessary to improve the studies in this area, to better understand if there are differences in the objects of awareness in young onset when compared to late onset dementia.
In relation to the perceived stress, unawareness had an impact on psychological markers of stress, but not on the physiological one (i.e.cortisol levels).An explanation was the small sample size of the study and the high variability of cortisol measurements across the days and seasons.It also explained the failure to find statistically significant group differences 21 .Thus, a certain level of perceived stress in AD may cause some problems due to the inability of PwD to be aware of their cognitive state 21 .
Neuropsychiatric symptoms are factors that contribute to unawareness, besides the neuropsychological aspects.In people with AD, unawareness of psychosis or behavior problems was related with lower scores on the MMSE and may be more prevalent or more severe as dementia progresses 42 .PwD with very poor awareness had significantly more neuropsychiatric symptoms than people who were fully aware of their cognitive deficits 16 .PwD with unawareness presented deficits in functional activities and higher levels of behavioral and psychological symptoms of dementia such as disinhibition, apathy, irritability and anxiety, agitation, and aberrant motor behavior 25 .
In mild AD, there was a relationship between unawareness of behavioral deficits and agitation and apathy, whereas global level of anosognosia was related to aberrant motor behaviors.The diagnosis of unawareness has been associated with severity of apathy symptoms as well as the categorical diagnosis of the apathy disorder 31 .A longitudinal assessment, during the first year, showed a decline in awareness score, which was not associated with change in any of the studied variables.However, neuropsychiatric symptoms of people with lower awareness after 36 months (as compared to baseline) increased, when compared to individuals with improved or stable awareness 14 .
The ability to inhibit a response, self-monitoring, and set-shifting appears to be important executive functions for awareness of functional deficits in AD 43 .Set-shifting and pro-cessing speed may have a role in awareness, but are likely to be part of a multicomponent process 15 .PwD showed decreased awareness of deficits in activities requiring executive function, such as handling money, practicing favorite hobbies and doing home activities 34 .In moderate AD, deficits in self-awareness were also apparent in the activities regarding communication and social interaction, such as communicating with people, or understanding conversations, the newspaper and the plot of a movie that involves communication of characters 34 .Ohman et al. 48reported individual variations of awareness of disability in participants with the same diagnosis and similar functional activities process skills measures.Several other factors (e.g.denial, or having experienced the problems in functional activities performances over a long period) may also impact on PwD experiences and descriptions of functional activities performance and, hence, may result as well in lower scores in the awareness evaluation 48 .
PWD tend to overestimate the awareness of functional activities 19 .Appraisal of daily activities possibly evokes judgments that are more straightforward than those involved in hypothetical memory tasks.The overestimation indicated that participants seemed to show more unawareness in relation to assessing their abilities to do specific tasks than in assessing their abilities to remember particular things 19 .
From a discrepancy analysis between PwD and caregivers reports, PwD with reduced awareness of instrumental functional activities ability performed better at letter fluency, indicating that awareness of functional deficits may be influenced by letter fluency 46 .
This systematic review has some limitations.We included studies that were not controlled and randomized.In addition, we selected studies that assessed only people with AD, which unable the observation of the particularities of awareness in different dementia etiologies.Despite these limitations, we add to literature emphasizing that the clinical phenomenon of awareness is determined to some extent by the "object" of awareness assessment.This means that there is a great need for more studies and further researches in this area, especially longitudinal studies that clearly define the assessed object and its specificities.

CONCLUSIONS
Even though many researches investigate the concept of awareness, the results are variable and inconsistent.Awareness is a complex and multidimensional construct, which needs to be carefully defined.Different objects elicit different levels of awareness.Therefore, the findings may change in relation to the chosen concept and according with the specific selected object of awareness.
The comparison between the studies shows the emphasis on cognitive domain in the assessments.Interestingly, the J Bras Psiquiatr.2016;65(1):99-109.
Lacerda IB et al.
findings of the cross-sectional studies between awareness and, more specifically, the cognitive domain were not observed in the longitudinal ones.Over time, awareness may improve or may remain stable for a considerable proportion of PwD, suggesting that there is no straightforward relationship with dementia severity or with the progression of cognitive impairments.
Furthermore, there are controversies about the role of the cognitive components in decreased awareness.Memory deficits are not sufficient to explain impaired unawareness, although a strong association has been observed between awareness and the memory domain.The relationship observed between awareness and attention, language and executive function suggests that memory is not the only cognitive domain that influence awareness.In addition, the inclusion of different subtypes of dementias may originate a lack of specificity, since different etiologies may lead to different cognitive and functional symptomatology, in which different domains of awareness may be affected.Moreover, the sociodemographic variables should be observed.
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 57 has recently included social cognition as a criterion that composes the basis for the diagnosis of dementia.Awareness of social-emotional functioning and behavioral impairment is a domain, which elicits complex judgements, regarding emotion recognition.Most studies investigate the cognitive and functional domains, but there is a need to further research on the recognition of social-emotional functioning.Lack of awareness of social-emotional functioning may cause relevant implications involving social comprehension and communication that can also lead to higher levels of carer burden and stress.

Table 1 .
and four studied the recognition of cognitive, functional, and social-emotional Selected studies and was associated with better perceived QoL-p in moderate dementia, whereas cognitive status did not influence the ratings of these patients, moreover anosognosia and cognition act as independent variables in relation to perceived quality of life 11) Rosen et al., 2014 39 Metacognition bvFTD AD HC Cross-sectional Cognition 20-item paired associates learning paradigm Significant impairments in feeling of knowing accuracy in bvFTD and AD