Abstract
Background:
To investigate the associations between unawareness of deficits and clinical correlates, including apathy and depression, among patients with dementia due to Alzheimer’s disease (AD).
Methods:
Fifty-five patients with AD were enrolled. Unawareness of memory deficits and psychosis or behavior problems was assessed. The Apathy Evaluation Scale informant version and the Cornell Scale for Depression in Dementia (CSDD) were used to measure apathy and depression, respectively.
Results:
In all, 32 (57.2%) and 27 (49.1%) participants were identified as being unaware of memory deficits and psychosis or behavior problems, respectively. Unawareness of memory deficits was associated with lower scores on the Mini-Mental State Examination (MMSE) and higher scores on the CSDD. Unawareness of psychosis or behavior problems was associated with lower scores on the MMSE.
Conclusion:
Unawareness of deficits among patients with AD was common. The 2 domains of unawareness showed different characteristics and may possibly present different etiologies.
Keywords: unawareness of deficits, Alzheimer’s disease, depression, apathy
Introduction
Unawareness of deficits means an inability to recognize the presence or appreciate the severity of deficits in sensory, perceptual, motor, affective, or cognitive functioning. 1 Unawareness of deficits is associated with a poor outcome and an increased caregiver burden. 2 As patients with dementia due to Alzheimer’s disease (AD) show significant impairment in memory monitoring, 3 it is possible that they do not acknowledge their own deficits. The literature supports the notion that unawareness of deficits is not uncommon in patients with dementia due to AD. 4,5 Studies on the pathology showed that unawareness of deficits was related to pathology in the frontal lobe, 6,7 medial temporal cortex, temporal–parietal cortex, 8 and temporal–occipital cortex. 9 The inconsistent results may arise from the heterogeneity of unawareness of deficits.
Two domains of unawareness of deficits, including memory deficits and behavioral disturbances, have been proposed. 10 However, in contrast to memory deficits, which have received much attention, less is known about unawareness of behavioral disturbances. Behavioral disturbance in AD has been clustered into several factors; for example, a 4-factor structure includes behavioral problems (agitation/aggressiveness, disinhibition, irritability, and aberrant motor behavior), psychosis (delusions and hallucinations), mood disturbance (depression, anxiety, sleep, appetite, and apathy), and euphoria. 11
Previous studies have also found that unawareness of memory deficits may be related to depression and apathy. Depression has been suggested to occur in patients with higher levels of awareness as an emotional response to cognitive decline 12 despite other reports not supporting the association. 13 –15 Apathy is the most common neuropsychiatric disturbance in AD and could be predicted by unawareness of memory deficits 14,16,17 ; however, research has failed to discover such an association. 18 Previous studies investigating the relationships of unawareness of memory deficits usually focused on either depression or apathy and few have focused on the 2 domains of unawareness of both memory deficits and behavioral problems.
Thus, the main purpose of this study was to examine the association of unawareness of deficits, both memory deficits and behavioral disturbances (including psychosis and behavioral problems), with apathy and depression and other clinical or demographic characteristics. We hypothesized that apathy and depression, and possibly demographic characteristics, would be associated with the patients’ unawareness of deficits, either memory or behavioral disturbances.
Methods
Participants
The study participants were recruited from among consecutive memory impairment outpatients; these patients were seen at outpatient units of a teaching hospital during a 1-year study period. The presence of a caregiver to serve as an informant was required. All participants met the criteria of the National Institute of Neurological and Communicable Diseases and Stroke-Alzheimer’s Disease and Related Disorders Association for probable AD and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for dementia of Alzheimer’s type. Participants were excluded from the study if they (1) had another major comorbid axis I psychiatric disorder according to the DSM-IV-TR; (2) had experienced a stroke; (3) had Parkinson’s disease; (4) had epilepsy; (5) had a severe traumatic head injury; or (6) were incapable of completing all the assessments. The study was approved by the institutional review board of Kaohsiung Medical University Hospital. All participants provided informed consent prior to participation. In total, 55 patients with dementia due to AD were included in the study.
Apathy and Depression
The Apathy Evaluation Scale Informant version (AES-I) and the Cornell Scale for Depression in Dementia (CSDD) were used to measure apathy and depression symptoms, respectively. The AES-I consists of 18 items; each item is rated on a 4-point scale: 1 = not at all true, 2 = slightly true, 3 = somewhat true, and 4 = very true. Higher scores on the AES-I represent a greater severity of apathy. This scale has been found to have excellent reliability and validity for patients with dementia. 19 Our study used the informant version and the information was provided by the patients’ caregivers. The CSDD was specifically developed to evaluate the symptoms of major depression in patients with dementia. It includes 19 items, which are rated on a 3-point scale: 0 = absent, 1 = mild, intermittent, and 2 = severe. Because the patients may give unreliable reports, the CSDD uses a comprehensive interviewing approach that derives information from both the patient and the informant. The final ratings of the CSDD items represent the rater’s clinical impression rather than the responses of the informant or the patient alone. Higher scores on the CSDD represent more severe depressive symptoms. 20
Psychosis and Behavioral Problems
The presence of psychosis and behavioral problems was assessed using the Neuropsychiatric Inventory (NPI). 21 The NPI is an interview-based instrument designed to evaluate the presence of behavioral disturbances commonly encountered in patients with dementia. Each caregiver was interviewed by a trained research nurse to define the presence of psychosis or behavioral problems. We adopted a 4-factor structure for the NPI which divides neuropsychiatric symptoms into behavioral problems, psychosis, mood disturbance, and euphoria. 11
Cognitive Function
The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function as a covariate because it has been reported that there is a negative association between unawareness of deficits and cognitive function. 22 The MMSE consists of 11 items, including orientation, registration, attention, calculation, language, and recall and has been widely used to assess the cognitive function of elderly people. 23 Moreover, it has been found to have satisfactory reliability and validity. 24
Unawareness of Deficits
The 2 domains of unawareness of deficits assessed in patients with dementia were unawareness of memory deficits and unawareness of psychosis or behavioral problems. 17,25 Unawareness of memory deficits indicated that patients with dementia due to AD were unable to recognize impairment of memory. Unawareness of psychosis or behavioral problems indicated that patients with dementia due to AD were unable to acknowledge the presence of psychotic symptoms, agitation and aggression, aberrant behavior, irritability, and disinhibition. The Guidelines for the Rating of Awareness Deficits (GRAD), a brief unawareness semistructured interview schedule derived from previous work by Verhey and colleagues, 13 were adapted and used to evaluate unawareness of deficits. An experienced clinician interviewed the patients, and the caregiver was requested to refrain from making any comment. The 4 opening questions designed to inquire into unawareness of memory deficits are as follows: (1) “Please tell me about the problems you are here for.” (2) When the patient has other complaints not directly related to dementia: “Do you have any other complaints?” (3) When the patient has no spontaneous complaints about his or her cognitive functions: “How is your memory functioning? Do you think you have a poor memory?” (4) When the patient denies deficits of memory or other cognitive functions. Whereas, based on the NPI items data provided by the caregiver informants, similar questions related to unawareness of psychosis or behavioral problems were asked of patients who had any positive responses to items regarding agitation/aggressiveness, disinhibition, irritability, and aberrant motor behavior, delusions, and hallucinations. By comparing the patients’ responses with the information obtained from caregivers, the objective NPI and cognitive evaluation results, and the clinician’s observation, the clinician was able to rate the unawareness of memory impairment and psychosis or behavioral problems separately on a 4-point scale, on which 4 = adequate awareness: the patient has adequate knowledge of his memory and behavioral problems. Those without psychosis and behavioral problems would be rated as having adequate awareness; for instance, patients with spontaneous complaints about memory or other behavioral problems and whose history is congruent with the history provided by the informant. 3 = mildly disturbed awareness: the patient has some knowledge of his or her cognitive or behavioral deficits but with some gaps. Patients had spontaneous complaints about memory or behavioral problems; however, their history shows some discrepancies with the history provided by the informant. 2 = moderately disturbed awareness: the patient has only vague and passive knowledge of cognitive or behavioral deficits. The patients had no spontaneous complaints and admitted to memory or behavioral problems only when questioned about them. There were obvious discrepancies with the history provided by the informant. 1 = severely disturbed awareness of memory and behavioral problems: denies any deficits. The patient had no complaints about memory or behavioral problems whatsoever even after explicit questioning. Participants who scored 4 (adequate awareness) were identified as having adequate awareness of deficits whereas those who scored lower than 4 were identified as having unawareness of deficits in the analyses of this study.
Statistical Analysis
Statistical analysis consisted of both descriptive and inferential measures. First, the occurrence of 2 domains of unawareness of deficits was calculated and reported. Second, the inferential statistics contained univariate and multivariate analyses to figure out the differences and associations between 2 domains of unawareness of deficits. Univariate analyses including chi-square analysis or Student t tests were conducted to examine the differences in apathy, depression, and demographic characteristics between patients with and without unawareness of deficits. Significant factors in the above-mentioned univariate analyses were put into a multivariate logistic regression model to ascertain the independent associated factors.
Results
The 55 participants in this study had a mean age of 76.7 ± 7.6 years and 58.2% were female. The educational level was 5.2 ± 5.3 years. The mean score on the MMSE was 18.6 ± 5.3, that of the AES-I was 44.5 ± 12.8, and that of the CSDD was 10.2 ± 7.2. The NPI was presented as frequency of symptoms. As the study participants did not always have psychosis or behavioral problems, those who had none of these symptoms were defined as “no” unawareness of psychosis and disturbed behavior. In all, 32 (57.2%) participants were identified as being unaware of memory deficits 27 (49.1%) were unaware of psychosis or behavioral problems; 23 (41.8%) patients had co-occurrence of unawareness of memory deficits and unawareness of psychosis or behavioral problems; 9 (16.4%) had unawareness of memory deficits alone; and 4 (7.3%) had unawareness of psychosis or behavioral problems alone (Table 1). The results of a comparison of the distributions of unawareness of memory deficits and unawareness of psychosis or behavioral problems showed that the distributions differed between the 2 (χ2 = 15.9; P < .001; Table 2).
Table 1.
Demographic and Clinical Characteristics of the Study Participants.a
| Characteristics | Mean (SD) | N (%) |
|---|---|---|
| Sex, female | 32 (58.2) | |
| Age, years | 76.7 (7.6) | |
| Education, years | 5.2 (5.3) | |
| MMSE score | 18.6 (5.3) | |
| AES-I | 44.5 (12.8) | |
| CSDD | 10.2 (7.2) | |
| NPI | ||
| Delusion | 19 (34.5) | |
| Hallucination | 10 (18.2) | |
| Agitation/aggression | 12 (21.8) | |
| Disinhibition | 13 (23.6) | |
| Aberrant motor behavior | 20 (36.4) | |
| Irritability | 29 (52.7) | |
| Depression | 25 (45.5) | |
| Anxiety | 25 (45.5) | |
| Apathy | 34 (61.8) | |
| Euphoria | 5 (9.1) | |
| Sleep | 20 (36.4) | |
| Appetite | 14 (25.5) | |
| Unawareness of memory deficits | 32 (58.2) | |
| Unawareness of psychosis or behavioral problems | 27 (49.1) | |
Abbreviations: AES-I, Apathy Evaluation Scale informant version; CSDD, Cornell Scale for Depression in Dementia; MMSE, Mini-Mental State Examination; NPI, Neuropsychiatric Inventory; SD, standard deviation.
aScores of the Neuropsychiatric Inventory subscales (frequency). N = 55.
Table 2.
The Distributions of Unawareness of Memory Deficits and Unawareness of Psychosis or Behavioral Problems.
| Unawareness of Psychosis and Behavioral Problems | Unawareness of Memory Impairment | ||
|---|---|---|---|
| No | Yes | Total | |
| Noa | 19 | 9 | 28 |
| Yes | 4 | 23 | 27 |
| Total | 23 | 32 | 55 |
a Including those who could be aware or in whom none of these symptoms occurred.
Clinical Correlates Between the 2 Domains of Deficits
Univariate analysis revealed associations between unawareness of memory deficits and gender, age, MMSE, and CSDD but not education or AES-I. However, unawareness of psychosis or behavioral problems was associated with gender, age, MMSE, and AES-I but not education or the CSDD (Table 3). Multivariate logistic regression analyses, using the absence and presence of unawareness of memory deficits and psychosis or behavioral problems as dependent variables, were conducted to identify the independent effects of the significant variables found in the univariate analyses. Logistic regression analysis for unawareness of memory deficits revealed that male gender (odds ratio [OR] = 8.53, 95% confidence interval [CI] = 1.23-59.02), older age (OR = 1.15, 95% CI = 1.01-1.31), and a lower score on the MMSE (OR = 1.35, 95% CI = 1.09-1.67) increased the risk of unawareness of memory deficits while a higher score on the CSDD (OR = 0.74, 95% CI = 0.62-0.89) reduced the risk. A similar logistic regression analysis was carried out for unawareness of psychosis or behavioral problems and the risk factors were male gender (OR = 6.23, 95% CI = 1.41-27.63), older age (OR = 1.09, 95% CI = 1.00-1.19), and a lower score on the MMSE (OR = 1.18, 95% CI = 1.00-1.39). However, the total score on the AES-I was not found to be a risk factor for unawareness of psychosis or behavioral problems in the controlled analysis (Table 4).
Table 3.
Univariate Analyses of Demographic Characteristics, Apathy, and Depression Among the Patients With and Without Unawareness of Deficits.a
| Unawareness of Memory Deficits | Unawareness of Psychosis or Behavioral Problems | |||||
|---|---|---|---|---|---|---|
| No; n = 23 | Yes, n = 32 | Statistics | No; n = 28 | Yes; n = 27 | Statistics | |
| Sex | ||||||
| Female | 17 (73.9%) | 15 (46.9%) | χ 2 = 4.02; P < .045b | 20 (71.4%) | 12 (44.4%) | χ 2 = 4.114; P < .043b |
| Male | 6 (26.1%) | 17 (53.1%) | 8 (28.6%) | 15 (55.6%) | ||
| Age | 74.2 (7.4) | 78.5 (7.3) | t = −2.14; P < .037b | 74.7 (6.2) | 78.7 (8.4) | t = −2.04; P < .046b |
| Education | 4.8 (5.7) | 5.5 (5.1) | t = −0.47; P < .64 | 5.7 (6.0) | 4.7 (4.4) | t = 0.71; P < .484 |
| MMSE | 20.6 (4.7) | 17.2 (5.3) | t = 2.48; P < .017b | 20.3 (5.2) | 16.9 (4.9) | t = 2.43; P < .018b |
| AES-I | 42.5 (11.6) | 45.9 (13.7) | t = −0.98; P < .329 | 40.9 (11.6) | 48.2 (13.2) | t = −2.16; P < .035b |
| CSDD | 14.7 (8) | 7 (4.5) | t = 4.14; P < .001c | 11.3 (7.9) | 9.1 (6.4) | t = 1.10; P < .278 |
Abbreviations: MMSE, Mini-Mental State Examination; AES-I, Apathy Evaluation Scale informant version; CSDD, Cornell Scale for Depression in Dementia.
a P < .01.
b P < .05.
c P < .001.
Table 4.
Logistic Regression of Related Factors of Unawareness of Memory Deficits and Psychosis or Behavioral Problems.a
| Unawareness of Memory Deficits | Unawareness of Psychosis or Behavioral Problems | ||||
|---|---|---|---|---|---|
| Variables | OR (95% CI) | P | Variables | OR (95% CI) | P |
| Sex, M/F | 8.53 (1.23-59.02) | .030b | Sex, M/F | 6.23 (1.41-27.63) | .016b |
| Age | 1.15 (1.01-1.31) | .035b | Age | 1.09 (1.00-1.19) | .043b |
| MMSE | 1.35 (1.09-1.67) | .006b | MMSE | 1.18 (1.00-1.19) | .044b |
| CSDD | 0.74 (0.62-0.89) | .001c | AES-I | 1.00 (0.94-1.06) | .968 |
Abbreviations: MMSE, Mini-Mental State Examination; CSDD, Cornell Scale for Depression in Dementia; M, male; F, female; OR, odds ratio; CI, confidence interval.
a P < .001.
b P < .05.
c P < .01.
Similar analyses were conducted for those with behavioral disturbance (N = 44) alone, and the distributions still differed between the 2 domains of unawareness of deficits (χ2 = 13.1; P < .001). Multivariate logistic regression analysis for unawareness of psychosis or behavioral problems showed that a lower score on the MMSE (OR = 1.25, 95% CI = 1.05-1.49) was a risk factor but male gender (P = .09) and an older age (P = .53) became marginal significant and nonsignificant factors.
Discussion
In this study, nearly two-thirds of the patients with dementia due to AD presented with either unawareness of memory deficits or psychosis or behavioral problems. These results indicated that unawareness of deficits was prevalent in patients with dementia due to AD. Male gender, older age, and a lower score on the MMSE were associated with both unawareness of memory deficits and psychosis or behavioral problems. In contrast, a higher score on the CSDD was negatively correlated with unawareness of memory deficits alone. The association between total score on the AES-I and unawareness of psychosis or behavioral problems that was present in the univariate analysis disappeared after adjusting for the MMSE in a controlled logistic regression analysis.
The differences in distributions between unawareness of memory deficits and unawareness of psychosis or behavioral problems may represent distinct presentations among patients with dementia due to AD. It also suggested that patients may be unaware of only some or certain aspects of impairments but not all. This finding suggests that there was a dissociation between the 2 domains of unawareness of deficits which was consistent with the findings of Starkstein and colleagues 17 who also separated awareness into cognitive and behavioral domains. Starkstein et al 17 used the anosognosia scale based on the discrepancy between the patient and the caregiver. The validity of the rating of the caregivers may be compromised by the caregiver’s personality, emotional status, and relationship with the patient. 26 In this study, we strengthened the rating using multiple resources, including the patient’s report, the caregiver’s report, and direct clinical observation. Therefore, our study may contribute more reliable and compatible information to the growing body of evidence.
Similar to previous studies, patients with more severe cognitive impairment showed more prominent unawareness of memory deficits. 4,5,15,27,28 Such relationships seem to be common in AD and tend to be more pronounced as the disease progresses. Further, we also found an association between cognitive function and unawareness of psychosis or behavioral problems. This may suggest that the unawareness of psychosis or disturbed behavior may be more prevalent or more severe as dementia progresses so clinicians and caregivers should pay more attention to this aspect. The association of cognitive deficits with both domains of unawareness indicates that cognition may be a basis for self-insight and self-awareness, thus cognitive deficits may lead to global unawareness.
Male gender and older age were found to be associated with unawareness of memory deficits and psychosis or behavioral problems in this study unlike in previous studies. 27,29 –31 We speculate that this inconsistency between study results may arise from the differences in cultural context between our study and others, as patients’ social status and culture could shape their awareness of illness. 32,33 One study reported that Chinese patients with AD may overrate their quality of life due to fear of shame. 34 The stigma issue is common in several Asian cultures. People tend not to express their real feelings, especially in poor situations, in order to avoid embarrassing themselves and their family and to maintain interpersonal harmony. 35 It is generally believed that this phenomenon is more common in older male patients than in younger female patients because they possess more traditional beliefs. However, such unawareness of deficits in males and older patients might be regarded as a psychological reaction of denial and not always anosognosia. 36 Also, the duration of illness could be a possible confounding or mediating factor that influences males and older patients. However, this association was not examined in this study and so the interpretations should be treated with caution.
Apathy was associated with neither unawareness of memory deficits nor unawareness of psychosis and behavioral problems. Some studies found that a greater degree of apathy was associated with decreased awareness of deficits but they did not adjust for other possible significant confounding factors or adjusted only for cognitive function. 14,37 In our study, unawareness of psychosis or behavioral problems was correlated with apathy but the association did not exist after controlling for gender, age, and cognitive function. As apathy is more common in male patients with AD than in female patients 38 and is associated with cognitive deficits, the association between apathy and unawareness of psychosis or behavioral problems may be confounded by gender, age, and dementia severity. The mean scores of the AES-I were higher in the groups with unawareness of memory and unawareness of psychosis or behavioral problems although without a significant difference (Table 3). It is possible that the small case number in our study may limit significant associations.
Depression was correlated only with unawareness of memory deficits and not with unawareness of psychosis or behavioral problems. There are conflicting results regarding the relationship between depression and unawareness of illness in dementia in the literature. 22,39 –41 It has been suggested that the relationship exists only in patients with mild depression. 42 This is compatible with our study result of participants who presented a milder degree of depression (CSDD mean = 10 ± 7.2). It has also been suggested that depression may occur in patients with higher levels of awareness as an emotional response to cognitive decline. Meanwhile, unawareness has been construed as the product of a defense mechanism—the denial of cognitive deficits—that protects patients from depression 43 and may explain the inverse association between unawareness of memory deficits and depression in our study.
Some researchers have tried to understand the mechanism of unawareness from the perspective of various disciplines. Clare et al 44 proposed a biopsychosocial model. At the biological level, disturbances of awareness may arise from brain damage and different neuroanatomical pathologies may result in different manifestations of unawareness. At the psychological level, personality, coping strategies, values, beliefs, and prior life experiences may all affect individuals and their reaction to change as a result of the disease. Finally, at the social level, interactions with others and the context, social representations, and cultural narratives of dementia are likely to influence the expression of awareness. 44 Our study showed that unawareness of memory deficits and unawareness of psychosis or behavioral problems each had different associated factors. The dissociation between the 2 types of unawareness may imply that each may have a different combination of the above-mentioned biopsychosocial mechanisms. For example, in the neuroanatomical view, most brain imaging studies focused on unawareness of cognitive deficits and showed an association with frontal lobe pathology. 6,7 Unawareness of psychosis or behavioral problems may be associated with brain deficits in distinct areas; however, further imaging studies focusing on unawareness of psychosis or behavioral problems are needed.
The novelty of this study was the assessment of unawareness of psychosis or behavioral problems, which has been given less attention in the literature. However, there are still some limitations in this study that need to be mentioned. First, it has been suggested that the 4-point GRAD scale limits its sensitivity to detect small changes in insight 5 and that it is too global and general to assess the complex phenomenon of awareness. 13 However, there should be a trade-off consideration. As raters use the GRAD and judge patients’ unawareness levels based on their answers, as well as their actual state derived from the reports of caregivers and clinical observations, their judgment tends to be more objective than that based on the discrepancy between the reports of patients and their caregivers. 31 Meanwhile, since awareness of deficits had best not be judged as all or nothing, we did not treat it as a continuous variable in analysis, to avoid skewing the distribution of our data. Further studies defining unawareness of deficits as continuous variables of varying degrees are needed. The second limitation was the small sample size. The small number of participants may lead to type II errors. Further, as our study sample was recruited from geriatric psychiatric outpatient units, a larger proportion tended to present with neuropsychiatric symptoms and the severities of these symptoms may therefore be greater. Such characteristics may limit our ability to generalize our findings to include all patients with AD. Further studies with larger sample sizes from a community sample are needed to validate our findings. The third limitation was that we assessed global cognitive function according to the MMSE alone; assessments of specific cognitive domains such as memory and executive function should be considered in further research to identify the relationships between unawareness of deficits and specific cognitive functions. Finally, because unawareness of psychosis and unawareness of behavioral problems may have different characteristics, and that unawareness may be part of the symptoms of patients with psychosis, further studies should proceed with caution in this respect and the evaluations of unawareness of deficits in behavioral problems and psychosis should be separated. In addition, unawareness of mood disturbance (eg, depression and apathy) is also an important issue that has been observed in patients with AD. 45
In conclusion, the present study found that unawareness of deficits was not uncommon in patients with dementia due to AD. The findings demonstrated some degree of independence between the 2 domains of unawareness, memory deficits, and psychosis or behavioral problems. This suggests that unawareness of deficits may not be a single unit and further studies should focus on the different domains of unawareness.
Footnotes
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The study was funded by a grant from the Kaohsiung Medical University Hospital, Taiwan (KMUH97-7R20).
References
- 1. Antoine C, Antoine P, Guermonprez P, Frigard B. Awareness of deficits and anosognosia in Alzheimer's disease. Encephale. 2004;30(6):570–577. [DOI] [PubMed] [Google Scholar]
- 2. Clare L. Managing threats to self: awareness in early stage Alzheimer's disease. Soc Sci Med. 2003;57(6):1017–1029. [DOI] [PubMed] [Google Scholar]
- 3. Galeone F, Pappalardo S, Chieffi S, Iavarone A, Carlomagno S. Anosognosia for memory deficit in amnestic mild cognitive impairment and Alzheimer's disease. Int J Geriatr Psychiatry. 2011;26(7):695–701. [DOI] [PubMed] [Google Scholar]
- 4. McDaniel KD, Edland SD, Heyman A. Relationship between level of insight and severity of dementia in Alzheimer disease. CERAD clinical investigators. consortium to establish a registry for Alzheimer's disease. Alzheimer Dis Assoc Disord. 1995;9(2):101–104. [DOI] [PubMed] [Google Scholar]
- 5. Zanetti O, Vallotti B, Frisoni GB, et al. Insight in dementia: When does It occur? Evidence for a nonlinear relationship between insight and cognitive status. J Gerontol Series B Psychol Sci Soci Sci. 1999;54(2):P100–P106. [DOI] [PubMed] [Google Scholar]
- 6. Starkstein SE, Garau ML. Awareness and theory of mind in dementia. In: Martin Brüne, Hedda Ribbert, Wulf Schiefenhövel, eds. The Social Brain: Evolution and Pathology. Hoboken, NJ: John Wiley & Sons, Ltd; 2003:419–431. [Google Scholar]
- 7. Starkstein SE, Vazquez S, Migliorelli R, Teson A, Sabe L, Leiguarda R. A single-photon emission computed tomographic study of anosognosia in Alzheimer's disease. Arch Neurol. 1995;52(4):415–420. [DOI] [PubMed] [Google Scholar]
- 8. Salmon E, Perani D, Herholz K, et al. Neural correlates of anosognosia for cognitive impairment in Alzheimer's disease. Hum Brain Mapp. 2006;27(7):588–597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Ott BR, Noto RB, Fogel BS. Apathy and loss of insight in Alzheimer's disease: a SPECT imaging study. J Neuropsychiatry Clin Neurosci. 1996;8(1):41–46. [DOI] [PubMed] [Google Scholar]
- 10. Vasterling JJ, Seltzer B, Foss JW, Vanderbrook V. Unawareness of deficit in Alzheimer's disease: domain-specific differences and disease correlates. Neuropsychiatry Neuropsychol Behav Neurol. 1995;8(1):26–32. [Google Scholar]
- 11. Cheng S-T, Kwok T, Lam LCW. Neuropsychiatric symptom clusters of Alzheimer's disease in Hong Kong Chinese: prevalence and confirmatory factor analysis of the neuropsychiatric inventory. Int Psychogeriatr. 2012;24(9):1465–1473. [DOI] [PubMed] [Google Scholar]
- 12. Aalten P, van Valen E, de Vugt ME, Lousberg R, Jolles J, Verhey FRJ. Awareness and behavioral problems in dementia patients: a prospective study. Int Psychogeriatr. 2006;18(1):3–17. [DOI] [PubMed] [Google Scholar]
- 13. Verhey FRJ, Rozendaal N, Ponds RWHM, Jolles J. Dementia, awareness and depression. Int J Geriatr Psychiatry. 1993;8(10):851–856. [Google Scholar]
- 14. Derouesne C, Thibault S, Lagha-Pierucci S, Baudouin-Madec V, Ancri D, Lacomblez L. Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type. Int J Geriatr Psychiatry. 1999;14(12):1019–1030. [PubMed] [Google Scholar]
- 15. Lopez OL, Becker JT, Somsak D, Dew MA, DeKosky S. Awareness of cognitive deficits and anosognosia in probable Alzheimer’s disease. Eur Neurol. 1994;34(5):277–282. [DOI] [PubMed] [Google Scholar]
- 16. Starkstein SE, Brockman S, Bruce D, Petracca G. Anosognosia is a significant predictor of apathy in Alzheimer's disease. J Neuropsychiatry Clin Neurosci. 2010;22(4):378–383. [DOI] [PubMed] [Google Scholar]
- 17. Starkstein SE, Sabe L, Chemerinski E, Jason L, Leiguarda R. Two domains of anosognosia in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1996;61(5):485–490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Tremont G, Alosco ML. Relationship between cognition and awareness of deficit in mild cognitive impairment. Int J Geriatr Psychiatry. 2011;26(3):299–306. [DOI] [PubMed] [Google Scholar]
- 19. Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the apathy evaluation scale. Psychiatry Res. 1991;38(2):143–162. [DOI] [PubMed] [Google Scholar]
- 20. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell scale for depression in dementia. Biol Psychiatry. 1988;23(3):271–284. [DOI] [PubMed] [Google Scholar]
- 21. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308–2314. [DOI] [PubMed] [Google Scholar]
- 22. Harwood DG, Sultzer DL, Wheatley MV. Impaired insight in Alzheimer disease: association with cognitive deficits, psychiatric symptoms, and behavioral disturbances. Cogn Behav Neurol. 2000;13(2):83–88. [PubMed] [Google Scholar]
- 23. Cockrell JR, Folstein MF. Mini-mental state examination. Principles and Practice of Geriatric Psychiatry. Hoboken, NJ: John Wiley & Sons, Ltd; 2002:140–141. [Google Scholar]
- 24. Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40(9):922–935. [DOI] [PubMed] [Google Scholar]
- 25. Sato J, Nakaaki S, Murata Y, et al. Two dimensions of anosognosia in patients with Alzheimer's disease: Reliability and validity of the Japanese version of the Anosognosia questionnaire for dementia (AQ-D). Psychiatry Clin Neurosci. 2007;61(6):672–677. [DOI] [PubMed] [Google Scholar]
- 26. Mangone CA, Hier DB, Gorelick PB, et al. Impaired insight in Alzheimer's disease. J Geriatr Psychiatry Neurol. 1991;4(4):189–193. [DOI] [PubMed] [Google Scholar]
- 27. Stewart G, McGeown WJ, Shanks MF, Venneri A. Anosognosia for memory impairment in Alzheimer's disease. Acta Neuropsychiatrica. 2010;22(4):180–187. [DOI] [PubMed] [Google Scholar]
- 28. Starkstein SE, Jorge R, Mizrahi R, Robinson RG. A diagnostic formulation for anosognosia in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2006;77(6):719–725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Aalten P, Van Valen E, Clare L, Kenny G, Verhey F. Awareness in dementia: a review of clinical correlates. Aging Ment Health. 2005;9(5):414–422. [DOI] [PubMed] [Google Scholar]
- 30. Amanzio M, Torta DME, Sacco K, et al. Unawareness of deficits in Alzheimer’s disease: role of the cingulate cortex. Brain. 2011;134(pt 4):1061–1076. [DOI] [PubMed] [Google Scholar]
- 31. Kashiwa Y, Kitabayashi Y, Narumoto JIN, Nakamura K, Ueda H, Fukui K. Anosognosia in Alzheimer's disease: association with patient characteristics, psychiatric symptoms and cognitive deficits. Psychiatry Clin Neurosci. 2005;59(6):697–704. [DOI] [PubMed] [Google Scholar]
- 32. Saravanan B, Jacob KS, Prince M, Bhugra D, David AS. Culture and insight revisited. Br J Psychiatry. 2004;184(2):107–109. [DOI] [PubMed] [Google Scholar]
- 33. Johnson S, Orrell M. Insight and psychosis: a social perspective. Psychol Med. 1995;25(3):515–520. [DOI] [PubMed] [Google Scholar]
- 34. Lin Kiat Yap P, Yen Ni Goh J, Henderson LM, et al. How do Chinese patients with dementia rate their own quality of life? Int Psychogeriatr. 2008;20(3):482–493. [DOI] [PubMed] [Google Scholar]
- 35. Tse DK, Kam-hon L, Vertinsky I, Wehrung DA. Does culture matter? A cross-cultural study of executives' choice, decisiveness, and risk adjustment in international marketing. J Mark. 1988;52(4):81–95. [Google Scholar]
- 36. Kortte KB, Wegener ST, Chwalisz K. Anosognosia and denial: their relationship to coping and depression in acquired brain injury. Rehabil Psychol. 2003;48(3):131. [Google Scholar]
- 37. Robert PH, Clairet S, Benoit M, et al. The apathy inventory: assessment of apathy and awareness in Alzheimer's disease, Parkinson's disease and mild cognitive impairment. Int J Geriatr Psychiatry. 2002;17(12):1099–1105. [DOI] [PubMed] [Google Scholar]
- 38. Ott BR, Tate CA, Gordon NM, Heindel WC. Gender differences in the behavioral manifestations of Alzheimer's disease. J Am Geriatr Soc. 1996;44(5):583–587. [DOI] [PubMed] [Google Scholar]
- 39. Seltzer B, Vasterling JJ, Hale MA, Khurana R. Unawareness of memory deficit in Alzheimer's disease: relation to mood and other disease variables. Neuropsychiatry Neuropsychol Behav Neurol. 1995;8(3):176–181. [Google Scholar]
- 40. Cummings JL, Ross W, Absher J, Gornbein J, Hadjiaghai L. Depressive symptoms in Alzheimer disease: assessment and determinants. Alzheimer Dis Assoc Disord. 1995;9(2):87–93. [DOI] [PubMed] [Google Scholar]
- 41. Reed BR, Jagust WJ, Coulter L. Anosognosia in Alzheimer's disease: relationships to depression, cognitive function, and cerebral perfusion. J Clin Exp Neuropsychol. 1993;15(2):231–244. [DOI] [PubMed] [Google Scholar]
- 42. Starkstein SE, Chemerinski E, Sabe L, et al. Prospective longitudinal study of depression and anosognosia in Alzheimer's disease. Br J Psychiatry. 1997;171(1):47–52. [DOI] [PubMed] [Google Scholar]
- 43. Migliorelli R, Teson A, Sabe L, et al. Anosognosia in Alzheimer's disease: a study of associated factors. J Neuropsychiatry Clin Neurosci. 1995;7(3):338–344. [DOI] [PubMed] [Google Scholar]
- 44. Clare L. The construction of awareness in early-stage Alzheimer's disease: a review of concepts and models. Br J Clin Psychol. 2004;43(2):155–175. [DOI] [PubMed] [Google Scholar]
- 45. Teri L, Wagner AW. Assessment of depression in patients with Alzheimer's disease: concordance among informants. Psychol Aging. 1991;6(2):280. [DOI] [PubMed] [Google Scholar]