Unawareness of deficits after right hemisphere stroke: double-dissociations of anosognosias

OBJECTIVES: The aim was to study whether anosognosia for hemiparesis, anosognosia for neglect and general unawareness of illness double-dissociate, indicating that anosognosias are specific and independent impairments of awareness. On the other hand, anosognosias may be associated with one another and with general cognitive dysfunction, which decreases awareness of deficits. The persistence and predictive value of anosognosias was examined during a 1-year follow-up. PATIENTS AND METHODS: Fifty-seven consecutive patients with acute right hemisphere infarction underwent neurological and neuroradiological examinations, neuropsychological testing and an interview 10 days, 3 months and 1 year after onset. RESULTS: Anosognosia for neglect and anosognosia for hemiparesis double-dissociated, as did unawareness of illness and anosognosia for neglect. Patients showing unawareness of illness or anosognosia for neglect and anosognosia for hemiparesis had poorer orientation and verbal memory than patients who were aware of these defects. Unawareness of illness and anosognosia for hemiparesis disappeared during 3-month follow-up. CONCLUSION: Double-dissociations demonstrate that anosognosias for different defects are independent and specific impairments of awareness, although general cognitive disorder may also reduce awareness of defects. Unawareness of illness and anosognosia for hemiparesis disappear rapidly and can hardly be direct causes of poor long-term recovery. However, transient anosognosia may be associated with persistent disorders which result in poor outcome.     

Two domains of anosognosia in Alzheimer''s disease.

OBJECTIVE: To examine the presence of different dimensions of unawareness in patients with probable Alzheimer's disease. METHODS: A consecutive series of 170 patients with probable Alzheimer's disease were assessed with the anosognosia questionnaire-dementia (AQ-D) which includes items related to cognitive deficits and behavioural problems. RESULTS: A factor analysis of the AQ-D produced two factors: a "cognitive unawareness" factor, which loaded on items of memory, spatial and temporal orientation, calculation, abstract reasoning, and praxis, and a "behavioural unawareness" factor which loaded on items of irritability, selfishness, inappropriate emotional display, and instinctive disinhibition. A stepwise forward regression analysis showed significant correlations between the cognitive unawareness factor and more severe cognitive deficits, delusions, and apathy, but less depression. On the other hand, the behavioural unawareness factor correlated significantly with higher mania and pathological laughing scores. Whereas the cognitive unawareness factor showed a significant correlation with cognitive tests assessing verbal comprehension and long term memory, and was significantly associated with a longer duration of illness, no significant correlations were found between the behavioural unawareness factor and the neuropsychological tasks. CONCLUSION: Unawareness of cognitive deficits and unawareness of behavioural problems may constitute independent phenomena in Alzheimer's disease. Whereas unawareness of cognitive deficits is related to the severity of intellectual impairment and the presence of delusional apathetic mood, unawareness of behavioural problems may be part of a disinhibition syndrome.     

Neural correlates of anosognosia for cognitive impairment in Alzheimer's disease

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients' cognitive impairment by answering a structured questionnaire. Subjects rated 13 cognitive domains as not impaired or associated with mild, moderate, severe, or very severe difficulties, and a sum score was calculated. Two measures of anosognosia were derived. A patient's self assessment, unconfounded by objective measurements of cognitive deficits such as dementia severity and episodic memory impairment, provided an estimate of impaired self-evaluative judgment about cognition in AD. Impaired self-evaluation was related to a decrease in brain metabolism measured with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in orbital prefrontal cortex and in medial temporal structures. In a cognitive model of anosognosia, medial temporal dysfunction might impair a comparison mechanism between current information on cognition and personal knowledge. Hypoactivity in orbitofrontal cortex may not allow AD patients to update the qualitative judgment associated with their impaired cognitive abilities. Caregivers perceived greater cognitive impairments than patients did. The discrepancy score between caregiver's and patient's evaluations, an other measure of anosognosia, was negatively related to metabolic activity located in the temporoparietal junction, consistent with an impairment of self-referential processes and perspective taking in AD.     

Anosognosia and neuropsychiatric symptoms and disorders in mild Alzheimer disease and mild cognitive impairment

Anosognosia is a multidimensional phenomenon that negatively affects course of illness. This study aimed to explore the association between anosognosia and neuropsychiatric phenomena in mild Alzheimer's disease (AD) and in mild cognitive impairment (MCI). The Anosognosia Questionnaire for Dementia to assess anosognosia, and the Neuropsychiatric Inventory to assess neuropsychiatric symptoms were administered to 209 patients (103 mild AD, 52 amnestic-MCI, and 54 amnestic multidomain-MCI). Categorical diagnoses of apathy, depression, and psychosis were made using specific criteria for dementia. With regard to continuous scores, in mild AD, we found positive correlation between symptoms of anosognosia and apathy, agitation and aberrant motor behaviors, while in MCI, we did not find significant association. At a categorical level, the diagnosis of anosognosia in mild AD was associated with the diagnosis of apathy. In mild AD, the frequent co-occurrence of frontally mediated behavioral disorders and anosognosia, particularly apathy, supports the hypothesis of a shared neuropsychogenic process due to the disruption of frontal brain networks.     

Phenomenology and clinical correlates of delusions in Alzheimer disease.

OBJECTIVES: The objectives of this study were to determine whether anosognosia, depression, and elevated mood are associated with delusions in Alzheimer disease (AD), and to examine the validity of standardized diagnostic criteria for psychosis of dementia. METHOD: The authors assessed a consecutive series of 771 patients with AD attending a dementia clinic with a comprehensive neuropsychologic and psychiatric evaluation that included specific measures of delusions, hallucinations, anosognosia, depression, and elevated mood. RESULTS: Delusions were found in one-third of the patients and hallucinations in 7%. Most patients with hallucinations also had delusions. A principal component analysis of the Psychosis Dementia Scale, which rates the presence and severity of delusions, produced the factors of paranoid misidentification and expansive delusions. Paranoid, but not expansive, delusions increased across the stages of the illness. Anosognosia and depression were significantly and independently associated with the presence of delusions, whereas elevated mood was significantly associated with expansive, but not paranoid, delusions. A multiple logistic regression analysis demonstrated that delusions in AD were significantly associated with depression, anosognosia, overt aggression, and agitation. CONCLUSIONS: Anosognosia, depression, global cognitive deficits, and elevated mood are the main psychiatric correlates of paranoid misidentification and expansive delusions in AD, whereas overt aggression and agitation are the most frequent behavioral concomitants of psychosis in AD.     

Anosognosia: patients' distress and self-awareness of deficits in Alzheimer's disease

We aimed to study how patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) suffer from awareness of their deficits. Self-awareness was assessed using the Anosognosia Questionnaire for Dementia in 12 pairs of MCI outpatients and caregivers, 23 with mild AD, and 18 with moderate AD. The discrepancy between patient's and caregiver's evaluation (anosognosia) became greater as AD progressed. The predictors of patients' distress, shown by multiple linear regression analyses, were awareness of decline in intellectual or social functioning; self-awareness of deficits in remembering appointments in MCI; in remembering appointments, writing, mental calculation, and understanding the newspaper in mild AD; and in mental calculation and doing clerical work in moderate AD. Caregivers assumed the predictors of patients' distress differently: awareness of deterioration of memory in MCI and mild AD, and basic activities of daily living in moderate AD. Understanding patients' disability from patients' perspective is required for successful care.     

Anosognosia in Alzheimer's disease: association with patient characteristics, psychiatric symptoms and cognitive deficits

Anosognosia is one of the major problems in the treatment and care of Alzheimer's disease (AD) patients. The aim of the study was to determine the patient characteristics, psychiatric symptoms, and cognitive deficits associated with anosognosia, because these are currently poorly understood. Eighty-four patients who met the National Institute of Neurological and Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD were examined for anosognosia based on the difference between questionnaire scores of the patient and their caregiver. The relationship of anosognosia with patient characteristics (age, age at onset, duration of illness, education, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hyogo Activities of Daily Living Scale (HADLS)), psychiatric symptoms (Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS)), and cognitive function (Digit Span, Word Fluency Test, Trail Making Test, Stroop Test, Raven's Coloured Progressive Matrices Test) were studied. Anosognosia showed positive correlations with age, age at onset, duration of illness, CDR, HADLS, and NPI disinhibition, and negative correlations with MMSE and GDS. Regarding cognitive function, only Part III of the Stroop Test was a predictor of anosognosia. The severity of anosognosia increased with disease progression and with a later age at onset. Subjective complaints of depression requiring self-monitoring of mood tended to decrease and, in contrast, inhibition of socially unsuitable behavior became more difficult as anosognosia worsened. Regarding cognitive function, anosognosia appeared to be associated with response inhibition impairment. Both disinhibition, as a psychiatric symptom, and response inhibition impairment are known to be correlated with disturbance of orbitofrontal function, which therefore may be associated with anosognosia.     

Unawareness of motor impairment and emotions in right hemispheric stroke: a preliminary investigation

BACKGROUND: Awareness may lack in some stroke patients who are not capable of evaluating the nature and severity of illness. Thus, unawareness may have different forms such as anosognosia, neglect, and alexithymia or unawareness of emotions. In this study we investigated the relationship among anosognosia, neglect, alexithymia, and cognition. METHODS: Fifty consecutive right stroke inpatients were approached within the first 3 months from the acute event. Anosognosia was measured with the Bisiach scale, alexithymia with the TAS-20 scale and neglect with line crossing, letter cancellation, figure and shape copying, and line bisection tests. A neuropsychological test battery was used to measure different areas of cognition. RESULTS: despite the strong comorbidity rate among the different forms of unawareness, there are patients who suffer from pure forms of these types of lack of awareness. A multivariate logistic regression model evidenced that presence of neglect (OR = 10.3; 95% CI = 1.4-76.3; p = 0.023) and more difficulty in describing feelings (TAS-20 F2 subscore; OR = 1.3; 95% CI = 1.1-1.7; p = 0.014) were the only predictors of anosognosia. In addition, anosognosics with alexithymia performed worst in a frontal task such as the verbal fluency task (p = 0.042) and in the verbal span forward task (p = 0.026) than pure anosognosics. CONCLUSIONS: Anosognosia for motor impairment is strictly associated with a specific form of unawareness of emotions. Future studies have to clarify if frontal cognitive impairment previously described in anosognosics is a manifestation of unawareness of emotions or anosognosia for motor impairment.     

Anosognosia in neurodegenerative disease

Patients with neurological disorders are often partially or completely unaware of the deficits caused by their disease. This impairment is referred to as anosognosia, and it is very common in neurodegenerative disease, particularly in frontotemporal dementia. Anosognosia has significant impacts on function and quality of life for patients with neurodegenerative disease and their caregivers, but the phenomenon has received little formal study, especially in non-Alzheimer's (non-AD) dementias. Furthermore, few studies have attempted to systematically verify the potential role of specific cognitive impairments in producing anosognosia. As a result, the mechanisms underlying this phenomenon are poorly understood. Episodic memory likely plays an important role. In addition, the frontal lobe systems are important for intact self-awareness, but the most relevant frontal functions have not been identified. Motivation required to engage in self-monitoring and emotional activation marking errors as significant are often-overlooked aspects of performance monitoring that may underlie anosognosia in some patients. The present review offers a working model that incorporates these functions and stipulates specific processes that may be important for awareness of changes in one's abilities. Specification of the specific processes whose potential failure results in anosognosia can establish a roadmap for future studies.     

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)

Although a number of studies have examined anosognosia of cognitive deficits in patients with Alzheimer's disease (AD), not much is known about the anosognosia of behavioral symptoms in AD. The aims of the present study were to establish a Japanese version of the Anosognosia Questionnaire-Dementia (AQ-D) and to examine its factor structure, reliability and validity, and to identify the effects of various variables on the AQ-D. Factor structure, internal consistency, test-retest reliability and concurrent validity of the Japanese version of the AQ-D were analyzed. Multiple regression was then done using the results of the AQ-D as dependent variables and entering all relevant predictor variables. Both the internal consistency and the test-retest reliability of the AQ-D were excellent. Factor analysis indicated four factors: anosognosia of basic and instrumental activities of daily living; that of episodic memory and orientation; that of disinhibited behaviors; and that of apathy and depression. The first two factors were regarded as anosognosia of cognitive deficits and were associated with Mini-Mental State Examination scores, while the latter two factors were regarded as anosognosia of behavioral symptoms and were associated with the Neuropsychiatric Inventory (NPI) score. A dissociation between the two domains of anosognosia was confirmed, namely of cognitive deficits and of behavioral symptoms using the Japanese version of the AQ-D. The knowledge that various factors may have different effects on different domains of anosognosia in patients with AD may serve as useful information for clinicians assessing anosognosia in AD.     

On-line anosognosia: unawareness for chorea in real time but not on videotape delay

In hemiplegics, anosognosia (unawareness of deficit) rests on a mismatch between expected and actual movement: a feedback hypothesis emphasizes sensory deficits or neglect, a feedforward hypothesis postulates impaired intention to move. Anosognosia for other problems is less studied. The authors report a man without sensory deficits who was unaware of choreiform movements, except on videotape delay. The authors believe that a feed-forward mechanism underlies his "on-line" unawareness.     

Patient versus informant reported quality of life in the earliest phases of Alzheimer's disease

OBJECTIVES: The study investigated if patient and informant reported Quality of Life (QoL) differed in early Alzheimer's disease (AD). In addition, we examined whether anosognosia had an impact on the agreement between patient and informant ratings of QoL and whether anosognosia, dementia severity, depression and behavioural symptoms were significantly correlated to QoL in early AD. METHODS: From a prospective research program including newly referred patients (age >60 years and MMSE > or = 20), 48 patients with very early AD were included. QoL was assessed using the QoL-AD and EQ-5D scales. Anosognosia was rated on a categorical scale by an examiner. MMSE, Geriatric Depression Scale, Danish Adult Reading Test and Frontal Behavioural Inventory were also administered. RESULTS: On most QoL measures patients rated their QoL higher than their informants. Anosognosia was not associated with QoL but significantly with an inverse impact on the agreement between patient and informant ratings of QoL. Self-reported QoL was significantly correlated to depression but not to age, dementia severity, behavioural symptoms or memory impairment. Informant ratings of QoL were significantly correlated to behavioural symptoms and informant ratings on the EQ-5D Visual Analogue Scale were significantly correlated to patient reported depression. CONCLUSION: Patients with early AD generally reported higher QoL than their informants. This disagreement was associated with the presence of anosognosia. Self-reported QoL did not correlate with the MMSE score. Behavioural changes and depressive symptoms may be associated with low QoL.     

Anosognosia in patients with Alzheimer's disease: current perspectives

Alzheimer?s disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self‐awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self‐underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub‐symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self‐awareness include ‘denying’ and ‘confabulation’, and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one?s own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective.     

The heterogeneity of anosognosia for memory impairment in Alzheimer's disease: A review of the literature and a proposed model

Anosognosia for memory impairment is a phenomenon in Alzheimer's disease that has historically only been noted anecdotally. It is only recently that it has been investigated independently. Varying methodologies have been employed to examine the neuropsychological correlates of anosognosia in AD. There have been markedly discrepant results with severity of disease, extent of memory deficit and dysexecutive syndrome being those correlates most widely reported. A review of this literature is given and previously proposed models discussed critically in terms of three widely accepted phenomena: the variability in degree of anosognosia and the specificity with regard to cognitive domain and personal deficit as opposed to a generalized deficit in judgement. The case for heterogeneity of anosognosia for memory impairment is made and a comprehensive cognitive model is presented.     

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type

OBJECTIVE: To study the unawareness of cognitive deficits in patients with mild dementia of Alzheimer type (DAT). DESIGN: Retrospective study. We surveyed the medical records of outpatients meeting the NINCDS-ADRDA criteria for probable DAT who were able to complete the Cognitive Difficulties Scale (CDS) and had a close informant relative (IR) who could complete the family form of the same questionnaire. SETTING: A department of neurology in a general teaching hospital. SUBJECTS: Eighty-eight patients, aged 73.2+/-8.6 years with a mean MMSE score of 22.5+/-3.2. Fifty-two of the 88 patients had a follow-up examination after a mean interval of 21 months. METHODS: Awareness of cognitive deficits was mainly assessed as the difference between the scores on the CDS completed by the IR and the patient (Index of Unawareness, IU). Two secondary assessments of unawareness were performed: (1) an assessment by the clinician on the basis of the patient's answers to questions probing the awareness of memory deficits; (2) an evaluation by the IR of the frequency of behavioural manifestations of unawareness in everyday life. SPECT was performed in 78 patients to study the relationship between unawareness and the topography of perfusion deficits. RESULTS: Awareness of the cognitive deficits varied greatly between patients, according to the assessment method used and the stage of progression of the disease. Most patients with mild DAT were cognitively aware of their cognitive deficits but failed to appraise their severity and their consequences in everyday life. Decreased awareness was positively correlated with age and perfusion deficits in the frontal regions and negatively with the anxious symptomatology. However, the main correlate of unawareness was apathy. CONCLUSION: The nature of unawareness of cognitive deficits appeared to be more dimensional than categorical. In patients with mild dementia, decreased awareness appeared to be more related to affective disturbances, especially to emotional deficit or apathy, than to cognitive deficits.     

Awareness of deficit in multiple sclerosis

The present study examined awareness of deficits among individuals with multiple sclerosis (MS). A total of 74 pairs of persons with MS and their significant others participated. Awareness of cognitive deficit was measured by discrepancy scores between patient reports of their cognitive abilities and objective test results. Awareness of functional deficit was measured by the discrepancy between the patient and significant other reports of the functional abilities of the patient. Results suggest that about one third of MS patients have diminished awareness of their cognitive and/or functional deficits. Unawareness of deficit was more common among patients with secondary-progressive MS than among those with relapse-remitting MS. Executive dysfunction was strongly associated with unawareness of cognitive deficits but not unawareness of functional deficits. Unawareness of cognitive deficits and unawareness of functional deficits appear to be tapping different aspects of unawareness of deficit.     

Awareness of deficits in mild cognitive impairment and Alzheimer's disease: do MCI patients have impaired insight?

In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective research program 36 consecutive patients with mild AD (MMSE above 19), 30 with amnesic MCI and 33 matched controls were examined. Using three methods for awareness assessment we found no significant differences in the level of awareness between MCI and AD. Both groups had impaired awareness and significant heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected dementia disorders.     

Primary and secondary anosognosia for memory impairment in patients with Alzheimer's disease

The neuropsychology of anosognosia for memory impairment in Alzheimer's disease (AD) was examined in 92 AD patients and 92 case matched individuals for comparison, using three quantitative methods of assessment: Experimenter Rating Scale (ERS), Objective Judgement Discrepancy (OJD) and Subjective-Rating Discrepancy (SRD). The OJD showed significant domain specific correlations with memory functioning as well as a significant correlation with susceptibility to intrusional errors. Memory or executive dysfunction may affect the immediate ability to judge cognitive performance in a domain specific manner (secondary anosognosia). Longer-term awareness of cognitive deficit appears less influenced by impaired basic cognitive functions, than by the decline of metacognitive function (primary anosognosia).