Detecting Anosognosia from the Prodromal Stage of Alzheimer's Disease.

BACKGROUND: Though not originally developed for this purpose, the Healthy Aging Brain Care Monitor (HABC-M) seems a valuable instrument for assessing anosognosia in Alzheimer's disease (AD). OBJECTIVES: Our study aimed at 1) investigating the validity of the HABC-M (31 items), and its cognitive, psychological, and functional subscales, in discriminating AD patients from controls; 2) exploring whether the HABC-M discrepancy scores between the self-reports of patients/controls in these different domains and the respective ratings provided by their caregivers/informants correlate with an online measure of self-awareness; 3) determining whether the caregiver burden level, also derived from the HABC-M, could add additional support for detecting anosognosia. METHODS: The HABC-M was administered to 30 AD patients and 30 healthy controls, and to their caregivers/informants. A measure of online awareness was established from subjects' estimation of their performances in a computerized experiment. RESULTS: The HABC-M discrepancy scores distinguished AD patients from controls. The cognitive subscale discriminated the two groups from the prodromal AD stage, with an AUC of 0.88 [95% CI: 0.78;0.97]. Adding the caregiver burden level raised it to 0.94 [0.86;0.99]. Significant correlations between the HABC-M and online discrepancy scores were observed in the patients group, providing convergent validity of these methods. CONCLUSIONS: The cognitive HABC-M (six items) can detect anosognosia across the AD spectrum. The caregiver burden (four items) may corroborate the suspicion of anosognosia. The short-hybrid scale, built from these 10 items instead of the usual 31, showed the highest sensitivity for detecting anosognosia from the prodromal AD stage, which may further help with timely diagnosis.

The Auditory Agnosias: a Short Review of Neurofunctional Evidence.

PURPOSE OF REVIEW: To investigate the neurofunctional correlates of pure auditory agnosia and its varieties (global, verbal, and nonverbal), based on 116 anatomoclinical reports published between 1893 and 2022, with emphasis on hemispheric lateralization, intrahemispheric lesion site, underlying cognitive impairments. RECENT FINDINGS: Pure auditory agnosia is rare, and observations accumulate slowly. Recent patient reports and neuroimaging studies on neurotypical subjects offer insights into the putative mechanisms underlying auditory agnosia, while challenging traditional accounts. Global auditory agnosia frequently results from bilateral temporal damage. Verbal auditory agnosia strictly correlates with language-dominant hemisphere lesions. Damage involves the auditory pathways, but the critical lesion site is unclear. Both the auditory cortex and associative areas are reasonable candidates, but cases resulting from brainstem damage are on record. The hemispheric correlates of nonverbal auditory input disorders are less clear. They correlate with unilateral damage to either hemisphere, but evidence is scarce. Based on published cases, pure auditory agnosias are neurologically and functionally heterogeneous. Phenotypes are influenced by co-occurring cognitive impairments. Future studies should start from these facts and integrate patient data and studies in neurotypical individuals.

Can a failure in the error-monitoring system explain unawareness of memory deficits in Alzheimer's disease?

Unawareness of memory deficits is an early manifestation in patients with Alzheimer's disease (AD), which often delays diagnosis. This intriguing behavior constitutes a form of anosognosia, whose neural mechanisms remain largely unknown. We hypothesized that anosognosia may depend on a critical synaptic failure in the error-monitoring system, which would prevent AD patients from being aware of their own memory impairment. To investigate, we measured event-related potentials (ERPs) evoked by erroneous responses during a word memory recognition task in two groups of amyloid positive individuals with only subjective memory complaints at study entry: those who progressed to AD within the five-year study period (PROG group), and those who remained cognitively normal (CTRL group). A significant reduction in the amplitude of the positivity error (Pe), an ERP related to error awareness, was observed in the PROG group at the time of AD diagnosis (vs study entry) in intra-group analysis, as well as when compared with the CTRL group in inter-group analysis, based on the last EEG acquisition for all subjects. Importantly, at the time of AD diagnosis, the PROG group exhibited clinical signs of anosognosia, overestimating their cognitive abilities, as evidenced by the discrepancy scores obtained from caregiver/informant vs participant reports on the cognitive subscale of the Healthy Aging Brain Care Monitor. To our knowledge, this is the first study to reveal the emergence of a failure in the error-monitoring system during a word memory recognition task at the early stages of AD. This finding, along with the decline of awareness for cognitive impairment observed in the PROG group, strongly suggests that a synaptic dysfunction in the error-monitoring system may be the critical neural mechanism at the origin of unawareness of deficits in AD.

Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Awareness is in the eye of the observer: Preserved third-person awareness of deficit in anosognosia for hemiplegia.

In recent decades, the research traditions of (first-person) embodied cognition and of (third-person) social cognition have approached the study of self-awareness with relative independence. However, neurological disorders of self-awareness offer a unifying perspective to empirically investigate the contribution of embodiment and social cognition to self-awareness. This study focused on a neuropsychological disorder of bodily self-awareness following right-hemisphere damage, namely anosognosia for hemiplegia (AHP). A previous neuropsychological study has shown AHP patients, relative to neurological controls, to have a specific deficit in third-person perspective taking and allocentric stance (the other unrelated to the self) in higher order mentalizing tasks. However, no study has tested if verbal awareness of motor deficits is influenced by perspective-taking and centrism and identified the related anatomical correlates. Accordingly, two novel experiments were conducted with right-hemisphere stroke patients with (n = 17) and without AHP (n = 17) that targeted either their own (egocentric, experiment 1) or another stooge patients (allocentric, experiment 2) motor abilities from a first-or-third person perspective. In both experiments, neurological controls showed no significant difference in perspective-taking, suggesting that social cognition is not a necessary consequence of right-hemisphere damage. More specifically, experiment 1 found AHP patients more aware of their own motor paralysis (egocentric stance) when asked from a third compared to a first-person perspective, using both group level and individual level analysis. In experiment 2, AHP patients were less accurate than controls in making allocentric judgements about the stooge patient, but with only a trend towards significance and with no difference between perspectives. As predicted, deficits in egocentric and allocentric third-person perspective taking were associated with lesions in the middle frontal gyrus, superior temporal and supramarginal gyri, and white matter disconnections were more prominent with deficits in allocentricity. Behavioural and neuroimaging results demonstrate the intersecting relationship between bodily self-awareness and self-and-other-directed metacognition or mentalisation.

Benson's Disease or Posterior Cortical Atrophy, Revisited.

BACKGROUND: D. Frank Benson and colleagues first described the clinical and neuropathological features of posterior cortical atrophy (PCA) from patients in the UCLA Neurobehavior Program. OBJECTIVE: We reviewed the Program's subsequent clinical experience with PCA, and its potential for clarifying this relatively rare syndrome in comparison to the accumulated literature on PCA. METHODS: Using the original criteria derived from this clinic, 65 patients with neuroimaging-supported PCA were diagnosed between 1995 and 2020. RESULTS: On presentation, most had visual localization complaints and related visuospatial symptoms, but nearly half had memory complaints followed by symptoms of depression. Neurobehavioral testing showed predominant difficulty with visuospatial constructions, Gerstmann's syndrome, and Balint's syndrome, but also impaired memory and naming. On retrospective application of the current Consensus Criteria for PCA, 59 (91%) met PCA criteria with a modification allowing for "significantly greater visuospatial over memory and naming deficits." There were 37 deaths (56.9%) with the median overall survival of 10.3 years (95% CI: 9.6-13.6 years), consistent with a slow neurodegenerative disorder in most patients. CONCLUSION: Together, these findings recommend modifying the PCA criteria for "relatively spared" memory, language, and behavior to include secondary memory and naming difficulty and depression, with increased emphasis on the presence of Gerstmann's and Balint's syndromes.

Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease.

Importance: Recent studies have suggested that unawareness, or anosognosia, of memory decline is present in predementia stages of Alzheimer disease (AD) and may serve as an early symptomatic indicator of AD. Objective: To investigate the evolution of anosognosia of memory decline in individuals who carry the PSEN1 E280A variant for autosomal dominant AD compared with family members who do not carry the variant. Design, Setting, and Participants: This cohort study investigated a total of 2379 members of a Colombian kindred with autosomal dominant AD who were part of the Alzheimer's Prevention Initiative Registry. Assessments were completed at the University of Antioquia, Colombia, with data collected between January 1, 2000, and July 31, 2019. Main Outcomes and Measures: Awareness of memory function was operationalized using the discrepancy between self-report and study partner report on a memory complaint scale. Linear mixed effects models were used to assess memory self-awareness over age separately in variant carriers and noncarriers. Results: This study included 396 variant carriers (mean [SD] age, 32.7 [11.9] years; 200 [50.5%] female), of whom 59 (14.9%) were cognitively impaired, and 1983 cognitively unimpaired noncarriers (mean [SD] age, 33.5 [12.5] years; 1129 [56.9%] female). The variant carriers demonstrated increased awareness until the mean (SD) age of 35.0 (2.0) years and had anosognosia at approximately 43 years of age, approximately 6 years before their estimated median age of dementia onset (49 years; 95% CI, 49-51 years). Cognitively unimpaired noncarriers reported more complaints than their study partners aged 20 and 60 years (10.1 points, P < .001). On the awareness index, a decrease with age (mean [SE] estimate, -0.04 [0.02] discrepant-points per years; t = -2.2; P = .03) in the noncarriers and in the variant carriers (mean [SE] estimate, -0.21 [0.04] discrepant-points per years; t = -5.1; P < .001) was observed. Conclusions and Relevance: In this cohort study, increased participant complaints were observed in both groups, suggesting that increased awareness of memory function was common and nonspecific to AD in this cohort. In variant carriers, awareness of memory function decreased in the predementia stages, reaching anosognosia close to the age of mild cognitive impairment onset, providing support for the usefulness of awareness of memory decline.

Mnemonic monitoring in anosognosia for memory loss.

OBJECTIVE: Anosognosia, or unawareness, for memory loss has been proposed to underlie cognitive functions such as memory and executive function. However, there is an inconsistent association between these constructs. Recent studies have shown that compromise ongoing self-monitoring of one's memory associates with anosognosia for memory loss. Yet to date it is unclear which memory monitoring mechanisms are impaired in these patients. In this study, we examined the extent to which temporal monitoring or orbitofrontal reality filtering (e.g., ability to monitor the temporal relevance of a memory) and source monitoring (e.g., the ability to distinguish which memories stem from internal as opposed to external sources) are associated with awareness of memory deficits. METHOD: A total of 35 patients (M = 69 years; M = 14 years of education) with memory difficulties following a stroke were recruited from outpatient clinics. Patients were assessed with measures of self-awareness of memory difficulties, cognitive abilities and 2 experimental paradigms assessing source and temporal monitoring. RESULTS AND CONCLUSION: Results showed that patients unaware of their memory difficulties were more likely to externalize the source of their memories. Specifically, those unaware of their deficits were more likely to assign an external source to memories that were internally produced (e.g., imagined). No differences were observed in relation to temporal monitoring between patients aware and unaware of their deficits. This study informs current theoretical models of self-awareness of memory loss. Future studies should attempt to replicate these findings and explore different memory monitoring mechanisms in relation to anosognosia for memory loss. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

What are the neural correlates of meta-cognition and anosognosia in Alzheimer's disease? A systematic review.

Awareness of one's own cognitive processes (metacognition) or of one's own illness or deficits (anosognosia) can be impaired in people with Alzheimer's disease (AD). The neural correlates of anosognosia within AD remain inconclusive. Understanding anosognosia is of importance because of its impact on carer burden and increased institutionalization. A systematic review of structural and functional neuroimaging studies was conducted to identify specific brain regions associated with anosognosia within AD. Thirty-two studies were included in the systematic review. Reduced gray matter density, cerebral blood flow, and hypometabolism in 8 key regions were significantly associated with increased anosognosia scores in people with AD. The most frequently associated regions were the inferior frontal gyrus, anterior cingulate cortex, and medial temporal lobe. Other key regions include the superior frontal gyrus, medial frontal gyrus, orbitofrontal cortex, posterior cingulate cortex, and the insula. Identifying brain regions associated with anosognosia can aid understanding and identification of anosognosia in people with AD and potentially facilitate improvements in care.

Auditory Agnosia for Environmental Sounds in Alzheimer's Disease: Not Hearing and Not Listening?

Auditory agnosia for environmental sounds (AES) is an example of central auditory dysfunction. It is presumed to be independent of language deficits and in presence of normal hearing. We undertook a detailed neuropsychological assessment including environmental sound naming and recognition in 34 clinically mild Alzheimer's disease (AD) patients and 29 age-matched healthy control subjects. In patients with AD, audiometry was performed to assess the impact on test performance, and in normal controls the Hearing Handicap Inventory for the Elderly - Screening Version to exclude more than mild hearing loss. We adapted a validated environmental sound battery and found near perfect scores in controls. We found that environmental sound agnosia is common in mild AD. We found a statistically significant difference in mean pure tone audiometry in the best ear between patients with and those patients without naming deficits of 11.3 dB (p = 0.010) and of 14.7 dB (p = 0.000) between those with and without recognition deficits. Statistical significance remained after correcting for age, aphasia, Mini-Mental State Examination score, and working memory. Slight and moderate peripheral hearing loss increases the odds ratio of recognition deficits by 13.75 (confidence interval 2.3-81.5) compared to normal hearing patients. We did not find evidence for different forms of AES. This work suggests that an interaction between peripheral hearing loss and AD pathology produces problems with environmental sound recognition. It confirms that the relationship between hearing and dementia is complex but also suggests that interventions to prevent and treat hearing loss could have an effect on AD in its clinical expression.

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.

Lifetime PTSD is associated with impaired emotion recognition in veterans and their offspring.

PTSD is associated with emotion dysregulation. Studies have found inconsistent impaired facial emotion recognition ability (ERA) in patients with PTSD and intergenerational transmission of PTSD has been reported, although no studies exist regarding ERA. Our objective was to characterise the facial ERA of a group of traumatised war veterans with, and without lifetime PTSD, and also of their respective adult offspring. Sixty-one veterans with, and without lifetime PTSD and 73 offspring were tested for ERA of seven basic facial emotions expressions, 40 years after veterans had been exposed to war-related trauma. Veterans with lifetime PTSD showed impairment of recognition of all emotions, irrespective of the type, when compared with veterans without PTSD. This result was maintained after adjusting for potential confounders-including depressive symptoms. Offspring of veterans with lifetime PTSD also showed impaired recognition of all emotions, including after adjustment for the same variables. Offspring of veterans with lifetime PTSD also showed specific impairment in recognising the emotions of happiness and disgust. These results confirm that PTSD has negative effects with regards to emotion regulation and also on the next generation. This could result in this population being at increased risk of suffering from relationship problems and psychopathology.

Evolution of anosognosia in alzheimer's disease and its relationship to amyloid.

OBJECTIVE: Unawareness, or anosognosia, of memory deficits is a challenging manifestation of Alzheimer's disease (AD) that adversely affects a patient's safety and decision-making. However, there is a lack of consensus regarding the presence, as well as the evolution, of altered awareness of memory function across the preclinical and prodromal stages of AD. Here, we aimed to characterize change in awareness of memory abilities and its relationship to beta-amyloid (Aß) burden in a large cohort (N = 1,070) of individuals across the disease spectrum. METHODS: Memory awareness was longitudinally assessed (average number of visits = 4.3) and operationalized using the discrepancy between mean participant and partner report on the Everyday Cognition scale (memory domain). Aß deposition was measured at baseline using [18F]florbetapir positron emission tomographic imaging. RESULTS: Aß predicted longitudinal changes in memory awareness, such that awareness decreased faster in participants with increased Aß burden. Aß and clinical group interacted to predict change in memory awareness, demonstrating the strongest effect in dementia participants, but could also be found in the cognitively normal (CN) participants. In a subset of CN participants who progressed to mild cognitive impairment (MCI), heightened memory awareness was observed up to 1.6 years before MCI diagnosis, with memory awareness declining until the time of progression to MCI (-0.08 discrepant-points/yr). In a subset of MCI participants who progressed to dementia, awareness was low initially and continued to decline (-0.23 discrepant-points/yr), reaching anosognosia 3.2 years before dementia onset. INTERPRETATION: Aß burden is associated with a progressive decrease in self-awareness of memory deficits, reaching anosognosia approximately 3 years before dementia diagnosis. ANN NEUROL 2020;87:267-280.

Associations between emotion recognition and social networking site addiction.

With the widespread use of the internet today, many studies have been conducted regarding the use of social networking sites (SNS). Despite the growing literature on the effects of SNS on human life, there are limited successful therapeutic interventions for SNS addiction. Our study aimed to elucidate the potential role of emotion recognition in the development of SNS addiction and to propose novel strategies for alleviating problems emerging from SNS addiction. A total of 337 individuals participated in the study. A sociodemographic data form, the Reading the Mind in the Eyes Test (RMET), and the Social Media Addiction Scale (SMAS) were administered. The results revealed the presence of emotion recognition deficits among individuals with SNS addiction, relative to non-addicts. RMET positive and negative scores were associated with SNS addiction in a negative direction. Additionally, RMET negative scores predicted SNS addiction. Our findings indicate a possible link between SNS addiction and emotion recognition, which might serve as a crucial target in novel treatment strategies.

Avian agnosia: A window into auditory semantics.

The functional and neural organisation of auditory knowledge is relatively poorly understood. The breakdown of conceptual knowledge in semantic dementia has revealed that pre-morbid expertise influences the extent to which knowledge is differentiated. Whether this principle applies to a similar extent in the auditory domain is not yet known. Previous reports of patients with impaired auditory vs. intact visual expert knowledge suggest that expertise may have differential effects upon the organisation of auditory and visual knowledge. An equally plausible alternative, however, is that auditory knowledge is simply more vulnerable to deterioration. Thus, expertise effects in the auditory domain may not yet have been observed because knowledge of auditory expert vs. non-expert knowledge has yet to be compared. We had the opportunity to address this issue by studying SA, a patient with semantic dementia and extensive pre-morbid knowledge of birds. We undertook a systematic investigation of SA's auditory vs. visual knowledge from matched expert vs. non-expert categories. Relative to a group of 10 age, education and IQ matched bird experts, SA showed impaired auditory vs. intact visual avian knowledge, despite intact basic auditory perceptual abilities. This was explained by independent effects of modality and expertise. Thus, he was also disproportionately impaired for auditory vs. visual knowledge of items from non-expert categories. In both auditory and visual modalities, his performance was relatively more impaired on tests of non-expert vs. expert knowledge. These findings suggest that, while auditory knowledge may be more vulnerable to deterioration, expertise modulates visual and auditory knowledge to a similar extent.

Computer-Based Cognitive Rehabilitation in Patients with Visuospatial Neglect or Homonymous Hemianopia after Stroke.

OBJECTIVES: The purpose of this pilot study was to investigate the feasibility and effects of computer-based cognitive rehabilitation (CBCR) in patients with symptoms of visuospatial neglect or homonymous hemianopia in the subacute phase following stroke. METHOD: A randomized, controlled, unblinded cross-over design was completed with early versus late CBCR including 7 patients in the early intervention group (EI) and 7 patients in the late intervention group (LI). EI received CBCR training immediately after inclusion (m = 19 days after stroke onset) for 3 weeks and LI waited for 3 weeks after inclusion before receiving CBCR training for 3 weeks (m = 44 days after stroke onset). RESULTS: CBCR improved visuospatial symptoms after stroke significantly when administered early in the subacute phase after stroke. The same significant effect was not found when CBCR was administered later in the rehabilitation. The difference in the development of the EI and LI groups during the first 3 weeks was not significant, which could be due to a lack of statistical power. CBCR did not impact mental well-being negatively in any of the groups. In the LI group, the anticipation of CBCR seemed to have a positive impact of mental well-being. CONCLUSION: CBCR is feasible and has a positive effect on symptoms in patients with visuospatial symptoms in the subacute phase after stroke. The study was small and confirmation in larger samples with blinded outcome assessors is needed.

The Effect of Continuous Theta-Burst Transcranial Magnetic Stimulation Combined with Prism Adaptation on the Neglect Recovery in Stroke Patients.

OBJECTIVES: This study was designed to investigate the effect of prism adaptation (PA) combined with continuous theta-burst transcranial magnetic stimulation (cTBS) on the neglect recovery of stroke patients with unilateral neglect. METHODS: A total of 14 stroke patients with unilateral neglect were randomly assigned to 2 groups including an intervention group undergone PA combined with cTBS over the left intact parietal cortex and a control group. PA combined with sham cTBS was perfomed for 2 weeks in 10 daily sessions. Before and after the intervention, patients were evaluated for visuospatial neglect measured using the Star Cancellation Test (SCT), Line Bisection Task (LBT), Figure Copying Test, and Clock Drawing Task. Neurological function was evaluated using the Modified Rankin Scale (MRS). RESULTS: Both groups (PA alone and PA+ cTBS) showed improvement in their neglected symptoms (measured by SCT, LBT, Figure Copying Test, and Clock Drawing Task), and in their disability in the neurological function (measured by MRS) (P< .05). CONCLUSIONS: The results of the present study showed that, transcranial magnetic stimulation did not increase the effect of PA on neglect symptoms in stroke patients.

Anosognosia and default mode subnetwork dysfunction in Alzheimer's disease.

Research on the neural correlates of anosognosia in Alzheimer's disease varied according to methods and objectives: they compared different measures, used diverse neuroimaging modalities, explored connectivity between brain networks, addressed the role of specific brain regions or tried to give support to theoretical models of unawareness. We used resting-state fMRI connectivity with two different seed regions and two measures of anosognosia in different patient samples to investigate consistent modifications of default mode subnetworks and we aligned the results with the Cognitive Awareness Model. In a first study, patients and their relatives were presented with the Memory Awareness Rating Scale. Anosognosia was measured as a patient-relative discrepancy score and connectivity was investigated with a parahippocampal seed. In a second study, anosognosia was measured in patients with brain amyloid (taken as a disease biomarker) by comparing self-reported rating with memory performance, and connectivity was examined with a hippocampal seed. In both studies, anosognosia was consistently related to disconnection within the medial temporal subsystem of the default mode network, subserving episodic memory processes. Importantly, scores were also related to disconnection between the medial temporal and both the core subsystem (participating to self-reflection) and the dorsomedial subsystem of the default mode network (the middle temporal gyrus that might subserve a personal database in the second study). We suggest that disparity in connectivity within and between subsystems of the default mode network may reflect impaired functioning of pathways in cognitive models of awareness.

Awareness of Self and Disease Assessment: Development and Validation of a Subjective Measure in People with Alzheimer's Disease.

BACKGROUND: People with Alzheimer's disease (PwAD) remain able to speak coherently about their daily life for a long time, and their level of awareness could be determined through their discourse. In a grounded-theory approach, awareness of self and awareness of disease are intertwined and can be observed through three domains: mechanisms, objects and modes of expression. OBJECTIVE: Based on preliminary results, in this article, we present the ASDA (Awareness of Self and Disease Assessment), a new subjective measurement tool for awareness in PwAD. To consider its use in research and practice, we initially performed validation analyses, including internal consistency, test-retest reliability and interrater reliability analyses. METHODS: The new assessment tool consists of a semi-structured interview and ratings of 22 items divided into three categories. As part of our observational study, we assessed a sample of 28 PwAD who participated in four interviews (one every two weeks). RESULTS: The ASDA shows good homogeneity within the domains of awareness and a certain degree of stability between two measurement times and between investigators. Missing values in the results provided information regarding awareness levels within and across the subjects. CONCLUSION: The results suggest that awareness could be assessed through subjective experience without reference to a comparison.