The unique role of anosognosia in the clinical progression of Alzheimer's disease: a disorder-network perspective.

Alzheimer's disease (AD) encompasses a long continuum from a preclinical phase, characterized by neuropathological alterations albeit normal cognition, to a symptomatic phase, marked by its clinical manifestations. Yet, the neural mechanisms responsible for cognitive decline in AD patients remain poorly understood. Here, we posit that anosognosia, emerging from an error-monitoring failure due to early amyloid-ß deposits in the posterior cingulate cortex, plays a causal role in the clinical progression of AD by preventing patients from being aware of their deficits and implementing strategies to cope with their difficulties, thus fostering a vicious circle of cognitive decline.

Structural MRI Correlates of Anosognosia in Huntington's Disease.

Background: Anosognosia, or unawareness of symptoms, is common in Huntington's disease (HD), but the neuroanatomical basis of this is unknown. Objective: To identify neuroanatomical correlates of HD anosognosia using structural MRI data. Methods: We leveraged a pre-processed dataset of 570 HD participants across the well-characterized PREDICT-HD and TRACK-HD cohort studies. Anosognosia index was operationalized as the score discrepancies between HD participants and their caregivers on the Frontal Systems Behavior Scale (FrSBe). Results: Univariate correlation analyses identified volumes of globus pallidus, putamen, caudate, basal forebrain, substantia nigra, angular gyrus, and cingulate cortex as significant correlates of anosognosia after correction for multiple comparisons. A multivariable model constructed with stepwise regression that included volumetric data showed globus pallidus volume alone explained more variance in anosognosia severity than motor impairment or CAP score alone. Conclusions: Anosognosia appears to be related to degeneration affecting both cortical and subcortical areas. Globus pallidus neurodegeneration in particular appears to be a key process of importance.

Symptomatology after damage to the angular gyrus through the lenses of modern lesion-symptom mapping.

Brain-behavior relationships are complex. For instance, one might know a brain region's function(s) but still be unable to accurately predict deficit type or severity after damage to that region. Here, I discuss the case of damage to the angular gyrus (AG) that can cause left-right confusion, finger agnosia, attention deficit, and lexical agraphia, as well as impairment in sentence processing, episodic memory, number processing, and gesture imitation. Some of these symptoms are grouped under AG syndrome or Gerstmann's syndrome, though its exact underlying neuronal systems remain elusive. This review applies recent frameworks of brain-behavior modes and principles from modern lesion-symptom mapping to explain symptomatology after AG damage. It highlights four major issues for future studies: (1) functionally heterogeneous symptoms after AG damage need to be considered in terms of the degree of damage to (i) different subdivisions of the AG, (ii) different AG connectivity profiles that disconnect AG from distant regions, and (iii) lesion extent into neighboring regions damaged by the same infarct. (2) To explain why similar symptoms can also be observed after damage to other regions, AG damage needs to be studied in terms of the networks of regions that AG functions with, and other independent networks that might subsume the same functions. (3) To explain inter-patient variability on AG symptomatology, the degree of recovery-related brain reorganisation needs to account for time post-stroke, demographics, therapy input, and pre-stroke differences in functional anatomy. (4) A better integration of the results from lesion and functional neuroimaging investigations of AG function is required, with only the latter so far considering AG function in terms of a hub within the default mode network. Overall, this review discusses why it is so difficult to fully characterize the AG syndrome from lesion data, and how this might be addressed with modern lesion-symptom mapping.

Clinical and structural disconnectome evaluation in a case of optic aphasia.

Optic Aphasia (OA) and Associative Visual Agnosia (AVA) are neuropsychological disorders characterized by impaired naming on visual presentation. From a cognitive point of view, while stimulus identification is largely unimpaired in OA (where access to semantic knowledge is still possible), in AVA it is not. OA has been linked with right hemianopia and disconnection of the occipital right-hemisphere (RH) visual processing from the left hemisphere (LH) language areas.In this paper, we describe the case of AA, an 81-year-old housewife suffering from a deficit in naming visually presented stimuli after left occipital lesion and damage to the interhemispheric splenial pathway. AA has been tested through a set of tasks assessing different levels of visual object processing. We discuss behavioral performance as well as the pattern of lesion and disconnection in relation to a neurocognitive model adapted from Luzzatti and colleagues (1998). Despite the complexity of the neuropsychological picture, behavioral data suggest that semantic access from visual input is possible, while a lesion-based structural disconnectome investigation demonstrated the splenial involvement.Altogether, neuropsychological and neuroanatomical findings support the assumption of visuo-verbal callosal disconnection compatible with a diagnosis of OA.

Undoubtedly unaware of homonymous hemianopia: The contribution of overconfidence to anosognosia of hemianopia.

A new functional deficit caused by a stroke can be understood as a situation of uncertainty that has to prompt deficit discovery and subsequent incorporation into an altered self-perception. Anosognosia for visual field deficits is frequent after stroke. For hemiplegia, patients' performance in a riddle test provided evidence that the inability to generate and adjust beliefs in face of uncertainty contributes to anosognosia for hemiplegia. In this prospective study, the same riddles are used in patients with homonymous hemianopia due to a first-ever stroke in the posterior cerebral artery territory and in an age-matched control cohort. The riddles create a situation of uncertainty that is resolved with five successive clues which progressively delimit the target word. After each clue, patients have to guess the target word and rate their confidence in the answer's correctness. Patients were tested once during the hospital stay. According to the Bisiach score for anosognosia, 12 out of 29 patients were unaware of their visual field deficits. All patients with anosognosia for hemianopia had right hemisphere lesions. Patients with and without anosognosia did not differ significantly in global cognitive impairment, mental flexibility or memory function. Importantly, patients with anosognosia showed higher confidence ratings than patients without anosognosia and controls in the first two clues (situations of uncertainty). This was demonstrated by a significant interaction effect in a mixed ANOVA with the factors group (anosognosia, nosognosia, controls) and riddle clues. An exploratory lesion subtraction analysis showed a high proportion of deficit unawareness in patients with lesions in the right fusiform and (para)hippocampal gyri. Our findings suggest that overconfidence in situations of uncertainty might contribute to the appearance of anosognosia for hemianopia. Because this has been demonstrated before in anosognosia for hemiplegia, we suggest that overconfidence is a supra-modal contributor to deficit unawareness.

Influence of anosognosia on patient-reported outcomes for psychiatric symptoms and quality of life in Huntington's disease.

INTRODUCTION: Anosognosia, defined as reduced awareness of one's deficit or symptom, is common in Huntington's disease (HD) and detectable at each disease stage. The impact of anosognosia on self-reporting in HD populations is critical to understand given growing use of patient-reported outcomes in HD clinical care and research. We aimed to determine the influence of anosognosia on patient-reported outcome measures assessing psychiatric symptoms and quality of life in HD. METHODS: We enrolled HD patients to complete a battery of patient-reported and rater-administered measures, including the Anosognosia Scale, at baseline and 6 months later. Patient-reported outcome measures included NeuroQoL short forms for depression, anxiety, satisfaction with social roles and activities, and positive affect and well-being and Patient-Reported Outcomes Measurement Information System short forms for emotional distress-anger and sleep-related impairment. Anosognosia Scale-Difference Score indexed patient-clinician agreement on patient motor, cognitive, and behavioral abilities. We conducted multivariable linear regression analyses to quantify the association of baseline anosognosia with 6-month patient-reported outcomes. RESULTS: Of 79 patients with complete Anosognosia Scale data at baseline, 25 (31.6 %) met the scale's criterion for anosognosia. In the regression analyses, baseline Difference Score improved prediction of 6-month patient-reported outcomes for depression, anxiety, anger, and positive affect and well-being (χ2(1) value range for likelihood ratio tests contrasting models with and without Difference Score: 13.1-20.9, p-values <0.001). Patients with more anosognosia self-reported less severe psychiatric symptoms and more positive affect and well-being. CONCLUSION: Study results suggest that anosognosia influences patient-reported outcomes for psychiatric symptoms and quality of life in HD populations.

Anosognosia in Alzheimer's Pathology: Validation of a New Measure.

OBJECTIVE: Two studies were performed to validate a brief measure of cognitive insight and compare it to an empirical model - the Cognitive Awareness Model (CAM). METHOD: A pilot study included 31 (52% male; Mage = 69.42) patients from an outpatient neuropsychological assessment clinic. Seven patients were diagnosed with likely Alzheimer's dementia (AD), 15 mild cognitive impairment (MCI), and 9 no diagnosis (i.e., cognitively normal; CN). The Cognitive Coding Form (CCF) and several other measures were administered. Study 2 entailed archival data extraction of 240 patients (80 CN, 80 MCI, and 80 AD; 53.3% female; Mage = 72.8) to examine whether the CCF predicts memory (Wechsler Memory Scale - IV) and executive functioning (Trail-Making Test B). RESULTS: The pilot study found preliminary evidence of convergent and discriminant validity for the 8-item CCF. Study 2 confirmed that both patient-reported cognitive concerns (F(2,237) = 10.40, p < .001, ω2 = .07, power = .99) and, more strongly, CCF informant-patient discrepancy scores (F(2,237) = 24.52, p < .001, ω2 = .16, power = .99) can distinguish CNs from those with MCI and AD. A regression indicated that depression (5.5%; ß = -.38, p < .001) and TMT-B (13%; ß = -.43, p < .001), together accounted for 18.5% of the variance in insight (R2 = .19, F(2,219) = 26.10, p < .001), supporting the CAM. CONCLUSIONS: These studies establish an efficient measure of insight with high clinical utility and inform the literature on the role of insight in predicting performance in those with Alzheimer's pathology.

Insights into Anton Syndrome: When the brain denies blindness.

INTRODUCTION: Anosognosia, a neurological condition, involves a lack of awareness of one's neurological or psychiatric deficits. Anton Syndrome (AS), an unusual form of anosognosia, manifests as bilateral vision loss coupled with denial of blindness. This systematic review delves into 64 studies encompassing 72 AS cases to explore demographics, clinical presentations, treatments, and outcomes. MATERIALS AND METHODS: The study rigorously followed PRISMA guidelines, screening PubMed, Google Scholar, and Scopus databases without timeframe limitations. Only English human studies providing full text were included. Data underwent thorough assessment, examining patient demographics, etiological variables, and treatment modalities. RESULTS: Sixty-four studies met the stringent inclusion criteria. Examining 72 AS cases showed a median age of 55 (6 to 96 years) with no gender preference. Hypertension (34.7 %) and visual anosognosia (90.3 %) were prevalent. Stroke (40.3 %) topped causes. Management included supportive (30.6 %) and causal approaches (30.6 %). Improvement was seen in 45.8 %, unchanged in 22.2 %, and deterioration in 11.1 %. Anticoagulation correlated with higher mortality (p < 0.05). DISCUSSION: AS, an unusual manifestation of blindness, stems mainly from occipital lobe damage, often due to cerebrovascular incidents. The syndrome shares features with Dide-Botcazo syndrome and dates back to Roman times. Its causes range from strokes to rare conditions like multiple sclerosis exacerbation. Accurate diagnosis involves considering clinical presentations and imaging studies, distinguishing AS from similar conditions. CONCLUSION: This comprehensive review sheds light on AS's complex landscape, emphasizing diverse etiologies, clinical features, and treatment options. Tailored treatments aligned with individual causes are crucial. The study's findings caution against blanket anticoagulation therapy, suggesting a nuanced approach. Further research is pivotal to refine diagnostics and optimize care for AS individuals.

Generalized anosognosia, anosodiaphoria, and visual hallucinations with bilateral enucleation after severe bifrontal brain injury: a case report describing similarities with and differences from Anton syndrome.

Visual anosognosia, associated with confabulations and cortical blindness in the context of occipital lobe injury, is known as Anton syndrome. Patients with this syndrome strongly deny their vision loss and confabulate to compensate for both visual loss and memory impairments. In this article, we present a case of a patient with some similarities to Anton syndrome, however, with several differences in clinical presentation. Bifrontal brain injury, bilateral enucleation, affective indifference (anosodiaphoria), generalized anosognosia, and the conviction that vision will resume mark clear clinical differences with Anton syndrome. Differentiating these findings from Anton syndrome will help occupational therapists, neuropsychologists, speech-language pathologists, physical therapists, and physicians when assessing frontal lobe brain injury with total and partial visual loss. This case demonstrates that visual anosognosia and confabulations can occur without occipital lobe dysfunction or cortical blindness.

[Willingness to age in place and anosognosia of risks in Alzheimer's disease]. / Volonté de rester à domicile et anosognosie des risques associés à la maladie neurodégénérative de type Alzheimer.

Alzheimer's disease leads to an alteration of decision-making abilities which may increase risk-taking behaviours, particularly associated anosognosia. Anticipating the progression of the disease raises a number of questions, particularly in relation to aging in place. Our qualitative study aimed to identify the arguments used by older patients with Alzheimer's disease when choosing a place to age. The study included 22 older adults, living at home, and diagnosed as mild dementia. The patients' arguments in favour of ageing in place were based mainly on the preservation of internal security, through the familiarity of places and relations as well as the maintenance of their independence and their lifestyle habits, allowing stability in their daily lives. Despite the identification of memory loss, the associated risks were minimized or hidden from the reflection on the choice of the place to age.

En kvinne i 60-årene som ikke lenger gjenkjente det hun så.

BACKGROUND: Neurological disorders can present with a vast array of visual disturbances. The constellation of symptoms and findings in this patient prompted workup for unusual causes of both stroke and neurodegenerative disorder. CASE PRESENTATION: A woman in her sixties presented with visual disturbances, followed by weakness in her right arm and aphasia three days later. Her close acquaintances had suspected progressive cognitive decline during the previous year. CT and MRI showed an occluded left posterior cerebral artery with a subacute occipito-temporal infarction. The finding of extensive white matter lesions and segmental arterial vasoconstriction necessitated further workup of vasculitis and hereditary small vessel disease, which were ruled out. The stroke aetiology was considered to be atherosclerotic intracranial large vessel disease. FDG-PET scan revealed decreased metabolism in the left hemisphere, and cerebrospinal biomarkers had slightly decreased beta-amyloid. The findings were suggestive of early Alzheimer's disease or primary progressive aphasia, but currently inconclusive. INTERPRETATION: Based on clinical-anatomical correlation, the patient's visual disturbances, in this case right hemianopsia and object agnosia, were solely related to the stroke and not to a neurodegenerative disorder. Knowledge and interpretation of visual agnosias can in many cases be clinically valuable.

[Simultanagnosia caused by cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions].

A 76-year-old male patient was admitted to our hospital for the treatment of acute cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions. Although his overall cognitive function was almost normal, he exhibited reduced visual sensitivity in the homonymous lower left quadrant of the visual field, left unilateral spatial neglect (USN), and simultanagnosia. Left USN improved 4 months after the onset of infarction; however, simultanagnosia persisted. To the best of our knowledge, this is the first case of simultanagnosia caused by cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions.

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.

Shadowing Behavior May Be Associated with an Inability to Recognize the External World: A Case Report of Shadowing in a Patient with Posterior Cortical Atrophy.

Although shadowing behavior- when one individual closely follows another- is routinely documented among patients with dementia, its mechanisms have yet to be elucidated. In particular, there have been no detailed descriptions of patients with shadowing behavior. To propose its potential backgrounds, we describe a patient with posterior cortical atrophy who exhibited prominent shadowing behavior. He also experienced severe difficulties recognizing external stimuli, including visuospatial dysfunction, several types of agnosia, difficulties in verbal comprehension, disorientation, and its associated depression. This shadowing behavior may be adaptive relative to his extreme difficulty with recognizing the world around him.

[Updates on anosognosia in Alzheimer's disease]. / Actualités sur l'anosognosie dans la maladie d'Alzheimer.

Impaired awareness increases dependency of patients suffering from Alzheimer's Disease (AD) and caregivers' burden but remains insufficiently evaluated in clinical practice. The numerous conceptualisations of this symptomatology (anosognosia, denial, insight…) have only a slight impact on the three main assessment methodologies which are: the patient-caregiver discrepancy; the clinician rating of patients' awareness of illness; and the prediction of performance discrepancy methods. Nevertheless, most of evaluating tools are not validated yet, in particular regarding the clinician rating, leading to contrasted results. Most of recent studies reported positive correlations with apathy and AD severity, and negative relationships with depressive symptoms. Therefore, impaired awareness seems to be mainly influenced by patient's depression and apathy. We discuss these correlates and shared aspects of apathy and impaired awareness from neuroanatomical, clinical and conceptual viewpoints. We also highlight the relevance and limits of quantitative and qualitative assessment methods, in particular phenomenological.

Anosognosia in HD: Comparison of self-report and caregiver ratings with objective performance measures.

INTRODUCTION: Individuals with Huntington's disease (HD) commonly experience anosognosia, a lack of awareness of deficits. Thus, it is important to examine the accuracy of patient vs caregiver ratings on the basis of objective performance-based measures. METHODS: The Anosognosia Scale (AS) was given to 33 patients with manifest HD and their caregivers. The AS consists of 8 items in which individuals rate their global abilities relative to same-aged peers. Scores range from very impaired to excellent. Caregiver and patient ratings were then correlated with objective measures. RESULTS: Caregivers' evaluations of patients' cognitive and motoric abilities were more highly correlated with objective measures than patients' ratings. Specifically, caregivers' AS item scores were highly correlated with objective measures of walking (Unified Huntington Disease Rating Scale (UHDRS) tandem walking score [r = 0.57, p = .001] vs. patient [r = 0.39, p = .031]); dexterity (UHDRS pronation supination score [r = 0.55, p = .011] vs. patient [r = 0.18, p = .393]); speech (UHDRS dysarthria score [r = 0.55, p = .004] vs. patient [r = 0.03, p = .854]); memory (MoCA score [r = -.45, p = .048] vs. patient [r = -.11, p = .963]); attention (Trails Making Test A score [r = 0.58, p = .004] vs. patient [r = 0.08, p = .686]); and word retrieval (category fluency ([r = -.58, p = .004] vs. patient [r = -.02, p = 1.00]). Moreover, both the UHDRS total motor score (TMS) (F(1,29) = 7.50, p = .010) and the Mini Mental Status Exam (MMSE) (F(1,31) = 5.40, p = .027) were significant predictors of patient levels of anosognosia. CONCLUSIONS: Our findings indicate that caregivers may be better able to rate HD patients' cognitive and motor abilities than patients themselves. Both cognitive and motor severity are significant predictors of levels of anosognosia in HD.

Tactually-related cognitive impairments: sharing of neural substrates across associative tactile agnosia, agraphesthesia, and kinesthetic reading difficulty.

INTRODUCTION: A precise understanding of the neural substrates underlying tactually-related cognitive impairments such as bilateral tactile agnosia, bilateral agraphesthesia, kinesthetic alexia and kinesthetic reading difficulty is currently incomplete. In particular, recent data have implicated a role for the lateral occipital tactile visual region, or LOtv, in tactile object naming (Amedi et al. Cerebral Cortex 2002). Thus, this study set out to examine the degree to which the LOtv may be involved in tactually-related cognitive impairments by examining two unique cases. METHODS: To assess whether LOtv or the visual word form area (VWFA) is involved in tactually-related cognitive impairments, the average activation point of LOtv and that of VWFA were placed on the single-photon emission computed tomography (SPECT) cerebral blood flow images of two patients: one with bilateral associative tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading, and the other with kinesthetic reading difficulty. RESULTS: The average LOtv coordinate was involved in the area of hypoperfusion in both patients, whereas that of VWFA was not included in any of the hypoperfused areas. CONCLUSIONS: The results support the view that interruption of LOtv or disconnection to LOtv and to VWFA may cause these tactually-related cognitive impairments. Further, bilateral associative tactile agnosia and bilateral agraphesthesia are attributable toward the damage of the occipital lobe, whereas unilateral or predominantly one-sided associative tactile agnosia and agraphesthesia are attributable toward the damage of the parietal lobe.

Visual imagery deficits in posterior cortical atrophy.

Visual imagery has a close overlapping relationship with visual perception. Posterior cortical atrophy (PCA) is a neurodegenerative syndrome marked by early impairments in visuospatial processing and visual object recognition. We asked whether PCA would therefore also be marked by deficits in visual imagery, tested using objective forced-choice questionnaires, and whether imagery deficits would be selective for certain properties. We recruited four patients with PCA and a patient with integrative visual agnosia due to bilateral occipitotemporal strokes for comparison. We administered a test battery probing imagery for object shape, size, colour lightness, hue, upper-case letters, lower-case letters, word shape, letter construction, and faces. All subjects showed significant impairments in visual imagery, with imagery for lower-case letters most likely to be spared. We conclude that PCA subjects can show severe deficits in visual imagery. Further work is needed to establish how frequently this occurs and how early it can be found.

Distinguishing transient from persistent tactile agnosia after partial anterior circulation infarcts - Behavioral and neuroimaging evidence for white matter disconnection.

From a cohort of 36 patients presenting apperceptive tactile agnosia after first cortical ischemic stroke, 14 showed temporary impairment at admission. A previous multi-voxel analysis of the cortical lesions, using as explanatory variable the course of tactile object recognition performance over the recovery period of 9 months, partitioned the cohort into three subgroups. Of the 14 patients constituting two of the subgroups, 7 recovered from their impairment whereas 7 did not. These two subgroups could not be distinguished at admission. The primary aim of the present study is to present two assessments that can do so. The first assessment comprises a pattern of behavioral measures, determined via principal component analysis, encoded in three tests: picking small objects, macrogeometrical discrimination and tactile object recognition. The receiver operating characteristic curve derived from permutation of the behavioral test scores yielded an 80% probability of correct identification of the patient subgroup and an 8% probability for false identification. As done with the permuted scores, the pattern could predict the persistence of affliction of new stroke patients with tactile agnosia. The second predictive assessment extends our previous evaluation of cortical MRI lesion maps to include subcortical regions. Confirming our previous study, the lesions of the persistently impaired subgroup disrupted significantly the anterior arcuatus fasciculus and associated superior longitudinal fasciculus III in the ipsilesional hemisphere, impeding reciprocal information transfer between supramarginal gyrus and both the ventral premotor cortex and Brodmann area 44. Due to the importance of interhemispheric information transfer in tactile agnosia, we performed a supplementary analysis of tactile object recognition scores. It showed that haptic information transfer from the non-affected to the affected hands in the persistent cases partly restored function during the nine months, possibly following restoration of functional interhemispheric haptic information transfer at the border of posterior corpus callosum and splenium. In conclusion, the combined findings of the cortical lesion at subarea PFt of the inferior parietal lobule and the associated subcortical tract lesions permit almost perfect prediction of persistent impairment of tactile object recognition. The study substantiates the need for combined analysis of both cortical lesions and white matter tract disconnections.