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| Positive correlations between functional connectivity of the anterior default mode network (aDMN) and (A) non-memory and (B) total anosognosia.
Source publication
Decline in self-awareness is a prevalent symptom in Alzheimer’s disease (AD). Current data suggest that an early breakdown in the brain’s default mode network (DMN) is closely associated with the main symptomatic features in AD patients. In parallel, the integrity of the DMN has been shown to be heavily implicated in retained self-awareness abiliti...
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Background : Characterizing self- and informant-reported cognitive complaints, as well as awareness of cognitive decline (ACD), is useful for an early diagnosis of Alzheimer’s disease (AD). However, complaints and ACD related to cognitive functions other than memory are poorly studied. Furthermore, it remains unclear which source of information is...
(1) Background: Considerable inconsistency exists regarding the neural substrates of anosognosia in dementia in previous neuroimaging studies. The purpose of this study was the evaluation of anosognosia perfusion correlates across various types of dementia using automated Brodmann areas (BAs) analysis and comparison with a database of normal subjec...
Background
Following a stroke, patients may suffer from alterations in the perception of their own body due to an acquired deficit in body representations. While such changes may impact their quality of life as well as recovery, they are not systematically assessed in clinical practice. This study aims at providing a better understanding of the pre...
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 discri...
Citations
... It has been suggested that the disruption of the FPN may be associated with dysfunctions of the comparator system leading to anosognosia (Tagai et al., 2020). A reduced inter-communication between the DMN and the executive FPN was also demonstrated in a study exploring different forms of anosognosia in MCI and AD patients (Valera-Bermejo et al., 2021). ...
... In line with previous literature (Zamboni et al., 2013b;De Bruycker et al., 2017;Vannini et al., 2017;Valera-Bermejo et al., 2021), we observed a significant negative correlation between functional connectivity within DMN nodes and awareness, meaning that higher levels of anosognosia were associated with lower functional connectivity of these areas. In particular, we found decreased connectivity with PCC and PCU, key structures of the DMN. ...
... Several neuroimaging studies showed that middle temporal gyrus is implicated in autobiographical memory suggesting that this area could be a key region for the personal database in the CAM leading to "the petrification of the self " as a core feature of anosognosia in AD (Salmon et al., 2024). Previous fMRI studies investigating network connectivity in anosognosia demonstrated temporal cortical connectivity involvement when using measures of memory anosognosia: Antoine et al. reported disconnection within the medial temporal subsystem of the default mode network, subserving episodic memory processes, using a Memory Awareness Rating Scale (Antoine et al., 2019); Valera-Bermejo et al. showed that memory anosognosia scores were associated with selective lower frontotemporal connectivity and higher parietotemporal connectivity, whereas total anosognosia scores were associated with large-scale network alterations, namely reduced left-FPN expression in the left posterior cingulate, reduced right-FPN expression in the left inferior lingual gyrus and adjacent inferior occipital cortex, and increased right-FPN expression in the right anterior cingulate (Valera-Bermejo et al., 2021). Therefore, activation/deactivation of subregions of the DMN may be differentially elicited for mnemonic, not mnemonic, and global anosognosia. ...
Background
Recent evidence suggests that anosognosia or unawareness of cognitive impairment in Alzheimer’s Disease (AD) may be explained by a disconnection between brain regions involved in accessing and monitoring information regarding self and others. It has been demonstrated that AD patients with anosognosia have reduced connectivity within the default mode network (DMN) and that anosognosia in people with prodromal AD is positively associated with bilateral anterior cingulate cortex (ACC), suggesting a possible role of this region in mechanisms of awareness in the early phase of disease. We hypothesized that anosognosia in AD is associated with an imbalance between the activity of large-scale resting-state functional magnetic resonance imaging (fMRI) networks, in particular the DMN, the salience network (SN), and the frontoparietal network (FPN).
Methods
Sixty patients with MCI and AD dementia underwent fMRI and neuropsychological assessment including the Anosognosia Questionnaire Dementia (AQ-D), a measure of anosognosia based on a discrepancy score between patient’s and carer’s judgments. After having applied Independent Component Analysis (ICA) to resting fMRI data we performed: (i) correlations between the AQ-D score and functional connectivity in the DMN, SN, and FPN, and (ii) comparisons between aware and unaware patients of the DMN, SN, and FPN functional connectivity.
Results
We found that anosognosia was associated with (i) weak functional connectivity within the DMN, in posterior and middle cingulate cortex particularly, (ii) strong functional connectivity within the SN in ACC, and between the SN and basal ganglia, and (iii) a heterogenous effect concerning the functional connectivity of the FPN, with a weak connectivity between the FPN and PCC, and a strong connectivity between the FPN and ACC. The observed effects were controlled for differences in severity of cognitive impairment and age.
Conclusion
Anosognosia in the AD continuum is associated with a dysregulation of the functional connectivity of three large-scale networks, namely the DMN, SN, and FPN.
... All these regions are known to be involved in executive-monitoring processing; in particular, the dorsolateral prefrontal cortex is a principal region of the "executive-control network" [32], while anterior cingulate and anterior insula are major nodes of the "salience network" [31]. These networks are involved in controlling or coordinating multiple domains of cognitive and executive functioning, which enable the abilities of self-monitoring and feedback integration and are known to be involved in unawareness and anosognosia in AD patients [41]. The inferior frontal gyrus is known to be involved in interoception, social cognition, and emotion [42], which serves as a sensory-cognitive integration area for the frontoparietal network [32]. ...
... Only two studies explored cognitive awareness domain in drug-naïve [27] or OFF state [29] patients: Maier et al. found significant cortical region involvement (bilateral superior medial frontal gyrus, anterior cingulate cortex, midcingulate cortex, and supplementary motor area) in cognitive unawareness, whereas the disruption of matter integrity of midline regions in the anterior corpus callosum and anterior limb of internal capsule was demonstrated in the study of Yoo et al. [27]. There results seem to converge, highlighting the major contribution of the regions interconnected within salience network to cognitive awareness, in line with findings for other neurodegenerative diseases, such as AD [41]. Regarding the motor awareness domain, alterations in functional or structural measures in inferior frontal gyrus, insular cortex, anterior cingulate cortex, and dorsolateral prefrontal cortex were found [15,25], confirming the potential interplay between salience and frontoparietal networks. ...
Little is known about the brain correlates of anosognosia or unawareness of disease in Parkinson’s Disease (PD) and Huntington’s Disease (HD). The presence of unawareness or impaired self-awareness (ISA) of illness has profound implications for patients and their caregivers; therefore, studying awareness and its brain correlates should be considered a key step towards developing effective recognition and management of this symptom as it offers a window into the mechanism of self-awareness and consciousness as critical components of the human cognition. We reviewed research studies adopting MRI or other in vivo neuroimaging technique to assess brain structural and/or functional correlates of unawareness in PD and HD across different cognitive and motor domains. Studies adopting task or resting-state functional magnetic resonance imaging, and/or 18-F fluorodeoxyglucose positron emission tomography brain imaging and/or magnetic resonance imaging structural measures were considered. Only six studies investigating neuroimaging features of unawareness in PD and two in HD were identified; there was great heterogeneity in the clinical characteristics of the study participants, domain of unawareness investigated, method of unawareness assessment, and neuroimaging technique used. Nevertheless, some data converge in identifying regions of the salience and frontoparietal networks to be associated with unawareness in PD patients. In HD, the few data are affected by the variability in the severity of motor symptoms. Further studies are needed to better understand the mechanisms and brain correlates of unawareness in PD and HD; in addition, the use of dopaminergic medications should be carefully considered.
... Resting-state functional magnetic resonance imaging (rs-fMRI) is a powerful and non-invasive tool for exploring brain functional changes in vivo, and it has been widely used in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease. [5][6][7][8][9][10] Previous research has highlighted that the pathological deposition associated with Alzheimer's disease can impair synaptic communication, thereby leading to the disruption of brain networks. [11][12][13] In this framework, viewing the whole brain as an interconnected network, graph theoretical centrality metrics can be employed to quantify the nodal importance and network alterations in specific brain regions. ...
... The DMN includes a set of brain regions that play an important role in cognition, 46 and previous studies have demonstrated that dysregulation of functional connectivity in DMN areas is closely associated with disease progression of Alzheimer's disease. 5,47,48 In our longitudinal studies, we found that the follow-up DC value of three groups all decreased in comparison with their baseline data, in which the Obj-SCD group showed the most pronounced decline rate. Previous studies have also observed a decline in precuneus brain activity as the disease progresses. ...
The objectively-defined subtle cognitive decline individuals had higher progression rates of cognitive decline and pathological deposition than healthy elderly, indicating a higher risk of progressing to Alzheimer’s disease. However, little is known about the brain functional alterations during this stage. Thus, we aimed to investigate the functional network patterns in objectively-defined subtle cognitive decline cohort. Forty-two cognitive normal, 29 objectively-defined subtle cognitive decline and 55 mild cognitive impairment subjects were included based on neuropsychological measures from the Alzheimer’s disease Neuroimaging Initiative dataset. Thirty cognitive normal, 22 objectively-defined subtle cognitive declines and 48 mild cognitive impairment had longitudinal MRI data. The degree centrality and eigenvector centrality for each participant were calculated by using resting-state functional MRI. For cross-sectional data, analysis of covariance was performed to detect between-group differences in degree centrality and eigenvector centrality after controlling age, sex and education. For longitudinal data, repeated measurement analysis of covariance was used for comparing the alterations during follow-up period among three groups. In order to classify the clinical significance, we correlated degree centrality and eigenvector centrality values to Alzheimer’s disease biomarkers and cognitive function. The results of analysis of covariance showed significant between-group differences in eigenvector centrality and degree centrality in left superior temporal gyrus and left precuneus, respectively. Across groups, the eigenvector centrality value of left superior temporal gyrus was positively related to recognition scores in auditory verbal learning test, whereas the degree centrality value of left precuneus was positively associated with mini-mental state examination total score. For longitudinal data, the results of repeated measurement analysis of covariance indicated objectively-defined subtle cognitive decline group had the highest declined rate of both eigenvector centrality and degree centrality values than other groups. Our study showed an increased brain functional connectivity in objectively-defined subtle cognitive decline individuals at both local and global level, which were associated with Alzheimer’s disease pathology and neuropsychological assessment. Moreover, we also observed a faster declined rate of functional network matrix in objectively-defined subtle cognitive decline individuals during the follow-ups.
... In addition, the precuneus, a part of the default mode network, is related to performing a variety of highly integrated cognitive tasks involving visuo-spatial imagery, retrieval of episodic memory, and self-processing operations 60,61 . As patients with severe DCM have severe movement disorders, it can be assumed that patients with severe DCM need to functionally compensate for impaired motor functions to maintain their motor ability 33,62 . The role of the precuneus in integrating sensorimotor and other endo/exogenous information is also crucial 63 . ...
The age-related degenerative pathologies of the cervical spinal column that comprise degenerative cervical myelopathy (DCM) cause myelopathy due spinal cord compression. Functional neurological assessment of DCM can potentially reveal the severity and pathological mechanism of DCM. However, functional assessment by conventional MRI remains difficult. This study used resting-state functional MRI (rs-fMRI) to investigate the relationship between functional connectivity (FC) strength and neurophysiological indices and examined the feasibility of functional assessment by FC for DCM. Preoperatively, 34 patients with DCM underwent rs-fMRI scans. Preoperative central motor conduction time (CMCT) reflecting motor functional disability and intraoperative somatosensory evoked potentials (SEP) reflecting sensory functional disability were recorded as electrophysiological indices of severity of the cervical spinal cord impairment. We performed seed-to-voxel FC analysis and correlation analyses between FC strength and the two electrophysiological indices. We found that FC strength between the primary motor cortex and the precuneus correlated significantly positively with CMCT, and that between the lateral part of the sensorimotor cortex and the lateral occipital cortex also showed a significantly positive correlation with SEP amplitudes. These results suggest that we can evaluate neurological and electrophysiological severity in patients with DCM by analyzing FC strengths between certain brain regions.
... These regions are closely associated with the development of AD. The caudate nucleus is a gray matter mass embedded in the medulla, buried deep in the base of the brain, responsible for the fine-tuning and coordination of movements (Valera-Bermejo et al., 2021). The hippocampus is a memory and cognitive center and is related to the occurrence and progression of AD (Dautricourt et al., 2021). ...
... Additionally, our results highlight the role of anosognosia, as this domain was impaired in 37.5% of SCA1 patients. Even though cognitive mechanisms of anosognosia remain uncertain, previous evidence suggested in AD a significant correlation between anosognosia scores and the atrophy of the cerebellar vermis [48] and an interplay between the cerebellum and the anterior default mode network in nonmemory anosognosia [49], thus supporting the need for a thorough assessment of self-awareness in cerebellar patients. Nonetheless, no significant correlations were found between VATA-m scores and ERPs, thus suggesting the limited feasibility of these electrophysiological measures as biomarkers of anosognosia. ...
Background:
Event-related potentials (ERPs) reflect cognitive processing: negative early components (N100, N200) are involved in the sensory and perceptual processing of a stimulus, whereas late positive component P300 requires conscious attention. Both neuropsychological and affective disorders are present in patients with spinocerebellar ataxia type 1 (SCA1), but the underlying mechanisms need further clarification.
Materials and methods:
In this pilot study, we assessed cognitive processing by recording auditory ERPs in 16 consecutive SCA1 patients and 16 healthy controls (HC) matched for age and sex. Motor and nonmotor symptoms were evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) and an extensive neuropsychological battery. ERPs were recorded using an oddball paradigm, and peak latency and amplitude of N100, N200, and P300 were measured in the averaged responses to target tones.
Results:
We found in SCA1 significantly increased latencies of N200 and P300 (p=0.033, p=0.007) and decreased amplitudes of N100 and P300 (p=0.024, p=0.038) compared with HC. Furthermore, P300 latency had the highest AUC in the discrimination of SCA1 in ROC analysis. The expansion of trinucleotide repeats correlated with P300 latency (r=-0.607, p=0.048), whereas both P300 and N100 amplitudes correlated with the severity of motor symptoms (r=-0.692, p=0.003; r=-0.621; p=0.010). Significant correlations between P300 latency and the scores of Emotion Attribution Task (r=-0.633, p=0.027), as well as between N200 latency and the scores of Frontal Assessment Battery and Stroop test (r=-0.520, p=0.047; r=0.538, p=0.039), were observed.
Conclusions:
This research provides for the first time an extensive characterization of ERPs as useful electrophysiological markers to identify early cognitive dysfunction in SCA1.
... The responses provided by the patient in the double modality were compared to quantify the number of discrepant answers. Discrepancy scores were used to quantify the presence of anosognosia [37,38]. ...
Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by a (CTG) expansion in the DM protein kinase (DMPK) gene, representing the most common adult muscular dystrophy, characterized by a multisystem involvement with predominantly skeletal muscle and brain affection. Neuroimaging studies showed widespread white matter changes and brain atrophy in DM1, but only a few studies investigated the role of white matter metabolism in the pathophysiology of central nervous system impairment. We aim to reveal the relationship between the metabolic profile of parieto-occipital white matter (POWM) as evaluated with proton MR spectroscopy technique, with the visuoperceptual and visuoconstructional dysfunctions in DM1 patients. MR spectroscopy (3 Tesla) and neuropsychological evaluations were performed in 34 DM1 patients (19 F, age: 46.4 ± 12.1 years, disease duration: 18.7 ± 11.6 years). The content of neuro-axonal marker N-acetyl-aspartate, both relative to Creatine (NAA/Cr) and to myo-Inositol (NAA/mI) resulted significantly lower in DM1 patients compared to HC (p-values < 0.0001). NAA/Cr and NAA/mI correlated with the copy of the Rey-Osterrieth complex figure (r = 0.366, p = 0.033; r = 0.401, p = 0.019, respectively) and with Street’s completion tests scores (r = 0.409, p = 0.016; r = 0.341, p = 0.048 respectively). The proportion of white matter hyperintensities within the MR spectroscopy voxel did not correlate with the metabolite content. In this study, POWM metabolic alterations in DM1 patients were not associated with the white matter morphological changes and correlated with specific neuropsychological deficits.
... These regions are closely associated with the development of AD. The caudate nucleus is a gray matter mass embedded in the medulla, buried deep in the base of the brain, responsible for the fine-tuning and coordination of movements (Valera-Bermejo et al., 2021). The hippocampus is a memory and cognitive center and is related to the occurrence and progression of AD (Dautricourt et al., 2021). ...
Background
Pseudo-continuous arterial spin labeling (pCASL) is widely used to quantify cerebral blood flow (CBF) abnormalities in patients with Alzheimer’s disease (AD). T1-mapping techniques assess microstructural characteristics in various pathologic changes, but their application in AD remains in the exploratory stage. We hypothesized that combining quantitative CBF and T1 values would generate diagnostic results with higher accuracy than using either method alone in discriminating AD patients from cognitively normal control (NC) subjects.
Materials and methods
A total of 45 patients diagnosed with AD and 33 NC subjects were enrolled, and cognitive assessment was performed for each participant according to the Chinese version of the Mini-Mental State Examination (MMSE). T1-weighted magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) and pCASL sequence were scanned on a 3T MR scanner. A brain morphometric analysis was integrated into prototype sequence, providing tissue classification and morphometric segmentation results. Quantitative CBF and T1 values of each brain region were automatically generated inline after data acquisition. Independent samples t-test was used to compare regional CBF and T1 values controlled by false discovery rate correction (corrected p < 0.01). The model with combined CBF and T1 values was compared with the individual index by performing receiver operating characteristic curves analysis. The associations between the MMSE score and CBF and T1 values of the brain were investigated using partial correlations.
Results
Cerebral blood flow of the right caudate nucleus (RCc) and left hippocampus (LHc) was significantly lower in the AD group compared with the NC group, while the T1 values of the right caudate nucleus (RCt) and left hippocampus (LHt) increased in the AD group. Prediction accuracies of 73.1, 77.2, 75.9, and 81.3% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using the corresponding optimized cut-off values, most combinations of parameters were elevated (area under curve = 0.775–0.894). The highest area under curve value was 0.944, by combining RCc, LHc, RCt, and LHt.
Conclusion
In this preliminary study, the combined model based on pCASL and T1-mapping improved the diagnostic performance of discriminating AD and NC groups. T1-mapping may become a competitive technique for quantitatively measuring pathologic changes in the brain.
... Deficits in three aspects of attention performance (alerting, orienting, and executive control) can also be predicted by the degenerated functional connectivity within the DAN in MCI and AD patients (Zhang et al., 2015). Multi-domain anosognosia was also shown to be associated with specific dynamic changes in functional connectivity of the frontoparietal control, DMN and salience networks (Valera-Bermejo et al., 2022). ...
Ketones, the brain's alternative fuel to glucose, bypass the brain glucose deficit and improve cognition in mild cognitive impairment (MCI). Our goal was to assess the impact of a 6-month ketogenic intervention on the functional connectivity within eight major brain resting-state networks, and its possible relationship to improved cognitive outcomes in the BENEFIC trial. MCI participants were randomized to a placebo (n= 15) or ketogenic medium chain triglyceride (kMCT; n= 17) intervention. kMCT was associated with increased functional connectivity within the dorsal attention network (DAN), which correlated to improvement in cognitive tests targeting attention. Ketone uptake (¹¹C-acetoacetate PET) specifically in DAN cortical regions was highly increased in the kMCT group and was directly associated with the improved DAN functional connectivity. Analysis of the structural connectome revealed increased fiber density within the DAN following kMCT. Our findings suggest that ketones in MCI may prove beneficial for cognition at least in part because they improve brain network energy status, functional connectivity and axonal integrity.
The cause(s) of lack of awareness of cognitive decline in neurodegenerative diseases can be multifactorial. Yet neurologically oriented research on anosognosia of cognitive decline almost exclusively assumes that the underlying disturbance of neuro-networks that support various cognitive functions accounts for the reduced self-awareness. Cultural and psychosocial factors, including the person’s emotional state, however, can contribute to the underreporting or avoidance of admitting to cognitive impairments in neurodegenerative diseases. Research on the causes of lack of awareness of cognitive decline in neurodegenerative disorders needs to include these variables. We briefly present two case examples of underreporting or “unawareness” of memory difficulties in persons with mild cognitive impairment (MCI) (or minor neurocognitive disorder). One presented with classic anosognosia for memory impairment, while the other initially reported no memory impairment but later admitted to “denying” her memory difficulties secondary to anxiety. Based on these patients’ clinical presentations and available research, we suggest three potential screening items that may help identify probable denial of memory impairments when studying anosognosia in MCI.
