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Frontiers in Aging Neuroscience 2023Alzheimer's disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental... (Review)
Review
Alzheimer's disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients' families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aβ), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aβ and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD.
PubMed: 37600514
DOI: 10.3389/fnagi.2023.1206572 -
Cortex; a Journal Devoted To the Study... Oct 2023People with aphantasia have a markedly impaired ability to form visual images in the mind's eye. Here, by testing people with and without aphantasia, we examine the...
People with aphantasia have a markedly impaired ability to form visual images in the mind's eye. Here, by testing people with and without aphantasia, we examine the relationship between visual imagery and face processing. We show that aphantasics have weaker face recognition than people with visual imagery, using both self-report (Prosopagnosia Index) and behavioural measures (Cambridge Face Memory Test). However, aphantasics nonetheless have a fully intact ability to construct facial composites from memory (i.e., composites produced using EFIT6 by aphantasics and imagers were rated as equally accurate in terms of their resemblance to a target face). Additionally, we show that aphantasics were less able than imagers to see the resemblance between composites and a target face, suggestive of potential issues with face matching (perception). Finally, we show that holistic and featural methods of composite construction using EFIT6 produce equally accurate composites. Our results suggest that face recognition, but not face composite construction, is facilitated by the ability to represent visual properties as 'pictures in the mind'. Our findings have implications for the study of aphantasia, and also for forensic settings, where face composite systems are commonly used to aid criminal investigations.
Topics: Humans; Facial Recognition; Imagery, Psychotherapy; Prosopagnosia; Recognition, Psychology; Self Report; Visual Perception
PubMed: 37597266
DOI: 10.1016/j.cortex.2023.06.015 -
Arquivos de Neuro-psiquiatria Jul 2023Huntington's disease (HD) is an inherited disease that leads to an inexorable progression of motor, cognitive and psychiatric disturbances. In the initial stages, the...
Huntington's disease (HD) is an inherited disease that leads to an inexorable progression of motor, cognitive and psychiatric disturbances. In the initial stages, the symptoms are not clearly disabling, and the patient may present a lack of awareness about the symptoms themselves, which we call anosognosia. However, anosognosia might not justify all passivity of the HD patient in face of the diagnosis. Patients may also experience the denial of illness, as a stage of grief, expected to happen in the face of the diagnosis of any neurodegenerative disorder. In addition, people with HD tend to be more apathetic, and more silent, in regular consultations. In the present article, the authors express a point of view, discussing the behavior of the HD patient, in which there is a multifactorial passivity, in the face of the diagnosis and of the disease itself. Having the proper knowledge of this situation may prepare the neurologist to better understand the patient and the evolution of the disease.
Topics: Humans; Huntington Disease; Agnosia
PubMed: 37494950
DOI: 10.1055/s-0043-1768158 -
PeerJ 2023Developmental prosopagnosia is a relatively common visuo-cognitive condition, characterised by impaired facial identity recognition. Impairment severity appears to...
Developmental prosopagnosia is a relatively common visuo-cognitive condition, characterised by impaired facial identity recognition. Impairment severity appears to reside on a continuum, however, it is unknown whether instances of milder deficits reflect the successful use of spontaneous (typical) face recognition strategies, or the application of extraneous compensatory cues to recognition. Here, we explore this issue in two studies. First, 23 adults with developmental prosopagnosia were asked about their use of spontaneous versus compensatory face recognition techniques in everyday life, using a series of closed- and open-ended questions. Second, the same participants performed a computerised famous face recognition task where they were asked to provide reasons why they could make any successful identifications. Findings from both studies suggest that people with developmental prosopagnosia can successfully, and quite frequently, use compensatory strategies to recognition, and that these cues support the majority of instances of preserved familiar face recognition. In contrast, 16 of the 23 participants were able to spontaneously recognise familiar faces on at least some occasions, but there were vast individual differences in frequencies of success. These findings have important implications for our conceptualisation of the condition, as well as for diagnostic practice.
Topics: Adult; Humans; Cues; Facial Recognition; Prosopagnosia; Recognition, Psychology; Male; Female; Middle Aged
PubMed: 37483961
DOI: 10.7717/peerj.15497 -
Cortex; a Journal Devoted To the Study... Sep 2023It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the...
It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the parietal lobe. However, patterns of white matter tract disconnection following parietal damage have been barely investigated. This single case study allows characterising Gerstmann's syndrome in terms of disconnected networks. We report the case of a left parietal patient affected by Gerstmann's tetrad: agraphia, acalculia, left/right orientation problems, and finger agnosia. Lesion mapping, atlas-based estimation of probability of disconnection, and DTI-based tractography revealed that the lesion was mainly located in the superior parietal lobule, and it caused disruption of both intraparietal tracts passing through the inferior parietal lobule (e.g., tracts connecting the angular, supramarginal, postcentral gyri, and the superior parietal lobule) and fronto-parietal long tracts (e.g., the superior longitudinal fasciculus). The lesion site appears to be located more superiorly as compared to the cerebral regions shown active by other studies during tasks impaired in the syndrome, and it reached the subcortical area potentially critical in the emergence of the syndrome, as hypothesised in previous studies. Importantly, the reconstruction of tracts connecting regions within the parietal lobe indicates that this critical subcortical area is mainly crossed by white matter tracts connecting the angular gyrus and the superior parietal lobule. Taken together, these findings suggest that this case study might be considered as empirical evidence of Gerstmann's tetrad caused by disconnection of intraparietal white matter tracts.
Topics: Humans; Gerstmann Syndrome; White Matter; Parietal Lobe; Brain; Agnosia
PubMed: 37478549
DOI: 10.1016/j.cortex.2023.05.016 -
BMC Neurology Jul 2023Creutzfeldt-Jakob disease (CJD), is a deadly degenerative condition of the central nervous system marked by rapidly progressive dementia. Magnetic resonance imaging...
BACKGROUND
Creutzfeldt-Jakob disease (CJD), is a deadly degenerative condition of the central nervous system marked by rapidly progressive dementia. Magnetic resonance imaging (MRI) abnormalities in the cerebral cortex, basal ganglia, thalamus, and cerebellum could indicate severe acute diseases caused by a variety of factors. Although their MRI patterns may resemble those of CJD, clinical history, additional MRI findings, and laboratory testing are all necessary to provide a reliable difference. Here, we report a misdiagnosed case of probable VV1 subtype of sporadic CJD (sCJD) in which follow-up MRI supported the diagnosis.
CASE PRESENTATION
A 41-year-old male patient attended the Neuropsychiatry Department with rapidly progressive dementia, akinetic mutism, and difficulty walking and speaking. His problem began with forgetfulness, disorganized behavior, and disorganized speech 7 months earlier which progressed rapidly and was accompanied by aphasia, apraxia, agnosia, and akinetic mutism in the last 2 months. On neurologic examination, hypertonia, hyperreflexia, frontal ataxia, bradykinesia, gait apraxia, and aphasia were noted. Based on clinical features and rapid symptoms progression the likely diagnosis of CJD was suspected. MRI and electroencephalography (EEG) were advised. MRI revealed features of diffuse cortical injury of both cerebral hemispheres also involving bilateral corpus striatum with evidence of cerebral volume loss. EEG showed lateralized periodic theta slow waves on the right side. According to the CDC's diagnostic criteria for CJD, the diagnosis of probable sCJD was established. Supportive care and symptomatic treatment are provided for the patient. After a 1-month follow up the patient's condition deteriorated significantly. The time-lapse from the first reported symptom to death was about 13 months.
CONCLUSION
The need of addressing CJD in patients presenting with rapidly progressive dementia is highlighted in this case report. In the early stages of the disease, interpretation of MRI results might cause diagnostic difficulties; therefore, follow-up MRI is critical in obtaining the correct diagnosis.
Topics: Male; Humans; Adult; Creutzfeldt-Jakob Syndrome; Akinetic Mutism; Magnetic Resonance Imaging; Electroencephalography; Diagnostic Errors
PubMed: 37464286
DOI: 10.1186/s12883-023-03318-z -
Journal of Alzheimer's Disease : JAD 2023Although shadowing behavior- when one individual closely follows another- is routinely documented among patients with dementia, its mechanisms have yet to be elucidated....
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.
Topics: Humans; Male; Alzheimer Disease; Agnosia; Comprehension; Atrophy
PubMed: 37458035
DOI: 10.3233/JAD-230257 -
Alzheimer's Research & Therapy Jul 2023Alzheimer's disease (AD) is a common age-related neurodegenerative disease in the central nervous system and is the primary cause of dementia. It is clinically... (Review)
Review
Alzheimer's disease (AD) is a common age-related neurodegenerative disease in the central nervous system and is the primary cause of dementia. It is clinically characterized by the memory impairment, aphasia, apraxia, agnosia, visuospatial and executive dysfunction, behavioral changes, and so on. Incidence of this disease was bound up with age, genetic factors, cardiovascular and cerebrovascular dysfunction, and other basic diseases, but the exact etiology has not been clarified. MicroRNAs (miRNAs) are small endogenous non-coding RNAs that were involved in the regulation of post-transcriptional gene expression. miRNAs have been extensively studied as noninvasive potential biomarkers for disease due to their relative stability in bodily fluids. In addition, they play a significant role in the physiological and pathological processes of various neurological disorders, including stroke, AD, and Parkinson's disease. MiR-155, as an important pro-inflammatory mediator of neuroinflammation, was reported to participate in the progression of β-amyloid peptide and tau via regulating immunity and inflammation. In this review, we put emphasis on the effects of miR-155 on AD and explore the underlying biological mechanisms which could provide a novel approach for diagnosis and treatment of AD.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; MicroRNAs; Amyloid beta-Peptides; Risk Factors
PubMed: 37452431
DOI: 10.1186/s13195-023-01264-z -
Cortex; a Journal Devoted To the Study... Sep 2023Unawareness of memory deficits is an early manifestation in patients with Alzheimer's disease (AD), which often delays diagnosis. This intriguing behavior constitutes a...
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.
Topics: Humans; Male; Female; Aged; Aged, 80 and over; Alzheimer Disease; Memory Disorders; Electroencephalography; Evoked Potentials; Agnosia; Synapses; Neuropsychological Tests; Recognition, Psychology
PubMed: 37423786
DOI: 10.1016/j.cortex.2023.05.014