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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 -
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 -
Current Neurology and Neuroscience... Nov 2023To investigate the neurofunctional correlates of pure auditory agnosia and its varieties (global, verbal, and nonverbal), based on 116 anatomoclinical reports published... (Review)
Review
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.
Topics: Humans; Agnosia; Auditory Perception
PubMed: 37747655
DOI: 10.1007/s11910-023-01302-1 -
Cortex; a Journal Devoted To the Study... Mar 2024
PubMed: 38594164
DOI: 10.1016/j.cortex.2024.03.006 -
Annals of Neurology Sep 2023Unawareness of a deficit, anosognosia, can occur for visual or motor deficits and lends insight into awareness itself; however, lesions associated with anosognosia occur...
OBJECTIVE
Unawareness of a deficit, anosognosia, can occur for visual or motor deficits and lends insight into awareness itself; however, lesions associated with anosognosia occur in many different brain locations.
METHODS
We analyzed 267 lesion locations associated with either vision loss (with and without awareness) or weakness (with and without awareness). The network of brain regions connected to each lesion location was computed using resting-state functional connectivity from 1,000 healthy subjects. Both domain specific and cross-modal associations with awareness were identified.
RESULTS
The domain-specific network for visual anosognosia demonstrated connectivity to visual association cortex and posterior cingulate while motor anosognosia was defined by insula, supplementary motor area, and anterior cingulate connectivity. A cross-modal anosognosia network was defined by connectivity to the hippocampus and precuneus (false discovery rate p < 0.05).
INTERPRETATION
Our results identify distinct network connections associated with visual and motor anosognosia and a shared, cross-modal network for awareness of deficits centered on memory-related brain structures. ANN NEUROL 2023;94:434-441.
Topics: Humans; Awareness; Brain; Agnosia; Cerebral Cortex; Gyrus Cinguli; Magnetic Resonance Imaging
PubMed: 37289520
DOI: 10.1002/ana.26709