A Review of the Role of Anticholinergic Activity in Lewy Body Disease and Delirium
We have previously proposed a hypothesis in which we argue that anticholinergic activity (AA) appears endogenously in Alzheimer's disease (AD). Acetylcholine (ACh) controls both cognitive function and inflammation. Consequently, when the downregulation of ACh reaches critical levels, the inflammatory system is upregulated and proinflammatory cytokines with AA appear. However, factors other than downregulation of ACh can produce AA; even if ACh downregulation does not reach critical levels, AA can still appear if one of these other AA-producing factors is added. These factors can include neurocognitive disorders other than ...
Source: Neurodegenerative Diseases - June 30, 2015 Category: Neurology Source Type: research
Pharmacotherapy for Neurocognitive Disorders Based on the Hypothesis of Endogenous Appearance of Anticholinergic Activity
We previously proposed the hypothesis of endogenous anticholinergic activity (AA) in Alzheimer's disease (AD). According to this hypothesis, the downregulation of acetylcholine seen in AD is associated with upregulation/hyperactivity of N-methyl-D-aspartate receptor (NMDAR). The hyperactivation of NMDAR then induces inflammation, which, in turn, causes AA to appear endogenously. Based on this hypothesis, we commented that cholinesterase inhibitors (ChEIs) are ‘preventative' therapy for AD and NMDAR antagonists are the true ‘treatment' for AD. We also noted that ChEIs, such as donepezil, could treat delirium. Moreover, ...
Source: Neurodegenerative Diseases - June 30, 2015 Category: Neurology Source Type: research
Hypothesis of Endogenous Anticholinergic Activity in Alzheimer's Disease
In this article, we review and repropose our hypothesis of the endogenous appearance of anticholinergic activity (AA) in Alzheimer's disease (AD). First, we introduce our previous articles and speculate that, because acetylcholine (ACh) regulates both cognitive function and inflammation, downregulation of this neurotransmitter causes upregulation of the inflammatory system. AA then appears endogenously with the production of cytokines and the downregulation of ACh in AD. To support our hypothesis, we present a female AD patient whose AA was considered to occur endogenously through her AD pathology. Her serum anticholinergi...
Source: Neurodegenerative Diseases - June 30, 2015 Category: Neurology Source Type: research
Does Anticholinergic Activity Affect Neuropathology? Implication of Neuroinflammation in Alzheimer's Disease
One characteristic neuropathological feature of Alzheimer's disease (AD) is profound neuronal loss in the nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex. Clinically, anticholinergic activity causes a decline in cognitive function and increases the risk of dementia, thus possibly enhancing AD pathologies and neurodegeneration. Until now there has been insufficient human neuropathological data to support this conclusion. Experimental studies using a tauopathy mouse model demonstrated anticholinergics enhanced tau pathology and neurodegeneration corresponding to central antichol...
Source: Neurodegenerative Diseases - June 30, 2015 Category: Neurology Source Type: research
Serum Anticholinergic Activity as an Index of Anticholinergic Activity Load in Alzheimer's Disease
We reported a procedure of serum anticholinergic activity (SAA) measurement and the reliability and reproducibility of the receptor binding assay, and we also described the usefulness of SAA measurement reflecting the anticholinergic activity (AA) in the central nervous system (CNS). According to the results of a 10 times repeated measurement of standard atropine binding, the relative error was between -5.5 and +3.7%, and we considered that measurement of SAA in our studies is accurate and validated. Downregulation of acetylcholine activates inflammation in both CNS and peripheral tissue, which causes AA in both sites. The...
Source: Neurodegenerative Diseases - June 30, 2015 Category: Neurology Source Type: research
Anticholinergic Activity and Alzheimer's Disease
Neurodegener Dis 2015;15:131-133 (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - June 30, 2015 Category: Neurology Source Type: research
Title Page / Table of Contents
Neurodegener Dis 2015;15:127-130 (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - June 30, 2015 Category: Neurology Source Type: research
Influence of Lentiviral β-Synuclein Overexpression in the Hippocampus of a Transgenic Mouse Model of Alzheimer's Disease on Amyloid Precursor Protein Metabolism and Pathology
Conclusion: The initially reported beneficial effects of β-Syn could be partially reproduced, but locally elevated levels of β-Syn might also cause neurodegeneration. To enlighten the controversial pathological mechanism of β-Syn, further examinations considering the relationship between concentration and exposure time of β-Syn are needed.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - June 25, 2015 Category: Neurology Source Type: research
Combined Treatment of an Amyotrophic Lateral Sclerosis Rat Model with Recombinant GOT1 and Oxaloacetic Acid: A Novel Neuroprotective Treatment
Conclusion: In this study we bring evidence that the administration of Glu scavengers to rats with sporadic ALS inhibited the massive death of spinal cord motor neurons, slowed the onset of motor weakness and prolonged survival. This treatment may be of high clinical significance for the future treatment of chronic neurodegenerative diseases.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - June 23, 2015 Category: Neurology Source Type: research
Downregulation of β-Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein: Proteomics-Based Identification in Early-Stage Prion Disease
Prion diseases are known as neurodegenerative diseases of the central nervous system with a long incubation period. Alzheimer's disease (AD) and prion diseases share the hallmark of severe neuronal loss, although their pathogenic mechanisms are similarly incomplete. It appears that these two neurodegenerative diseases share a complex deterioration of function involved in the onset of neuronal loss. To investigate presymptomatic biochemical changes indicative of the initial stage of prion diseases and decipher the pathophysiological mechanisms of these two neurodegenerative diseases, we performed a differential proteomic an...
Source: Neurodegenerative Diseases - May 22, 2015 Category: Neurology Source Type: research
The Evaluation of Abnormal Voice Qualities in Patients with Amyotrophic Lateral Sclerosis
Conclusions: Analysis of voice qualities among patients with ALS allows for the detection of various abnormalities associated with the natural progression of the disease.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - May 7, 2015 Category: Neurology Source Type: research
Overexpression of BDNF and Full-Length TrkB Receptor Ameliorate Striatal Neural Survival in Huntington's Disease
Conclusion: The results highlight the importance of BDNF-induced TrkB receptor signaling in rescuing HD-mediated apoptotic features in striatal cells.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - April 20, 2015 Category: Neurology Source Type: research
The Epidemiology of Amyotrophic Lateral Sclerosis in New Hampshire, USA, 2004-2007
Conclusion: While localized areas in N.H. with high ALS incidence rates have been reported previously, the overall incidence and mortality rates of ALS in N.H. are similar to those in other industrialized nations.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - April 15, 2015 Category: Neurology Source Type: research
The Relationship between Age-Related Macular Degeneration and Olfactory Function
Conclusion: This study demonstrated that AMD had significant negative effects on all orthonasal olfactory tasks, particularly in advanced stages. Similar to other neurodegenerative diseases, odor discrimination and identification seemed to be more affected than odor detection threshold tasks.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - April 10, 2015 Category: Neurology Source Type: research
Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels
Conclusions: Dopaminergic neuronal dysfunction is a key early event in HD disease progression. The initial increase in dopamine release appears to be related to a loss of SK3 channel function, a protein containing a polyglutamine tract. Implications for polyglutamine-mediated sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion are discussed in the context of HD.Neurodegener Dis (Source: Neurodegenerative Diseases)
Source: Neurodegenerative Diseases - April 8, 2015 Category: Neurology Source Type: research
