Pub Date : 2017-10-23DOI: 10.4172/2161-0460.1000389
S. Ballesteros, M. Redondo
Alzheimer´s disease (AD) accounts for more than half of all the cases of dementia. T2DM is a highly prevalent chronic metabolic condition among older adults, and is considered a risk factor to develop AD and other types of dementia. Currently, the incidence of both, AD and type 2 Diabetes Mellitus (T2DM) is a major public health problem in developed countries. Given the similarities between the metabolic and vascular changes occurring in the brain of diabetic patients and in AD patients, a relevant question is whether a series of main cognitive abilities, including episodic memory, working memory and executive functions are similarly impaired in AD and T2DM patients. Recent research has shown a clear dissociation between implicit and explicit memory. Results have shown intact implicit memory in both clinical groups, similar to that of healthy older adults, and impaired episodic (explicit) memory in both groups of patients, especially in ADs. At the same time, visuospatial and verbal working memory (updating and maintenance of information assessed with n-back tasks) showed significant declines in AD and T2DM but larger in ADs. Executive control assessed with the Wisconsin Card Sorting Test (WCST) showed similar declines in both groups of patients. Neuropsychologists and clinicians need to take into account the decline of long-term episodic memory and executive control processes in T2DM for their negative impact on treatment management. At the same time, the spared implicit memory of AD and T2DM patients could be used to support rehabilitation.
{"title":"Alzheimer’s disease and Type 2 Diabetes Mellitus: Similar Memory and Executive Functions Impairments?","authors":"S. Ballesteros, M. Redondo","doi":"10.4172/2161-0460.1000389","DOIUrl":"https://doi.org/10.4172/2161-0460.1000389","url":null,"abstract":"Alzheimer´s disease (AD) accounts for more than half of all the cases of dementia. T2DM is a highly prevalent chronic metabolic condition among older adults, and is considered a risk factor to develop AD and other types of dementia. Currently, the incidence of both, AD and type 2 Diabetes Mellitus (T2DM) is a major public health problem in developed countries. Given the similarities between the metabolic and vascular changes occurring in the brain of diabetic patients and in AD patients, a relevant question is whether a series of main cognitive abilities, including episodic memory, working memory and executive functions are similarly impaired in AD and T2DM patients. Recent research has shown a clear dissociation between implicit and explicit memory. Results have shown intact implicit memory in both clinical groups, similar to that of healthy older adults, and impaired episodic (explicit) memory in both groups of patients, especially in ADs. At the same time, visuospatial and verbal working memory (updating and maintenance of information assessed with n-back tasks) showed significant declines in AD and T2DM but larger in ADs. Executive control assessed with the Wisconsin Card Sorting Test (WCST) showed similar declines in both groups of patients. Neuropsychologists and clinicians need to take into account the decline of long-term episodic memory and executive control processes in T2DM for their negative impact on treatment management. At the same time, the spared implicit memory of AD and T2DM patients could be used to support rehabilitation.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"697 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84731880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-16DOI: 10.4172/2161-0460.1000387
B. Bianca, Ransmayr Gerhard, Zimprich Alexander, S. Walter
A new autosomal dominant Parkinson´s disease mutation in the VPS35 (Vacuolar sorting protein 35) gene has been discovered in 2011. The VPS35 gene encodes a key component of the membrane protein-recycling retromer complex. Consequences of the D620N mutation and retromer dysfunction are perturbations in organelle/ vesicle trafficking, recycling and turnover which may result in reduction of cellular survival and gain of α-synuclein accumulation via impaired lysosomal function. VPS35-linked PD resembles the idiopathic disease. In reported cases symptoms were unilateral at the beginning in most cases and progression was slow. Initial symptoms were tremor, bradykinesia, rigidity and postural instability. Resting tremor, rigidity and bradykinesia were dominant. Almost every patient showed good response to levodopa. The frequency of VPS35 PD cases has been estimated to be rare. Until now data are missing on whether the VPS35 variant is associated with classical Lewy body pathology in the brainstem or not. We need more human case reports including neuropathology to find a specific clinical marker of VPS35 patients to allow a targeted referral to genetic testing.
{"title":"VPS35-Linked Parkinson’s Disease Resembles the Idiopathic Disease: A Review of Clinical Trials","authors":"B. Bianca, Ransmayr Gerhard, Zimprich Alexander, S. Walter","doi":"10.4172/2161-0460.1000387","DOIUrl":"https://doi.org/10.4172/2161-0460.1000387","url":null,"abstract":"A new autosomal dominant Parkinson´s disease mutation in the VPS35 (Vacuolar sorting protein 35) gene has been discovered in 2011. The VPS35 gene encodes a key component of the membrane protein-recycling retromer complex. Consequences of the D620N mutation and retromer dysfunction are perturbations in organelle/ vesicle trafficking, recycling and turnover which may result in reduction of cellular survival and gain of α-synuclein accumulation via impaired lysosomal function. VPS35-linked PD resembles the idiopathic disease. In reported cases symptoms were unilateral at the beginning in most cases and progression was slow. Initial symptoms were tremor, bradykinesia, rigidity and postural instability. Resting tremor, rigidity and bradykinesia were dominant. Almost every patient showed good response to levodopa. The frequency of VPS35 PD cases has been estimated to be rare. Until now data are missing on whether the VPS35 variant is associated with classical Lewy body pathology in the brainstem or not. We need more human case reports including neuropathology to find a specific clinical marker of VPS35 patients to allow a targeted referral to genetic testing.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"8 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82026297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-09-30DOI: 10.4172/2161-0460.1000370
Panzao Yang, Xiao-li Min, M. Mohammadi, C. Turner, R. Faull, H. Waldvogel, M. Dragunow, J. Guan
Objective: We previously reported that the ability of vascular remodelling is impaired in human Parkinson’s disease, leading to endothelial degeneration and vascular dysfunction. Aggregation of α-synuclein is a hallmark of neurodegeneration in Parkinson’s disease and inflammation and autophagy may contribute to secondary neuronal degeneration. The current study examined the association between these characteristic pathologies and endothelial cell degeneration in Parkinson’s disease. Methods: The study used the post-mortem grey matter from middle frontal gyrus (MFG) of human Parkinson’s disease and age-matched control cases. Immunohistochemical staining of phosphorylated α-synuclein, p62 for autophagy, Human Leukocyte Antigen-antigen D Related (HLA-DR) for activated microglia, Factor VIII for endothelial cells and Neuronal Nuclei for neurons were performed using either tissue microarray or free-floating sections. The expression of these factors were quantified by analysing the images of the stained sections and compared between the Parkinson’s disease and the age-matched control groups. Results: Compared to the control cases the expression of phosphorylated α-synuclein and p62 was increased in Parkinson’s disease, whereas both neurons and endothelial cells were significantly reduced, with no changes in the number of microglial cells. The density of phosphorylated α-synuclein was negatively correlated with the total length of endothelial cell associated blood vessels when compared across normal and Parkinson’s disease cases combined. However, using double label immunohistochemistry we found that the degree of endothelial cell degeneration in Parkinson’s disease was not directly related to the degree of neuronal degeneration and accumulation of phosphorylated α-synuclein. Conclusion: α-synuclein and autophagy are associated with endothelial degeneration in Parkinson’s disease. The degree of endothelial degeneration was not related to the extent of neuronal degeneration, both of which were copathological changes in PD brains. Alpha-synuclein-associated endothelial degeneration was also age-related pathology.
{"title":"Endothelial Degeneration of Parkinson's Disease is Related to Alpha-Synuclein Aggregation","authors":"Panzao Yang, Xiao-li Min, M. Mohammadi, C. Turner, R. Faull, H. Waldvogel, M. Dragunow, J. Guan","doi":"10.4172/2161-0460.1000370","DOIUrl":"https://doi.org/10.4172/2161-0460.1000370","url":null,"abstract":"Objective: We previously reported that the ability of vascular remodelling is impaired in human Parkinson’s disease, leading to endothelial degeneration and vascular dysfunction. Aggregation of α-synuclein is a hallmark of neurodegeneration in Parkinson’s disease and inflammation and autophagy may contribute to secondary neuronal degeneration. The current study examined the association between these characteristic pathologies and endothelial cell degeneration in Parkinson’s disease. Methods: The study used the post-mortem grey matter from middle frontal gyrus (MFG) of human Parkinson’s disease and age-matched control cases. Immunohistochemical staining of phosphorylated α-synuclein, p62 for autophagy, Human Leukocyte Antigen-antigen D Related (HLA-DR) for activated microglia, Factor VIII for endothelial cells and Neuronal Nuclei for neurons were performed using either tissue microarray or free-floating sections. The expression of these factors were quantified by analysing the images of the stained sections and compared between the Parkinson’s disease and the age-matched control groups. Results: Compared to the control cases the expression of phosphorylated α-synuclein and p62 was increased in Parkinson’s disease, whereas both neurons and endothelial cells were significantly reduced, with no changes in the number of microglial cells. The density of phosphorylated α-synuclein was negatively correlated with the total length of endothelial cell associated blood vessels when compared across normal and Parkinson’s disease cases combined. However, using double label immunohistochemistry we found that the degree of endothelial cell degeneration in Parkinson’s disease was not directly related to the degree of neuronal degeneration and accumulation of phosphorylated α-synuclein. Conclusion: α-synuclein and autophagy are associated with endothelial degeneration in Parkinson’s disease. The degree of endothelial degeneration was not related to the extent of neuronal degeneration, both of which were copathological changes in PD brains. Alpha-synuclein-associated endothelial degeneration was also age-related pathology.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"1 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2017-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89827026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-09-26DOI: 10.4172/2161-0460.1000378
G. Morrill, A. Kostellow, Raj K. Gupta
Alpha-synuclein (α-syn) protein is the major component of Lewy bodies, which are characteristic pathological trademarks for neurodegenerative diseases (e.g. Parkinson’s and Alzheimer’s diseases). It is primarily expressed in neural tissue, with smaller amounts found in heart, muscle and other tissues. The canonical form found in Homo sapiens (α-syn-1) contains 140 residues and interacts with neuronal mitochondria via an N-terminal 32 residue mitochondrial-targeting signal. All isoforms (there are 3) have multiple highly conserved lipid binding (KTKE(Q)G(Q) V) motifs, thought to mediate binding to phospholipid membranes. Two isoforms also contain an EF-hand-like (helixloop- helix) sequence found in a large family of calcium-binding proteins, as well as three copper binding sites. We investigate protein topology using computational analysis and find that each isoform contains a pore-lining region, two cholesterol-binding (CRAC/CARC) and three or four lipid binding motifs, with one cholesterol motif overlapping the pore-lining region. Two lipid-binding motifs also overlap the N-terminal mitochondrial-targeting region consistent with evidence that α-syn inserts into mitochondrial inner membrane. α-Syn-1 reportedly occurs physiologically as a helically folded tetramer that requires N-terminal acetylation. Thus, each α-syn-1 tetramer could contain 4 mitochondrial targeting regions, up to 4 pore-lining regions, 4 EF-hand domains, 8 bound cholesterol molecules and 16 lipid binding motifs with pore-lining regions merging to form a membrane channel. Cholesterol binding to CRAC motifs may in turn facilitate protein folding, Ca2+-channel formation, as well as mitochondrial membrane lipid-protein interactions, altering mitochondrial bioenergetics. Disruption of mitochondrial bioenergetics may be involved in the pathogenesis of Alzheimer’s disease and Parkinsonism.
{"title":"Computational Analysis of Cholesterol Binding and Pore-Lining Regions in Alpha-Synuclein: Role in Mitochondrial Function","authors":"G. Morrill, A. Kostellow, Raj K. Gupta","doi":"10.4172/2161-0460.1000378","DOIUrl":"https://doi.org/10.4172/2161-0460.1000378","url":null,"abstract":"Alpha-synuclein (α-syn) protein is the major component of Lewy bodies, which are characteristic pathological trademarks for neurodegenerative diseases (e.g. Parkinson’s and Alzheimer’s diseases). It is primarily expressed in neural tissue, with smaller amounts found in heart, muscle and other tissues. The canonical form found in Homo sapiens (α-syn-1) contains 140 residues and interacts with neuronal mitochondria via an N-terminal 32 residue mitochondrial-targeting signal. All isoforms (there are 3) have multiple highly conserved lipid binding (KTKE(Q)G(Q) V) motifs, thought to mediate binding to phospholipid membranes. Two isoforms also contain an EF-hand-like (helixloop- helix) sequence found in a large family of calcium-binding proteins, as well as three copper binding sites. We investigate protein topology using computational analysis and find that each isoform contains a pore-lining region, two cholesterol-binding (CRAC/CARC) and three or four lipid binding motifs, with one cholesterol motif overlapping the pore-lining region. Two lipid-binding motifs also overlap the N-terminal mitochondrial-targeting region consistent with evidence that α-syn inserts into mitochondrial inner membrane. α-Syn-1 reportedly occurs physiologically as a helically folded tetramer that requires N-terminal acetylation. Thus, each α-syn-1 tetramer could contain 4 mitochondrial targeting regions, up to 4 pore-lining regions, 4 EF-hand domains, 8 bound cholesterol molecules and 16 lipid binding motifs with pore-lining regions merging to form a membrane channel. Cholesterol binding to CRAC motifs may in turn facilitate protein folding, Ca2+-channel formation, as well as mitochondrial membrane lipid-protein interactions, altering mitochondrial bioenergetics. Disruption of mitochondrial bioenergetics may be involved in the pathogenesis of Alzheimer’s disease and Parkinsonism.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"123 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2017-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73755419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-09-03DOI: 10.4172/2161-0460.1000309
C. Ambrose
Many of the minor complaints of old age may have a common etiology and are grouped together here under the term ‘the lesser ailments of aging’ (LAA). This essay proposes that they are due in large part to an age-linked reduced microcirculation. Capillary density (CD) in the tissues is determined by levels of angiogenic growth factors (AGFs). Over 47 studies have reported a reduced CD and/or waning AGFs throughout the bodies of aging animals and people. More convincing than such a generalization are the 80 sets of data comparing these two parameters in adult vs. the aged. These data have led to a hypothesis whose corollary proposes a specific treatment for the LAA. While genetically controlled, the waning levels of AGFs theoretically could be countered by pro-angiogenesis therapy and thus might ease the LAA or delay their onset. Therapies mentioned here include recombinant AGFs and inhibitors of type 5 phosphodiesterases, such a tadalafil/Cialis. Finally, Alzheimer’s disease (AD) is generally an illness of the elderly and may have a single or multiple causes. However, its clinical course may be influenced secondarily by conditions affecting the LAA. Therefore, any effective treatment of them may influence favorably the clinical course of AD.
{"title":"Capillaries, Old Age and Alzheimer’s Disease","authors":"C. Ambrose","doi":"10.4172/2161-0460.1000309","DOIUrl":"https://doi.org/10.4172/2161-0460.1000309","url":null,"abstract":"Many of the minor complaints of old age may have a common etiology and are grouped together here under the term ‘the lesser ailments of aging’ (LAA). This essay proposes that they are due in large part to an age-linked reduced microcirculation. Capillary density (CD) in the tissues is determined by levels of angiogenic growth factors (AGFs). Over 47 studies have reported a reduced CD and/or waning AGFs throughout the bodies of aging animals and people. More convincing than such a generalization are the 80 sets of data comparing these two parameters in adult vs. the aged. These data have led to a hypothesis whose corollary proposes a specific treatment for the LAA. While genetically controlled, the waning levels of AGFs theoretically could be countered by pro-angiogenesis therapy and thus might ease the LAA or delay their onset. Therapies mentioned here include recombinant AGFs and inhibitors of type 5 phosphodiesterases, such a tadalafil/Cialis. Finally, Alzheimer’s disease (AD) is generally an illness of the elderly and may have a single or multiple causes. However, its clinical course may be influenced secondarily by conditions affecting the LAA. Therefore, any effective treatment of them may influence favorably the clinical course of AD.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"7 2 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82644865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-09-02DOI: 10.4172/2161-0460.1000366
F. C. Størmer
The time it takes from the first plaque is formed and to clinical signs of Alzheimer’s disease is observed, is unknown. I have described herein the possible connection between the plaque development and memory loss. The signals from the sense organs to the possible magnetite-prion part of the information storage in the neurons will be hampered and finally the neurons will disintegrate. Each step will probably affect the short term memory.
{"title":"Alzheimer's Disease: What is the Connection between Amyloid Plaques, Magnetite and Memory?","authors":"F. C. Størmer","doi":"10.4172/2161-0460.1000366","DOIUrl":"https://doi.org/10.4172/2161-0460.1000366","url":null,"abstract":"The time it takes from the first plaque is formed and to clinical signs of Alzheimer’s disease is observed, is unknown. I have described herein the possible connection between the plaque development and memory loss. The signals from the sense organs to the possible magnetite-prion part of the information storage in the neurons will be hampered and finally the neurons will disintegrate. Each step will probably affect the short term memory.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"472 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2017-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79917524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-08-25DOI: 10.4172/2161-0460.1000364
Shiping Li, Runjing Cao, Li Guo, Jiong Shi
Neuroinflammation is a double edge sword: it plays both destructive and regenerative roles in a variety of neurological diseases, such stroke and Alzheimer’s disease (AD). In the central nervous system, these inflammatory changes are restricted exclusively to microglia. Ischemic stroke causes an acute cascade of events, including excitotoxicity, inflammatory responses, oxidative stress and apoptosis, whereas AD is a chronic progressive process. As the blood–brain barrier separates the central nervous system and the peripheral immune system, the brain is used to be considered an immune-privileged organ. However, accumulating evidence reveals mononuclear phagocytes and the resident microglia play a key role in modulating the development and progression of brain pathology. In this mini review, we summarize the role of microglia in the brain and in disease states. Microglia serves different roles at different stages of the diseases. We emphasize the regulatory role of CX3CR1, which may provide a novel and effective means for therapy.
{"title":"Different Roles of Microglia/Macrophage in Ischemic Stroke and Alzheimer's Disease","authors":"Shiping Li, Runjing Cao, Li Guo, Jiong Shi","doi":"10.4172/2161-0460.1000364","DOIUrl":"https://doi.org/10.4172/2161-0460.1000364","url":null,"abstract":"Neuroinflammation is a double edge sword: it plays both destructive and regenerative roles in a variety of neurological diseases, such stroke and Alzheimer’s disease (AD). In the central nervous system, these inflammatory changes are restricted exclusively to microglia. Ischemic stroke causes an acute cascade of events, including excitotoxicity, inflammatory responses, oxidative stress and apoptosis, whereas AD is a chronic progressive process. As the blood–brain barrier separates the central nervous system and the peripheral immune system, the brain is used to be considered an immune-privileged organ. However, accumulating evidence reveals mononuclear phagocytes and the resident microglia play a key role in modulating the development and progression of brain pathology. In this mini review, we summarize the role of microglia in the brain and in disease states. Microglia serves different roles at different stages of the diseases. We emphasize the regulatory role of CX3CR1, which may provide a novel and effective means for therapy.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"31 2 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89116678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-08-16DOI: 10.4172/2161-0460.1000363
Y. Lim, J. Ham, A. Lee, E. Oh
Objective: The pathophysiology of gait disturbance in early Parkinson’s disease (PD) is not fully understood, but cholinergic dysfunction may be associated with gait disturbance. Central cholinergic activity is closely related with olfaction in PD and it can be estimated with short-latency afferent inhibition (SAI). We hypothesize that cholinergic dysfunction, especially olfactory dysfunction, could be associated with gait disturbance in early PD. Methods: A total of 57 early PD patients were enrolled. Olfaction was examined using the Korean version of the Sniffin’ stick (KVSS) test. The PD patients were grouped as anosmia, hyposmia and normosmia according to the KVSS score. The gait parameters examined during 10 m of gait. SAI was measured by conditioning motor-evoked potentials, elicited by single transmagnetic stimulation (TMS) of the motor cortex, with electrical stimuli delivered to the contralateral median nerve at intervals ranging from N20 to N20+4 ms. Results: The SAI response (N20 to N20+4 ms) and integrated SAI were less inhibited in PD for the anosmia and hyposmia groups than for the normosmia group (for all values, p<0.01). In the PD anosmia group, the walking time was longer and more steps were taken during the 10 m gait than in the PD hyposmia and normosmia groups (p=0.01, p<0.01). In addition, gait speed was slower and stride length was shorter in the PD anosmia group than in the other groups (p=0.01, p<0.01). The TDI score was an independent factor that showed a correlation (R2=0.261, 0.257) with gait speed in PD patients. A reduced TDI score was an independent determinant of reduced gait speed, explaining 25% of the variability even after correction of various factors related to cholinergic dysfunction. Conclusion: Central cholinergic system influences cognition, gait, and olfaction in the early stage of PD.
{"title":"Gait Disturbance Associated with Cholinergic Dysfunction in Early Parkinson's Disease","authors":"Y. Lim, J. Ham, A. Lee, E. Oh","doi":"10.4172/2161-0460.1000363","DOIUrl":"https://doi.org/10.4172/2161-0460.1000363","url":null,"abstract":"Objective: The pathophysiology of gait disturbance in early Parkinson’s disease (PD) is not fully understood, but cholinergic dysfunction may be associated with gait disturbance. Central cholinergic activity is closely related with olfaction in PD and it can be estimated with short-latency afferent inhibition (SAI). We hypothesize that cholinergic dysfunction, especially olfactory dysfunction, could be associated with gait disturbance in early PD. \u0000Methods: A total of 57 early PD patients were enrolled. Olfaction was examined using the Korean version of the Sniffin’ stick (KVSS) test. The PD patients were grouped as anosmia, hyposmia and normosmia according to the KVSS score. The gait parameters examined during 10 m of gait. SAI was measured by conditioning motor-evoked potentials, elicited by single transmagnetic stimulation (TMS) of the motor cortex, with electrical stimuli delivered to the contralateral median nerve at intervals ranging from N20 to N20+4 ms. \u0000Results: The SAI response (N20 to N20+4 ms) and integrated SAI were less inhibited in PD for the anosmia and hyposmia groups than for the normosmia group (for all values, p<0.01). In the PD anosmia group, the walking time was longer and more steps were taken during the 10 m gait than in the PD hyposmia and normosmia groups (p=0.01, p<0.01). In addition, gait speed was slower and stride length was shorter in the PD anosmia group than in the other groups (p=0.01, p<0.01). The TDI score was an independent factor that showed a correlation (R2=0.261, 0.257) with gait speed in PD patients. A reduced TDI score was an independent determinant of reduced gait speed, explaining 25% of the variability even after correction of various factors related to cholinergic dysfunction. \u0000Conclusion: Central cholinergic system influences cognition, gait, and olfaction in the early stage of PD.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"97 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77870982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-08-11DOI: 10.4172/2161-0460.1000361
P. FélixBermejo
Elderly cognitive decline is a well-known disorder that affects many people. One of the first medical definitions for this clinical reality was Kral’s “benign and malignant senescent forgetfulness”. After Kral, many authors proposed other entities of memory impairment or cognitive decline in the elderly: “Age-associated memory impairment”, “Agerelated memory decline”, “Ageing-associated cognitive decline”, Mild Cognitive Impairment (MCI) and “Cognitive Impairment Non-Dementia” (CIND) of the Canadian Study. And very recently, the DSM-V defined the elderly cognitive decline as a “Minor Neurocognitive Disorder”. By large, MCI had far more citations than any other predementia state in MEDLINE (more than 8,000 reviews in this medical database). This success in the medical literature is rather the expression of a controversy than a well-defined clinical disorder. In fact, its medical birth, near 30 years ago, was as a research entity that precludes dementia. The theoretical definition of MCI is quite clear (A cognitive decline with an increased dementia risk); the problem is the operational definition of this cognitive decline in many elderly that have produced, along the time many definitions and subtypes. In summary, MCI is defined as cognitive decline (of one or more cognitive domains, mainly memory) with normal or near normal functional activities of the patient, and obviously, no dementia. According to the type and extension of the affected cognitive domain, MCI has received several subtyping: Amnestic- only memory affected, non-amnestic- deficit in another cognitive domain different from the memory, such as executive capacities. Both of them could be shown alone or in combination (only amnestic MCI, only non-amnestic, or amnestic o non-amnestic plus other cognitive domain affected. There are several well-known characteristics of this entity. First, it is prevalent in the elderly, more prevalent (about 10-15%) that the dementia states (5-10%). Obviously, in both conditions, its prevalence oscillates with the operational definitions used and with the population demographic characteristics studied: age, sex and education. Second, MCI involves an increased risk of dementia and mortality in relation to the normal cognition elders. Third, it is an unstable disorder, many MCI cases do not evolve to dementia, and many others change to normal cognition in a period of 2-3 years. Fourth, MCI is a heterogeneous entity with many risk factors and aetiologies; it is not always the predementia state of the main neurodegenerative disorders of the elderly: Alzheimer disease (AD), Parkinson disease (PD) and others; cerebral vascular diseases, depression and elderly co-morbidities underpinning many MCI cases. From an epidemiological point of view, it is interesting to comment the MCI definition in three different scenarios: the clinical setting, the population-based surveys, and the trial studies because in these three scenarios, MCI had different characteristics an
{"title":"The Mild Cognitive Impairment (MCI) in Searching for its Clinical Identity,Comment of the NEDICES Cohort Data","authors":"P. FélixBermejo","doi":"10.4172/2161-0460.1000361","DOIUrl":"https://doi.org/10.4172/2161-0460.1000361","url":null,"abstract":"Elderly cognitive decline is a well-known disorder that affects many people. One of the first medical definitions for this clinical reality was Kral’s “benign and malignant senescent forgetfulness”. After Kral, many authors proposed other entities of memory impairment or cognitive decline in the elderly: “Age-associated memory impairment”, “Agerelated memory decline”, “Ageing-associated cognitive decline”, Mild Cognitive Impairment (MCI) and “Cognitive Impairment Non-Dementia” (CIND) of the Canadian Study. And very recently, the DSM-V defined the elderly cognitive decline as a “Minor Neurocognitive Disorder”. By large, MCI had far more citations than any other predementia state in MEDLINE (more than 8,000 reviews in this medical database). This success in the medical literature is rather the expression of a controversy than a well-defined clinical disorder. In fact, its medical birth, near 30 years ago, was as a research entity that precludes dementia. The theoretical definition of MCI is quite clear (A cognitive decline with an increased dementia risk); the problem is the operational definition of this cognitive decline in many elderly that have produced, along the time many definitions and subtypes. In summary, MCI is defined as cognitive decline (of one or more cognitive domains, mainly memory) with normal or near normal functional activities of the patient, and obviously, no dementia. According to the type and extension of the affected cognitive domain, MCI has received several subtyping: Amnestic- only memory affected, non-amnestic- deficit in another cognitive domain different from the memory, such as executive capacities. Both of them could be shown alone or in combination (only amnestic MCI, only non-amnestic, or amnestic o non-amnestic plus other cognitive domain affected. There are several well-known characteristics of this entity. First, it is prevalent in the elderly, more prevalent (about 10-15%) that the dementia states (5-10%). Obviously, in both conditions, its prevalence oscillates with the operational definitions used and with the population demographic characteristics studied: age, sex and education. Second, MCI involves an increased risk of dementia and mortality in relation to the normal cognition elders. Third, it is an unstable disorder, many MCI cases do not evolve to dementia, and many others change to normal cognition in a period of 2-3 years. Fourth, MCI is a heterogeneous entity with many risk factors and aetiologies; it is not always the predementia state of the main neurodegenerative disorders of the elderly: Alzheimer disease (AD), Parkinson disease (PD) and others; cerebral vascular diseases, depression and elderly co-morbidities underpinning many MCI cases. From an epidemiological point of view, it is interesting to comment the MCI definition in three different scenarios: the clinical setting, the population-based surveys, and the trial studies because in these three scenarios, MCI had different characteristics an","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"118 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88022181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：