Cholinergic Contributions to Behavioral Disturbances in Alzheimer's Disease

2000 ◽  
Vol 12 (S1) ◽  
pp. 231-235 ◽  
Author(s):  
Trey Sunderland
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Challenge Test ◽  
Neuronal Loss ◽  
Cholinergic Receptors ◽  
Behavioral Disturbances ◽  
Cholinergic Antagonist ◽  
Normal Controls

The identification of cholinergic contributions to the dysfunction in patients with Alzheimer's disease (AD) appears straightforward at first. However, complicating questions arose more than a decade ago. For example, why, if AD patients indeed experienced cholinergic damage, was the number of cholinergic receptors similar in both AD patients and normal controls at autopsy? Researchers speculated about the possibility of an upregulation of cholinergic receptors in response to the loss of functional receptors subsequent to presynaptic cholinergic neuronal loss. This led to research on the consequences of administering a cholinergic antagonist rather than an agonist in AD patients as a pharmacologic challenge test in an attempt to test the functional sensitivity of the remaining cholinergic receptors.

Spinal Alterations of Reil Insula in Alzheimer’s Disease

2017 ◽  
Vol 32 (4) ◽  
pp. 222-229 ◽  
Author(s):  
Foivos E. Petrides ◽  
Ioannis A. Mavroudis ◽  
Martha Spilioti ◽  
Fotios G. Chatzinikolaou ◽  
Vasiliki G. Costa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Statistical Analysis ◽  
Morphological Changes ◽  
Neuronal Loss ◽  
Silver Impregnation ◽  
Important Target ◽  
Impregnation Technique ◽  
Biochemical Mechanisms ◽  
Normal Controls

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that involves numerous cellular and biochemical mechanisms resulting in synaptic alterations and extensive neuronal loss. It is primarily characterized by impairment of memory, associated frequently with mood disorders. Continuous studies have shown that insula may be an important target of AD, but neuropathological alterations have not been described extensively. In the present study, we attempted to describe the morphometric and morphological changes of the spines of Reil insula in AD in comparison with normal aging using a silver impregnation technique. We classified spines into 3 types: (1) long neck, (2) short stubby, and (3) other types; and we measured and correlated the length of them in normal controls and in individuals with AD using ImageJ application. Statistical analysis was based on the Student t test on the basis of 360 cells in SPSS v.17.0, and significance was taken as P < .05.

Subjective Spatial Navigation Complaints - A Frequent Symptom Reported by Patients with Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease

2018 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Jiri Cerman ◽  
Ross Andel ◽  
Jan Laczo ◽  
Martin Vyhnalek ◽  
Zuzana Nedelska ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Spatial Navigation ◽  
Subjective Cognitive Decline ◽  
Great Effort ◽  
Frequent Symptom ◽  
Normal Controls

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.

Allocentric to Egocentric Spatial Switching: Impairment in aMCI and Alzheimer's Disease Patients?

2018 ◽  
Vol 15 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Gennaro Ruggiero ◽  
Alessandro Iavarone ◽  
Tina Iachini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Reference Frame ◽  
Reference Frames ◽  
Memory Task ◽  
Spatial Representations ◽  
The Novel ◽  
Spatial Memory Task ◽  
Switching Condition ◽  
Normal Controls

Objective: Deficits in egocentric (subject-to-object) and allocentric (object-to-object) spatial representations, with a mainly allocentric impairment, characterize the first stages of the Alzheimer's disease (AD). Methods: To identify early cognitive signs of AD conversion, some studies focused on amnestic-Mild Cognitive Impairment (aMCI) by reporting alterations in both reference frames, especially the allocentric ones. However, spatial environments in which we move need the cooperation of both reference frames. Such cooperating processes imply that we constantly switch from allocentric to egocentric frames and vice versa. This raises the question of whether alterations of switching abilities might also characterize an early cognitive marker of AD, potentially suitable to detect the conversion from aMCI to dementia. Here, we compared AD and aMCI patients with Normal Controls (NC) on the Ego-Allo- Switching spatial memory task. The task assessed the capacity to use switching (Ego-Allo, Allo-Ego) and non-switching (Ego-Ego, Allo-Allo) verbal judgments about relative distances between memorized stimuli. Results: The novel finding of this study is the neat impairment shown by aMCI and AD in switching from allocentric to egocentric reference frames. Interestingly, in aMCI when the first reference frame was egocentric, the allocentric deficit appeared attenuated. Conclusion: This led us to conclude that allocentric deficits are not always clinically detectable in aMCI since the impairments could be masked when the first reference frame was body-centred. Alongside, AD and aMCI also revealed allocentric deficits in the non-switching condition. These findings suggest that switching alterations would emerge from impairments in hippocampal and posteromedial areas and from concurrent dysregulations in the locus coeruleus-noradrenaline system or pre-frontal cortex.

scholarly journals Deep Learning with Neuroimaging and Genomics in Alzheimer’s Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7911
Author(s):  
Eugene Lin ◽  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Learning ◽  
Future Research ◽  
Learning Approaches ◽  
Learning Models ◽  
Learning Techniques ◽  
Neuroimaging Data ◽  
Similarities And Differences ◽  
Normal Controls

A growing body of evidence currently proposes that deep learning approaches can serve as an essential cornerstone for the diagnosis and prediction of Alzheimer’s disease (AD). In light of the latest advancements in neuroimaging and genomics, numerous deep learning models are being exploited to distinguish AD from normal controls and/or to distinguish AD from mild cognitive impairment in recent research studies. In this review, we focus on the latest developments for AD prediction using deep learning techniques in cooperation with the principles of neuroimaging and genomics. First, we narrate various investigations that make use of deep learning algorithms to establish AD prediction using genomics or neuroimaging data. Particularly, we delineate relevant integrative neuroimaging genomics investigations that leverage deep learning methods to forecast AD on the basis of incorporating both neuroimaging and genomics data. Moreover, we outline the limitations as regards to the recent AD investigations of deep learning with neuroimaging and genomics. Finally, we depict a discussion of challenges and directions for future research. The main novelty of this work is that we summarize the major points of these investigations and scrutinize the similarities and differences among these investigations.

scholarly journals Defining early changes in Alzheimer’s disease from RNA sequencing of brain regions differentially affected by pathology

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Boris Guennewig ◽  
Julia Lim ◽  
Lee Marshall ◽  
Andrew N. McCorkindale ◽  
Patrick J. Paasila ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rna Sequencing ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Post Mortem ◽  
Tau Pathology ◽  
Membrane Spanning ◽  
Immune Related Genes ◽  
Vesicle Secretion

AbstractTau pathology in Alzheimer’s disease (AD) spreads in a predictable pattern that corresponds with disease symptoms and severity. At post-mortem there are cortical regions that range from mildly to severely affected by tau pathology and neuronal loss. A comparison of the molecular signatures of these differentially affected areas within cases and between cases and controls may allow the temporal modelling of disease progression. Here we used RNA sequencing to explore differential gene expression in the mildly affected primary visual cortex and moderately affected precuneus of ten age-, gender- and RNA quality-matched post-mortem brains from AD patients and healthy controls. The two regions in AD cases had similar transcriptomic signatures but there were broader abnormalities in the precuneus consistent with the greater tau load. Both regions were characterised by upregulation of immune-related genes such as those encoding triggering receptor expressed on myeloid cells 2 and membrane spanning 4-domains A6A and milder changes in insulin/IGF1 signalling. The precuneus in AD was also characterised by changes in vesicle secretion and downregulation of the interneuronal subtype marker, somatostatin. The ‘early’ AD transcriptome is characterised by perturbations in synaptic vesicle secretion on a background of neuroimmune dysfunction. In particular, the synaptic deficits that characterise AD may begin with the somatostatin division of inhibitory neurotransmission.

P4-182: The behavioral disturbances in mild-moderate and severe stages of Alzheimer's disease

2006 ◽  
Vol 2 ◽  
pp. S569-S570
Author(s):  
Mari Feli Gonzalez ◽  
Javier Yanguas ◽  
Cristina Buiza ◽  
Igone Etxeberria ◽  
Nerea Galdona ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Behavioral Disturbances

scholarly journals Ceramide and Related-Sphingolipid Levels Are Not Altered in Disease-Associated Brain Regions of APPSLand APPSL/PS1M146LMouse Models of Alzheimer's Disease: Relationship with the Lack of Neurodegeneration?

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Laurence Barrier ◽  
Bernard Fauconneau ◽  
Anastasia Noël ◽  
Sabrina Ingrand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neuronal Death ◽  
Time Course ◽  
Neuronal Loss ◽  
Brain Regions ◽  
App Processing ◽  
Ceramide Accumulation ◽  
The Brain

There is evidence linking sphingolipid abnormalities, APP processing, and neuronal death in Alzheimer's disease (AD). We previously reported a strong elevation of ceramide levels in the brain of the APPSL/PS1Ki mouse model of AD, preceding the neuronal death. To extend these findings, we analyzed ceramide and related-sphingolipid contents in brain from two other mouse models (i.e., APPSLand APPSL/PS1M146L) in which the time-course of pathology is closer to that seen in most currently available models. Conversely to our previous work, ceramides did not accumulate in disease-associated brain regions (cortex and hippocampus) from both models. However, the APPSL/PS1Ki model is unique for its drastic neuronal loss coinciding with strong accumulation of neurotoxic Aβisoforms, not observed in other animal models of AD. Since there are neither neuronal loss nor toxic Aβspecies accumulation in APPSLmice, we hypothesized that it might explain the lack of ceramide accumulation, at least in this model.

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