C-32 A Neuropsychological Case Study of Very-Late-Onset Psychosis

2019 ◽  
Vol 34 (6) ◽  
pp. 1061-1061
Author(s):  
V Sekunda
Keyword(s):  
Visual Information ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Demographic History ◽  
Lewy Bodies ◽  
Long Term Memory ◽  
Urine Drug Screen ◽  
Impaired Performance ◽  
Neuropsychological Profile ◽  
Neurocognitive Profile

Abstract Objective Studies have established a relationship between earlier-onset (< 40 years of age) and late-onset (between 40 and 60 years of age) psychosis symptoms on cognitive functioning, but little is known about the neurocognitive profile of very-late-onset psychosis (≥60 years of age) (Sharma et al., 2014; Howard et al., 2000). This case highlights the neuropsychological profile in an older adult with very-late-onset psychosis. Method 84-year-old, right-handed, Caucasian female with no significant medical or psychiatric history prior to 2013. Onset of delusions, paranoia, and tactile, auditory, and visual hallucinations initially beginning in 2013 with no identifiable trigger and worsening symptoms in 2018. Labs within normal limits and urine drug screen was negative. Results Her estimated premorbid verbal functioning fell within the average range which fell slightly below her score as predicted by her demographic history (i.e., education, occupation, region, sex, and race/ethnicity), which fell within the high average range. Her overall objective testing indicated that she demonstrated relative weaknesses encoding increasingly complex auditory and visual information and reliably retrieving the information from her long-term memory on command. She demonstrated intact orientation, impaired performance on a cognitive switching task, and a visuospatial task. Conclusions The patient demonstrated grossly intact performance across many cognitive domains. This paradox highlights the need for further investigation of the neuroanatomical correlates of psychosis in older-adults and its longitudinal neurocognitive profile as often, individuals are presumed to be suffering from a neurodegenerative disorder such as Alzheimer’s type dementia or Dementia with Lewy bodies (Assche et al., 2018).

scholarly journals Pesticides and Parkinson’s Disease

2001 ◽  
Vol 1 ◽  
pp. 207-208 ◽  
Author(s):  
Todd B. Sherer ◽  
Ranjita Betarbet ◽  
J. Timothy Greenamyre
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Selective Death ◽  
Underlying Mechanisms ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD), a common neurodegenerative disorder affects approximately 1% of the population over 65. PD is a late-onset progressive motor disease characterized by tremor, rigidity (stiffness), and bradykinesia (slowness of movement). The hallmark of PD is the selective death of dopamine-containing neurons in the substantia nigra pars compacta which send their projections to the striatum and the presence of cytoplasmic aggregates called Lewy bodies [1-2]. Most cases of PD are sporadic but rare cases are familial, with earlier onset. The underlying mechanisms and causes of PD still remain unclear.

scholarly journals Concomitant AD and DLB pathologies shape subfield microglia responses in the hippocampus

2022 ◽  
Author(s):  
Sonja Fixemer ◽  
Corrado Ameli ◽  
Gael P. Hammer ◽  
Luis M. Salamanca ◽  
Oihane Uriarte Huarte ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Lewy Bodies ◽  
Volumetric Analysis ◽  
Alpha Synuclein ◽  
Dependent Manner ◽  
Double Positive ◽  
Atrophy Rate ◽  
Age Related ◽  
Highly Correlated

Hippocampal alteration is at the centre of memory decline in the most common age-related neurodegenerative diseases: Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB). However, the subregional deterioration of the hippocampus differs between both diseases with more severe atrophy in the CA1 subfield of the AD patients. How AD and DLB-typical pathologies compose the various local microenvironment of the hippocampus across AD and DLB needs to be further explored to understand this process. Additionally, microglia responses could further impact the atrophy rate. Some studies suggest that microglia react differently according to the underlying neurodegenerative disorder. How microglia are transformed across hippocampal subfields in AD and DLB, and how their changes are associated with disease-typical pathologies remains to be determined. To these purposes, we performed a volumetric analysis of phospho-Tau (P-Tau), Amyloid-beta (Abeta), and phospho-alpha-Synuclein (P-Syn) loads, quantified and classified microglia according to distinct morphological phenotypes using high-resolution confocal 3D microscopy of hippocampal CA1, CA3 and DG/CA4 subfields of late-onset AD (n=10) and DLB (n=8) as well as age-matched control samples (n=11). We found that each of the Tau, Abeta and Synuclein pathologies followed a specific subregional distribution, relatively preserved across AD and DLB. P-Tau, Abeta and P-Syn burdens were significantly exacerbated in AD, with Tau pathology being particularly severe in the AD CA1. P-Tau and P-Syn burdens were highly correlated across subfields and conditions (R2Spear = 0.79; P < 0.001) and result from a local co-distribution of P-Tau and P-Syn inclusions in neighbouring neurons, with only a low proportion of double-positive cells. In parallel, we assessed the changes of the microglia responses by measuring 16 morphological features of more than 35,000 individual microglial cells and classifying them into seven-distinct morphological clusters. We found microglia features- and clusters-variations subfield- and condition-dependent. Two of the seven morphological clusters, with more amoeboid and less branched forms, were identified as disease-enriched and found to be further increased in AD. Interestingly, some microglial features or clusters were associated with one but more often with a combination of two pathologies in a subfield-dependent manner. In conclusion, our study shows a multimodal association of the hippocampal microglia responses with the co-occurrence, distribution and severity of AD and DLB pathologies. In DLB hippocampi, pathological imprint and microglia responses follow AD trends but with lesser severity. Our study suggests that the increased pathological burdens of P-Tau and P-Syn and associated microglia alterations are involved in a more severe deterioration of the CA1 in AD as compared to DLB.

Effect of sleep on memory for binding different types of visual information

2020 ◽  
Author(s):  
John J Shaw ◽  
Zhisen Urgolites ◽  
Padraic Monaghan
Keyword(s):  
Visual Information ◽  
Storage Capacity ◽  
Declarative Memory ◽  
Recognition Task ◽  
Forced Choice ◽  
Long Term Memory ◽  
Term Memory ◽  
Different Types ◽  
Types Of Information

Visual long-term memory has a large and detailed storage capacity for individual scenes, objects, and actions. However, memory for combinations of actions and scenes is poorer, suggesting difficulty in binding this information together. Sleep can enhance declarative memory of information, but whether sleep can also boost memory for binding information and whether the effect is general across different types of information is not yet known. Experiments 1 to 3 tested effects of sleep on binding actions and scenes, and Experiments 4 and 5 tested binding of objects and scenes. Participants viewed composites and were tested 12-hours later after a delay consisting of sleep (9pm-9am) or wake (9am-9pm), on an alternative forced choice recognition task. For action-scene composites, memory was relatively poor with no significant effect of sleep. For object-scene composites sleep did improve memory. Sleep can promote binding in memory, depending on the type of information to be combined.

scholarly journals A glutaminyl cyclase-catalyzed α-synuclein modification identified in human synucleinopathies

2021 ◽  
Author(s):  
Maike Hartlage-Rübsamen ◽  
Alexandra Bluhm ◽  
Sandra Moceri ◽  
Lisa Machner ◽  
Janett Köppen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Size Exclusion ◽  
Lewy Neurites ◽  
Enzymatic Assays ◽  
Aβ Peptides ◽  
Glutaminyl Cyclase ◽  
Affect Cell Viability ◽  
Exclusion Chromatography

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder that is neuropathologically characterized by degeneration of dopaminergic neurons of the substantia nigra (SN) and formation of Lewy bodies and Lewy neurites composed of aggregated α-synuclein. Proteolysis of α-synuclein by matrix metalloproteinases was shown to facilitate its aggregation and to affect cell viability. One of the proteolysed fragments, Gln79-α-synuclein, possesses a glutamine residue at its N-terminus. We argue that glutaminyl cyclase (QC) may catalyze the pyroglutamate (pGlu)79-α-synuclein formation and, thereby, contribute to enhanced aggregation and compromised degradation of α-synuclein in human synucleinopathies. Here, the kinetic characteristics of Gln79-α-synuclein conversion into the pGlu-form by QC are shown using enzymatic assays and mass spectrometry. Thioflavin T assays and electron microscopy demonstrated a decreased potential of pGlu79-α-synuclein to form fibrils. However, size exclusion chromatography and cell viability assays revealed an increased propensity of pGlu79-α-synuclein to form oligomeric aggregates with high neurotoxicity. In brains of wild-type mice, QC and α-synuclein were co-expressed by dopaminergic SN neurons. Using a specific antibody against the pGlu-modified neo-epitope of α-synuclein, pGlu79-α-synuclein aggregates were detected in association with QC in brains of two transgenic mouse lines with human α-synuclein overexpression. In human brain samples of PD and dementia with Lewy body subjects, pGlu79-α-synuclein was shown to be present in SN neurons, in a number of Lewy bodies and in dystrophic neurites. Importantly, there was a spatial co-occurrence of pGlu79-α-synuclein with the enzyme QC in the human SN complex and a defined association of QC with neuropathological structures. We conclude that QC catalyzes the formation of oligomer-prone pGlu79-α-synuclein in human synucleinopathies, which may—in analogy to pGlu-Aβ peptides in Alzheimer’s disease—act as a seed for pathogenic protein aggregation.

scholarly journals Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes

2021 ◽  
Vol 22 (16) ◽  
pp. 8368
Author(s):  
Luis M. Valor ◽  
Jorge C. Morales ◽  
Irati Hervás-Corpión ◽  
Rosario Marín
Keyword(s):  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Fragile X ◽  
Endocrine System ◽  
Molecular Pathogenesis ◽  
Adult Women ◽  
Adult Men ◽  
Cgg Repeats ◽  
Reproductive Impairment ◽  
Ataxia Syndrome

Abnormal trinucleotide expansions cause rare disorders that compromise quality of life and, in some cases, lifespan. In particular, the expansions of the CGG-repeats stretch at the 5’-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In this review, we will describe the pathological mechanisms of the adult “gain-of-function” syndromes that are mainly caused by the toxic actions of CGG RNA and FMRpolyG peptide. There have been intensive attempts to identify reliable peripheral biomarkers to assess disease progression and onset of specific pathological traits. Mitochondrial dysfunction, altered miRNA expression, endocrine system failure, and impairment of the GABAergic transmission are some of the affectations that are susceptible to be tracked using peripheral blood for monitoring of the motor, cognitive, psychiatric and reproductive impairment of the CGG-expansion carriers. We provided some illustrative examples from our own cohort. Understanding the association between molecular pathogenesis and biomarkers dynamics will improve effective prognosis and clinical management of CGG-expansion carriers.

Processing of Information about Location during Locomotion: Effects of Amount of Visual Information about the Locomotor Patterns

1980 ◽  
Vol 51 (1) ◽  
pp. 231-238 ◽  
Author(s):  
Anders Böök ◽  
Tommy Gärling
Keyword(s):  
Visual Information ◽  
Concurrent Task ◽  
Negative Effects ◽  
Impaired Performance ◽  
Central Processing ◽  
Starting Point ◽  
Light Line ◽  
Locomotor Patterns ◽  
Dark Room

How maintenance of orientation during locomotion in unfamiliar environments is accomplished was investigated by presenting subjects ( n = 32) a target in different locations in a dark room, having them walk linearly behind a moving light line (1.12 m/sec.), and from a stopping point 12 and 22.6 m away, numerically estimate direction and distance to the target. An equal number of subjects was assigned to each of 2 × 2 treatment levels: the starting point either visible or invisible from the stopping point and the target either visible only from the starting point or throughout each trial. In the conditions with invisible targets there were mainly negative effects of the visible starting point, partially the same as those previously obtained for a concurrent task during locomotion. The results suggested that maintenance of orientation is achieved by recurrent central processing of information, which if postponed leads to impaired performance mainly because forgetting occurs.

Are lysosomes potential therapeutic targets for Parkinson’s disease?

2021 ◽  
Vol 20 ◽  
Author(s):  
A. Petese ◽  
V. Cesaroni ◽  
S. Cerri ◽  
F. Blandini
Keyword(s):  
Neurodegenerative Disorder ◽  
Association Studies ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Genome Wide Association Studies ◽  
Lysosomal Dysfunction ◽  
Genome Wide ◽  
Nigrostriatal Neurons ◽  
Disease Modifying Treatment ◽  
Alpha Synuclein Aggregation

Background: Parkinson´s disease (PD) is the second most common neurodegenerative disorder, affecting 2-3% of the population over 65 years old. In addition to progressive degeneration of nigrostriatal neurons, the histopathological feature of PD is the accumulation of misfolded α-synuclein protein in abnormal cytoplasmatic inclusions, known as Lewy bodies (LBs). Recently, genome-wide association studies (GWAS) have indicated a clear association of variants within several lysosomal genes with risk for PD. Newly evolving data have been shedding light on the relationship between lysosomal dysfunction and alpha-synuclein aggregation. Defects in lysosomal enzymes could lead to the insufficient clearance of neurotoxic protein materials, possibly leading to selective degeneration of dopaminergic neurons. Specific modulation of lysosomal pathways and their components could be considered a novel opportunity for therapeutic intervention for PD. Aim: The purpose of this review is to illustrate lysosomal biology and describe the role of lysosomal dysfunction in PD pathogenesis. Finally, the most promising novel therapeutic approaches designed to modulate lysosomal activity, as a potential disease-modifying treatment for PD will be highlighted.

Predicting progression in the late onset frontal lobe syndrome

2018 ◽  
Vol 31 (5) ◽  
pp. 743-748 ◽  
Author(s):  
Flora T. Gossink ◽  
Everard Vijverberg ◽  
Welmoed Krudop ◽  
Philip Scheltens ◽  
Max L. Stek ◽  
...  
Keyword(s):  
Frontal Lobe ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Clinical Syndrome ◽  
Clinical Markers ◽  
Neuropsychological Profile ◽  
Stereotypical Behavior ◽  
Executive Deficits ◽  
Magnetic Resonance Imaging Mri ◽  
Frontal Lobe Syndrome

ABSTRACTA late onset frontal lobe syndrome (LOF) refers to a clinical syndrome with apathy, disinhibition, or stereotypical behavior arising in middle or late adulthood. Diagnostics are challenging, and both clinicians and patients need reliable predictors of progression to improve clinical guidance. In this longitudinal multicenter and genetically screened prospective study, 137 LOF patients with frontal behavior (FBI score≥11) and/or stereotypical behavior (SRI≥10) were included. Progression was defined as institutionalization, death, or progression of frontal or temporal atrophy at magnetic resonance imaging (MRI) after two years of follow up. Absence of progression at MRI in addition to stable or improved Mini Mental State Examination and Frontal Assessment Battery scores after two years was indicative for non-progression. The presence of stereotypy and a neuropsychological profile with executive deficits at baseline were found to be predictive for progression, while a history and family history with psychiatric disorders were predictors for non-progression. The combination of these clinical markers had a predictive value of 80.4% (p < 0.05). In patients presenting with late onset behavioral symptoms, an appraisal of the rate of deterioration can be made by detailed mapping of clinical symptoms. Distinction of progressive discourses from non-progressive or treatable conditions is to be gained.

scholarly journals Gene4PD: A Comprehensive Genetic Database of Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Bin Li ◽  
Guihu Zhao ◽  
Qiao Zhou ◽  
Yali Xie ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Association Studies ◽  
Age At Onset ◽  
Genetic Data ◽  
Genome Wide Association Studies ◽  
Onset Age ◽  
Loss Of Function

Parkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs). By systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differentially expressed genes, and differential DNA methylation genes) and age at onset in PD. We integrated five layers of genetic data (8302 terms) with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30–50 years), whereas another 10 genes were associated with a late-onset (age &gt; 50 years). Notably, the AAOs of patients with loss of function variants in five genes were significantly lower than that of patients with deleterious missense variants, while patients with VPS13C (P = 0.01) was opposite. Finally, we developed an online database named Gene4PD (http://genemed.tech/gene4pd) which integrated published genetic data in PD, the PAGs, and 63 popular genomic data sources, as well as an online pipeline for prioritize risk variants in PD. In conclusion, Gene4PD provides researchers and clinicians comprehensive genetic knowledge and analytic platform for PD, and would also improve the understanding of pathogenesis in PD.

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