scholarly journals Characterization of cognitive impairment in adult polyglucosan body disease

2022 ◽  
Author(s):  
Paul Theo Zebhauser ◽  
Isabell Cordts ◽  
Holger Hengel ◽  
Bernhard Haslinger ◽  
Paul Lingor ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Memory Impairment ◽  
Neurodegenerative Disorder ◽  
Axonal Neuropathy ◽  
Case Series ◽  
Cognitive Symptoms ◽  
Pathogenic Variants ◽  
Neuropsychological Profile ◽  
Polyglucosan Body ◽  
Adult Polyglucosan Body Disease

AbstractAdult polyglucosan body disease (APBD) is a rare but probably underdiagnosed autosomal recessive neurodegenerative disorder due to pathogenic variants in GBE1. The phenotype is characterized by neurogenic bladder dysfunction, spastic paraplegia, and axonal neuropathy. Additionally, cognitive symptoms and dementia have been reported in APBD but have not been studied systematically. Using exome sequencing, we identified two previously unreported bi-allelic missense GBE1 variants in a patient with severe memory impairment along with the typical non-cognitive symptoms. We were able to confirm a reduction of GBE1 activity in blood lymphocytes. To characterize the neuropsychological profile of patients suffering from APBD, we conducted a systematic review of cognitive impairment in this rare disease. Analysis of 24 cases and case series (in total 58 patients) showed that executive deficits and memory impairment are the most common cognitive symptoms in APBD.

scholarly journals Fucosidosis—Clinical Manifestation, Long-Term Outcomes, and Genetic Profile—Review and Case Series

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1383 ◽  
Author(s):  
Karolina M. Stepien ◽  
Elżbieta Ciara ◽  
Aleksandra Jezela-Stanek
Keyword(s):  
Neurodegenerative Disorder ◽  
Respiratory Infections ◽  
Clinical Manifestations ◽  
Case Series ◽  
Genetic Profile ◽  
Nonsense Mutations ◽  
Pathogenic Variants ◽  
One Stop ◽  
Stop Loss

Fucosidosis is a neurodegenerative disorder which progresses inexorably. Clinical features include coarse facial features, growth retardation, recurrent upper respiratory infections, dysostosis multiplex, and angiokeratoma corporis diffusum. Fucosidosis is caused by mutations in the FUCA1 gene resulting in α-L-fucosidase deficiency. Only 36 pathogenic variants in the FUCA1 gene are related to fucosidosis. Most of them are missense/nonsense substitutions; six missense and 11 nonsense mutations. Among deletions there were eight small and five gross changes. So far, only three splice site variants have been described—one small deletion, one complete deletion and one stop-loss mutation. The disease has a significant clinical variability, the cause of which is not well understood. The genotype–phenotype correlation has not been well defined. This review describes the genetic profile and clinical manifestations of fucosidosis in pediatric and adult cases.

scholarly journals Zolpidem in Progressive Supranuclear Palsy

2013 ◽  
Vol 2013 ◽  
pp. 1-2 ◽  
Author(s):  
Sandip K. Dash
Keyword(s):  
Cognitive Impairment ◽  
Progressive Supranuclear Palsy ◽  
Effective Treatment ◽  
Globus Pallidus ◽  
Neurodegenerative Disorder ◽  
Motor Symptoms ◽  
Cognitive Symptoms ◽  
Gaba Agonist ◽  
Personality Changes ◽  
Number Of Patients

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder, characterized by motor symptoms, postural instability, personality changes, and cognitive impairment. There is no effective treatment for this disorder. Reduced neurotransmission of GABA in the striatum and globus pallidus may contribute to the symptoms of motor and cognitive symptoms seen in PSP. Zolpidem is a GABA agonist of the benzodiazepine subreceptor BZ1. Here a nondiabetic, normotensive case of PSP is (Progressive Supranuclear Palsy) described, which showed improvement in swallowing, speech, and gaze paresis after zolpidem therapy and possible mechanism of actions are discussed. However, more trials are needed with large number of patients to confirm the effectiveness of zolpidem in progressive supranuclear palsy.

scholarly journals Using amyloid PET imaging to diagnose Alzheimer’s disease in patients with multiple sclerosis

2020 ◽  
Vol 267 (11) ◽  
pp. 3268-3273 ◽  
Author(s):  
Magdalena Kolanko ◽  
Zarni Win ◽  
Neva Patel ◽  
Omar Malik ◽  
Christopher Carswell ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Pet Imaging ◽  
Case Series ◽  
Amyloid Pet ◽  
Neuropsychological Profile ◽  
Therapeutic Decisions ◽  
Amyloid Pet Imaging

Abstract Background Cognitive dysfunction affects 40–60% of individuals with multiple sclerosis (MS). The neuropsychological profile commonly consists of a subcortical pattern of deficits, although a proportion of patients have a severe progressive cortical dementia. However, patients with MS can be affected by other neurodegenerative diseases, such as Alzheimer’s disease (AD). Little is known about the co-existence of these two conditions but distinguishing dementia due to MS alone from a coexisting neurodegenerative disease is challenging. Amyloid PET imaging has allowed improved AD diagnosis, especially in patients with atypical presentations or multiple possible causes of cognitive impairment. Amyloid PET demonstrates increased cortical signal in AD, whereas reductions in subcortical uptake are associated with demyelination. To the authors knowledge, there are no reports of clinical Amyloid PET use in MS patients with dementia. Methods Here, three MS patients presenting to the Cognitive Neurology Clinic with progressive cognitive impairment are described. Due to lack of diagnostic clarity from standard investigations, they underwent Amyloid PET Imaging with 18F-florbetapir according to established appropriate use criteria and after review by a multidisciplinary team. Results Two patients were diagnosed with AD based on positive Amyloid PET imaging and were subsequently started on cholinesterase inhibitor treatment. The other patient had a negative scan, leading to further investigations and identification of another potential cause of worsening cognitive impairment. Conclusions The experience from this case series suggests that Amyloid PET Imaging may be of diagnostic value in selected patients with MS and dementia. In these individuals, it may provide diagnostic clarity and assist with therapeutic decisions.

Glycogen Storage Disorders

2016 ◽  
Author(s):  
David Cassiman ◽  
Pascal Laforêt ◽  
Fanny Mochel
Keyword(s):  
Axonal Neuropathy ◽  
Glycogen Storage ◽  
Exercise Intolerance ◽  
Polyglucosan Body ◽  
Major Energy Source ◽  
Cns Effects ◽  
The Brain ◽  
Adult Polyglucosan Body Disease ◽  
Storage Disorders ◽  
Gsd Ii

Glucose is the body’s major energy source, and carbohydrate serves as fuel—particularly during high-intensity exercise that requires rapid energy release. A deficiency of any of the enzymes involved in the catabolism of glycogen to glucose may cause symptoms, with hypoglycemia and exercise intolerance as the most common presentations. Glycogen storage disorders (GSD) affect muscle, liver, and brain. The most common GSDs affecting muscle are GSD II (Pompe disease) and GSD V (McArdle disease). GSDs affecting mainly the liver are GSD I, III, IV, VI, IX, XI. Most liver-GSDs present during infancy, with symptoms of hypoglycemia, impressive hepatomegaly, and retarded growth. Adult presentations have been reported for GSD Ia, III, IV, and IX.Adult polyglucosan body disease (APBD) is the main GSD affecting primarily the brain and mainly characterized by spastic paraplegia, axonal neuropathy and leukodystrophy. APBD is a subtype of GSD IV and is due to a deficiency of glycogen branching enzyme (GBE). Besides GSD IV, other GSDs have been reported to have CNS effects in some patients—notably GSD II and GSD III.

Estimation of premorbid intelligence and executive cognitive functions with lexical reading tasks

2020 ◽  
Author(s):  
Graham Pluck
Keyword(s):  
Cognitive Impairment ◽  
Lexical Decision ◽  
Cognitive Ability ◽  
Memory Span ◽  
Clinical Sample ◽  
Case Series ◽  
Stem Completion ◽  
Clinical Neuropsychology ◽  
Premorbid Intelligence ◽  
Highly Correlated

Introduction: Estimation of premorbid function is essential to accurate assessment of cognitive impairments in clinical neuropsychology and behavioral neurology, and has numerous research applications. However, current methods are rudimentary and imperfect. We explored how lexical tasks can be best used to accurately and precisely estimate intelligence and executive functions.Methods: We studied lexical word pronunciation, lexical decision, and stem-completion naming in the estimation of cognitive ability, in samples of healthy adults (n = 143), and patients with cognitive impairment due to neurological illness (n =15). Cognitive assessments included intelligence (WAIS-IV), episodic memory, and eight tests of executive functioning, including Theory of Mind.Results: When examined at the group level, single word pronunciation was particularly robust in the presence of cognitive impairment in patients with dementia. However, as a case series, patients showed idiosyncratic patterns of preservation of lexical skills including on tests of pronunciation, lexical decision and stem-completion naming. All of these tasks were highly correlated with IQ scores in a non-clinical sample, suggesting that they could be used as estimators of premorbid intelligence. Simulated impairments in non-clinical controls suggested that the median score from the three different tasks had the highest correlation with, and provided the most accurate and precise estimates of, intelligence, and was also the least sensitive to impairment. Finally, we show that these methods also predict executive functions, in particular, strong correlations were found for proverb interpretation, phonemic/semantic alternating verbal fluency, and working memory span performance. Conclusions: Several lexical tasks are potentially useful in predication of pre-illness cognitive ability in patients with neurological or psychiatric illness. However, due to the heterogeneity of impairments between patients, estimation of premorbid levels could be improved by the use of the median estimated values from multiple tests. This could potentially improve diagnostic accuracy and quantification of neuropsychological impairments.

The Anterior-posterior Functional Connectivity Disconnection in the Elderly with Subjective Memory Impairment and Amnestic Mild Cognitive Impairment

2020 ◽  
Vol 17 (4) ◽  
pp. 373-381
Author(s):  
Wuhai Tao ◽  
Jinping Sun ◽  
Xin Li ◽  
Wen Shao ◽  
Jing Pei ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Memory Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Magnetic Resonance Imaging Scan ◽  
Subjective Memory ◽  
Long Distance ◽  
Whole Brain ◽  
Subjective Memory Impairment

Background: Subjective Memory Impairment (SMI) may tremendously increase the risk of Alzheimer’s Disease (AD). The full understanding of the neuromechanism of SMI will shed light on the early intervention of AD. Methods: In the current study, 23 Healthy Controls (HC), 22 SMI subjects and 24 amnestic Mild Cognitive Impairment (aMCI) subjects underwent the comprehensive neuropsychological assessment and the resting-state functional magnetic resonance imaging scan. The difference in the connectivity of the Default Mode Network (DMN) and Functional Connectivity (FC) from the Region of Interest (ROI) to the whole brain were compared, respectively. Results: The results showed that HC and SMI subjects had significantly higher connectivity in the region of the precuneus area compared to aMCI subjects. However, from this region to the whole brain, SMI and aMCI subjects had significant FC decrease in the right anterior cingulum, left superior frontal and left medial superior frontal gyrus compared to HC. In addition, this FC change was significantly correlated with the cognitive function decline in participants. Conclusion: Our study indicated that SMI subjects had relatively intact DMN connectivity but impaired FC between the anterior and posterior brain. The findings suggest that long-distance FC is more vulnerable than the short ones in the people with SMI.

scholarly journals Fragile-X-Associated Tremor/Ataxia Syndrome or Alcohol-Induced Cerebellar Degeneration? A Case Report

2020 ◽  
Vol 12 (3) ◽  
pp. 466-471
Author(s):  
Giulia Grigioni ◽  
Christian Saleh ◽  
Phillip Jaszczuk ◽  
Dorothea Wand ◽  
Stefanie Wilmes ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Case Report ◽  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Disease Diagnosis ◽  
Cerebellar Degeneration ◽  
Gait Ataxia ◽  
Intention Tremor ◽  
Triplet Expansion ◽  
Ataxia Syndrome

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that manifests with intention tremor, progressive gait ataxia, and cognitive impairment. The disease is genetically characterized by a premutation of the <i>FMR1</i>gene on the X-chromosome manifesting with a CGG triplet expansion between 55 and 200. Given the phenotypical variety of this disease, diagnosis is frequently delayed. We present and discuss a male patient whose diagnosis of FXTAS was delayed due to his concomitant alcohol abuse.

scholarly journals Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction

2021 ◽  
pp. 1-16
Author(s):  
Wei Wei ◽  
Yinghua Liu ◽  
Chunling Dai ◽  
Narjes Baazaoui ◽  
Yunn-Chyn Tung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Early Development ◽  
Neurodegenerative Disorder ◽  
Synaptic Dysfunction ◽  
Early Postnatal Development ◽  
Wild Type Female

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction. Objective: To explore strategies for early intervention to prevent Alzheimer’s disease. Methods: In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated. Results: P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC/PKC, MEK/ERK and PI3K/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice. Conclusion: These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.

Cognitive Impairment after Lacunar Stroke and the Risk of Recurrent Stroke and Death

2021 ◽  
pp. 1-7
Author(s):  
Abraham Kwan ◽  
Jingkai Wei ◽  
N. Maritza Dowling ◽  
Melinda C. Power ◽  
Zurab Nadareshvili ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Memory Impairment ◽  
Recurrent Stroke ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Cognitive Screening ◽  
Lacunar Stroke ◽  
Domain Specific ◽  
Risk Of Death ◽  
Increased Risk

Introduction: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. Methods: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14–180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, <10 on the Clock Drawing on Command test to indicate executive function impairment, and domain-specific summary scores in the lowest quartile to indicate memory and nonmemory impairment. We used Cox proportional hazards models to estimate the association between poststroke cognitive impairment and subsequent risk of recurrent stroke and death. Results: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04–2.09) and death (hazard ratio, 1.87; 95% CI: 1.25–2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06–2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14–2.67) were associated with an increased risk of death. Discussion/Conclusion: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death.

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