Variable course of Unverricht-Lundborg disease

Neurology ◽  
2017 ◽  
Vol 89 (16) ◽  
pp. 1691-1697 ◽  
Author(s):  
Laura Canafoglia ◽  
Edoardo Ferlazzo ◽  
Roberto Michelucci ◽  
Pasquale Striano ◽  
Adriana Magaudda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Time Course ◽  
Proportional Hazards ◽  
Cell Damage ◽  
Age At Onset ◽  
Disease Onset ◽  
Rank Test ◽  
Genetically Determined

Objective:To explore the course of Unverricht-Lundborg disease (EPM1) and identify the risk factors for severity, we investigated the time course of symptoms and prognostic factors already detectable near to disease onset.Methods:We retrospectively evaluated the features of 59 Italian patients carrying the CSTB expansion mutation, and coded the information every 5 years after the disease onset in order to describe the cumulative time-dependent probability of reaching disabling myoclonus, relevant cognitive impairment, and inability to work, and evaluated the influence of early factors using the log-rank test. The risk factors were included in a Cox multivariate proportional hazards regression model.Results:Disabling myoclonus occurred an average of 32 years after disease onset, whereas cognitive impairment occurred a little later. An age at onset of less than 12 years, the severity of myoclonus at the time of first assessment, and seizure persistence more than 10 years after onset affected the timing of disabling myoclonus and cognitive decline. Most patients became unable to work years before the appearance of disabling myoclonus or cognitive decline.Conclusions:A younger age at onset, early severe myoclonus, and seizure persistence are predictors of a more severe outcome. All of these factors may be genetically determined, but the greater hyperexcitability underlying more severe seizures and myoclonus at onset may also play a role by increasing cell damage due to reduced cystatin B activity.

scholarly journals ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1348
Author(s):  
Rammohan V Rao ◽  
Sharanya Kumar ◽  
Julie Gregory ◽  
Christine Coward ◽  
Sho Okada ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Early Stage ◽  
Treatment Strategies ◽  
High Sensitivity ◽  
Rank Test ◽  
Proof Of Concept ◽  
Therapeutic Program

Background: Alzheimer’s disease (AD) is the major cause of age-associated cognitive decline, and in the absence of effective therapeutics is progressive and ultimately fatal, creating a dire need for successful prevention and treatment strategies. We recently reported results of a successful proof-of-concept trial, using a personalized, precision medicine protocol, but whether such an approach is readily scalable is unknown. Objective: In the case of AD, there is not a single therapeutic that exerts anything beyond a marginal, unsustained, symptomatic effect. This suggests that the monotherapeutic approach of drug development for AD may not be an optimal one, at least when used alone. Using a novel, comprehensive, and personalized therapeutic system called ReCODE (reversal of cognitive decline), which proved successful in a small, proof-of-concept trial, we sought to determine whether the program could be scaled to improve cognitive and metabolic function in individuals diagnosed with subjective cognitive impairment, mild cognitive impairment, and early-stage AD. Methods: 255 individuals submitted blood samples, took the Montreal Cognitive Assessment (MoCA) test, and answered intake questions. Individuals who enrolled in the ReCODE program had consultations with clinical practitioners, and explanations of the program were provided. Participants had follow-up visits that included education regarding diet, lifestyle choices, medications, supplements, repeat blood sample analysis, and MoCA testing between 2 and 12 months after participating in the ReCODE program. Pre- and post-treatment measures were compared using the non-parametric Wilcoxon signed rank test. Results and Conclusions: By comparing baseline to follow-up testing, we observed that MoCA scores either significantly improved or stabilized in the entire participant pool—results that were not as successful as those in the proof-of-concept trial, but more successful than anti-amyloid therapies—and other risk factors including blood glucose, high-sensitivity C-reactive protein, HOMA-IR, and vitamin D significantly improved in the participant pool. Our findings provide evidence that a multi-factorial, comprehensive, and personalized therapeutic program designed to mitigate AD risk factors can improve risk factor scores and stabilize or reverse the decline in cognitive function. Since superior results were obtained in the proof-of-concept trial, which was conducted by a small group of highly trained and experienced physicians, it is possible that results from the use of this personalized approach would be enhanced by further training and experience of the practicing physicians. Nonetheless, the current results provide further support indicating the potential of such an approach for the prevention and reversal of cognitive decline.

The Spectrum of Cerebrovascular Disease and Associated Cognitive Decline

2019 ◽  
pp. 574-599
Author(s):  
Victoria J. Williams ◽  
Steven E. Arnold ◽  
David H. Salat
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Structure And Function ◽  
Vascular Risk Factors ◽  
Vascular Health ◽  
Vascular Risk ◽  
And Function

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.

scholarly journals Cognitive Issues in Pediatric Multiple Sclerosis

2021 ◽  
Vol 11 (4) ◽  
pp. 442
Author(s):  
Emilio Portaccio ◽  
Ermelinda De Meo ◽  
Angelo Bellinvia ◽  
Maria Pia Amato
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Pediatric Patients ◽  
Leisure Activities ◽  
Disease Onset ◽  
Cognitive Profiles ◽  
Brain Growth ◽  
Network Activation ◽  
Definition Of

Multiple sclerosis (MS) is one of the leading causes of disability in young adults. The onset of MS during developmental age makes pediatric patients particularly susceptible to cognitive impairment, resulting from both disease-related damage and failure of age-expected brain growth. Despite different test batteries and definitions, cognitive impairment has been consistently reported in approximately one-third of pediatric patients with MS. However, the lack of a uniform definition of cognitive impairment and the adoption of different test batteries have led to divergent results in terms of cognitive domains more frequently affected across the cohorts explored. This heterogeneity has hampered large international collaborative studies. Moreover, research aimed at the identification of risk factors (e.g., demographic, clinical, and radiological features) or protective factors (e.g., cognitive reserve, leisure activities) for cognitive decline is still scanty. Mood disorders, such as depression and anxiety, can be detected in these patients alongside cognitive decline or in isolation, and can negatively affect quality of life scores as well as academic performances. By using MRI, cognitive impairment was attributed to damage to specific brain compartments as well as to abnormal network activation patterns. However, multimodal MRI studies are still needed in order to assess the contribution of each MRI metric to cognitive impairment. Importantly, longitudinal studies have recently demonstrated failure of age-expected brain growth and of white matter (WM) and gray matter (GM) maturation plays a relevant role in determining cognitive dysfunction, in addition to MS-related direct damage. Whether these growth retardations might result in specific cognitive profiles according to the age at disease onset has not been studied, yet. A better characterization of cognitive profiles in pediatric MS patients, as well as the definition of neuroanatomical substrates of cognitive impairment and their longitudinal evolution are needed to develop efficient therapeutic strategies against cognitive impairment in this patient population.

Analyses of Visuospatial and Visuoperceptual Errors as Predictors of Dementia in Parkinson’s Disease Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

2020 ◽  
pp. 1-11
Author(s):  
Iván Galtier ◽  
Antonieta Nieto ◽  
María Mata ◽  
Jesús N. Lorenzo ◽  
José Barroso
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Poor Performance ◽  
Subjective Cognitive Decline ◽  
Independent Risk Factors

ABSTRACT Objective: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Parkinson’s disease (PD) are considered as the risk factors for dementia (PDD). Posterior cortically based functions, such as visuospatial and visuoperceptual (VS-VP) processing, have been described as predictors of PDD. However, no investigations have focused on the qualitative analysis of the Judgment of Line Orientation Test (JLOT) and the Facial Recognition Test (FRT) in PD-SCD and PD-MCI. The aim of this work was to study the VS-VP errors in JLOT and FRT. Moreover, these variables are considered as predictors of PDD. Method: Forty-two PD patients and 19 controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Analyses of errors were conducted following the procedure described by Ska, Poissant, and Joanette (1990). Follow-up assessment was conducted to a mean of 7.5 years after the baseline. Results: PD-MCI patients showed a poor performance in JLOT and FRT total score and made a greater proportion of severe intraquadrant (QO2) and interquadrant errors (IQO). PD-SCD showed a poor performance in FRT and made mild errors in JLOT. PD-MCI and QO2/IQO errors were independent risk factors for PDD during the follow-up. Moreover, the combination of both PD-MCI diagnosis and QO2/IQO errors was associated with a greater risk. Conclusions: PD-MCI patients presented a greater alteration in VS-VP processing observable by the presence of severe misjudgments. PD-SCD patients also showed mild difficulties in VS-SP functions. Finally, QO2/IQO errors in PD-MCI are a useful predictor of PDD, more than PD-MCI diagnosis alone.

Air Pollution Is Associated with Cognitive Deterioration of Alzheimer’s Disease

Gerontology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Feng Cheng Lin ◽  
Chih Yin Chen ◽  
Chung Wei Lin ◽  
Ming Tsang Wu ◽  
Hsuan Yu Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Air Pollution ◽  
Social Engagement ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cognitive Deterioration ◽  
Clinical Dementia Rating ◽  
Severe Stage ◽  
Increased Risk

<b><i>Introduction:</i></b> Dementia is one of the major causes of disability and dependency among older people worldwide. Alz­heimer’s disease (AD), the most common cause of dementia among the elderly, has great impact on the health-care system of developed nations. Several risk factors are suggestive of an increased risk of AD, including APOE-ε4, male, age, diabetes mellitus, hypertension, and low social engagement. However, data on risk factors of AD progression are limited. Air pollution is revealed to be associated with increasing dementia incidence, but the relationship between air pollution and clinical AD cognitive deterioration is unclear. <b><i>Methods:</i></b> We conducted a case-control and city-to-city study to compare the progression of AD patients in different level of air-polluted cities. Clinical data of a total of 704 AD patients were retrospectively collected, 584 residences in Kaohsiung and 120 residences in Pingtung between 2002 and 2018. An annual interview was performed with each patient, and the Clinical Dementia Rating score (0 [normal] to 3 [severe stage]) was used to evaluate their cognitive deterioration. Air pollution data of Kaohsiung and Pingtung city for 2002–2018 were retrieved from Taiwan Environmental Protection Administration. Annual Pollutant Standards Index (PSI) and concentrations of particulate matter (PM<sub>10</sub>), sulfur dioxide (SO<sub>2</sub>), ozone (O<sub>3</sub>), nitrogen dioxide (NO<sub>2</sub>), and carbon monoxide (CO) were obtained. <b><i>Results:</i></b> The PSI was higher in Kaohsiung and compared with Pingtung patients, Kaohsiung patients were exposed to higher average annual concentrations of CO, NO<sub>2</sub>, PM<sub>10</sub>, and SO<sub>2</sub>. AD patients living in Kaohsiung suffered from faster cognitive deterioration in comparison with Pingtung patients (log-rank test: <i>p</i> = 0.016). When using multivariate Cox proportional hazards regression analysis, higher levels of CO, NO<sub>2</sub>, PM<sub>10</sub>, and SO<sub>2</sub> exposure were associated with increased risk of AD cognitive deterioration. Among all these air pollutants, high SO<sub>2</sub> exposure has the greatest impact while O<sub>3</sub> has a neutral effect on AD cognitive deterioration. <b><i>Conclusions:</i></b> Air pollution is an environment-related risk factor that can be controlled and is associated with cognitive deterioration of AD. This finding could contribute to the implementation of public intervention strategies of AD.

Reduced information processing speed as primum movens for cognitive decline in MS

2014 ◽  
Vol 21 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Jeroen Van Schependom ◽  
Marie B D’hooghe ◽  
Krista Cleynhens ◽  
Mieke D’hooge ◽  
Marie-Claire Haelewyck ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Information Processing ◽  
Processing Speed ◽  
Time Course ◽  
Age At Onset ◽  
Memory Task ◽  
Cognitive Domain ◽  
Information Processing Speed ◽  
Survival Curves ◽  
Cross Sectional

Background: Cognitive impairment affects half of the multiple sclerosis (MS) patient population and is an important contributor to patients’ daily activities. Most cognitive impairment studies in MS are, however, cross-sectional or/and focused on the early disease stages. Objective: We aim to assess the time course of decline of different cognitive domains. Methods: We collected neuropsychological data on 514 MS patients to construct Kaplan-Meier survival curves of the tests included in the Neuropsychological Screening Battery for MS (NSBMS) and the Symbol Digit Modalities Test (SDMT). Cox-proportional hazard models were constructed to examine the influence of MS onset type, age at onset, gender, depression and level of education on the time course, expressed as age or disease. Results: Survival curves of tests focusing on information processing speed (IPS) declined significantly faster than tests with less specific demands of IPS. Median age for pathological decline was 56.2 years (95% CI: 54.4–58.2) on the SDMT and 63.9 years (95% CI: 60–66.9) on the CLTR, a memory task. Conclusion: In conclusion, IPS is the cognitive domain not only most widely affected by MS but it is also the first cognitive deficit to emerge in MS.

scholarly journals RPE65-related retinal dystrophy: mutational and phenotypic spectrum in 45 affected patients

2021 ◽  
Author(s):  
R Lopez-Rodriguez ◽  
E Lantero ◽  
F Blanco-Kelly ◽  
A Avila-Fernandez ◽  
I Martin Merida ◽  
...  
Keyword(s):  
Age At Onset ◽  
Disease Onset ◽  
Retinal Dystrophy ◽  
Rank Test ◽  
Ophthalmological Examination ◽  
Symptomatic Disease ◽  
Inherited Retinal Dystrophies ◽  
Kaplan Meier ◽  
Almost All ◽  
First Year Of Life

ABSTRACTBackgroundBiallelic pathogenic RPE65 variants are related to a spectrum of clinically overlapping inherited retinal dystrophies (IRD). Most affected individuals show a severe progression, with 50% of patients legally blind by 20 years of age. A better knowledge of the mutational spectrum and the phenotype-genotype correlation in RPE65-related IRD is needed.MethodsForty-five affected subjects from 27 unrelated families with a clinical diagnosis of RPE65-related IRD were included. Clinical evaluation consisted on self-reported ophthalmological history and objective ophthalmological examination. Patients’ genotype was classified accordingly to variant class (truncating or missense) or to variant location at different protein domains. Main phenotypic outcome was age at onset (AAO) of the symptomatic disease and a Kaplan–Meier analysis of disease symptom event-free survival was performed.ResultsTwenty-nine different RPE65 variants were identified in our cohort, 7 of them novel. Most frequent variants were p.(Ile98Hisfs*26), p.(Pro111Ser) and p.(Gly187Glu) accounting for the 24% of the detected alleles. Patients carrying two missense alleles showed a later disease onset than those with 1 or 2 truncating variants (Log Rank test p<0.05). While the 60% of patients carrying a missense/missense genotype presented symptoms before or at the first year of life, almost all patients with at least 1 truncating allele (91%) had an AAO ≤1 year (p<0.05).ConclusionOur findings suggest an association between the type of the RPE65 carried variant and the AAO. Thus, our results provide useful data on RPE65-associated IRD phenotypes which may help to improve clinical and therapeutic management of these patients.

scholarly journals Selecting the most important self-assessed features for predicting conversion to mild cognitive impairment with random forest and permutation-based methods

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jaime Gómez-Ramírez ◽  
Marina Ávila-Villanueva ◽  
Miguel Ángel Fernández-Blázquez
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Random Forest ◽  
Cognitive Decline ◽  
Social Life ◽  
Healthy Aging ◽  
Personal Information ◽  
Disease Onset ◽  
Subjective Cognitive Decline ◽  
Comorbid Condition

AbstractAlzheimer’s Disease is a complex, multifactorial, and comorbid condition. The asymptomatic behavior in the early stages makes the identification of the disease onset particularly challenging. Mild cognitive impairment (MCI) is an intermediary stage between the expected decline of normal aging and the pathological decline associated with dementia. The identification of risk factors for MCI is thus sorely needed. Self-reported personal information such as age, education, income level, sleep, diet, physical exercise, etc. is called to play a key role not only in the early identification of MCI but also in the design of personalized interventions and the promotion of patients empowerment. In this study, we leverage a large longitudinal study on healthy aging in Spain, to identify the most important self-reported features for future conversion to MCI. Using machine learning (random forest) and permutation-based methods we select the set of most important self-reported variables for MCI conversion which includes among others, subjective cognitive decline, educational level, working experience, social life, and diet. Subjective cognitive decline stands as the most important feature for future conversion to MCI across different feature selection techniques.

scholarly journals Role of nurses in addressing modifiable risk factors for early Alzheimer's disease and mild cognitive impairment

2020 ◽  
Vol 29 (8) ◽  
pp. 460-469 ◽  
Author(s):  
Kevin Hope
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Health Professionals ◽  
Current Evidence ◽  
Modifiable Risk Factors ◽  
Early Alzheimer’S Disease

A multidisciplinary advisory group of health professionals involved in dementia care assessed the current evidence base regarding modifiable risk factors (MRFs) for early Alzheimer's disease and mild cognitive impairment. Based on evidence from the published literature and clinical experience, MRFs in four areas were identified where there is evidence to support interventions that may help delay cognitive decline or reduce the risk of developing Alzheimer's disease: medical (eg cardiovascular risk factors), psychosocial (eg depression, anxiety, social isolation), lifestyle (eg lack of physical activity, smoking) and nutrition (eg poor diet, lack of micronutrients). Practical guidance on how health professionals, but in particular nurses, may actively seek to address these MRFs in clinical practice was also developed. Nurses are at the forefront of patient care and, as such, are ideally placed to offer advice to patients that may proactively help mitigate the risks of cognitive decline and the development of Alzheimer's disease.

scholarly journals Poststroke Cognitive Decline: A Longitudinal Study from a Tertiary Care Center

2019 ◽  
Vol 10 (03) ◽  
pp. 459-464 ◽  
Author(s):  
Rameshwar Nath Chaurasia ◽  
Jitendra Sharma ◽  
Abhishek Pathak ◽  
Vijay Nath Mishra ◽  
Deepika Joshi
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Care Center ◽  
Tertiary Care ◽  
Rank Test ◽  
P Value ◽  
Stroke Patients ◽  
Stroke Registry ◽  
Chi Squared ◽  
The Difference

Abstract Objectives Poststroke cognitive decline (PSCD) is a serious disabling consequence of stroke. The purpose of this study is to find the prevalence of PSCD and sociodemographic and clinical determinants of risk factors of PSCD. Materials and Methods This study was a prospective, hospital-based study conducted on 200 stroke patients from stroke registry during October 2015 to April 2017. Detailed clinical evaluation was done. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were used to determine PSCD after 3 and 6 months as per the Diagnostic and Statistical Manual of Mental Disorders V. Chi-squared test was used to find the association between two variables. The Wilcoxon signed-rank test was used to compare the difference in cognitive impairment between two follow-ups at 3 and 6 months, respectively. A p-value < 0.05 was considered statistically significant. Results The prevalence of PSCD measured by MoCA scale at 3 and 6 months was 67 and 31.6%, respectively. By MMSE scale, cognitive decline prevalence at 3 months was found to be 87 (46.3%), which reduced to 22 (17.1%) at 6 months. The association between MMSE scale and type of stroke was significant at 3 months. Conclusion One-third of the stroke patients developed PSCD within 3 months of onset of stroke, with different levels of severity. The major predictors of new-onset poststroke cognitive impairment were diabetes and hypertension. The prevalence of PSCD reduced significantly at 6 months of stroke on follow-up.

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