Progressive Cognitive Impairment Research Articles

Early Diagnosing and Transformation Prediction of Alzheimer's Disease Using Multi-Scaled Self-Attention Network on Structural MRI Images with Occlusion Sensitivity Analysis.

Structural magnetic resonance imaging (sMRI) is vital for early Alzheimer's disease (AD) diagnosis, though confirming specific biomarkers remains challenging. Our proposed Multi-Scale Self-Attention Network (MUSAN) enhances classification of cognitively normal (CN) and AD individuals, distinguishing stable (sMCI) from progressive mild cognitive impairment (pMCI). This study leverages AD structural atrophy properties to achieve precise AD classification, combining different scales of brain region features. The ultimate goal is an interpretable algorithm for this method. The MUSAN takes whole-brain sMRI as input, enabling automatic extraction of brain region features and modeling of correlations between different scales of brain regions, and achieves personalized disease interpretation of brain regions. Furthermore, we also employed an occlusion sensitivity algorithm to localize and visualize brain regions sensitive to disease. Our method is applied to ADNI-1, ADNI-2, and ADNI-3, and achieves high performance on the classification of CN from AD with accuracy (0.93), specificity (0.82), sensitivity (0.96), and area under curve (AUC) (0.95), as well as notable performance on the distinguish of sMCI from pMCI with accuracy (0.85), specificity (0.84), sensitivity (0.74), and AUC (0.86). Our sensitivity masking algorithm identified key regions in distinguishing CN from AD: hippocampus, amygdala, and vermis. Moreover, cingulum, pallidum, and inferior frontal gyrus are crucial for sMCI and pMCI discrimination. These discoveries align with existing literature, confirming the dependability of our model in AD research. Our method provides an effective AD diagnostic and conversion prediction method. The occlusion sensitivity algorithm enhances deep learning interpretability, bolstering AD research reliability.

Anti-leucine-rich Glioma-inactivated 1 Protein-antibody Positive Encephalitis with Extensive Unilateral Cerebral Cortex and White Matter Lesions.

Encephalitis caused by antibodies targeting the leucine-rich glioma-inactivated 1 protein receptor, which belongs to the anti-voltage-gated potassium channel receptor complex, is characterized by hyponatremia, progressive cognitive impairment, seizures, and psychiatric disorders. The patient initially presented with faciobrachial dystonic seizures and subsequently developed encephalopathy. Brain magnetic resonance imaging revealed atypical unilateral hyperintense signals in the cerebral cortex and white matter. Intravenous corticosteroid pulse therapy effectively improved faciobrachial dystonic seizures and brain lesions.

Long-term clinical course and treatment outcomes of individuals with Nodding Syndrome

Nodding Syndrome is a poorly understood epilepsy disorder in sub-Saharan Africa. The cause(s) of the disease, risk factors and long-term outcomes are unknown or controversial. The objectives of this study were to describe the long-term clinical course and treatment outcomes of individuals suffering from Nodding Syndrome. In addition, we aimed to provide a comprehensive characterization of the epileptological and social features of patients with Nodding Syndrome.From 11/2014 to 4/2015, we conducted a hospital-based, cross-sectional and observational study in Mahenge, Tanzania. Seventy-eight individuals (female:male ratio: 40:38, age at examination: 21.1 ± 6.39 (SD) years) have been enrolled, of whom 38 (49%) had also been examined in 2005 and in 2009. The 10-year clinical course analysis of this revisited subgroup revealed a calculated case fatality of 0.8–2.3%. Progressive physical or cognitive deterioration has not been observed in any of the 78 individuals and more than half of the people studied (38/69; 55%) managed to live and work independently. 14/78 individuals (18%) were seizure-free, (no head nodding, no other seizure types), 13 of whom were taking antiseizure medication. Phenytoin was more effective against head nodding seizures (14/19 (74%)) than monotherapy with other available antiseizure medication (phenobarbitone 12/25 (48%) and carbamazepine 7/22 (32%), p = 0.02, chi-square test).Our ten-year clinical outcome data show that Nodding Syndrome is not a fatal disease, however, the response to treatment is worse than in epilepsy patients in general. Phenytoin may be more effective than carbamazepine and phenobarbitone, but further studies are needed to confirm this observation.

Orthostatic Hypotension Promotes the Progression From Mild Cognitive Impairment to Dementia in Type 2 Diabetes Mellitus.

In type 2 diabetes mellitus (T2DM), orthostatic hypotension (OH) is associated with cognition, but the mechanisms governing the link between OH and cognition are still unclear. We sought to analyze Alzheimer's disease (AD) biomarkers and the part of complement proteins in modulating the association of OH with cognitive impairment and examine whether OH could accelerate the clinical progression of mild cognitive impairment (MCI) to dementia in T2DM. We recruited patients with T2DM with MCI and collected general healthy information and blood samples. Complement proteins of astrocyte-derived exosomes were isolated and AD biomarkers of neuronal cell-derived exosomes isolated were quantified by enzyme-linked immunosorbent assay. Cognitive assessments were performed at patient enrollment and follow-up. Mediation analysis showed that the influence of OH on cognition in T2DM was partly mediated by baseline AD biomarkers and complement proteins. Cox proportional-hazards regression proved the OH group had a higher risk of developing dementia compared to the T2DM without OH group. In T2DM with MCI patients, AD biomarkers and complement proteins mediate the effects of OH on cognitive impairment and OH may be a risk factor of progression from MCI to dementia in T2DM.

The effect of insomnia on mild cognitive impairment in patients with vascular risks: results of a three-year longitudinal study

To assess the dynamics of sleep parameters based on the analysis of three items of HDRS-17, designed to measure the severity of insomnia, during 36 months of follow-up and their relationship with indicators of the cognitive phenotype in patients with vascular risk factors. The longitudinal study included 51 patients (mean age 57.7±6.2 years, 19 (37.3%) men)) who met the inclusion criteria. All participants underwent a general clinical examination with assessment of vascular risks and neuropsychological testing using the Montreal Cognitive Assessment (MoCA) and HDRS-17 at baseline and after 36 months. During the study, patients received stable basic therapy to prevent modifiable vascular risk factors. Sleeping pills were taken sporadically when there were complaints of problems falling asleep. During the 36-month study, as vascular cognitive impairment progressed from 23.7±2.6 to 22.1±2.4 points on the MoCA scale (p=0.01), mainly due to decreased attention (p=0.01), executive functions (EF) (p=0.01), memory (p=0.02), speech (p=0.02), an increase in sleep disturbances was observed (item 4: 0.8±0.02 to 1.9±0.1 points, p=0.01; point 5: 0.6±0.02 to 1.7±0.1 points, p=0.01) and depression (7.5±0.5 to 13.7±3.0 points, p=0.01) in patients with vascular risks. A strong inverse correlation was revealed between the values of items 4, 5, 6 on the HDRS-17 and the average MoCA-total scores (r=-0.85; r=-0.87; r=-0.8 (p<0.05)), memory index (r=-0.8; r=-0.75; r=-0.81 (p<0.05)), attention index (r=-0.88; r=-0.86; r=-0.83 (p<0.05)), index of executive functions (r=-0.87; r=-0.85; r=-0.8 (p<0.05)), respectively. The progression of cognitive impairment is associated with worsening insomnia disorders and depression in patients with vascular risks.

To Assess Caregiver Burden of Patients with Dementia: Its Sociodemographic and Clinical Correlates

Background and Aim: To assess the primary caregiver burden in the patients of dementia. Dementia is a chronic neurodegenerative disorder that refers to a disease process marked by progressive cognitive impairment in clear consciousness. The morbidities associated with dementia accounts for the poor quality of life. Equally affected are caregivers of these patients. The study aims to assess the caregiver burden (CGB) and how the care of these patients affect them. This further includes sociodemographic and clinical features of the caregivers. Materials and Methods: The cross-sectional study was conducted from June 2021 to May 2022 in the Department of Psychiatry, MGM medical college, Indore (M.P.) after approval from the institutional ethical committee. The study included 60 patients and 60 caregivers attending Psychiatry outpatient department (OPD). They were assessed using a semi-structured proforma consisting of socio-demographic and clinical variables. Clinical rating scale i.e., burden assessment schedule (BAS) was applied for caregivers and dementia severity rating scale (DSRS) for the patients. Pearson's and Spearman's correlation coefficient was applied with P-value &lt; 0.05 considered as significant. Result: The study finds that the mean age of the caregiver is 55.6 ± 10.01 years and that of patient is 69.81± 0.71 years. The mean BAS score is 68.3 ± 11.77. A negative correlation is established between BAS and income of the caregiver and is statistically significant (P &lt; .001), while a positive correlation between BAS and age, number of hospitalization, total duration of illness, and the mean of time spent with the patient during the day and is statistically significant (P &lt; .001). Factors like low income, advancing age, and time spent with the patients in the caregivers had affected the BAS score, and the score was found to be raised. Factors related to the patients affecting the BAS score was total duration of illness and number of hospitalization. Both factors played a key role in the addressed the overall care burden among the caregivers. Conclusion: Factors such as low income, advancing age, and time spent with the patients in the caregivers had affected the BAS score, and the score was found to be raised. Factors related to the patients affecting the BAS score was the total duration of illness and number of hospitalization. Both factors played a key role in the addressed the overall care burden among the caregivers.

The Multifocal Dural Arteriovenous Fistula Presumed to Present as a Progressive Cognitive Impairment.

The Multifocal Dural Arteriovenous Fistula Presumed to Present as a Progressive Cognitive Impairment.

Oral phytate supplementation on the progression of mild cognitive impairment, brain iron deposition and diabetic retinopathy in patients with type 2 diabetes: a concept paper for a randomized double blind placebo controlled trial (the PHYND trial).

Type 2 diabetes mellitus has a worldwide prevalence of 10.5% in the adult population (20-79 years), and by 2045, the prevalence is expected to keep rising to one in eight adults living with diabetes. Mild cognitive impairment has a global prevalence of 19.7% in adults aged 50 years. Both conditions have shown a concerning increase in prevalence rates over the past 10 years, highlighting a growing public health challenge. Future forecasts indicate that the prevalence of dementia (no estimations done for individuals with mild cognitive impairment) is expected to nearly triple by 2050. Type 2 diabetes mellitus is a risk factor for the development of cognitive impairment, and such impairment increase the likelihood of poor glycemic/metabolic control. High phytate intake has been shown to be a protective factor against the development of cognitive impairment in observational studies. Diary phytate intake might reduce the micro- and macrovascular complications of patients with type 2 diabetes mellitus through different mechanisms. We describe the protocol of the first trial (the PHYND trial) that evaluate the effect of daily phytate supplementation over 56 weeks with a two-arm double-blind placebo-controlled study on the progression of mild cognitive impairment, cerebral iron deposition, and retinal involvement in patients with type 2 diabetes mellitus. Our hypothesis proposes that phytate, by inhibiting advanced glycation end product formation and chelating transition metals, will improve cognitive function and attenuate the progression from Mild Cognitive Impairment to dementia in individuals with type 2 diabetes mellitus and mild cognitive impairment. Additionally, we predict that phytate will reduce iron accumulation in the central nervous system, mitigate neurodegenerative changes in both the central nervous system and retina, and induce alterations in biochemical markers associated with neurodegeneration.

Cognitive impairment in cerebrovascular diseases

Cognitive impairment, which is highly prevalent, especially among older people, leads to a decrease in the quality of life of patients, impairment of daily activities, and an increased risk of dementia and mortality. Currently, much attention is paid to mild cognitive impairment. The article discusses diagnostic criteria and possible clinical variants of this syndrome. Given the high rate of progression of mild cognitive impairment to dementia, it is necessary to identify risk groups and carry out therapeutic preventive measures. Correction of potentially modifiable risk factors is considered as a promising direction of therapy. Sufficient physical and mental activity, proper diet, normalization of sleep, visual acuity and hearing are necessary. Preventing stroke and controlling vascular risk factors may reduce the risk of mild cognitive impairment progressing to dementia.

A Novel Mutation of VPS13D-related Disorders with Parkinsonism.

We herein report a case of VPS13D-related disorder with a novel homogeneous variant. A 58-year-old Japanese woman was referred to our hospital with slowly progressive gait disturbance and cognitive impairment. A neurological examination revealed decreased spontaneity, recent memory impairment, Parkinsonism, cerebellar ataxia, pyramidal signs, and autonomic dysfunction. Dopamine transporter single-photon-emission computed tomography showed a markedly reduced uptake in the striatum bilaterally. Whole-exome sequencing revealed a novel homozygous missense variant of the VPS13D gene (Arg3267Pro). Our case suggests that mutations in VPS13D may cause parkinsonism, in addition to the previously reported cerebellar ataxia and spastic paraplegia.

Machine learning and texture features based approach for classifying Alzheimer’s disease

In order to gain more insight into the nature of the disease and fill in numerous gaps in predictions and treatment, the problem of Alzheimer’s disease (AD) has been extensively studied. A lot of research has already been done to assist identify AD patients utilizing structural and textural features. In this work, texture features based machine learning models are proposed for multi-stage classification of Alzheimer’s disease. Multi-stage classification helps in identifying the disease at early stages and will reduce the suffering of the patients and their family members. The patients in this study are divided into four groups: CN (Cognitive Normal), AD (Alzheimer’s Disease), pMCI (Progressive Mild Cognitive Impairment), and sMCI (Static Mild Cognitive Impairment). The dataset is collected from the ADNI database and has about 15000 MRI raw images in ‘NIFTI’ format. In the first step, the data is preprocessed. Images are converted to the ‘jpg’ format after being stripped of their skulls. 8856 images are selected after preprocessing. For Feature Extraction, FOS (First-Order Statistical) and GLCM (Gray-Level Co-occurrence Matrix) features are utilized. Using normalization, the extracted features are scaled between 0 and 1. The normalized features are then used as input by SVM, Random Forest, Artificial Neural Network, and Decision Tree machine learning methods. Input features used for classification include GLCM, FOS features, and a combination of both. The performance is evaluated using accuracy, recall, F1-score, and precision parameters. The suggested method performs best when both GLCM and FOS features are provided as input. The most accurate method is Random Forest, which has a 66.1% accuracy rate. Decision tree, ANN, and SVM also performed well, with accuracies of 56.4, 58.5, and 59.2 respectively. The proposed approach has the potential for multi-stage classification of Alzheimer’s disease.

Latest research in nootropic therapy of patients with chronic cerebral circulation insufficiency.

Aim: To analyze latest research on the usage of choline alfoscerate and ethylmethylhydroxypyridine succinate (EMHPS) as nootropic therapy for patients with chronic cerebral circulation insufficiency (CCCI). Materials and Methods: Bibliosemantic, comparative and system analysis methods were used in the study. The proposed recommendations are developed on the basis of the analysis of modern literature, the results of randomized studies and meta-analyses, authoritative studies devoted to the study of the CCCI problem. Conclusions: The combination of EMHPS with choline alfoscerate for the complex treatment of CCCI and associated syndromes improves the functions of the endothelium, leads to asthenic syndrome, indicators of stress, depression and anxiety decreasing has a positive effect on the cognitive impairment and complications' progress reduction.

Serum Tau-A and Tau-C Levels and Their Association with Cognitive Impairment and Dementia Progression in a Memory Clinic Derived Cohort.

Serum-measured fragments of Tau cleaved by ADAM-10 (Tau-A) and Caspase-3 (Tau-C) have been found linked to change in cognitive function and risk of dementia. 1) To determine the discriminatory abilities of Tau-A, and Tau-C in subjects with either mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or AD dementia compared to a control group. 2) To determine if there is a relation between Tau-A, and Tau-C and established cerebrospinal fluid (CSF) markers of AD- β-Amyloid1-42 (AB42), Phosphorylated-tau-181 (p-tau), and total-tau. 3) To determine if Tau-A and Tau-C are associated with progression rate from MCI due to AD to AD dementia. Cross-sectional and a substudy using a retrospective cohort design. Memory clinic derived subjects contributing to the Danish Dementia Biobank. Cognitively unimpaired subjects (n=49), patients with mild cognitive impairment (MCI) due to AD (n=45), and Alzheimer's dementia (n=52). Competitive enzyme-linked immunosorbent assay (ELISA)-measured serum levels of Tau-A, and Tau-C. The ratio between Tau-A and Tau-C differed between the three groups (p=0.015). Age- and sex-adjusted Tau-A differed between groups with lower ratios being associated with more severe disease (p=0.023). Tau-C was trending towards significant correlation to CSF-levels of AB42 (Pearson correlation coefficient 0.164, p=0.051). Those with Tau-C-levels in the 2nd quartile had a hazard ratio (HR) of 2.91 (95% CI 1.01 - 8.44, p=0.04) of progression compared to those in the 1st quartile. Those in the 3rd quartile was found to have a borderline significant (p=0.055) HR of 2.63 (95% CI 0.98 - 7.05) when compared to those in the lowest quartile. Tau-A and the ratio between Tau-A and Tau-C showed significant differences between groups and were correlated to CSF-AB42. Tau-C values in the middle range were associated with faster progression from MCI to dementia. This pilot study adds to the mounting data suggesting serum-measured Tau-A and Tau-C as biomarkers useful in relation to diagnosis and progression rate in AD but need further validation.

Machine Learning-Based Prediction Models for Cognitive Decline Progression: A Comparative Study in Multilingual Settings Using Speech Analysis.

Mild cognitive impairment (MCI) is a condition commonly associated with dementia. Therefore, early prediction of progression from MCI to dementia is essential for preventing or alleviating cognitive decline. Given that dementia affects cognitive functions like language and speech, detecting disease progression through speech analysis can provide a cost-effective solution for patients and caregivers. In our study, we examined spontaneous speech (SS) and written Mini Mental Status Examination (MMSE) scores from a 60-patient dataset obtained from the Mugla University Dementia Outpatient Clinic (MUDC) and a 153-patient dataset from the Alzheimer's Dementia Recognition through Spontaneous Speech (ADRess) challenge. Our study, for the first time, analyzed the impact of audio features extracted from SS in distinguishing between different degrees of cognitive impairment using both an Indo-European language and a Turkic language, which exhibit distinct word order, agglutination, noun cases, and grammatical markers. When each machine learning model was tested on its respective trained language, we attained a 95% accuracy using the random forest classifier on the ADRess dataset and a 94% accuracy on the MUDC dataset employing the multilayer perceptron (MLP) neural network algorithm. In our second experiment, we evaluated the effectiveness of each language-specific machine learning model on the dataset of the other language. We achieved accuracies of 72% for English and 76% for Turkish, respectively. These findings underscore the cross-language potential of audio features for automated tracking of cognitive impairment progression in MCI patients, offering a convenient and cost-effective option for clinicians or patients.

Mutation of TRPML1 Channel and Pathogenesis of Neurodegeneration in Haimeria.

Neurodegenerative diseases, a group of debilitating disorders, have garnered increasing attention due to their escalating prevalence, particularly among aging populations. Alzheimer's disease (AD) reigns as a prominent exemplar within this category, distinguished by its relentless progression of cognitive impairment and the accumulation of aberrant protein aggregates within the intricate landscape of the brain. While the intricate pathogenesis of neurodegenerative diseases has been the subject of extensive investigation, recent scientific inquiry has unveiled a novel player in this complex scenario-transient receptor potential mucolipin 1 (TRPML1) channels. This comprehensive review embarks on an exploration of the intricate interplay between TRPML1 channels and neurodegenerative diseases, with an explicit spotlight on Alzheimer's disease. It immerses itself in the intricate molecular mechanisms governing TRPML1 channel functionality and elucidates their profound implications for the well-being of neurons. Furthermore, the review ventures into the realm of therapeutic potential, pondering the possibilities and challenges associated with targeting TRPML1 channels as a promising avenue for the amelioration of neurodegenerative disorders. As we traverse this multifaceted terrain of neurodegeneration and the enigmatic role of TRPML1 channels, we embark on a journey that not only broadens our understanding of the intricate machinery governing neuronal health but also holds promise for the development of innovative therapeutic interventions in the relentless battle against neurodegenerative diseases.

Cognitive dysfunction in de novo Parkinson disease: Remitting vs. progressive cognitive impairment

IntroductionParkinson's disease (PD) exhibits divergent cognitive trajectories; however, the factors contributing to these variations remain elusive. This study aimed to examine the clinical features of patients with different long-term cognitive trajectories in de novo PD over a five-year follow-up. MethodsWe analyzed 258 patients who completed every annual evaluation for five years. According to the Montreal Cognitive Assessment (MoCA) scores, we classified patients into three groups: cognitively normal (n = 118, CN), remitting MoCA decline (n = 74, RMD), and progressive MoCA decline (n = 66, PMD). ResultsThe RMD group was associated with lower olfactory scores (Odds Ratio (OR) = 0.958, p = 0.040), whereas PMD was associated with higher depression scores (OR = 1.158, p = 0.045), probable RBD (OR = 3.169, p = 0.002), older age (OR = 1.132, p < 0.001) and lower educational attainment (OR = 0.828, p = 0.004). PMD had higher neurofilament light chain protein values than CN and RMD (p = 0.006, 0.015, respectively). Longitudinally, PMD showed a greater decline in all cognitive scores and hippocampus volumes (p = 0.004). Meanwhile, RMD exhibited intermediate cognitive and volumetric trajectories between CN and PMD and displayed worse score changes in memory tasks than CN. ConclusionsWhile PMD exhibited known risk factors for cognitive impairment, along with worse cognitive performance and hippocampal volume decline, RMD displayed baseline lower olfactory scores and intermediate cognitive and hippocampal volume decline between the two groups. These findings suggest individuals in RMD may still be at risk for cognitive deficits. However, further long-term follow-up data are needed to unravel the determinants and dynamics of cognitive functions.

What have clinical trials taught us about brain health?

The Global Burden of Disease Study projects an almost tripling of dementia cases worldwide in the next 30 years making it important to recognize and understand modifiable risks and preventatives for cognitive impairment. Recent studies suggest that prevention or treatment of cardiovascular risks may be an important strategy to prevent or slow the progression of cognitive impairment. In 2017, the American Heart Association and American Stroke Association introduced metrics for "optimal brain health". These metrics defined brain health in terms of ideal health behaviors and factors.Since then and leading up to 2017, a number of clinical trials have been conducted to investigate the potential of modification of cardiovascular risks on prevention of dementia or cognitive impairment and thus, enhancement of brain health. This discussion is a review of findings from clinical trials focusing on interventions, including antihypertensive agents, glycemic control and lipid-lowering therapies, multidomain approaches, and antithrombotic medications. Notably, the results highlight the promise of intensive blood pressure lowering strategies and multidomain approaches, as evidenced by the FINGER trial. The review also discusses the potential of treatment or prevention of cerebral small vessel disease (cSVD) and the application of Mendelian randomization as a strategy to preserve brain structure and function.

Research and progress of focused ultrasound in the treatment of Alzheimer's disease.

Alzheimer's disease is one of the most common degenerative diseases of the central nervous system, with progressive cognitive and memory impairment and decreased ability of daily life as the cardinal symptoms, influencing the life quality of patients severely. There are currently approximately 46 million people living with Alzheimer's disease worldwide, and the number is expected to triple by 2050, which will pose a huge challenge for healthcare. At present, the Food and Drug Administration of the United States has approved five main drugs for the clinical treatment of Alzheimer's disease, which are cholinesterase inhibitors tacrine, galantamine, capalatine and donepezil, and N-methyl-d-aspartate receptor antagonist memantine, although these drugs have shown good efficacy in clinical trials, the actual clinical effect is less effective due to the existence of blood brain barrier. With the continuous development of ultrasound technology in recent years, focused ultrasound, as a non-invasive treatment technique, may target ultrasound energy to the deep brain for treatment without damaging the surrounding tissue. For the past few years, some studies could use focused ultrasound combined with microvesicles to induce blood brain barrier opening and targeted drug delivery to treat Alzheimer's disease, providing new opportunities for the treatment of Alzheimer's disease. This article reviews the application research and progress of focused ultrasound in the treatment of Alzheimer's disease, in order to provide new directions and ideas for the treatment of Alzheimer's disease.

Intravascular Lymphoma-Associated Stroke: A Systematic Review of Case Studies.

Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL remain underexplored, contributing to diagnostic complexities and a high mortality rate. This study endeavors to elucidate the salient clinical and investigative features of stroke linked to this condition. A systematic review was performed using the PubMed database from the incident to August 2023 including search categories for IVL and stroke. All studies, excluding review articles, were included in this study. There were 58 cases with a confirmed diagnosis of IVL associated with stroke, with a mean age of 62.9 ± 9.6 years (female 50%). Classical lateralizing stroke symptoms were noted in only 69% of cases. Other clinical syndromes included altered sensorium (31%), rapidly progressive cognitive impairment (23%), seizures (22%), and gait disturbances (19%). Common hematological abnormalities included elevated lactate dehydrogenase (LDH, 97%), erythrocyte sedimentation rate (ESR, 79%), C-reactive protein (CRP, 61%), interleukin-2, microglobulins, and cerebrospinal fluid (CSF) protein. CSF flow cytometry was not diagnostic, and cytology was mostly negative. The dynamic pattern for DWI/T2 lesions was predominant and primarily located in the subcortical regions. Diffuse background slowing (64%) was a major finding in the electroencephalogram. Seventy-one percent of cases died (n=45) mostly due to delayed diagnosis. Only 31% were treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone) chemotherapy, among whom 25% died. This study suggests that IVL-associated strokes carry a high mortality rate, largely due to challenges in timely diagnosis and therapy. Unlike classical stroke syndrome, key indicators to aid in early diagnosis include a clinical syndrome of multiple non-lateralizing neurological symptoms, dynamic MRI DWI/T2-lesions primarily located in subcortical regions, elevated serum LDH, ESR, CRP, interleukins, microglobulin, CSF protein, and CSF polymerase chain reaction analysis, apart from tissue examination. Larger studies should be performed to establish diagnostic and predictive scores.

Pemphigus and pemphigoid are associated with Alzheimer’s disease in older adults: evidence from the US Nationwide inpatient sample 2016–2018

BackgroundPemphigus and pemphigoid are rare autoimmune skin disorders caused by autoantibodies against structural proteins and characterized by blistering of the skin and/or mucous membranes. Associations have been noted between skin diseases and Alzheimer’s dementia (AD). Dementia is a neurological disorder of progressive cognitive impairment with increasing incidence among older adults. This study aimed to assess the potential associations between pemphigus, pemphigoid and AD in a large, nationally representative US cohort.MethodsAll data of hospitalized patients aged 60 years or older were extracted from the US Nationwide Inpatient Sample (NIS) database 2016–2018. Patients with a history of head trauma, diagnosis of vascular dementia, history of cerebrovascular disease, or malformation of cerebral vessels were excluded. The study population was divided into those with and without pemphigus (cohort 1) and with and without pemphigoid (cohort 2).ResultsPemphigus was independently associated with a 69% increased risk of AD. Adults ≥80 years old with pemphigus were 72% more likely to develop AD than adults without pemphigus. Women with pemphigus were 78% more likely to develop AD than women without pemphigus. On the other hand, pemphigoid was independently associated with a 39% increased risk for AD and subjects ≥80 years with pemphigoid were 40% more likely to have AD than those without pemphigoid. Females with pemphigoid were 63% more likely to have AD than those without pemphigoid. Moreover, Hispanic older adults with pemphigus were 3-times more likely to have AD than those without pemphigoid.ConclusionsPemphigus and pemphigoid were both independently associated with AD in older adults, especially among females and octogenarians. Further studies addressing the etiology and mechanisms underlying these associations are highly warranted.