Neurologic Associations With Cardiac, Pulmonary, Renal, Hepatobiliary, and Hematologic Disease

The brain has a higher demand for cardiac output than any other organ, and it strictly relies on oxygen and glucose metabolism. Consequently, the brain is exquisitely sensitive to homeostatic disturbances and extraneural organ dysfunction leading to cardiac, pulmonary, renal, hepatobiliary, and hematologic diseases. The primary neurologic manifestation of extraneural organic dysfunction is diffuse bihemispheric dysfunction or encephalopathy, which often lacks lateralizing or localizing signs. Common clinical findings are lethargy, difficulty with attention and orientation, sleep-wake disturbance, and psychomotor slowing. As organic dysfunction progresses, a moderate encephalopathy ensues, with worsening cognitive function, gross disorientation, hypoactive or hyperactive psychomotor state, frontal release signs, asterixis, and myoclonus. If organ failure (eg, hepatic or renal) progresses further, stupor and coma may result unless organ function improves. Patients with underlying organic brain disease from degenerative dementia can decompensate out of proportion to neurologically normal counterparts, resulting in encephalopathy even from minor organ dysfunction or infection.

Analysis of Genotype-Phenotype Correlations in Patients With Degenerative Dementia Through the Whole Exome Sequencing

Background: Sporadic dementias generally occur in older age and are highly polygenic, which indicates some patients transmitted in a poly-genes hereditary fashion.Objective: Our study aimed to analyze the correlations of genetic features with clinical symptoms in patients with degenerative dementia.Methods: We recruited a group of 84 dementia patients and conducted the whole exome sequencing (WES). The data were analyzed focusing on 153 dementia-related causing and susceptible genes.Results: According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, we identified four reported pathogenic variants, namely, PSEN1 c.A344G, APP c.G2149A, MAPT c.G1165A, and MAPT c.G742A, one reported likely pathogenic variant, namely, PSEN2 c.G100A, one novel pathogenic variants, SQSTM1 c.C671A, and three novel likely pathogenic variants, namely, ABCA7 c.C4690T, ATP13A2 c.3135delC, and NOS3 c.2897-2A > G. 21 variants with uncertain significance in PSEN2, C9orf72, NOTCH3, ABCA7, ERBB4, GRN, MPO, SETX, SORL1, NEFH, ADCM10, and SORL1, etc., were also detected in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD).Conclusion: The new variants in dementia-related genes indicated heterogeneity in pathogenesis and phenotype of degenerative dementia. WES could serve as an efficient diagnostic tool for detecting intractable dementia.

551 - Case Report: De Archambault’s syndrome in the early stage of dementia with Lewy bodies

Background:Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia after Alzheimer’s disease. In some patients with DLB, relatively rare delusions are known to emerge, such as Othello syndrome, delusional parasitosis and delusion of duplication. Erotomania, also known as de Clerambault’s syndrome, is characterized by the delusion that a person has fallen in love with the patient. It occasionally appears secondary to psychiatric disorders and organic brain diseases. However, there have been no reports on cases secondary to patients with DLB.Case presentation:The patient was an 83-year-old woman who lived alone. Mild cognitive impairment appeared at the age of 82 years. Soon after, she had the delusional conviction that her family doctor was in love with her. Her symptoms, such as gradually progressive cognitive impairment, cognitive fluctuations, and parkinsonism, indicated DLB. Although small doses of quetiapine, brexpiprazole and risperidone were prescribed for the treatment of the delusion, each of them was discontinued soon because of the adverse reactions. Finally, the delusion was successfully treated with a small dose of blonanserin without sever side effects.Discussions and Conclusions:This case report suggests the possibility of de Clerambault’s syndrome during the early stages of DLB. Recently, psychiatric-onset DLB has increasingly gained attention in recent years. Further accumulation of knowledge about delusions in patients with DLB for an early diagnosis.

Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.

Role of Autoantibodies in Neurodegenerative Dementia: An Emerging Association

<b><i>Objective:</i></b> In the background of an emerging role for immune dysregulation in neurodegenerative dementias, this study aimed to investigate the relationship between systemic autoimmunity and dementia. The objective was to study the frequency and profile of disease-specific autoantibodies in Alzheimer’s dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). <b><i>Methods:</i></b> Immunological testing was performed in a large cohort of neurodegenerative dementia diagnosed based on standard clinical and imaging criteria. Patients were evaluated for the presence of autoantibodies specific for systemic autoimmune diseases that included anti-extractable nuclear antibody profile, rheumatoid factor antibody (RA), perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), and cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) in serum. <b><i>Results:</i></b> Of 174 patients with degenerative dementia (FTD = 114, AD = 53, and DLB = 7) evaluated with immunological testing, 18.9% (<i>n</i> = 33) were seropositive for autoantibodies. The common antibodies detected were anti-Scl-70 (25%), anti-Ro-52 (18.7%), anti-nRNP-Sm (12.5%), and anti-CENP-B (9.3%). There were no significant systemic complaints in the majority of patients. A wider range of antibodies were positive in FTD compared to AD and DLB. While no difference was observed in the mean age, sex, or duration of illness between seropositive and negative patients, family history of dementia was more frequent among seronegative patients. <b><i>Conclusion:</i></b> Our findings indicate an emerging role for immune dysregulation in patients with classical neurodegenerative dementias, especially those with FTD. These autoantibodies could play a role in immune degradation of protein aggregates that characterize neurodegeneration. Study findings emphasize the need to explore the complex relationship between systemic autoimmunity and neurodegenerative dementia.

Anosognosia in dementia with Lewy bodies: a systematic review

ABSTRACT Background: Anosognosia, i.e. lack of awareness of one’s own symptoms, is a very common finding in patients with dementia and is related to neuropsychiatric symptoms and worse prognosis. Although dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia, literature on anosognosia in this disease is scarce. Objectives: This paper aimed to review the current evidence on anosognosia in patients with DLB, including its prevalence in comparison with other neurological conditions, its severity and anatomical correlations. Methods: Database searches were performed in PubMed, Web of Knowledge and PsycINFO for articles assessing anosognosia in DLB. A total of 243 studies were retrieved, but only six were included in the review. Results: Potential risk of selection, comparison or outcome biases were detected in relation to all the studies selected. Most of the studies used self-report memory questionnaires to assess cognitive complaints and compared their results to scores from informant-based instruments or to participants’ cognitive performance in neuropsychological tasks. Subjects with DLB had worse awareness regarding memory than healthy older controls, but the results concerning differences in anosognosia between DLB and Alzheimer’s disease (AD) patients were inconsistent across studies. Presence of AD pathology and neuroimaging biomarkers appeared to increase the prevalence of anosognosia in individuals with DLB. Conclusion: Anosognosia is a common manifestation of DLB, but it is not clear how its prevalence and severity compare with AD. Co-existence of AD pathology seems to play a role in memory deficit awareness in DLB.

Relationship Between Chronic Noise Exposure, Cognitive Impairment, and Degenerative Dementia: Update on the Experimental and Epidemiological Evidence and Prospects for Further Research

Degenerative dementia, of which Alzheimer’s disease is the most common form, is characterized by the gradual deterioration of cognitive function. The events that trigger and promote degenerative dementia are not clear, and treatment options are limited. Experimental and epidemiological studies have revealed chronic noise exposure (CNE) as a potential risk factor for cognitive impairment and degenerative dementia. Experimental studies have indicated that long-term exposure to noise might accelerate cognitive dysfunction, amyloid-β deposition, and tau hyperphosphorylation in different brain regions such as the hippocampus and cortex. Epidemiological studies are increasingly examining the possible association between external noise exposure and dementia. In this review, we sought to construct a comprehensive summary of the relationship between CNE, cognitive dysfunction, and degenerative dementia. We also present the limitations of existing evidence as a guide regarding important prospects for future research.

Hyperhomocysteinemia and Dementia Associated With Severe Cortical Atrophy, but No Amyloid Burden

We report a case of a 77 years old patient who was admitted to our memory clinic because of progressive gait impairment and amnestic cognitive decline associated with extrapyramidal symptoms and behavioral changes. The clinical picture was consistent with a possible diagnosis of Alzheimer’s Disease associated with parkinsonian symptoms or with a Parkinson Plus syndrome. After a complete investigation, she was found to have a high plasma level of homocysteine due to homozygous methylene-tetrahydrofolate reductase (MTHFR) gene C665 T polymorphism, cognitive and motor impairment were associated with a severe cortical atrophy and mild subcortical vascular disease. PET neuroimaging excluded a significant amyloid load. Clinically, she showed improvement of the movement disorder and functional status after folate integration plus levodopa and memantine administration. We concluded for a primary degenerative dementia with movement impairment associated with persistent hyperhomocysteinemia. We hypothesized that neurodegeneration is driven by mechanisms linked to homocysteine metabolism possibly associated with tauopathy.

Hospitalization and Socio-Health Care for Dementia in Spain

Dementias are brain diseases that affect long-term cognitive and behavioral functions and cause a decrease in the ability to think and remember that is severe enough to disturb daily functioning. In Spain, the number of people suffering from dementia is rising due to population ageing. Reducing admissions, many of them avoidable, would be advantageous for patients and care-providers. Understanding the correlation of admission of people with dementia and its trends in hospitalization would help us to understand the factors leading to admission. We conducted a cross-sectional study of the hospital discharge database of Castilla y León from 2005 to 2015, selecting hospitalizations for dementia. Trends in hospitalizations by year and age quartiles were studied by joinpoint regression analysis. 2807 out of 2,717,192 total hospitalizations (0.10%) were due to dementias; the main groups were degenerative dementia (1907) followed by vascular dementia (607). Dementias are not a major cause of hospitalization, but the average stay and cost are high, and many of them seem avoidable. Decreasing trends were detected in hospitalization rates for all dementias except for the group of mild cognitive impairment, which grew. An increasing–decreasing joinpoint detected in 2007 for vascular dementia and the general downward hospitalization trends for most dementias suggest that socio-health measures established since 2007 in Spain might play a key role in reducing hospitalizations.