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PURPOSE: To examine the link between tremor and sex chromosome abnormalities, emphasizing the necessity of comprehensive physical examination. CASE DESCRIPTION: An 18-year-old man exhibited an isolated action tremor in both hands. Despite having no familial history of tremors and no identifiable secondary causes, his tall stature and learning difficulties suggested a genetic origin. His karyotype confirmed the diagnosis of Jacob's syndrome (XYY syndrome). Therapies with primidone and propranolol were ineffective for his tremor. CONCLUSIONS: Tremor can be caused by various conditions, and aneuploidies might often be overlooked as a cause. They should be considered in young patients with concrete phenotypes and negative familiar history of tremors. Karyotyping is a cost-effective diagnostic tool crucial for genetic counselling. Common treatments for tremors often yield unsatisfactory results in these cases.
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BACKGROUND: The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF. AIM: To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis. METHODS: We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years. RESULTS: Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders. DISCUSSION: According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults. CONCLUSIONS: Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.
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Enfermedad de Alzheimer , Demencia , Anciano , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/etiología , Estudios de Cohortes , Demencia/epidemiología , Demencia/etiología , Estado de Salud , Humanos , Incidencia , Factores de RiesgoRESUMEN
In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer's disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.
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Enfermedad de Alzheimer , Demencia , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Predisposición Genética a la Enfermedad , Humanos , Proteínas Relacionadas con Receptor de LDL/genética , Proteínas de Transporte de Membrana/genética , NeuroimagenRESUMEN
BACKGROUND: Predementia is a heuristic umbrella concept to classify older adults with cognitive impairment who do not suffer dementia. Many diagnostic entities have been proposed to address this concept, but most of them have not had widespread acceptance. AIMS: To review clinical definitions, epidemiologic data (prevalence, incidence) and rate of conversion to dementia of the main predementia constructs, with special interest in the two most frequently used: mild cognitive impairment (MCI) and minor neurocognitive disorder (miNCD). METHODS: We have selected in three databases (MEDLINE, Web of Science and Google scholar) the references from inception to 31 December 2019 of relevant reviews, population and community-based surveys, and clinical series with >500 participants and >3 years follow-up as the best source of evidence. MAIN RESULTS: The history of predementia constructs shows that MCI is the most referred entity. It is widely recognized as a clinical syndrome harbinger of dementia of several etiologies, mainly MCI due to Alzheimer's disease. The operational definition of MCI has shortcomings: vagueness of its requirement of "preserved independence in functional abilities" and others. The recent miNCD construct presents analogous difficulties. Current data indicate that it is a stricter predementia condition, with lower prevalence than MCI, less sensitivity to cognitive decline and, possibly, higher conversion rate to dementia. CONCLUSIONS: MCI is a widely employed research and clinical entity. Preliminary data indicate that the clinical use of miNCD instead of MCI requires more scientific evidence. Both approaches have common limitations that need to be addressed.
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BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of language. Being rare, reports of PPA in multilingual individuals are scarce, despite more than half of the world population being multilingual. METHODS: We describe clinical characteristics of 33 bilingual patients with PPA, including symptom presentation and language deficits pattern in their first (L1) and second language (L2), through a systematic literature review and new cases retrospectively identified in 5 countries. RESULTS: In total, 14 patients presented with nonfluent/agrammatic variant, 6 with semantic variant, and 13 with logopenic variant, with a median symptom onset of 2 years. Word-finding difficulties was the first symptom in 65% of all cases, initially noticed in L2, and not always the dominant language. Our group had 22 different languages as L1, and 9 as L2. At the whole-group level there was a tendency for parallel impairment in both languages, in line with the shared bilingual neural substrate hypothesis, but each PPA variant showed some heterogeneity. DISCUSSION: Each PPA variant showed heterogeneity, showing the need for comprehensive language and cognitive assessment across languages, as well as further clarification on the role of language mediators.
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Afasia Progresiva Primaria/diagnóstico , Lenguaje , Multilingüismo , Anciano , Afasia Progresiva Primaria/clasificación , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: To assess the diagnostic agreement of cognitive status (dementia, mild cognitive impairment (MCI), normal cognition) among neurologists in the field of neurological disorders in Central Spain 2 study. METHODS: Full medical histories of 30 individuals were provided to 27 neurologists: 9 seniors, 10 juniors and 8 residents. For each case, we were asked to assign a diagnosis of dementia, MCI or normal cognition using the National Institute on Aging-Alzheimer's Association workgroup (NIA-AA) core clinical criteria for all-cause dementia, Winblad et al. criteria for MCI, and analyze intensity and etiology if dementia was diagnosed. Inter-rater agreement was assessed both with percent concordance and non-weighted κ statistics. RESULTS: Overall inter-rater agreement on cognitive status was κ = 0.76 (95% CI 0.65-0.86), being slightly higher among junior neurologists (κ = 0.85, 95% CI 0.73-0.95) than among seniors (κ = 0.71, 95% CI 0.59-0.83) and residents (κ = 0.69, 95% CI 0.54-0.81) but without statistical significance among groups. Dementia severity showed an overall κ of 0.34, 0.44 and 0.64 for mild, moderate and severe dementia respectively. CONCLUSIONS: Substantial agreement was demonstrated for the diagnosis of cognitive status (dementia, MCI and normal cognition) among neurologists of different levels of experience in a population-based epidemiological study using NIA-AA and Winblad et al. CRITERIA: The agreement rate was lower in the diagnosis of dementia severity.
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Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Variaciones Dependientes del Observador , Humanos , Neurólogos , Reproducibilidad de los Resultados , EspañaRESUMEN
The aim of this study was to analyze whether physical activity (PA) is a protective factor for the incidence of dementia after 3 years of follow-up. The Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of older adults (age 65 years and older) that comprised 5278 census-based participants at baseline (1994-1995). A broad questionnaire was used to assess participants' sociodemographic characteristics, health status, and lifestyle. Subsequently, a modified version of Rosow-Breslau questionnaire was applied to classify individuals' baseline PA into groups (i.e., sedentary, light, moderate, and high). Cox regression models adjusted for several covariates (age, sex, education, previous stroke, alcohol consumption, hypertension, health related variables) were carried out to estimate the association between the PA groups and risk of dementia at the 3-year follow-up (1997-1998). A total of 134 incident dementia cases were identified among 3105 individuals (56.6% female; mean age=73.15 ± 6.26) after 3 years. Hazard ratios (HRs) of the light, moderate, and high PA groups (vs. sedentary group) were 0.40 (95% confidence interval {CI} [0.26, 0.62]; p<.001), 0.32 (95% CI [0.20, 0.54]; p<.001) and 0.23 (95% CI [0.13, 0.40]; p<.001), respectively. Even after controlling for covariates and the exclusion of doubtful dementia cases, HRs remained significant. However, a supplementary analysis showed that the dose-effect hypothesis did not reach statistical significance. PA is a protective factor of incident dementia in this population-based cohort.
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Actividades Cotidianas , Demencia/prevención & control , Actividad Motora/fisiología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Planificación en Salud Comunitaria , Femenino , Humanos , Masculino , Examen Neurológico , Pruebas Neuropsicológicas , Modelos de Riesgos Proporcionales , Escalas de Valoración PsiquiátricaRESUMEN
Alzheimer's disease (AD), the most common cause of dementia, is a complex and multifactorial condition without cure at present. The latest treatments, based on anti-amyloid monoclonal antibodies, have only a modest effect in reducing the progression of cognitive decline in AD, whereas the possibility of preventing AD has become a crucial area of research. In fact, recent studies have observed a decrease in dementia incidence in developed regions such as the US and Europe. However, these trends have not been mirrored in non-Western countries (Japan or China), and the contributing factors of this reduction remain unclear. The Lancet Commission has delineated a constrained classification of 12 risk factors across different life stages. Nevertheless, the scientific literature has pointed to over 200 factors-including sociodemographic, medical, psychological, and sociocultural conditions-related to the development of dementia/AD. This narrative review aims to synthesize the risk/protective factors of dementia/AD. Essentially, we found that risk/protective factors vary between individuals and populations, complicating the creation of a unified prevention strategy. Moreover, dementia/AD explanatory mechanisms involve a diverse array of genetic and environmental factors that interact from the early stages of life. In the future, studies across different population-based cohorts are essential to validate risk/protective factors of dementia. This evidence would help develop public health policies to decrease the incidence of dementia.
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OBJECTIVE: To study the correlation between a static PET image of the first-minute-frame (FMF) acquired with 18F-labeled amyloid-binding radiotracers and brain [18F]FDG PET in patients with primary progressive aphasia (PPA). MATERIAL AND METHODS: The study cohort includes 17 patients diagnosed with PPA with the following distribution: 9 nonfluent variant PPA, 4 logopenic variant PPA, 1 semantic variant PPA, 3 unclassifiable PPA. Regional SUVRs are extracted from FMFs and their corresponding [18F]FDG PET images and Pearson's correlation coefficients are calculated. RESULTS: SUVRs of both images show similar patterns of regional cerebral alterations. Intrapatient correlation analyses result in a mean coefficient of r=0.94±0.06. Regional interpatient correlation coefficients of the study cohort are greater than 0.81. Radiotracer-specific and variant-specific subcohorts show no difference in the similarity between the images. CONCLUSIONS: The static FMF could be a valid alternative to dynamic early-phase amyloid PET proposed in the literature, and a neurodegeneration biomarker for the diagnosis and classification of PPA in amyloid PET studies.
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Afasia Progresiva Primaria , Fluorodesoxiglucosa F18 , Humanos , Afasia Progresiva Primaria/diagnóstico por imagen , Encéfalo/metabolismo , Tomografía de Emisión de Positrones , AmiloideRESUMEN
PURPOSE: To assess the feasibility and effects on manual dexterity and the quality of life (QoL) of a 12-week home calligraphic training program in patients with Parkinson's disease (PD). METHODS: A pilot study with participants recruited from the Movement Disorders consultation at the Hospital 12 de Octubre (Madrid). The main outcome, manual dexterity, was assessed using the Purdue Pegboard Test (PPT). Secondary outcomes included clinical rating scales that contemplate aspects related to manual dexterity (DextQ-24, UPDRSII, UPDRSIII), and QoL (PDQ-39 and EuroQoL-5D). RESULTS: Thirty PD patients (57% males) with a mean age of 66.11 (9.76) years and 93% adherence rate. The PPT scores improved significantly (p < 0.0001) from T0 (start of the study) to T1 (after 24 weeks). No statistically significant change was found in DextQ-24, UPDRS-II and UPDRS-III, but a clear improvement was observed in the QoL measurement: EuroQoL-5D (p < 0.0001), PDQ-39 (p < 0.0001) and modified PDQ-39 (p = 0.022). CONCLUSIONS: This is the first study to demonstrate the feasibility and improvement in hand dexterity assessed by the PPT for patients diagnosed with PD after a 12-week home calligraphic training program. A significant improvement was noted in the QoL measurements, such as the PDQ-39, modified PDQ-39, and EuroQoL-5D.Implications for RehabilitationMost patients with Parkinson's disease suffer from impaired manual dexterity, making it difficult to perform activities of daily living such as eating, buttoning, or shaving.A 12-week home calligraphic training program could improve hand dexterity in these patients.The advantage of this home calligraphic trainingis is that it is an easy-to-perform, low-cost and no side effects.This training also improves their quality of life.
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BACKGROUND: A protective effect of education on cognitive decline after stroke has been claimed, but evidence from prospective population-based cohorts is very limited. The differential role of literacy and education on dementia after stroke remains unexplored. OBJECTIVE: This research addresses the role of education and literacy in dementia incidence after stroke and transient ischemic attack (TIA). METHODS: 131 participants with stroke or TIA were identified within the population-based NEDICES study (Nâ=â5,278 persons). Participants were fully assessed at baseline (1994-1995) and incident dementia diagnosis was made by expert neurologists (DSM-IV criteria) after a mean follow-up of 3.4 years. Adjusted Cox regression analyses were applied to test the association between education, literacy, and dementia risk. RESULTS: Within the 131 subjects with stroke or TIA, 19 (14%) developed dementia at follow-up. The Cox's regression model (age and sex adjusted) showed that low education (HRâ=â3.48, 95% CIâ=â1.28, 9.42, pâ=â0.014) and literacy (HRâ=â3.16, 95% CIâ=â1.08, 9.22, pâ=â0.035) were significantly associated with a higher dementia risk. Low education was also associated with dementia when main confounders (i.e., cognitive/functional performance) were considered in the Cox's model. However, after including stroke recurrence, only low/null literacy (versus education) remained as significant predictor of dementia. Finally, low/null literacy showed an effect over-and-above education on dementia risk when both factors were introduced in the adjusted Cox's regression. CONCLUSION: These findings underline the importance of literacy to estimate cognitive decline after stroke in low-educated populations.
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Demencia , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Demencia/diagnóstico , Demencia/epidemiología , Demencia/etiología , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/epidemiología , Alfabetización , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/complicacionesRESUMEN
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive vascular disorder caused by biallellic variants in HTRA1. Recently, it has been reported that several heterozygous mutations in HTRA1 are responsible for a milder late-onset cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. The majority of them are missense that affects the Htr1A protease activity due to a dominant-negative effect caused by defective trimerization or monomer activation. The molecular mechanism related to the structural destabilization of the protein supports the practical utility of integrating computational stability predictors to prioritize candidate variants in this gene. In this work, we report a family with several members diagnosed with subcortical ischemic events and progressive cognitive impairment caused by the novel c.820C > G, p.(Arg274Gly) heterozygous variant in HTRA1 segregating in an autosomal dominant manner and propose its molecular mechanism by a three-dimensional model of the protein's structure.
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Enfermedades de los Pequeños Vasos Cerebrales , Trastornos Cerebrovasculares , Leucoencefalopatías , Enfermedades de los Pequeños Vasos Cerebrales/genética , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Serina Peptidasa A1 que Requiere Temperaturas Altas/metabolismo , Humanos , Leucoencefalopatías/genética , Mutación , Estabilidad Proteica , Serina Endopeptidasas/genéticaRESUMEN
To investigate whether physical activity (PA) is a protective factor for the incidence of Parkinson's disease (PD) and parkinsonism after three years of follow-up. All participants of this study were obtained from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort survey of older subjects (≥65 years) that comprised 5278 census-based participants at baseline (1994-1995). A modified version of Rosow-Breslau questionnaire was applied to categorize PA into active versus sedentary group. The final diagnosis of PD and parkinsonism was made by an expert neurologist. Cox regression models (CRM) adjusted for several covariates (sex, age, education, alcohol consumption, tobacco, stroke, hypertension and body mass index) were used to calculate the association between PA (active group vs. sedentary) and risk of PD and parkinsonism after three years. 22 incident PD and 25 incident parkinsonism cases were identified among 2943 participants with available PA information (57.1% female; mean age = 73.28 ± 6.24 years) after three years of follow-up. The CRM showed that the active group (vs. sedentary) showed a lower risk of parkinsonism (Hazard ratio (HR) = 0.18; 95% CI [0.07-0.51]; p = 0.0001). However, this effect was restricted to men (HR = 0.34; 95% CI [0.11-0.99], p < 0.05) for incident PD. PA may be a protective factor for incident parkinsonism, whereas this effect was only significant for men in the case of PD. The mechanisms implicated for brain maintenance in active individuals and the neurophysiological differences behind the role of sex on PD are discussed.
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Milk and dairy (M&D) is a longstanding human food with widespread use. Many studies showed the preventive capacity of M&D in several human health disorders, but its utility in others is under discussion. Aging has been associated to elderly cognitive decline including dementia-Alzheimer syndrome (Dem-AD). The absence of a therapy to impede or postpone Dem-AD determines the need for its prevention, including nutritional factors. To evaluate the preventive capacity of M&D consumption in elderly Dem-AD we performed a systematic review in the main biomedical databases and information resources, but we present this study as a narrative review to discuss better the complexity of this subject. The elderly Dem-AD has a long pre-symptomatic period and the M&D intake has a widespread use. These determinants and the quality flaws of published studies impeach us to answer whether M&D consumption is preventive for Dem-AD. Moreover, two long Japanese cohorts suggest that M&D intake could prevent Dem-AD. Prospective cohorts beginning in midlife (or early life) could answer this question in the future.
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Enfermedad de Alzheimer , Cognición , Productos Lácteos , Demencia , Dieta , Leche , Anciano , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/prevención & control , Animales , Cognición/fisiología , Estudios de Cohortes , Productos Lácteos/estadística & datos numéricos , Demencia/prevención & control , Dieta/estadística & datos numéricos , Humanos , Leche/estadística & datos numéricosRESUMEN
The haploinsufficiency of the methyl-binding domain protein 5 (MBD5) gene has been identified as the determinant cause of the neuropsychiatric disorders grouped under the name MBD5-neurodevelopment disorders (MAND). MAND includes patients with intellectual disability, behavioral problems, and seizures with a static clinical course. However, a few reports have suggested regression. We describe a non-intellectually disabled female, with previous epilepsy and personality disorder, who developed early-onset dementia. The extensive etiologic study revealed a heterozygous nonsense de novo pathogenic variant in the MBD5 gene. This finding could support including the MBD5 gene in the study of patients with atypical early-onset dementia.
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Codón sin Sentido , Proteínas de Unión al ADN/genética , Demencia , Mutación/genética , Demencia/etiología , Demencia/genética , Epilepsia/complicaciones , Femenino , Heterocigoto , Humanos , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Trastornos de la Personalidad/complicaciones , Fenotipo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Problema de Conducta/psicologíaRESUMEN
Objective:SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. (Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (bvFTD). We review the literature on frontotemporal dementia (FTD) associated with SQSTM1. Methods: The index case and relatives were described, and a genetic study through Whole Exome Sequencing was performed. The literature was reviewed using Medline and Web of Science. Case reports, case series, and cohort studies were included if they provided information on SQSTM1 mutations associated with FTD. Results: Our patient is a 70-year-old man with a personality disorder since youth, familial history of dementia, and personality disorders with a 10-year history of cognitive decline and behavioral disturbances. A diagnosis of probable bvFTD was established, and the in-frame duplication c.436_462dup in the SQSTM1 gene was identified. Segregation analysis in the family confirmed that both affected sons with personality disorder were heterozygous carriers, but not his healthy 65-year-old brother. A total of 14 publications about 57 patients with SQSTM1-related FTD were reviewed, in which the bvFTD subtype was the main phenotype described (66.6%), with a predominance in men (63%) and positive family history in 61.4% of the cases. Conclusions: We describe a heterozygous in-frame duplication c.436_462dup p.(Pro146_Cys154dup) in the SQSTM1 gene, which affects the zinc-finger domain of p62, in a family with a personality disorder and bvFTD, expanding the genetics and clinical phenotype related to SQSTM1.
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Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Degeneración Lobar Frontotemporal , Adolescente , Anciano , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/genética , Humanos , Masculino , Trastornos de la Personalidad/genética , Proteína Sequestosoma-1/genéticaRESUMEN
PURPOSE OF REVIEW: To provide an updated analysis of the possible use of non-steroidal anti-inflammatory drugs (NSAIDs) as treatments for Alzheimer´s disease (AD). RECENT FINDINGS: Neuroinflammation in AD is an active field of research, with increasing evidence from basic and clinical studies for an involvement of innate or adaptive immune responses in the pathophysiology of AD. Few clinical trials with anti-inflammatory drugs have been performed in the last decade, with negative results. SUMMARY: Besides the information gathered from basic research, epidemiological studies have provided conflicting findings, with most case-control or prevalence studies suggesting an inverse relationship between NSAIDs use and AD, but divided results in prospective population-based incident cohort studies. Clinical trials with different NSAIDs are almost unanimous in reporting an absence of clear benefit in AD. CONCLUSION: The modulation of inflammatory responses is a promising therapeutic strategy in AD. After three decades of research, it seems that conventional NSAIDs are not the best pharmacological option, both for their lack of clear effects and for an unfavorable side-effect profile in long-term treatment. The development of other anti-inflammatory drugs as candidate treatments in AD may benefit from the knowledge acquired with NSAIDs.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Antiinflamatorios no Esteroideos/farmacología , Inflamación/tratamiento farmacológico , Enfermedad de Alzheimer/inmunología , Encéfalo/efectos de los fármacos , Ensayos Clínicos como Asunto , HumanosRESUMEN
The original version of this article unfortunately contained some mistakes.
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We analyzed the frequency of cognitive impairment (CI) in deceased COVID-19 patients at a tertiary hospital in Spain. Among the 477 adult cases who died after admission from March 1 to March 31, 2020, 281 had confirmed COVID-19. CI (21.1% dementia and 8.9% mild cognitive impairment) was a common comorbidity. Subjects with CI were older, tended to live in nursing homes, had shorter time from symptom onset to death, and were rarely admitted to the ICU, receiving palliative care more often. CI is a frequent comorbidity in deceased COVID-19 subjects and is associated with differences in care.
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COVID-19/psicología , Disfunción Cognitiva/psicología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/mortalidad , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Comorbilidad , Femenino , Mortalidad Hospitalaria , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Admisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , España/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. METHODS: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-ß (Aß) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. FINDINGS: The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0â¢95 (0â¢911-0â¢992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0â¢97 (0â¢924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0â¢93 (0â¢876-0â¢989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. INTERPRETATION: Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker. FUNDING: Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01) to E.C.; Spanish Ministry of Economy and Competitiveness (SAF2017-85310-R) to J.L.C., and (PSI2017-85311-P) to M.A.; International Centre on ageing CENIE-POCTEP (0348_CIE_6_E) to M.A.; Instituto de Salud Carlos III (PIE16/00021, PI17/01799), to H.B.