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1.
Mol Psychiatry ; 29(4): 992-1004, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38216727

RESUMEN

Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aß42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM; n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological Aß when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic clearance, other markers might rather reflect proinflammatory states that have detrimental impact on brain integrity.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Encéfalo , Cognición , Disfunción Cognitiva , Inflamación , Imagen por Resonancia Magnética , Sustancia Blanca , Proteínas tau , Humanos , Masculino , Femenino , Biomarcadores/líquido cefalorraquídeo , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/patología , Persona de Mediana Edad , Encéfalo/patología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Cognición/fisiología , Inflamación/líquido cefalorraquídeo , Imagen por Resonancia Magnética/métodos , Disfunción Cognitiva/líquido cefalorraquídeo , Sustancia Blanca/patología , Proteínas tau/líquido cefalorraquídeo , Estudios Longitudinales , Sustancia Gris/patología , Estudios de Cohortes
2.
Brain ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743817

RESUMEN

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants' whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aß-positive and Aß-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

3.
Curr Issues Mol Biol ; 46(1): 934-947, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38275674

RESUMEN

The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline were included. Among them, 62 individuals developed aMCI/AD at follow up. Genetic propensity to WMH was estimated using a polygenic risk score for WMHs (PRS WMH). The association of PRS WMH with aMCI/AD incidence was examined using COX models. A higher PRS WMH was associated with a 47.2% higher aMCI/AD incidence (p = 0.015) in the fully adjusted model. Subgroup analyses showed significant results in the older age group, in which individuals with a higher genetic predisposition for WMHs had a 3.4-fold higher risk for developing aMCI/AD at follow up (p < 0.001), as well as in the lower cognitive reserve (CR, proxied by education years) group, in which individuals with a higher genetic predisposition for WMHs had an over 2-fold higher risk (p = 0.013). Genetic predisposition for WMHs was associated with aMCI/AD incidence, particularly in the group of participants with a low CR. Thus, CR might be a modifier in the relationship between genetic predisposition for WMHs and incident aMCI/AD.

4.
Anal Bioanal Chem ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160437

RESUMEN

Queuosine (Q) is a hypermodified 7-deaza-guanosine nucleoside exclusively synthesized by bacteria. This micronutrient and its respective nucleobase form queuine (q) are salvaged by humans either from gut microflora or digested food. Depletion of Q-tRNA in human or mouse cells causes protein misfolding that triggers endoplasmic reticular stress and the activation of the unfolded protein responses. In vivo, this reduces the neuronal architecture of the mouse brain affecting learning and memory. Herein, a sensitive method for quantifying free q and Q in human blood was developed, optimised and validated. After evaluating q/Q extraction efficiency in several different solid-phase sorbents, Bond Elut PBA (phenylboronic acid) cartridges were found to have the highest extraction recovery for q (82%) and Q (71%) from pooled human plasma. PBS with 4% BSA was used as surrogate matrix for method development and validation. An LC-MS/MS method was validated across the concentration range of 0.0003-1 µM for both q and Q, showing excellent linearity (r2 = 0.997 (q) and r2 = 0.998 (Q)), limit of quantification (0.0003 µM), accuracy (100.39-125.71%) and precision (CV% < 15.68%). In a sampling of healthy volunteers (n = 44), there was no significant difference in q levels between male (n = 14; mean = 0.0068 µM) and female (n = 30; mean = 0.0080 µM) participants (p = 0.50). Q was not detected in human plasma. This validated method can now be used to further substantiate the role of q/Q in nutrition, physiology and pathology.

5.
Alzheimers Dement ; 20(6): 4345-4350, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38647197

RESUMEN

INTRODUCTION: We assessed a genetic risk score for Alzheimer's disease (AD-GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial. METHODS: 1260 at-risk older individuals without dementia were randomized to multidomain lifestyle intervention or health advice. N = 126 participants underwent magnetic resonance imaging (MRI), and N = 47 positron emission tomography (PET) scans (Pittsburgh Compund B [PiB], Fluorodeoxyglucose) at baseline; N = 107 and N = 38 had repeated 2-year scans. RESULTS: The APOE4 allele, but not AD-GRS, was associated with baseline lower hippocampus volume (ß = -0.27, p = 0.001), greater amyloid deposition (ß = 0.48, p = 0.001), 2-year decline in hippocampus (ß = -0.27, p = 0.01), total gray matter volume (ß = -0.25, p = 0.01), and cortical thickness (ß = -0.28, p = 0.003). In analyses stratified by AD-GRS (below vs above median), the PiB composite score increased less in intervention versus control in the higher AD-GRS group (ß = -0.60, p = 0.03). DISCUSSION: AD-GRS and APOE4 may have different impacts on potential intervention effects on amyloid, that is, less accumulation in the higher-risk group (AD-GRS) versus lower-risk group (APOE). HIGHLIGHTS: First study of neuroimaging and AD genetics in a multidomain lifestyle intervention. Possible intervention effect on brain amyloid deposition may rely on genetic risk. AD-GRS and APOE4 allele may have different impacts on amyloid during intervention.


Asunto(s)
Enfermedad de Alzheimer , Apolipoproteína E4 , Estilo de Vida , Imagen por Resonancia Magnética , Neuroimagen , Tomografía de Emisión de Positrones , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico por imagen , Masculino , Femenino , Anciano , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Predisposición Genética a la Enfermedad , Persona de Mediana Edad , Factores de Riesgo , Puntuación de Riesgo Genético
6.
Alzheimers Dement ; 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39072956

RESUMEN

INTRODUCTION: Subjective cognitive decline (SCD) in amyloid-positive (Aß+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies. METHODS: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models. RESULTS: In the combined and stratified cohorts, Aß+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aß- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings. DISCUSSION: Aß+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials. HIGHLIGHTS: SCD in amyloid-positive (Aß+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aß+ older adults with SCD could be a target population for interventional trials.

7.
Alzheimers Res Ther ; 16(1): 172, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085945

RESUMEN

BACKGROUND: Blood-brain barrier (BBB) alterations may contribute to AD pathology through various mechanisms, including impaired amyloid-ß (Aß) clearance and neuroinflammation. Soluble platelet-derived growth factor receptor beta (sPDGFRß) has emerged as a potential biomarker for BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a direct assessment of BBB permeability. However, the relationship between BBB dysfunction, cognitive impairment, and AD pathology remains unclear, with inconsistent findings in the literature. METHODS: We conducted a cross-sectional study using data from the DELCODE and DESCRIBE cohorts to investigate BBB dysfunction in participants with normal cognition (NC), mild cognitive impairment (MCI), and AD dementia. BBB function was assessed using DCE-MRI and sPDGFRß levels in cerebrospinal fluid and AD biomarkers Aß and tau were measured. In a subset of patients, the CSF/plasma-ratio of albumin (QAlb) as a standard marker of BBB integrity and markers of neuroinflammation were analyzed. RESULTS: 91 participants (NC: 44, MCI: 21, AD: 26) were included in the analysis. The average age was 74.4 years, 42% were female. Increased hippocampal BBB disruption was observed in the AD-group (Ktrans: 0.55 × 10- 3 min- 1 ± 0.74 × 10- 3 min- 1) but not the MCI-group (Ktrans: 0.177 × 10- 3 min- 1 ± 0.22 × 10- 3 min- 1), compared to the NC group (Ktrans: 0.19 × 10- 3 min- 1 ± 0.37 × 10- 3 min- 1, p < .01). sPDGFRß was not significantly different between the cognitive groups. However, sPDGFRß levels were significantly associated with age (r = .33, p < .01), independent of vascular risk factors. Further, sPDGFRß showed significant positive associations with soluble Aß levels (Aß40: r = .57, p < .01; Aß42: r = .39, p < .01) and YKL-40 (r = .53, p < .01), a marker of neuroinflammation. sPDGFRß/DCE-MRI was not associated with overall AD biomarker positivity or APOE-status. CONCLUSION: In dementia, but not MCI, hippocampal BBB disruption was observed. sPDGFRß increased with age and was associated with neuroinflammation independent of cognitive impairment. The association between Aß and sPDGFRß may indicate a bidirectional relationship reflecting pericytes' clearance of soluble Aß and/or vasculotoxic properties of Aß.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Barrera Hematoencefálica , Disfunción Cognitiva , Imagen por Resonancia Magnética , Enfermedades Neuroinflamatorias , Humanos , Barrera Hematoencefálica/patología , Femenino , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Masculino , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Estudios Transversales , Enfermedades Neuroinflamatorias/diagnóstico por imagen , Enfermedades Neuroinflamatorias/patología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/metabolismo , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Persona de Mediana Edad , Anciano de 80 o más Años , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Proteínas tau/líquido cefalorraquídeo , Proteínas tau/metabolismo
8.
Clin Neuropsychol ; : 1-17, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741352

RESUMEN

Objective: Our study aimed to explore whether physical condition might affect the association between genetic predisposition for Alzheimer's Disease (AD) and AD incidence. Methods: The sample of participants consisted of 561 community-dwelling adults over 64 years old, without baseline dementia (508 cognitively normal and 53 with mild cognitive impairment), deriving from the HELIAD, an ongoing longitudinal study with follow-up evaluations every 3 years. Physical condition was assessed at baseline through walking time (WT), while a Polygenic Risk Score for late onset AD (PRS-AD) was used to estimate genetic predisposition. The association between WT and PRS-AD with AD incidence was evaluated with Cox proportional hazard models adjusted for age, sex, education years, global cognition score and APOE ε-4 genotype. Then, the association between WT and AD incidence was investigated after stratifying participants by low and high PRS-AD. Finally, we examined the association between PRS-AD and AD incidence after stratifying participants by WT. Results: Both WT and PRS-AD were connected with increased AD incidence (p < 0.05), after adjustments. In stratified analyses, in the slow WT group participants with a greater genetic risk had a 2.5-fold higher risk of developing AD compared to participants with lower genetic risk (p = 0.047). No association was observed in the fast WT group or when participants were stratified based on PRS-AD. Conclusions: Genetic predisposition for AD is more closely related to AD incidence in the group of older adults with slow WT. Hence, physical condition might be a modifier in the relationship of genetic predisposition with AD incidence.

9.
Biomedicines ; 12(5)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38791015

RESUMEN

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer's Disease (AD), amyloid-beta 42 (Aß42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aß42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aß42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aß42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aß42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

10.
Alzheimers Res Ther ; 16(1): 171, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080778

RESUMEN

BACKGROUND: Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aß-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects. METHODS: Targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LCMS) in 147 paired plasma-CSF samples from the Ace Alzheimer Center Barcelona and 58 CSF samples of MCI patients from the Mannheim/Heidelberg cohort. Linear regression was used to evaluate the association of metabolites with CSF levels of ATN biomarkers in the overall sample and stratified by Aß-42 pathology and APOE genotype. We further evaluated the role of metabolites in MCI to AD dementia progression. RESULTS: Increased CSF levels of PGF2α, 8,12-iso-iPF2α VI, and 5-iPF2α VI were significantly associated (False discovery rate (FDR) < 0.05) with higher p-tau levels. Additionally, 8,12-iso-iPF2α VI was associated with increased total tau levels in CSF. In MCI due to AD, PGF2α was associated with both p-tau and total tau, whereases 8,12-iso-iPF2α VI was specifically associated with p-tau levels. In APOE stratified analysis, association of PGF2α with p-tau and t-tau was observed in only APOE ε4 carriers while 5-iPF2α VI showed association with both p-tau and t-tau in APOE ε33 carriers. CSF levels of 8,12- iso-iPF2α VI showed association with p-tau and t-tau in APOE ε33/APOE ε4 carriers and with t-tau in APOE ε3 carriers. None of the metabolites showed evidence of association with MCI to AD progression. CONCLUSIONS: Oxidative stress (8,12-iso-iPF2α VI) and inflammatory (PGF2α) biomarkers are correlated with biomarkers of AD pathology during the prodromal stage of AD and relation of PGF2α with tau pathology markers may be influenced by APOE genotype.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Disfunción Cognitiva , Estrés Oxidativo , Proteínas tau , Humanos , Disfunción Cognitiva/líquido cefalorraquídeo , Enfermedad de Alzheimer/líquido cefalorraquídeo , Estrés Oxidativo/fisiología , Biomarcadores/líquido cefalorraquídeo , Femenino , Masculino , Anciano , Proteínas tau/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Isoprostanos/líquido cefalorraquídeo , Progresión de la Enfermedad , Persona de Mediana Edad , Inflamación/líquido cefalorraquídeo , Metabolómica/métodos , Anciano de 80 o más Años , Prostaglandinas/líquido cefalorraquídeo
11.
Alzheimers Dement (Amst) ; 16(1): e12510, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38213951

RESUMEN

INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid. RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline. DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.

12.
Neurobiol Aging ; 136: 99-110, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38340637

RESUMEN

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.


Asunto(s)
Disfunción Cognitiva , Demencia , Dieta Mediterránea , Memoria Episódica , Humanos , Femenino , Anciano , Masculino , Estudios de Cohortes , Anisotropía , Imagen de Difusión Tensora , Disfunción Cognitiva/etiología , Disfunción Cognitiva/complicaciones
13.
Invest Radiol ; 59(9): 667-676, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38652067

RESUMEN

OBJECTIVES: Impaired perivascular clearance has been suggested as a contributing factor to the pathogenesis of Alzheimer disease (AD). However, it remains unresolved when the anatomy of the perivascular space (PVS) is altered during AD progression. Therefore, this study investigates the association between PVS volume and AD progression in cognitively unimpaired (CU) individuals, both with and without subjective cognitive decline (SCD), and in those clinically diagnosed with mild cognitive impairment (MCI) or mild AD. MATERIALS AND METHODS: A convolutional neural network was trained using manually corrected, filter-based segmentations (n = 1000) to automatically segment the PVS in the centrum semiovale from interpolated, coronal T2-weighted magnetic resonance imaging scans (n = 894). These scans were sourced from the national German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study. Convolutional neural network-based segmentations and those performed by a human rater were compared in terms of segmentation volume, identified PVS clusters, as well as Dice score. The comparison revealed good segmentation quality (Pearson correlation coefficient r = 0.70 with P < 0.0001 for PVS volume, detection rate in cluster analysis = 84.3%, and Dice score = 59.0%). Subsequent multivariate linear regression analysis, adjusted for participants' age, was performed to correlate PVS volume with clinical diagnoses, disease progression, cerebrospinal fluid biomarkers, lifestyle factors, and cognitive function. Cognitive function was assessed using the Mini-Mental State Examination, the Comprehensive Neuropsychological Test Battery, and the Cognitive Subscale of the 13-Item Alzheimer's Disease Assessment Scale. RESULTS: Multivariate analysis, adjusted for age, revealed that participants with AD and MCI, but not those with SCD, had significantly higher PVS volumes compared with CU participants without SCD ( P = 0.001 for each group). Furthermore, CU participants who developed incident MCI within 4.5 years after the baseline assessment showed significantly higher PVS volumes at baseline compared with those who did not progress to MCI ( P = 0.03). Cognitive function was negatively correlated with PVS volume across all participant groups ( P ≤ 0.005 for each). No significant correlation was found between PVS volume and any of the following parameters: cerebrospinal fluid biomarkers, sleep quality, body mass index, nicotine consumption, or alcohol abuse. CONCLUSIONS: The very early changes of PVS volume may suggest that alterations in PVS function are involved in the pathophysiology of AD. Overall, the volumetric assessment of centrum semiovale PVS represents a very early imaging biomarker for AD.


Asunto(s)
Enfermedad de Alzheimer , Aprendizaje Automático , Imagen por Resonancia Magnética , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Masculino , Femenino , Anciano , Imagen por Resonancia Magnética/métodos , Progresión de la Enfermedad , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Sistema Glinfático/diagnóstico por imagen , Anciano de 80 o más Años
15.
Rev. venez. cir ; 76(1): 21-27, 2023. tab, graf
Artículo en Español | LILACS, LIVECS | ID: biblio-1552937

RESUMEN

Las infecciones del sitio operatorio representan un desafío en el entorno hospitalario. El cierre primario diferido ha surgido como técnica para prevenirlas. Esta investigación busca explorar los beneficios del cierre primario diferido en la reducción de infecciones, estancia hospitalaria y costos, mejorando los resultados clínicos en cirugías abdominales. Objetivos. Evaluar el cierre primario diferido en pacientes laparotomizados de emergencia que acuden Hospital Universitario de Mérida ­Venezuela, con índice SENIC ≥ 3 puntos. Métodos. Se llevó a cabo un estudio experimental prospectivo para evaluar los efectos del cierre primario diferido en comparación con el cierre primario en laparotomías exploradoras. La muestra consistió en 160 pacientes. Se analizaron la presencia de infecciones, la duración de la estancia hospitalaria y la evolución temporal de las infecciones como desenlaces del estudio. Resultados. Se encontró que el cierre primario diferido redujo la presencia de infecciones en comparación con el cierre primario. La limpieza trans-operatoria y el diagnóstico de abdomen agudo quirúrgico infeccioso fueron factores beneficiosos. La antibioticoterapia continua en el postoperatorio también fue más efectiva. Se observó una disminución del riesgo de infección en el grupo experimental en un 37% en comparación con el grupo de control. Conclusiones. El cierre primario diferido de la herida reduce significativamente la probabilidad de infección del sitio operatorio en cirugías abdominales con heridas contaminadas. Es una técnica beneficiosa para pacientes con abdomen agudo quirúrgico infeccioso. Además, el cierre primario diferido resulta rentable al disminuir tanto la incidencia de ISO como la duración de la estancia hospitalaria


Surgical site infections pose a challenge in the hospital setting. Delayed primary closure has emerged as a technique to prevent such infections. This research aims to explore the benefits of delayed primary closure in reducing infections, hospital stay, and costs, thus improving clinical outcomes in abdominal surgeries. Objectives. To evaluate delayed primary closure in emergency laparotomized patients with SENIC index ≥ 3 points at the University Hospital of Mérida, Venezuela. Methods. A prospective experimental study was conducted to assess the effects of delayed primary closure compared to primary closure in exploratory laparotomies. The sample consisted of 160 patients. The presence of infections, duration of hospital stay, and temporal evolution of infections were analyzed as study outcomes. Results. Delayed primary closure was found to reduce the presence of infections compared to primary closure. Transoperative cleaning and the diagnosis of infectious surgical acute abdomen were beneficial factors. Continuous postoperative antibiotic therapy was also more effective. A 37% reduction in the risk of infection was observed in the experimental group compared to the control group. Conclusions. Delayed primary closure significantly reduces the probability of surgical site infection in abdominal surgeries with contaminated wounds. It is a beneficial technique for patients with infectious surgical acute abdomen. Additionally, delayed primary closure proves cost-effective by reducing both the incidence of surgical site infections and the duration of hospital stay(AU)


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Infección de la Herida Quirúrgica , Infección Hospitalaria , Servicio de Cirugía en Hospital
16.
Rev. venez. cir ; 74(2): 26-31, 2021. ilus, tab
Artículo en Español | LILACS, LIVECS | ID: biblio-1369626

RESUMEN

El tumor sólido pseudopapilar de páncreas tiene una incidencia de 0,13-2,7%, afectando preferentemente a mujeres jóvenes. Presentamos la experiencia en el manejo de tumores sólidos pseudopapilares de páncreas durante 10 años en el Hospital Coromoto de Maracaibo. Métodos: Estudio retrospectivo realizado en el Hospital Coromoto de Maracaibo desde enero 2010 hasta diciembre 2019. Se analizaron las variables edad, sexo, ubicación del tumor, procedimiento quirúrgico, tamaño del tumor, tiempo quirúrgico, tiempo de hospitalización y complicaciones. Resultados: De 183 casos totales de cirugía pancreática,15 casos presentaron diagnóstico anatomopatológico de tumor sólido pseudopapilar, representando un 8,20% del total de las cirugías pancreáticas; con edades comprendidas entre 15 a 56 años, con una media de 27,93 de los cuales el 93,33% fueron del género femenino. La ubicación más frecuente fue el cuerpo y la cola del páncreas con un 53,33%. El procedimiento quirúrgico más empleado fue la pancreatectomía distal en 8 casos. El tamaño promedio de los tumores fue de 6,47cm y el tiempo quirúrgico empleado fue de 254 minutos para las pancreatectomías distales y 412 minutos para los procedimientos de Whipple, con una media de hospitalización de 4,6 y 7,2 días respectivamente. Presentaron complicaciones 2 pacientes y sin decesos. Conclusiones: El tumor sólido pseudopapilar es una neoplasia pancreática de comportamiento incierto, con una baja incidencia entre todos los tumores de páncreas, donde la laparoscopia es un método de abordaje seguro en las pancreatectomías distales, sin diferencias en estancia hospitalaria y tiempo quirúrgico. La resección quirúrgica con márgenes libres es curativa(AU)


The solid pseudopapillary tumor of the pancreas has an incidence of 0.13-2.7%, preferentially affecting young women. We present the experience in the management of solid pseudopapillary tumors of the pancreas for 10 years at the Coromoto Hospital in Maracaibo. Methods: Retrospective study carried out at the Coromoto Hospital in Maracaibo from January 2010 to December 2019. The variables age, sex, tumor location, surgical procedure, tumor size, surgical time, hospitalization time and complications were analyzed. Results: Of 183 total cases of pancreatic surgery, 15 cases had a pathological diagnosis of a solid pseudopapillary tumor, representing 8.20% of the total of pancreatic surgeries; with ages ranging from 15 to 56 years, with an average of 27.93 of which 93.33% were female. The most frequent location was the body and tail of the pancreas with 53.33%. The most used surgical procedure was distal pancreatectomy in 8 cases. The average size of the tumors was 6.47cm and the surgical time used was 254 minutes for distal pancreatectomies and 412 minutes for Whipple procedures, with a mean hospital stay of 4.6 and 7.2 days, respectively. Two patients presented complications and no deaths. Conclusions: The solid pseudopapillary tumor is a pancreatic neoplasm of uncertain behavior, with a low incidence among all pancreatic tumors, where laparoscopy is a safe approach to distal pancreatectomies, without differences in hospital stay and surgical time. Surgical resection with free margins is curative(AU)


Asunto(s)
Humanos , Femenino , Adulto , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/patología , Procedimientos Quirúrgicos Operativos , Estudios Retrospectivos , Laparoscopía
17.
Rev. venez. cir ; 74(2): 51-54, 2021. ilus, tab
Artículo en Español | LILACS, LIVECS | ID: biblio-1369845

RESUMEN

El íleo biliar es una complicación poco frecuente de la colelitiasis o colecistitis litiásica, aparece en menos del 1-3% de los pacientes con estas enfermedades, se define como una obstrucción intestinal mecánica debido a la impactación de uno o más cálculos biliares dentro del tracto gastrointestinal. Ubicaciones menos comunes incluyen estómago y duodeno (síndrome de Bouveret) y el colon. El diagnóstico del síndrome de Bouveret (SB) suele iniciar con una radiografía simple de abdomen; la ecografía abdominal confirma el síndrome de Bouveret si revela neumobilia y ubicación ectópica del cálculo biliar, sin embargo, en la mayoría de los casos se necesita una tomografía computarizada que permite una evaluación completa.Caso Clínico : Se presenta caso de masculino de 57 años de edad quien 8 días previo a su ingreso presenta dolor abdominal en epigastrio de moderada intensidad acompañado de pirosis, halitosis, náuseas, vómitos, intolerancia a la vía oral y ausencia de evacuaciones; acude inicialmente a gastroenterólogo que realiza endoscopia digestiva superior encontrando una imagen de obstrucción a nivel de primera porción de duodeno, motivo por el cual refiere a servicio de cirugía general donde es intervenido quirúrgicamente, se diagnostica el SB realizando gastrotomía, extracción del lito y piloroplastia, presentando adecuada evolución postoperatoria.Conclusión : El SB es un diagnóstico raro que afecta a <0,5% de los pacientes con cálculos biliares por lo que requiere un grado extremadamente alto de sospecha para el diagnóstico y puede observarse de manera incidental en estudios de imágenes en pacientes que presentan síntomas de obstrucción del vaciamiento gástrico(AU)


Biliary ileus is a rare complication of cholelithiasis or lithiasic cholecystitis, appearing in less than 1 to 3% of patients with these diseases, it is a mechanical intestinal obstruction due to the impaction of one or more gallstones within the gastrointestinal tract. Less common locations include the stomach and duodenum (Bouveret syndrome) and the colon. For the diagnosis of Bouveret's syndrome (BS) the initial step is usually a simple abdominal X-ray, while an abdominal ultrasound confirms Bouveret's syndrome if it reveals pneumobilia and ectopic location of the gallstone, in most cases a computed tomography (CT) scan is needed for diagnosis and full evaluation.Clinical Case: We present the clinical case of a 57-year-old male who 8 days prior to his admission presented with moderate intensity abdominal pain in the epigastrium accompanied by heartburn, halitosis, nausea, vomiting, intolerance to oral intake, and absence of evacuations; initially went to a gastroenterologist who performed upper digestive endoscopy, finding an image of obstruction at the level of the first portion of the duodenum, which is why he refers to the general surgery department where he underwent surgery, diagnosing BS by performing gastrotomy, stone extraction, and pyloroplasty, presenting adequate postoperative evolution.Conclusion : BS is a rare diagnosis that affects <0.5% of patients with gallstones and therefore requires an extremely high degree of suspicion for the diagnosis and can be seen incidentally on imaging studies in patients with symptoms of obstruction of gastric emptying(AU)


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Colelitiasis , Cálculos Biliares , Dolor Abdominal , Colecistitis , Cirugía General , Obstrucción Intestinal/etiología
18.
Med. interna Méx ; 35(5): 819-826, sep.-oct. 2019. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1250277

RESUMEN

Resumen: El embarazo es un estado que impone un verdadero reto para el sistema cardiovascular materno. Existe remodelamiento cardiaco, que, junto con el incremento de la masa miocárdica y del tamaño del ventrículo izquierdo y la contractilidad miocárdica disminuida agravada por los cambios del embarazo, pueden condicionar insuficiencia cardiaca aguda durante el periodo periparto. Se considera miocardiopatía periparto cuando la función sistólica del ventrículo izquierdo y los síntomas de insuficiencia cardiaca ocurren en el último mes del embarazo y en los cinco meses posteriores al parto con incidencia de 1 por cada 1300 a 15,000 embarazos. Se comunica el caso de una paciente de 26 años, con antecedente de catarata congénita, que tuvo embarazo normoevolutivo, con parto eutócico, durante el puerperio tuvo disnea y datos de hipoperfusión, mediante evaluación ultrasonográfica pulmonar y cardiaca mostró datos de miocardiopatía dilatada periparto, fue trasladada a un hospital de tercer nivel, donde a pesar del tratamiento intensivo multidisciplinario, falleció. La miocardiopatía periparto es una enfermedad subvalorada con alta mortalidad materna y perinatal; sin embargo, la detección oportuna puede mejorar el tratamiento y el pronóstico. Con la comunicación de este caso, se pretende demostrar la importancia de la detección temprana de una afección poco diagnosticada, como es la miocardiopatía periparto.


Abstract: Pregnancy is a state that imposes a real challenge for the maternal cardiovascular system. There is a cardiac remodeling, which along with an increase in myocardial mass, in left ventricular size and decreased myocardial contractility aggravated by changes in pregnancy, can condition acute heart failure during the peripartum period. Peripartum cardiomyopathy is when the systolic function of the left ventricle and the symptoms of heart failure occur in the last month of pregnancy and in the five months after delivery with an incidence ranging from 1/1300 to 1/15,000 pregnancies. This paper reports the case of a 26-year-old female patient, who had a history of congenital cataract, with normal pregnancy and eutocic delivery; during the puerperium patient showed dyspnea, hypoperfusion data and pulmonary and cardiac ultrasonographic evaluation of peripartum dilated cardiomyopathy, being transferred at a third level, where despite intensive multidisciplinary treatment, the patient died. Peripartum cardiomyopathy is an undervalued disease that has a high maternal and perinatal mortality; however, a timely detection can improve treatment and prognosis. The purpose of this case report is to demonstrate the importance of early detection of a poorly diagnosed entity, such as peripartum cardiomyopathy.

19.
Bol. méd. Hosp. Infant. Méx ; 67(3): 238-247, may.-jun. 2010.
Artículo en Español | LILACS | ID: lil-701025

RESUMEN

Los niños, como menores de edad, dependen de las decisiones que sus padres toman por ellos. En la inmensa mayoría de los casos, las decisiones son benéficas para los infantes; sin embargo, con cierta frecuencia en el campo de la salud se toman determinaciones maleficentes, es decir, en total perjuicio de los hijos, que incluso pueden terminar en un desenlace fatal. Por ello, se presenta la situación jurídica de los niños en México, que dictamina el derecho a recibir los mejores tratamientos, aún en contra de la opinión de los padres. También esto se ha mencionado desde un panorama internacional.


Children, as minors, depend on the choices made by their parents on their behalf. In the vast majority of cases, parental decisions are beneficial to their children but regarding health issues, harmful determinations are often made. This may result in total harm of children, which may even result in the death of a child. Thus, the legal situation of children in Mexico is presented here and grants them the right to receive the most optimal treatments, even against their parents wishes. This premise is also upheld internationally.

20.
Rev. colomb. obstet. ginecol ; 61(2): 160-164, abr.- jun. 2010.
Artículo en Español | LILACS | ID: lil-555200

RESUMEN

Objetivo: presentar una revisión de la literatura sobre la fragmentación del ADN espermático, su impacto en las técnicas de reproducción asistida y la calidad embrionaria. Metodología: se utilizó la base de datos MEDLINE/PubMed. Los términos de búsqueda fueron: fragmentación espermática, parámetros seminales, técnicas de reproducción asistida y calidad embrionaria. Se revisaron los artículos publicados entre 1999 y 2010. Resultados: los estudios de fragmentación espermática proveen información complementaria acerca de la calidad espermática del paciente, siendo una prueba paralela al análisis seminal. Partiendo del diagnóstico de dichas pruebas se puede tomar la decisión acerca de la técnica de reproducción a emplear. Conclusión: el índice de fragmentación de ADN espermático es una herramienta valiosa para conocer la capacidad fecundante del paciente.


Objective: presenting a review of the literature about sperm DNA fragmentation, its impact on assisted reproduction techniques and embryo quality. Methodology: the MEDLINE/PubMed database was searched; the search terms used were: sperm fragmentation, semen parameters, assisted reproduction techniques and embryo quality. Articles published from 1999 to 2010 were reviewed. Results: sperm fragmentation studies provided complementary information about a patient’s sperm quality, this being a parallel test to semen analysis. Such tests’ diagnoses represent the starting point for taking decisions about the reproduction technique to be used. Conclusion: the sperm ADN fragmentation index represents a valuable tool for ascertaining a patient’s fertilising ability.


Asunto(s)
Humanos , Masculino , Adulto , Femenino , Fragmentación del ADN , Infertilidad Masculina
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