RESUMO
Background/Aims: We aimed to assess the association between in volumetric measures of hippocampal sub-regions - in healthy older controls (HC), subjects with mild cognitive impairment (MCI) and AD- with circulating levels of IL-4. Methods: From AddNeuroMed Project 113 HC, 101 stable MCI (sMCI), 22 converter MCI (cMCI) and 119 AD were included. Hippocampal subfield volumes were analyzed using Freesurfer 6.0.0 on high-resolution sagittal 3D-T1W MP-RAGE acquisitions. Plasmatic IL-4 was measured using ELISA assay. Results: IL-4 was found to be (a) positively associate with left subiculum volume (ß = 0.226, p = 0.037) in sMCI and (b) negatively associate with left subiculum volume (ß = -0.253, p = 0.011) and left presubiculum volume (ß = -0.257, p = 0.011) in AD. Conclusion: Our results indicate a potential neuroprotective effect of IL-4 on the areas of the hippocampus more vulnerable to aging and neurodegeneration.
RESUMO
INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.
Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Transtornos Cognitivos/etiologia , Diagnóstico por Computador , Hipocampo/patologia , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Transtornos Cognitivos/diagnóstico por imagem , Diagnóstico Diferencial , Progressão da Doença , Europa (Continente) , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Proteínas tau/líquido cefalorraquidianoRESUMO
The old age population is increasing worldwide as well as age related diseases, including neurodegenerative disorders, such as Alzheimer's disease (AD), which negatively impacts on the health care systems. Aging represents per se a risk factor for AD. Thus, the study and identification of pathways within the biology of aging represent an important end point for the development of novel and effective disease-modifying drugs to treat, delay, or prevent AD. Cellular senescence and telomere shortening represent suitable and promising targets. Several studies show that cellular senescence is tightly interconnected to aging and AD, while the role of telomere dynamic and stability in AD pathogenesis is still unclear. This review will focus on the linking mechanisms between cellular senescence, telomere shortening, and AD.
