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2.
J Rheumatol ; 50(2): 166-174, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36319020

RESUMO

OBJECTIVE: Morbidity and mortality in rheumatoid arthritis (RA) is partly mitigated by maintaining immune and hematologic homeostasis. Identification of those at risk is challenging. Red cell distribution width (RDW) and absolute lymphocyte count (ALC) associate with cardiovascular disease (CVD) and mortality in the general population, and with disease activity in RA. How these variables relate to inflammation and mortality in RA was investigated. METHODS: In a retrospective single Veterans Affairs (VA) Rheumatology Clinic cohort of 327 patients with RA treated with methotrexate (MTX)+/- a tumor necrosis factor (TNF) inhibitor (TNFi), we evaluated RDW and ALC before and during therapy and in relation to subsequent mortality. Findings were validated in a national VA cohort (n = 13,914). In a subset of patients and controls, we evaluated inflammatory markers. RESULTS: In the local cohort, high RDW and low ALC prior to MTX treatment was associated with subsequent mortality over 10 years (both P < 0.001). The highest mortality was observed in those with both high RDW and low ALC. This remained after adjusting for age and comorbidities and was validated in the national RA cohort. In the immunology cohort, soluble and cellular inflammatory markers were higher in patients with RA than in controls. ALC correlated with age, plasma TNF receptor II, natural killer HLA-DR mean fluorescence intensity, and CD4CM/CD8CM HLA-DR/CD38%, whereas RDW associated with age and ALC. MTX initiation was followed by an increase in RDW and a decrease in ALC. TNFi therapy added to MTX resulted in an increase in ALC. CONCLUSION: RDW and ALC before disease-modifying antirheumatic drug therapy are associated with biomarkers of monocyte/macrophage inflammation and subsequent mortality. The mechanistic linkage between TNF signaling and lymphopenia found here warrants further investigation.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Índices de Eritrócitos , Estudos Retrospectivos , Inflamação/tratamento farmacológico , Metotrexato/uso terapêutico , Antirreumáticos/uso terapêutico , Biomarcadores , Contagem de Linfócitos
3.
J Alzheimers Dis ; 78(2): 721-734, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044176

RESUMO

BACKGROUND: Whether brain-derived neurotrophic factor (BDNF) Met carriage impacts the risk or progression of Alzheimer's disease (AD) is unknown. OBJECTIVE: To evaluate the interaction of BDNF Met and APOE4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study. METHODS: 114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B (PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years. RESULTS: Among APOE4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE4 non-carriers. CONCLUSION: Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE4 on amyloid-ß plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity-findings that would need to be confirmed in larger studies.


Assuntos
Doença de Alzheimer/metabolismo , Apolipoproteína E4/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Metionina/metabolismo , Valina/metabolismo , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Estudos de Coortes , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Metionina/genética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Ligação Proteica/fisiologia , Valina/genética
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