Premature immunosenescence is associated with memory dysfunction in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) has been associated with premature immunosenescence and an increased prevalence of age-related morbidities including poor cognitive function. OBJECTIVE: We explored the relationships among lymphocyte subsets and memory in RA. METHODS: Thirty patients with RA and 19 age-matched healthy controls took part in this study. Cognitive function stress and depression scores were evaluated by structured clinical questionnaires. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate the following subsets: B cells, activated and naïve/memory T cells, regulatory FoxP3+ T (Treg) cells, Th17+ cells, NK cells and senescence-associated CD28- T cells. RESULTS: RA patients were more depressed than controls, but stress levels were similar in the 2 groups. Patients had impaired memory performance compared to controls, demonstrated by lower Mini-Mental State Examination scores and logical and working memories (all p < 0.0001). These group effects remained significant after correcting for depression and age. Patients had expansion of regulatory T cells, naïve CD4+ T cells and CD8+CD28- cells but reduced percentages of B cells and memory CD8+CD45RO+ T cells compared to controls. CD8+CD28- and CD8+CD45RO+ T cells were found to be negatively associated with memory. CONCLUSION: RA patients had reduced memory performance compared to healthy controls. Expansion of activated and senescence-associated T cells was correlated with poor memory performance.

Cognitive impairment in rheumatoid arthritis: role of lymphocyte subsets, cytokines and neurotrophic factors.

To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated by autoimmune and/or inflammatory activity is largely unknown. The aim of this study was to investigate the role of peripheral inflammation on cognitive functions of patients with active (Ac-), controlled (Co-) RA and healthy controls. In a cross-sectional study, 102 RA patients and 30 matched healthy controls were recruited. B and T cell subsets were immunophenotyped by flow cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and ELISA, respectively. Cognitive performance, depression and stress were evaluated by structured clinical interviews. Generalized linear modeling (GzLM) was used to compare differences between groups and multiple linear regression models were used to explore the predictive value of immune variables on cognitive performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had the poorest performance on digit span (DST) and N-back when compared to Co-RA and control group (DST 9.9 ± 2.1, 12.9 ± 4.2, 15.5 ± 4.7, respectively; N-back 49.2 ± 8.3, 55.5 ± 11.1, 60.8 ± 9.1, respectively, all p < 0.0001). RA patients had expansions of immature B cells (Ac-RA 11.2 ± 7.1, Co-RA: 9 ± 5.7, control 5.9 ± 2.1) and plasma cells (Ac-RA 5.2 ± 2.5, Co-RA 6.9 ± 3.7, control 2.8 ± 1.7) as compared to controls, all p < 0.05. RA patients (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6 and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac-RA 17,354.4 ± 5357.3, Co-RA 13,841.2 ± 5953.7, control 11,543.3 ± 3772), but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0 pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA patients had global cognitive impairment, which was associated with disease activity and immune changes.

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

OBJECTIVE:: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. METHODS:: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. RESULTS:: BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). CONCLUSION:: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Autoantibodies against myelin sheath and S100ß are associated with cognitive dysfunction in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding ß (S100ß) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100ß, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100ß levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100ß protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100ß levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = -0.42, p = 0.005), Stroop Color-Word (r = -0.48, p = 0.004), and N-Back Total scores (r = -0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = -0.64, p < 0.0001), N-Back Total scores (r = -0.35, p = 0.03), Stroop Color-Word (r = -0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100ß levels were associated with DVR (r = -0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = -0.67, p < 0.0001), and N-Back Total (r = -0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100ß levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.

Crack-cocaine dependence and aging: effects on working memory.

OBJECTIVE: To compare the working memory (WM) performance of young adult crack-cocaine dependent users, healthy older adults, and a control group of healthy young adults. METHODS: A total of 77 female participants took part in this study: 26 young adult crack-cocaine dependent users (CRK), 19 healthy older adults (HO), and 32 healthy younger adults (HC). All participants completed the N-back verbal task. RESULTS: A multivariate analysis of covariance was performed. The model included education, income, and medication use as covariates. A group effect (F6,140 = 7.192, p < 0.001) was found. Post-hoc analyses showed that the performance of the CRK and HO groups was reduced compared to the HC group in two N-back conditions. No differences between the HO and CRK groups on WM performance were found. CONCLUSIONS: CRK participants perform similar to HO participants on a WM task, despite the well-known effects of age on WM and the young age of CRK. These data point to a possible parallel between cognitive declines associated with crack use and developmental aging.

Crack cocaine addiction, early life stress and accelerated cellular aging among women.

BACKGROUND: Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence. METHODS: This study included treatment seeking crack cocaine dependents women (n=127) and elderly women without a psychiatric diagnosis (ELD, n=49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay. RESULTS: CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores. CONCLUSIONS: These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience.

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults

Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Crack-cocaine dependence and aging: effects on working memory

Objective: To compare the working memory (WM) performance of young adult crack-cocaine dependent users, healthy older adults, and a control group of healthy young adults. Methods: A total of 77 female participants took part in this study: 26 young adult crack-cocaine dependent users (CRK), 19 healthy older adults (HO), and 32 healthy younger adults (HC). All participants completed the N-back verbal task. Results: A multivariate analysis of covariance was performed. The model included education, income, and medication use as covariates. A group effect (F6,140 = 7.192, p < 0.001) was found. Post-hoc analyses showed that the performance of the CRK and HO groups was reduced compared to the HC group in two N-back conditions. No differences between the HO and CRK groups on WM performance were found. Conclusions: CRK participants perform similar to HO participants on a WM task, despite the well-known effects of age on WM and the young age of CRK. These data point to a possible parallel between cognitive declines associated with crack use and developmental aging.

Déficits na memória de trabalho em idosos com depressão maior: uma revisão sistemática / Impairment of working memory during a depression of the elderly: a systematic review

A depressão em idosos é associada com prejuízos cognitivos, entretanto a extensão destes à Memória de Trabalho (MT) ainda não é consensual. Portanto, o objetivo deste estudo é revisar sistematicamente as associações encontradas entre MT e depressão em idosos. Para tanto conduzimos uma revisão sistemática dos artigos publicados entre 2000 e 2011 nas principais bases de dados internacionais. Posteriormente a aplicação dos critérios de exclusão, 17 artigos foram revisados integralmente. Os resultados apresentam evidências da associação entre depressão geriátrica e prejuízos da MT, que em alguns trabalhos ainda foram mantidos mesmo após a remissão da sintomatologia de humor.

Geriatric depression is related with cognitive impairments, but how this is connected to specific Working Memory deficits is still unknown. Hence, the aim of this study is to systematically review the literature about the associations between Working Memory impairments and major depression in the elderly. Thus we performed a systematic review, considering published articles in major international databases between 2000 and 2011. After exclusion criteria, 17 articles were fully reviewed. There is evidence that there is indeed an association between depression in elderly and Working Memory impairments. In addition, some articles found that such deficits are sustained even after mood symptoms remission.

Tarefa N-back auditiva: desempenho entre diferentes grupos etários / Auditory N-back task: different age groups performance

Um dos instrumentos mais utilizados internacionalmente para avaliação da Memória de Trabalho (MT) é a Tarefa N-back Auditiva. Recursos para avaliação desse sistema são escassos no Brasil. O presente estudo objetiva observar o desempenho da Tarefa N-back Auditiva em indivíduos de diferentes faixas etárias: 27 crianças, 22 pré-adolescentes, 26 adultos e 27 idosos. Os resultados mostram que o grupo etário influencia no desempenho da Tarefa N-back Auditiva. A acurácia foi aumentando na transição da infância para a pré-adolescência e seguiu em crescimento até a adultez. Observou-se um declínio no desempenho de idosos. Os dados da Tarefa N-back Auditiva corrobora a trajetória desenvolvimental, sugerindo que essa tarefa possa ser utilizada no contexto experimental. Pesquisas de normatização contribuirão para melhor compreensão dessa tarefa.

One of the most internationally used instruments for evaluation of Working Memory (WM) is the Auditory N-Back Task. In Brazil, resources to evaluate this system are scarce. The aim of this study is to investigate the performance of different age subjects in auditory n-back tasks. We divided the 102 subjects in four groups: 27 children, 22 adolescents, 26 young adults and 27 older adults. The results demonstrate an age-related difference in the n-back task performance. The accuracy increased in the transition from childhood to adolescence and kept growing from adolescence to adulthood. We also found a decrease in the performance of aged subjects. The Auditory N-Back Task results are in agreement with WM development trajectory, and so, it demonstrates to be an adjusted instrument to evaluate this system in experimental setting.