Age moderates associations between dementia worry and subjective cognition.

The present study assessed whether dementia worry is associated with adults' subjective cognitive difficulties, and whether any associations are moderated by age. Participants were 477 adults aged 18-90 years. They completed standard, subjective measures of dementia worry and everyday cognitive difficulties (i.e. attention, language, verbal and visual-spatial memory, and visual-perceptual ability). Moderated regression analyses included dementia worry as a predictor of specific cognitive difficulties, and age as a moderator. Covariates included gender, trait cognitive and somatic anxiety, general aging-related anxiety, depression, stress, mental health treatment status, and health status. Greater overall dementia worry, and specifically more frequent dementia worry, were both associated with greater attentional difficulty in middle-aged and older adults, but not in young adults. Cognitions about developing dementia in reaction to memory lapses were also associated with greater cognitive difficulties across the adult lifespan for multiple cognitive domains. Results highlight a robust relationship between dementia worry and subjective attentional difficulties, especially in middle-aged and older adults. Worry frequency is also more influential with adult aging. A cognitive or meta-cognitive mechanism may underlie subjective cognitive concerns across the adult lifespan.

Adult Aging Moderates the Relationship Between Trait Cognitive Anxiety and Subjective Everyday Cognitive Difficulties.

The present aim was to determine, across the adult lifespan, the extent to which different dimensions of trait anxiety might affect subjective cognitive difficulties in everyday life. Following Attentional Control Theory (ACT; Eysenck et al., 2007), we predicted that trait anxiety would have a greater effect on attention and verbal abilities than on visual abilities. We also expected trait cognitive anxiety to exhibit more robust relationships with cognition than trait somatic anxiety. Importantly, we predicted that effects of anxiety would be greater in older adults, in line with the Strength and Vulnerability Integration model (SAVI; Charles, 2010). The sample comprised 286 United Kingdom-based adults aged 18-93 years. Participants completed self-report measures of trait cognitive and somatic anxiety (the State-Trait Inventory for Cognitive and Somatic Anxiety; STICSA, Ree et al., 2008) and everyday cognitive difficulties (the Multiple Abilities Self-Report Questionnaire; MASQ, Seidenberg et al., 1994). Moderated regression models were constructed, including trait cognitive or somatic anxiety as a predictor of cognitive difficulties, and age as the moderator variable. Covariates included depression, stress (the Depression Anxiety Stress Scales-short form; DASS-21, Lovibond and Lovibond, 1995), gender, current mental health treatment status, and physical health status. When cognitive anxiety was the predictor variable, somatic anxiety was also included as a covariate, and vice-versa. Trait cognitive anxiety and age interacted to predict all MASQ subscales other than visual-perceptual ability. Difficulties with attention, verbal memory, and language abilities were significantly greater at higher levels of anxiety for all age groups, with the effect greatest in older adults. Difficulties with visual-spatial memory were significantly greater at higher levels of anxiety in middle-aged and older adults only. Higher trait somatic anxiety predicted difficulties with verbal memory and language ability independently of age, and interacted with age to predict language difficulties. Interestingly, age also significantly predicted less subjective difficulty with attention, independently of anxiety level. The results show that trait cognitive and somatic anxiety are both related to subjective, everyday cognitive difficulties. However, effects of trait cognitive anxiety are more robust across cognitive domains and tend to increase, or first appear, over the course of the adult lifespan.

A systematic review of the impacts of intergenerational engagement on older adults' cognitive, social, and health outcomes.

BACKGROUND: Intergenerational engagement could benefit health and wellbeing within an ageing population. This systematic review evaluated the impacts of intergenerational engagement on cognitive, social, and health outcomes in healthy older adults and older adults with mild cognitive impairment. RESEARCH DESIGN AND METHODS: Comprehensive literature searches were undertaken, with records filtered according to pre-registered criteria. Study quality was formally assessed, and a narrative synthesis of the findings produced. RESULTS: Forty-four studies were reviewed. Regarding quantitative evidence, 4 out of 8 studies found significant intergenerational engagement effects on cognitive outcomes, 15 of 24 on social outcomes, and 21 of 31 on health-related outcomes. Qualitative evidence was also important for understanding perceived impacts and experiences of intergenerational programmes. Only 11 studies fully met criteria for high quality research, of which the majority focused on social outcomes. DISCUSSION AND IMPLICATIONS: There are a range of potential benefits of intergenerational engagement, most notably regarding anxiety, generativity, cross-age attitudes, and physical activity. However, heterogeneity in programme context, sample design, dosage, and duration indicate that more research is required to enable wider implementation and generalisability. Scientific rigour in both quantitative and qualitative research should also be employed as far as possible, to provide the highest quality evidence.

Impacts of trait anxiety on visual working memory, as a function of task demand and situational stress.

Higher trait anxiety can impair cognitive functioning via attention, but relatively little is known about the impacts on visual working memory. These were investigated using previously validated visual feature binding tasks. In Study 1, participants' memory for visual features (shapes) and feature bindings (coloured shapes) was assessed. Stimulus presentation was simultaneous or sequential, varying attentional demand, and participants were grouped according to trait cognitive anxiety (low, moderate, high). No reliable effect of trait anxiety, either cognitive or somatic, was found on memory accuracy, but moderate trait cognitive anxiety was associated with faster correct response times (i.e. increased efficiency) when stimuli were sequentially presented. In Study 2, the role of situational stress was explored during a simultaneously presented task. Higher trait cognitive and somatic anxiety were both associated with poorer efficiency during both shape and binding memory tasks. Trait somatic anxiety also predicted poorer binding effectiveness (i.e. accuracy), in those reporting higher state cognitive anxiety. Situational stress predicted binding effectiveness, but never interacted with trait anxiety, and was therefore not necessary to observe these trait anxiety-visual working memory relationships. Trait cognitive and somatic anxiety, and situational stress, therefore each influence visual working memory performance.

Inhibition of fucosylation reshapes inflammatory macrophages and suppresses type II collagen-induced arthritis.

OBJECTIVE: Fucosylation catalyzed by fucosyltransferases (FUTs) is an important posttranslational modification involved in a variety of biologic processes. This study was undertaken to determine the roles of fucosylation in rheumatoid arthritis (RA) and to assess the efficacy of reestablishing immune homeostasis with the use of 2-deoxy-d-galactose (2-d-gal), a fucosylation inhibitor. METHODS: Quantitative polymerase chain reaction was performed to determine the expression of FUT genes in synovial tissue from RA and osteoarthritis (OA) patients and in fluorescence-activated cell-sorted cells from RA synovial fluid. The in vivo inhibitory effect of 2-d-gal was evaluated in a murine collagen-induced arthritis (CIA) model. The in vitro effects of 2-d-gal on differentiation of inflammatory macrophages, production of cytokines, and antigen uptake, processing, and presentation functions were analyzed. RESULTS: FUTs that are involved in terminal or subterminal fucosylation, but not those involved in core fucosylation or O-fucosylation, were up-regulated in RA compared to OA synovial tissue. The expression of terminal FUTs was highly positively correlated with the expression of TNF (encoding for tumor necrosis factor α). Terminal FUTs were predominantly expressed in M1 macrophages. In vivo, 2-d-gal treatment of mice precluded the development of CIA by reducing inflammatory macrophages and Th17 cells in the draining lymph nodes and decreasing the levels of TNFα, interleukin-6 (IL-6), and antibodies to type II collagen in the serum. In vitro, treatment with 2-d-gal skewed the differentiation of M1 macrophages to IL-10-producing M2 macrophages. Furthermore, 2-d-gal significantly inhibited the antigen-presenting function of M1 macrophages. CONCLUSION: Terminal fucosylation is a novel hallmark of inflammatory macrophages. Inhibition of terminal FUTs reshapes the differentiation and functions of M1 macrophages, leading to resolution of inflammation in arthritis.

Death receptor 5-targeted depletion of interleukin-23-producing macrophages, Th17, and Th1/17 associated with defective tyrosine phosphatase in mice and patients with rheumatoid arthritis.

OBJECTIVE: Bidirectional interactions between granulocyte-macrophage colony-stimulating factor-positive (GM-CSF+) T cells and interferon regulatory factor 5-positive (IRF-5+) macrophages play a major role in autoimmunity. In the absence of SH2 domain-containing phosphatase 1 (SHP-1), GM-CSF-stimulated cells are resistant to death receptor (DR)-mediated apoptosis. The objective of this study was to determine whether TRA-8, an anti-DR5 agonistic antibody, can eliminate inflammatory macrophages and CD4 T cells in the SHP-1-deficient condition. METHODS: Ubiquitous Cre (Ubc.Cre) human/mouse-chimeric DR5-transgenic mice were crossed with viable SHP-1-defective motheaten (mev/mev) mice. TRA-8 was administered weekly for up to 4 weeks. The clinical scores, histopathologic severity, and macrophage and CD4 T cell phenotypes were evaluated. The role of TRA-8 in depleting inflammatory macrophages and CD4 T cells was also evaluated, using synovial fluid obtained from patients with rheumatoid arthritis (RA). RESULTS: The levels of inflammatory macrophages (interleukin-23-positive [IL-23+] IRF-5+) and CD4 T cells (IL-17+ GM-CSF+) were elevated in mev/mev mice. In DR5-transgenic mev/mev mice, DR5 expression was up-regulated in these 2 cell populations. TRA-8 treatment depleted these cell populations and resulted in a significant reduction in inflammation and in the titers of autoantibodies. In synovial cells from patients with RA, the expression of IRF5 and DR5 was negatively correlated with the expression of PTPN6. TRA-8, but not TRAIL, suppressed RA inflammatory macrophages and Th17 cells under conditions in which the expression of SHP-1 is low. CONCLUSION: In contrast to TRAIL, which lacks the capability to counteract the survival signal in the absence of SHP-1, TRA-8 eliminated both IRF-5+ IL-23+ M1 macrophages and pathogenic GM-CSF+ IL-17+ CD4 T cells in a SHP-1-independent manner. The results of the current study suggest that TRA-8 can deplete inflammatory cell populations that result from a hyperactive GM-CSF/IRF-5 axis.