Lifestyle for brain health and cognitive functioning in midlife to early late-life New Zealanders: Utility of the LIBRA index.

OBJECTIVES: There is enormous potential to improve brain health and reduce the risk of cognitive decline and dementia based on modifiable risk factors. The Lifestyle for Brain Health (LIBRA) index was developed to quantify modifiable dementia risk or room for brain health improvement. The objective of the study was to investigate the utility of the LIBRA index in relation to cognitive functioning in a midlife to early late-life sample of New Zealanders. METHODS: A subsample (n = 1001) of the longitudinal New Zealand Health, Work and Retirement (NZHWR) study completed face-to-face cognitive assessments using the 'Kiwi' Addenbrooke's Cognitive Examination-Revised (ACE-R) in 2010 and again in 2012, in addition to completing biennial NZHWR surveys on socioeconomic, health and wellbeing aspects. The LIBRA index was calculated incorporating information on 8 out of 12 modifiable health and lifestyle factors for dementia. Unadjusted and adjusted regression models and mixed effects models were used to inspect associations of LIBRA with cognitive functioning, cognitive impairment, and cognitive decline. RESULTS: The analytical sample (n = 881 [88.0%], after considering exclusion criteria and missing data) had a mean age of 63.1 (SD = 6.5) years, 53.3% were female, 26.2% were Maori, and 61.7% were highly educated. Higher LIBRA scores (indicating higher modifiable dementia risk) were associated with lower cognitive functioning (B = -0.33, 95% CI = -0.52;-0.15, p < 0.001) and a higher likelihood of cognitive impairment (OR = 1.22, 95% CI = 1.04; 1.42, p = 0.013), but did not predict cognitive decline over 2 years (B = -0.03, 95% CI = -0.22; 0.16, p = 0.766), adjusted for age, age2, gender, education, and ethnicity. CONCLUSIONS: The LIBRA index indicated promising utility for quantifying modifiable dementia risk in midlife and early late-life New Zealanders. For local use, refinement of the LIBRA index should consider cultural differences in health and lifestyle risk factors, and further investigate its utility with a wider range of modifiable factors over a longer observation period.

Social network type contributes to purpose in life among older people, mediated by social support.

A sense of Purpose in Life is an important aspect of ageing well which is related to older adult's social relationships. Social network types and the different sources of support they provide are theorized here as a pathway to maintaining a sense of purpose as we age. The study utilized a population sample from the 2016 and 2020 NZ Health, Work, and Retirement (NZHWR) longitudinal survey waves; N = 2869 (mean age of 65.82 years (SD = 6.40). A structural equation model investigated the relationship between Social Network Type and Purpose in Life and the mediating role of Social Support. The final model had a good fit to the data and explained 33.7% of the variance in Purpose in Life. Private, Self-Contained and Family Dependent network types (2016) were negatively related to Purpose in Life 4 years later (2020). Support from sense of Attachment, Reassurance of Worth, Reliable Alliance and Social Integration played a mediating role between Social Network type and Purpose in Life. These findings highlight the importance of social networks in maintaining a sense of purpose among older adults and highlight pathways for the types of networks, and kinds of social support they offer, which contribute to a sense of purpose in life. They underscore the importance of social support for the well-being of older adults and highlight the need to consider the quality and type of social networks and support they provide, when designing interventions to enhance well-being.

An Examination of Coping Strategies that Moderated the Effects of COVID-19-Related Stress on Anxiety Among Older Adults in Aotearoa/NZ.

Objectives: 1. To describe perceived stress and changes in anxiety and coping among older adults between 2018 and 2020. 2. To examine the moderating roles of social support, exercise, alcohol use, and smoking on the relationship between perceived stress and anxiety. Methods: Longitudinal data collected from 3275 participants (M = 68.1 years) as part of the NZ Health, Work, and Retirement study's 2018 and 2020 biennial surveys, were analyzed using hierarchical regression. Results: Older adults perceived COVID-19 as a low-level source of stress. Social support and alcohol use moderated the relationship between perceived mental stress and anxiety. At high-stress levels, only social support exerted a protective effect against the negative impact of stress on anxiety. Discussion: These findings support the general resilience of many older adults and highlight the effectiveness of coping strategies used by those groups who are more likely to be vulnerable to mental stress during a pandemic.

Immunological imprinting of humoral immunity to SARS-CoV-2 in children.

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

Local knowledge and unliveable narratives: How insights from family caregiving narratives can inform locally relevant ageing policy.

BACKGROUND AND OBJECTIVES: Accommodating local knowledge in national ageing policy demonstrates a country's intention to preserve local values, including cultural values of older adults' care. However, including local knowledge must provide space for nuanced and adaptive responses to it so that ageing policies can support families in adapting to changes and challenges around caregiving. RESEARCH DESIGN AND METHODS: This study interviewed members of 11 multigenerational households in Bali to understand the ways family carers use and resist local knowledge about multigenerational caregiving for older adults. RESULTS: Using qualitative analysis of the interplay between personal and public narratives, we found that narratives of local knowledge provide moral imperatives related to care, which shape expectations and a standard for evaluating the younger generations' behaviour. While most of the participants' accounts fit comfortably with these local narratives, some described challenges in which their life circumstances prevented them from identifying themselves as a virtuous carer. DISCUSSION AND IMPLICATIONS: Findings provide insight into the role of local knowledge in constructing caregiving function, carers' identities, family relationships, families' adaptation, and the influence of social structure (e.g., poverty and gender) on caregiving issues in Bali. These local narratives both confirm and dispute findings from other locations.

Home drinking practices among middle-class adults in midlife during the COVID-19 pandemic: Material ubiquity, automatic routines and embodied states.

INTRODUCTION: Harmful drinking is increasing among mid-life adults. Using social practice theory, this research investigated the knowledge, actions, materials, places and temporalities that comprise home drinking practices among middle-class adults (40-65 years) in Aotearoa New Zealand during 2021-2022 and post the COVID-19 pandemic lockdowns. METHODS: Nine friendship groups (N = 45; 26 females, 19 males from various life stages and ethnicities) discussed their drinking practices. A subset of 10 participants (8 female, 2 male) shared digital content (photos, screenshots) about alcohol and drinking over 2 weeks, which they subsequently discussed in an individual interview. Group and interview transcripts were thematically analysed using the digital content to inform the analysis. RESULTS: Three themes were identified around home drinking practices, namely: (i) alcohol objects as everywhere, embedded throughout spaces and places in the home; (ii) drinking practices as habitual, automatic and conditioned to mundane everyday domestic chores, routines and times; and (iii) drinking practices intentionally used by participants to achieve desired embodied states to manage feelings linked to domestic and everyday routines. DISCUSSION AND CONCLUSIONS: Alcohol was normalised and everywhere within the homes of these midlife adults. Alcohol-related objects and products had their own agency, being entangled with domestic routines and activities, affecting drinking in both automatic and intentional ways. Developing alcohol policy that would change its ubiquitous and ordinary status, and the 'automatic' nature of many drinking practices, is needed. This includes restricting marketing and availability to disrupt the acceptability and normalisation of alcohol in the everyday domestic lives of adults at midlife.

Early expression of CD94 and loss of CD96 on CD8+ T cells after allogeneic stem cell tranplantation is predictive of subsequent relapse and survival.

Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy. However, relapse of malignant disease is the primary cause of treatment failure and reflects loss of immunological graft-versus-leukemia effect. We studied the transcriptional and phenotypic profile of CD8+ T cells in the first month following transplantation and related this to risk of subsequent relapse. Single cell transcriptional profiling identified five discrete CD8+ T-cell clusters. High levels of T-cell activation and acquisition of a regulatory transcriptome were apparent in patients who went on to suffer disease relapse. A relapse-associated gene signature of 47 genes was then assessed in a confirmation cohort of 34 patients. High expression of the inhibitory receptor CD94/NKG2A on CD8+ T cells within the first month was associated with 4.8 fold increased risk of relapse and 2.7 fold reduction in survival. Furthermore, reduced expression of the activatory molecule CD96 was associated with 2.2 fold increased risk of relapse and 1.9 fold reduction in survival. This work identifies CD94 and CD96 as potential targets for CD8-directed immunotherapy in the very early phase following allogeneic transplantation with the potential to reduce long term relapse rates and improve patient survival.

Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation.

Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy although graft versus host disease and relapse remain major complications. We measured the serum protein expression of 92 inflammation-related markers from 49 patients at Day 0 (D0) and 154 patients at Day 14 (D14) following transplantation and related values to subsequent clinical outcomes. Low levels of 7 proteins at D0 were linked to GvHD whilst high levels of 7 proteins were associated with relapse. The concentration of 38 proteins increased over 14 days and higher inflammatory response at D14 was strongly correlated with patient age. A marked increment in protein concentration during this period associated with GvHD but reduced risk of disease relapse, indicating a link with alloreactive immunity. In contrast, patients who demonstrated low dynamic elevation of inflammatory markers during the first 14 days were at increased risk of subsequent disease relapse. Multivariate time-to-event analysis revealed that high CCL23 at D14 was associative of AGvHD, CXCL10 with reduced rate of relapse, and high PD-L1 with reduced overall survival. This work identifies a dynamic pattern of inflammatory biomarkers in the very early post-transplantation period and reveals early protein markers that may help to guide patient management.

CMV reactivation initiates long-term expansion and differentiation of the NK cell repertoire.

Introduction: NK cells play an important role in suppression of viral replication and are critical for effective control of persistent infections such as herpesviruses. Cytomegalovirus infection is associated with expansion of 'adaptive-memory' NK cells with a characteristic CD56dimCD16bright NKG2C+ phenotype but the mechanisms by which this population is maintained remain uncertain. Methods: We studied NK cell reconstitution in patients undergoing haemopoietic stem cell transplantation and related this to CMV reactivation. Results: NK cells expanded in the early post-transplant period but then remained stable in the absence of viral reactivation. However, CMV reactivation led to a rapid and sustained 10-fold increase in NK cell number. The proportion of NKG2C-expressing cells increases on all NK subsets although the kinetics of expansion peaked at 6 months on immature CD56bright cells whilst continuing to rise on the mature CD56dim pool. Phenotypic maturation was observed by acquisition of CD57 expression. Effective control of viral reactivation was seen when the peripheral NK cell count reached 20,000/ml. Discussion: These data show that short term CMV reactivation acts to reprogramme hemopoiesis to drive a sustained modulation and expansion of the NK cell pool and reveal further insight into long term regulation of the innate immune repertoire by infectious challenge.

Vaccine subtype and dose interval determine immunogenicity of primary series COVID-19 vaccines in older people.

Age is the strongest determinant of COVID-19 mortality, and over 2 billion people have received primary series vaccination with BNT162b2 (mRNA) or ChAdOx1 (adenoviral vector). However, the profile of sustained vaccine immunogenicity in older people is unknown. Here, we determine spike-specific humoral and cellular immunity to 8 months following BNT162b2 or ChAdOx1 in 245 people aged 80-98 years. Vaccines are strongly immunogenic, with antibodies retained in every donor, while titers fall to 23%-26% from peak. Peak immunity develops rapidly with standard interval BNT162b2, although antibody titers are enhanced 3.7-fold with extended interval. Neutralization of ancestral variants is superior following BNT162b2, while neutralization of Omicron is broadly negative. Conversely, cellular responses are stronger following ChAdOx1 and are retained to 33%-60% of peak with all vaccines. BNT162b2 and ChAdOx1 elicit strong, but differential, sustained immunogenicity in older people. These data provide a baseline to assess optimal booster regimen in this vulnerable age group.

Older People's Neighborhood Perceptions Are Related to Social and Emotional Loneliness and Mediated by Social Network Type.

BACKGROUND AND OBJECTIVES: Loneliness among older people is a public health issue; however, there is very weak support for the efficacy of individually focused interventions. A public health model, which includes the environmental influence on the formation of social networks and protection from loneliness, and theoretical approaches differentiating between social and emotional loneliness, suggest the importance of neighborhoods in preventing loneliness. This approach was used to test the influence of neighborhood factors on loneliness and the mediating role of social networks. RESEARCH DESIGN AND METHODS: A questionnaire survey of 917 people aged 60-100 years was conducted in one region of Aotearoa/New Zealand to assess loneliness, social network types, social participation, marital status, gender, health, and four aspects of neighborhood perceptions. RESULTS: Social and emotional loneliness scores were regressed on predicted demographic and social variables, followed by perceptions of Housing Satisfaction, Neighborhood Accessibility, Neighborhood Security, and Neighborhood Social Cohesion. Neighborhood variables added significant explanation of variance in both social and emotional loneliness. Mediation tests using PROCESS showed that the effects of all neighborhood variables were mediated by Private-Restricted or Locally Integrated Network types on Social Loneliness only. DISCUSSION AND IMPLICATIONS: These findings highlight the importance of neighborhood factors in relation to feelings of loneliness and the recognition of social network types as mediators of these relationships for social loneliness. The aspects of neighborhoods that prevent loneliness provide directions for planners and prevention programs. Interventions to prevent social loneliness can usefully and practicably focus on the housing and neighborhood environment.

Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia.

BACKGROUND: Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses. METHOD: We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms. RESULTS: Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination. CONCLUSIONS: These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.

Extended interval BNT162b2 vaccination enhances peak antibody generation.

The BNT162b2 vaccine is highly effective against COVID-19 infection and was delivered with a 3-week time interval in registration studies1. However, many countries extended this interval to accelerate population coverage with a single vaccine. It is not known how immune responses are influenced by delaying the second dose. We provide the assessment of immune responses in the first 14 weeks after standard or extended-interval BNT162b2 vaccination and show that delaying the second dose strongly boosts the peak antibody response by 3.5-fold in older people. This enhanced antibody response may offer a longer period of clinical protection and delay the need for booster vaccination. In contrast, peak cellular-specific responses were the strongest in those vaccinated on a standard 3-week vaccine interval. As such, the timing of the second dose has a marked influence on the kinetics and magnitude of the adaptive immune response after mRNA vaccination in older people.

Older People as Active Agents in Their Neighborhood Environments: Moving House Can Improve Quality of Life.

BACKGROUND AND OBJECTIVES: Neighborhood environments are an important aspect of well-being for older people. Developments of the general ecological model recognize older people as active agents who adapt their environments to fit their changing needs. We provide empirical support for a model suggested by Wahl et al., by examining interactions between neighborhood environments, personal situations, relocation, and quality of life (QoL) among older people. RESEARCH DESIGN AND METHODS: Two statistical models were tested with a sample of community-dwelling participants (aged 55-89) in the New Zealand Health, Work, and Retirement longitudinal surveys conducted in 2016 (T1) and 2018 (T2). Multiple linear regression assessed the association of perceptions of housing and neighborhood with QoL at T1 (n = 3682). RESULTS: QoL was predicted by housing satisfaction, and neighborhood satisfaction, accessibility, and trust (controlling for age, gender, marital status, home ownership, socioeconomic status, physical health, and mental health). Mixed analysis of variance showed that those who moved house between T1 and T2 reported lower housing and neighborhood satisfaction than nonmovers at T1. Over time T1-T2, movers reported less decline in housing satisfaction, and more positive change on all neighborhood perceptions, with higher perceptions of neighborhood accessibility than nonmovers at T2. DISCUSSION AND IMPLICATIONS: These findings support the theoretical model and provide the impetus for a more detailed study of the effects of the environment on well-being in older age. Housing and neighborhood environments are a very practical focus for social policy change at local and national levels.

Diverse experiences among older adults in Aotearoa/New Zealand during COVID-19 lockdown: A qualitative study.

OBJECTIVES: There are mixed results from studies of COVID-19-related anxiety. We explored older people's perspectives on anxiety and support during lockdown. METHODS: We thematically analysed 730 written comments from older community-dwelling adults aged 55-85 years in Aotearoa/New Zealand. RESULTS: Despite some anxiety during lockdown, for those who were retired, working at home or receiving wage subsidies, the experience was very enjoyable. Whether living alone or in households, anxieties were largely ameliorated by a sense of support from family, fellow citizens and government. In contrast, essential workers, those who lost employment and informal carers did not feel sufficient community support to alleviate their anxiety. CONCLUSIONS: Concerns about the plight of older people focus on stereotypes of isolated elders, ignoring the needs of workers and carers. The inductive approach taken to this study provided useful information about the success of supportive measures and highlighted the need to broaden the focus of concern.

Daytime fatigue as a predictor for subsequent retirement among older New Zealand workers.

OBJECTIVES: There is limited information on the role of fatigue on retirement, either independently or in association with poor sleep. The aim of this study was to examine the prospective association between daytime fatigue, measured as feeling tired or feeling worn out, independently and in relation to dissatisfaction with sleep, and subsequent retirement among 960 older workers in New Zealand. METHODS: Data from 2 consecutive surveys (2008 and 2010) of the New Zealand Health, Work, and Retirement Longitudinal Study were used. Poisson regression was used to investigate whether feeling tired and feeling worn out in 2008, along with dissatisfaction with sleep, were associated with self-reported retirement either due to health reasons or other reasons by 2010. RESULTS: The risk for retirement due to health reasons during a 2-year follow-up was 1.80-fold (95% confidence interval [CI] 1.16-2.45) among those who felt tired and 1.99-fold (95% CI 1.34-2.64) among those who felt worn out when compared to those not tired or not feeling worn out after adjusting for several sociodemographic, work characteristics and self-rated health. The risk for retirement due to health reasons was even higher when participant experienced both tiredness and feeling worn out. Dissatisfaction with sleep did not predict retirement due to health or other reasons. CONCLUSIONS: Our results highlight that workers at risk of subsequent retirement due to health reasons may be identified with rather simple questions on tiredness and feeling worn out even among generally healthy older workers.

mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant.

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80-96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.