Cognitive Ageing

Cognitive decline is the first outward sign of dementia, which has a major public health impact on individuals and governments around the world. As individuals age, cognitive abilities gradually start to deteriorate for independent or combined genetic and environmental causes. Given that very little can be done regarding our genetic inheritance, the focus of the current research is on modifiable risk factors across the life course. There is a well-established relationship between specific lifestyle behaviours and cognitive decline, but extremely limited research on the role of combined lifestyle factors. This chapter aims to describe the process of cognitive ageing on multiple cognitive domains (fluid and crystallised), highlighting the changes in cognitive performance occurring as a normal process of ageing, as well as the most severe forms of cognitive impairment indicative of probable risk of dementia. Also, the role of modifiable risk factors such as lifestyle behaviours (alcohol, smoking, physical activity and dietary patterns) will be evaluated in relation to healthy cognitive ageing and preventions of cognitive decline. There are many questions to be answered regarding the biological foundations of cognitive ageing across the spectrum, and the potential role of lifestyle behaviours in reverting the accelerated changes in the cognitive ageing process

The mediating role of low-grade inflammation on the prospective association between sleep and cognitive function in older men and women: 8-year follow-up from the English Longitudinal Study of Ageing

Suboptimal sleep patterns predict poorer cognitive function in older adults and induce inflammatory responses. Inflammation could also adversely affect cognitive function. This study explored whether systemic inflammation may be one biological mechanism through which sleep influences cognitive performance. Participants were 4877 men and women from the English Longitudinal Study of Ageing who were followed-up for 8 years starting at wave 4 (2008-09), through wave 6 (2012-13), and until wave 8 (2016-17). Sleep quality and duration were measured with self-reported questionnaires. Cognitive function was assessed objectively with tests of verbal fluency, memory (immediate and delayed recall) and time orientation. Analyses were stratified by sex and adjusted for socio-economic circumstances, health behaviours, limiting long-standing illness, medication, depressive symptoms, and baseline inflammation and cognition. In men, in comparison with optimal sleep duration, short sleep (≤6 h: β = -0.343, C.I. -0.611 to -0.076; >6-7 h: β = -0.263, C.I. -0.506 to -0.020) and long sleep (β = -0.536, C.I. -1.019 to -0.053) measured at baseline predicted lower scores in delayed memory recall at follow-up. In women, sleep duration was unrelated to cognitive performance at follow-up, and in both sexes, there was no relationship between sleep quality and follow-up cognitive performance. There was no evidence of mediating effects of inflammatory markers in the relationship between sleep measures and cognitive performance in both sexes. In conclusion, baseline short and long sleep duration is associated with follow-up cognitive performance in older men, but we found no evidence of any mediating effects of inflammation

Increased physical fitness is associated with higher executive functioning in people with dementia

Physical fitness (PF) has been associated with improved cognition in older age, but less is known about its effects on different cognitive domains in individuals diagnosed with dementia. We explored the associations between PF and cognitive performance in 40 healthy elderly and 30 individuals with dementia. Participants completed a battery of standardized cognitive tests (Mini-Mental State Exam, Verbal Fluency, Prospective and Retrospective Memory Questionnaire, Clock Drawing, and California Verbal Learning Test) and were classified into high versus low levels of PF based on their score on the Physical Fitness Questionnaire. Analyses took into account age, gender, education, occupation, head injury, Internet use, brain training, and past levels of exercise and revealed overall benefits of PF, in particular for the people with dementia. Discriminant analysis showed high accuracy of reclassification, with most errors being due to the misclassification of dementia cases as healthy when they had high PF. The first discriminant function accounted for 83% of the variance. Using individual estimates of this function, which reflected global cognitive performance, confirmed the beneficial role of PF in dementia, even when taking into account age, past level of exercise, and the number of years since the dementia diagnosis. Finally, univariate analyses confirmed the differential sensitivity of the cognitive tests, with MMSE and clock drawing showing reliable interaction effects. This work shows that PF is associated with a reduced level of cognitive deterioration expected with dementia, especially in executive functioning and provides empirical support for the cognitive benefits of interventions promoting PF for individuals with dementia

Role of inflammation in the socioeconomic inequalities of neurocognitive disorders

Background: Socioeconomic position has been shown to be associated with inflammation. However, little is known about the role of inflammation in socioeconomic inequalities in relation to neurocognitive disorders in later life and the potential underlying inflammatory mechanisms. This study has used longitudinal data to investigate the mediation effects of inflammation in the relationship between socioeconomic position and neurocognitive disorders in older adults. // Methods: Using data from the English Longitudinal Study of Ageing (ELSA, n = 4,815), we ascertained neurocognitive disorders using a recognised consensus criterion and included the following categories: (1) No Cognitive Impairment (NOCI) (2) Cognitive Impairment No Dementia (CIND) and (3) Dementia. We examined whether socioeconomic position (education, occupation, and wealth) measured in 2008/09 was associated with neurocognitive disorders measured in 2018/19. Mediation analyses were carried out to investigate the role of inflammatory markers [C-Reactive Protein (CRP), plasma fibrinogen and white blood cells (WBC)] in the association between socioeconomic inequalities and subsequent neurocognitive disorders. Sensitivity analyses were conducted to assess the mediating role of lifestyle behaviours and body mass index (BMI). // Results: Higher education, occupation and wealth were longitudinally associated with a lower likelihood of cognitive impairment and dementia. WBC mediated the association between latent socioeconomic position and CIND [β = -0.037 (CI: −0.06 to −0.01)], but not the association with dementia. Indirect effects were attenuated but remained significant when other mediators, such as lifestyle behaviours and BMI were considered. In a separate analysis accounting for main confounders, CRP and fibrinogen mediated the association between education and CIND, all three inflammatory biomarkers mediated the association of occupation and CIND, while WBC mediated the association between wealth and CIND. // Conclusion: These findings emphasise that socioeconomic inequalities in mid and later life could contribute to the prevalence of neurocognitive disorders in later life. Our results provide some evidence for the biological embedding of WBC in the association between socioeconomic inequalities and cognitive impairment via elevated inflammation. Future studies should explore other plausible biological mechanisms

The long arm of childhood intelligence on terminal decline:Evidence from the Lothian Birth Cohort 1921

The current study investigates the heterogeneity of cognitive trajectories at the end of life by assigning individuals into groups according to their cognitive trajectories prior to death. It also examines the role of childhood intelligence and education on these trajectories and group membership. Participants were drawn from the Lothian Birth Cohort of 1921 (LBC1921), a longitudinal study of individuals with a mean age of 79 years at study entry, and observed up to a maximum of five times to their early 90s. Growth mixture modelling was employed to identify groups of individuals with similar trajectories of global cognitive function measured with the Mini-Mental State Examination (MMSE) in relation to time to death, accounting for childhood intelligence, education, the time to death from study entry, and health conditions (hypertension, diabetes and cardiovascular disease). Two distinct groups of individuals (classes) were identified: a smaller class (18% of the sample) of individuals whose MMSE scores dropped linearly with about 0.5 MMSE points per year closer to death, and a larger group (82% of the sample) with stable MMSE across the study period. Only childhood intelligence was found to be associated with an increased probability of belonging to the stable class of cognitive functioning prior to death (odds ratio=1.08, standard error=0.02, p≤.001). These findings support a protective role of childhood intelligence, a marker of cognitive reserve, against the loss of cognitive function prior to death. Our results also suggest that terminal decline is not necessarily a normative process

Age-related deficits in memory encoding and retrieval in word list free recall

Although ageing is known to affect memory, the precise nature of its effect on retrieval and encoding processes is not well understood. Here, we examine the effect of ageing on the free recall of word lists, in which the semantic structure of word sequences was manipulated from unrelated words to pairs of associated words with various separations (between pair members) within the sequence. We find that ageing is associated with reduced total recall, especially for sequences with associated words. Furthermore, we find that the degree of semantic clustering (controlled for chance clustering) shows an age effect and that it interacts with the distance between the words within a pair. The results are consistent with the view that age effects in memory are mediated both by retrieval and by encoding processes associated with frontal control and working memory

Is engagement in intellectual and social leisure activities protective against dementia risk? Evidence from the English longitudinal study of ageing

Background: Studies have suggested that mentally stimulating activities and socially engaged lifestyles may reduce dementia risk; however, it is unclear which activities are more beneficial. Objective: We investigated intellectual and social leisure activities in relation to dementia incidence and explored the modifying role of sex and marital status in these associations. Methods: The sample was comprised of 8,030 participants aged 50+ from the English Longitudinal Study of Ageing, who joined at wave 1 (2002-2003), or waves 3 (2006-2007), or 4 (2008-2009). The end of the study period was wave 8 (2016-2017). Subdistribution hazard models investigated the role of leisure activities grouped into intellectual and social domains in relation to dementia while accounting for the risk of death. Subsequent analyses were conducted with individual leisure activities. Results: During the study period of up to 15 years, 412 participants developed dementia, and 2,192 died. We found that increased engagement in the intellectual activities’ domain was associated with a decreased dementia incidence (SHR 0.85, 95% CI 0.76–0.96, p = 0.007), independent of the risk of death in married individuals, but not in those who were single, divorced, or widowed. Individual analyses for each leisure activity showed independent associations for reading newspapers in females (SHR 0.65, 95% CI 0.49–0.84, p = 0.001), mobile phone usage in males (SHR 0.61, 95% CI 0.45–0.84, p = 0.002), and having hobbies for married individuals (SHR 0.70, 95% CI 0.51–0.95, p = 0.02). Conclusion: We found that intellectual leisure activities contribute to lower dementia risk in a representative population of English adults, suggesting intervention opportunities

Systemic inflammation and emotional responses during the COVID-19 pandemic

The impact of the COVID-19 pandemic on population mental health is of global concern. Inflammatory processes are thought to contribute to mental ill-health, but their role in experiences of psychological distress during the pandemic has not been investigated. We tested the hypothesis that elevated inflammatory biomarkers (high-sensitivity plasma C-reactive protein [CRP] and plasma fibrinogen) measured pre-pandemic would be positively predictive of increased depressive symptoms experienced during the pandemic. Data were analysed from the English Longitudinal Study of Ageing (ELSA), with 3574 individuals aged >50 for CRP and 3314 for fibrinogen measured in waves 8 (2016/17) or 9 (2018/19). Depressive symptoms were measured with a short version of the Centre for Epidemiological Studies Depression Scale (CES-D) pre-pandemic (2016–2019) and during the pandemic (June/July 2020). Participants with higher baseline CRP concentrations had 40% higher odds of developing depressive symptoms during the pandemic (ORadjusted = 1.40, 95% CI 1.12–1.73, p = 0.003) after full adjustment. Fibrinogen concentrations were also associated with depressive symptoms during the pandemic (ORadjusted = 1.23, 95% CI 1.04–1.46, p = 0.019), but this association was no longer significant after controlling for lifestyle factors (smoking status, alcohol consumption and physical activity). In this large population study, systemic inflammation measured 1–3 years pre-pandemic was associated with greater depressed mood during the early months of the pandemic. This finding is consistent with the hypothesis that higher levels of inflammation increase the vulnerability of older people to impaired mental health in the presence of the widespread stress of the COVID-19 pandemic