Dr David Batty

Are subjective memory complaints indicative of objective cognitive decline or depressive symptoms? Findings from the English Longitudinal Study of Ageing.

BACKGROUND: Maintaining cognitive function is an important aspect of healthy ageing. In this study, we examined age trajectories of cognitive decline in a large nationally representative sample of older people in England. We explored the factors that influence such decline and whether these differed by gender.

Key Points Question What is the association between various socioeconomic markers and dementia incidence? Findings This longitudinal cohort study found that lower wealth in late life, but not education, was associated with increased risk for dementia, suggesting that people with fewer financial resources were at higher risk. No substantive differences were identified in relation to the area of neighborhood deprivation; an age-cohort effect was observed, highlighting that socioeconomic inequalities were more robust among people born in later years. Meaning The association between socioeconomic status and dementia incidence in a contemporary cohort of older adults may be driven by wealth rather than education.

Socio-economic trajectories and cardiovascular disease mortality in older people: the English Longitudinal Study of Ageing

OBJECTIVE: To examine the prospective relation between animal companionship and biomarkers of ageing in older people

Insulin-like Growth Factor 1 (IGF-1) is associated with cardiovascular disease, itself a risk factor for hearing impairment, and, in animal studies, molecular evidence suggests a role for IGF-1 in hearing function. However, the link between IGF-1 and the occurrence of hearing impairment is untested in population-based studies of humans. A total of 4390 participants aged ≥50 y (mean [SD] age 64.2 [8.0] years at baseline, 55% women) from the English Longitudinal Study of Ageing provided serum levels of IGF-1 in 2008 and again in 2012. Hearing acuity was assessed by an objective hearing test (HearCheck handheld device) in 2014 when the prevalence was 38.2%. In the full cohort, IGF-1 was not associated with subsequent hearing impairment (OR5nmol/L increase; 95% CI: 1.01; 0.94, 1.09). However, this relationship appeared to differ by age (p-value for interaction = 0.03). Thus, in younger participants (aged 50-60 y, n = 1400), IGF-1 was associated with lower odds of hearing impairment (0.86; 0.73, 1.00) after adjustment for a range of potential confounders. Among people ≥60 y (n = 2990) there was a non-significant 'J'-shaped association. Our observational evidence that higher levels of IGF-1 appeared to confer some protection against hearing impairment in some older adults warrants replication in other prospective cohort studies.

Hearing loss is a major cause of disability: in people over 70 years of age in the UK around two-thirds report some form of hearing loss. The social and health consequences of hearing impairment are as considerable as the economic implications for care. There is strong evidence that several age-related chronic conditions, particularly cardiovascular disease (CVD), have their origins in early life and a shared aetiology between hearing impairment and CVD has been advanced in adults. Physical stature (height) captures exposure to early life psychosocial stress, adversity, somatic illness, and nutrition, and reveals an inverse relationship with CVD but studies on hearing impairment are very scarce. We related measured height (mean measure at wave 4 [2008] and 6 [2012]) to performance on an objective hearing examination at wave 7 (2014). In an analytical sample of 4,398 there were 1,682 cases (38%) of hearing impairment. We found evidence of an inverse relationship between height and later hearing impairment, such that taller study members experienced a lower risk. The odds ratio (95% confidence interval) for the increase of 5cm in height in a fully adjusted model was 0.92 (0.87, 0.98). While low height per se is of course not a risk factor for hearing impairment, it is more likely that one or more of the characteristics that it proxies – early life diet, illness, social adversity, cognition – has a role. Future research should therefore attempt to relate these individual, prospectively gathered indicators in childhood populations to hearing impairment in later life.

Depressive disorders are a leading cause of disability in older age. Although the role of psychosocial and behavioural predictors has been well examined, little is known about the biological origins of depression. Findings from animal studies have implicated insulin-like growth factor 1 (IGF-1) in the aetiology of this disorder. A total of 6017 older adults (mean age of 65.7 years; 55% women) from the English Longitudinal Study of Ageing provided serum levels of IGF-1 (mean=15.9 nmol l(-1), s.d. 5.7) during a nurse visit in 2008. Depression symptoms were assessed in the same year and again in 2012 using the eight-item Center for Epidemiologic Studies Depression Scale. Self-reports of a physician-diagnosis of depression were also collected at both time points. In separate analyses for men and women, the results from both the cross-sectional and longitudinal analyses revealed a 'U'-shaped pattern of association, such that lower and higher levels of IGF-1 were associated with a slightly elevated risk of depression, whereas the lowest risk was seen around the median levels. Thus, in men, with the lowest quintile of IGF-1 as the referent, the age-adjusted odds ratios (95% confidence interval) of developing depression symptoms after 4 years of follow-up, for increasing quintiles of IGF-1, were: 0.51 (0.28-0.91), 0.50 (0.27-0.92), 0.63 (0.35-1.15) and 0.63 (0.35-1.13) (P-value for quadratic association 0.002). Some attenuation of these effects was apparent after adjustment for co-morbidity, socioeconomic status and health behaviours. In conclusion, in the present study of older adults, there was some evidence that moderate levels of IGF-1 levels conferred a reduced risk of depression.

Our findings suggest the C-reactive protein-depression association is symptom-specific and modified by antidepressant treatment.

Authors reply: Duration of depressive symptoms significantly related to increase in mortality

We examined the little-tested associations between general cognitive function in middle and older age and later risk of death from chronic diseases. In the English Longitudinal Study of Ageing (2002-2012), 11,391 study participants who were 50-100 years of age at study induction underwent a battery of cognitive tests and provided a range of collateral data. In an analytical sample of 9,204 people (4,982 women), there were 1,488 deaths during follow-up (mean duration, 9.0 years). When we combined scores from 4 cognition tests that represented 3 acknowledged key domains of cognitive functioning (memory, executive function, and processing speed), cognition was inversely associated with deaths from cancer (per each 1-standard-deviation decrease in general cognitive function score, hazard ratio = 1.21, 95% CI: 1.10, 1.33), cardiovascular disease (hazard ratio = 1.71, 95% CI: 1.55, 1.89), other causes (hazard ratio = 2.07, 95% CI: 1.79, 2.40), and respiratory illness (hazard ratio = 2.48, 95% CI: 2.12, 2.90). Controlling for a range of covariates, such as health behaviors and socioeconomic status, and left-censoring to explore reverse causality had very little impact on the strength of these relationships. These findings indicate that cognitive test scores can provide relatively simple indicators of the risk of death from an array of chronic diseases and that these associations appear to be independent of other commonly assessed risk factors.

Abstract We examined the association between lifecourse socioeconomic status (SES) and the risk of type 2 diabetes at older ages, ascertaining the extent to which adult lifestyle factors and systemic inflammation explain this relationship. Data were drawn from the English Longitudinal Study of Ageing (ELSA) which, established in 2002, is a representative cohort study of ≥50-year olds individuals living in England. SES indicators were paternal social class, participants' education, participants' wealth, and a lifecourse socioeconomic index. Inflammatory markers (C-reactive protein and fibrinogen) and lifestyle factors were measured repeatedly; diabetes incidence (new cases) was monitored over 7.5 years of follow-up. Of the 6218 individuals free from diabetes at baseline (44% women, mean aged 66 years), 423 developed diabetes during follow-up. Relative to the most advantaged people, those in the lowest lifecourse SES group experienced more than double the risk of diabetes (hazard ratio 2.59; 95% Confidence Interval (CI) = 1.81-3.71). Lifestyle factors explained 52% (95%CI:30-85) and inflammatory markers 22% (95%CI:13-37) of this gradient. Similar results were apparent with the separate SES indicators. In a general population sample, socioeconomic inequalities in the risk of type 2 diabetes extend to older ages and appear to partially originate from socioeconomic variations in modifiable factors which include lifestyle and inflammation.

Duration of depressive symptoms and mortality risk: the English Longitudinal Study of Ageing (ELSA)

Abstract OBJECTIVE: Metabolically healthy obesity possibly reflects a transitional stage before the onset of metabolic dysfunction, but few studies have characterised this transition. We examined the behavioural and biological characteristics of healthy obese adults that progressed to an unhealthy state over 8 years follow-up. METHODS: Participants were 2422 men and women (aged 63.3±7.7 years, 44.2% men) from the English Longitudinal Study of Ageing. Obesity was defined as BMI ≥30 kg/m(2). Based on blood pressure (BP), HDL-cholesterol, triglycerides, HbA1c and C-reactive protein (CRP) participants were classified as 'healthy' (0 or 1 metabolic abnormality) or 'unhealthy' (≥2 metabolic abnormalities). RESULTS: Over 8 years follow-up, 44.5% of healthy obese subjects had transitioned into an unhealthy state, compared to only 16.6 and 26.2% of healthy normal-weight and overweight adults respectively. Compared with healthy obese adults who remained stable, those who progressed to an unhealthy state were more likely to have high BP (75.0% vs 37.0%, age- and sex-adjusted odds ratio (OR) 8.9, 95% CI 4.7-17.0), high CRP (53.7% vs 17.0%, OR=8.6, 95% CI 4.1-18.0), high HbA1c (46.3% vs 5.9%, OR=13.8, 95% CI 6.1-31.2) and high triglycerides (45.4% vs 11.9%, OR=5.9, 95% CI 2.9-12.0) at follow-up, with excess risk remaining independent of lifestyle factors including self-reported physical activity. Progression to an unhealthy state was also linked with significant gains in waist circumference (B=2.7, 95% CI, 0.5-4.9 cm). CONCLUSION: These data show that a healthy obesity phenotype is relatively unstable. Transition to an unhealthy state is characterised by multiple biological changes that are not fully explained by lifestyle risk factors.

Abstract BACKGROUND: Major depressive disorder and subthreshold depression have been associated with premature mortality. We investigated the association between depressive symptoms and mortality across the full continuum of severity. METHOD: We used Cox proportional hazards models to examine the association between depressive symptom severity, assessed using the eight-item Center for Epidemiological Studies Depression Scale (CES-D; range 0-8), and the risk of all-cause mortality over a 9-year follow-up, in 11 104 members of the English Longitudinal Study of Ageing. RESULTS: During follow-up, one fifth of study members died (N = 2267). Depressive symptoms were associated with increased mortality across the full range of severity (p trend < 0.001). Relative to study members with no symptoms, an increased risk of mortality was found in people with depressive symptoms of a low [hazard ratio (HR) for a score of 2 was 1.59, 95% confidence interval (CI) 1.40-1.82], moderate (score of 4: HR 1.80, 95% CI 1.52-2.13) and high (score of 8: HR 2.27, 95% CI 1.69-3.04) severity, suggesting risk emerges at low levels but plateaus thereafter. A third of participants (36.4%, 95% CI 35.5-37.3) reported depressive symptoms associated with an increased mortality risk. Adjustment for physical activity, physical illnesses, and impairments in physical and cognitive functioning attenuated this association (p trend = 0.25). CONCLUSIONS: Depressive symptoms are associated with an increased mortality risk even at low levels of symptom severity. This association is explained by physical activity, physical illnesses, and impairments in physical and cognitive functioning.

Metabolically healthy obesity: what is the role of sedentary behaviour?