The associations of socioeconomic status with incident dementia and Alzheimer's disease are modified by leucocyte telomere length: a population-based cohort study.

Socio-economic status (SES) and biological aging are risk factors for dementia, including Alzheimer's disease, however, it is less clear if the associations with SES vary sufficiently across different biological age strata. We used data from 331,066 UK Biobank participants aged 38-73 with mean follow-up of 12 years to examine if associations between SES (assessed by educational attainment, employment status and household income) and dementia and Alzheimer's disease are modified by biological age (assessed by leucocyte telomere length: LTL). Diagnosis of events was ascertained through hospital admissions data. Cox regressions were used to estimate hazard ratios [HRs]. A consistent dose-response relationship was found, with participants in low SES and shorter LTL strata (double-exposed group) reporting 3.28 (95% confidence interval [CI] 2.57-4.20) and 3.44 (95% CI 2.35-5.04) times higher risks of incident dementia and Alzheimer's disease respectively, compared to those of high SES and longer LTL (least-exposed group). Of interest is a synergistic interaction between SES and LTL to increase risk of dementia (RERI 0.57, 95% CI 0.07-1.06) and Alzheimer's disease (RERI 0.79, 95% CI 0.02-1.56). Our findings that SES and biological age (LTL) are synergistic risk factors of dementia and Alzheimer's disease may suggest the need to target interventions among vulnerable sub-groups.

Neighbourhood residential density, urbanicity and incident dementia and Alzheimer's disease: A 12-year prospective cohort study from the UK Biobank.

INTRODUCTION: An increasing proportion of global population is exposed to urban densification in an aging society. However, little is known of the role of residential density and urbanicity on the risk of developing dementia including Alzheimer's disease. We examined long-term associations between residential density and urbanicity and risks of incident dementia and Alzheimer's disease. METHODS: This prospective cohort study included participants from the UK Biobank who lived at the same residential address, had no self-reported neurological conditions and without dementia at baseline. Residential density was measured as the number of dwelling units within 1-km street neighbourhood of participant's home address. A composite index of urbanicity was developed from neighbourhood-level z-standardized densities of housing, retail, public transport and street centrality. Hazard ratios were derived from Cox proportional hazard models adjusted for known risk factors. RESULTS: The analytic sample included 239,629 participants aged 38-72 years. During a median follow-up of 12.3 years (interquartile range 11.5-13.0 years), 2,176 participants developed dementia and 1,004 Alzheimer's disease. After adjustments for potential risk factors, each 1,000 units/Km2 increment in residential density was associated with higher risks of dementia (hazard ratio [HR]=1.10, 95% confidence interval [CI]: 1.06-1.15) and Alzheimer's disease (HR=1.10, 95% CI: 1.04-1.16). Consistently, categorical models showed that living in neighbourhoods of higher residential density and urbanicity were associated with higher risks of dementia (HR = 1.30, 95% CI: 1.12-1.51 for the highest density quintile compared to the lowest and HR = 1.21, 95% CI: 1.05-1.39 for the highest urbanicity quintile relative to the lowest). The associations were more pronounced in female, age >65 years, and among participants of the low income and those being frail and having shorter leucocyte telomere length (LTL). CONCLUSIONS: Higher residential density and urbanicity was found to be positively associated with elevated risks of dementia and Alzheimer's disease. Optimizing neighbourhood residential density maybe one of the upstream considerations for mitigating against neurodegenerative diseases.

Recurrent depression has persistent effects on cognition but this does not appear to be mediated by neuroinflammation.

BACKGROUND: Later-life depression appears to be different to depression in younger adults. The underlying pathology may also differ. Depression is linked to dementia but whether it is a risk factor or an early sign of a developing dementia remains unclear. Neuroinflammation is increasingly recognised in both depression and Alzheimer's Disease. AIMS: To investigate the link between depression, inflammation and dementia. We hypothesised that recurrent depression has adverse effects on performance in cognitive tests in middle to older age and that this effect is modified by anti-inflammatory medication. METHODS: We identified UK based cohort studies which included individuals aged >50, had medical information, results from detailed cognitive testing and had used reliable measures to assess depression. Individuals with recurrent depression had ≥ 2 episodes of depression. Controls had no history of depression. The presence/absence of inflammatory illness was assessed using a standardised list of inflammatory conditions. Individuals with dementia, chronic neurological and psychotic conditions were excluded. Logistic and linear regression were used to examine the effect of depression on cognitive test performance and the mediating effect of chronic inflammation. RESULTS: Unexpectedly in both studies there was evidence that those with recurrent depression performed better in some cognitive tasks (e.g Mill Hill vocabulary) but worse in others (e.g. reaction time). In UK Biobank there was no evidence that anti-inflammatories moderated this effect. LIMITATIONS: Cross-sectional assessment of cognition. CONCLUSIONS: Although previous recurrent depression has small effects on cognitive test performance this does not appear to be mediated by chronic inflammatory disease.

Sleep disturbance and daytime sleepiness predict vascular dementia.

BACKGROUND: Disturbed sleep is common throughout the community and is associated with an increase in daytime sleepiness, both of which, in turn are associated with an increased risk of ischaemic vascular disease. The hypothesis that sleep disturbances are predictive of dementia, and in particular vascular dementia was tested in a large community-based cohort of older men. METHODS: A questionnaire on sleep disturbances was administered to 1986 men aged 55-69 years in the Caerphilly Cohort Study and 10 years later the men were examined clinically for evidence of dementia or cognitive impairment with no dementia (CIND). FINDINGS: Approximately 20% of the men reported disturbed sleep and 30% reported 'severe' daytime sleepiness. Ten years later 1,225 men (75% of the surviving men in the cohort) were tested and 268 (22%) were found to be cognitively impaired with 93 (7.6%) showing clear evidence of dementia and the remaining 175 (14.3%) showing evidence of CIND. After adjustment for possible confounding, including cognitive function and the taking of sleeping tablets at baseline, sleep disturbances appeared to be predictive of dementia and CIND of vascular origin, while there was no suggestion of prediction of non-vascular cognitive impairment by sleep. Prediction of vascular dementia appeared to be particularly strong for daytime sleepiness, with an adjusted OR of 4.44 (95% CI 2.05 to 9.61). Further adjustments for psychological distress at baseline reduced the size of the relationships, but the ORs remain large, consistent with a direct positive effect of sleep disturbance on vascular dementia. INTERPRETATION: Sleep disturbances, and in particular severe daytime sleepiness, appear to be strongly predictive of vascular dementia, but have no predictive power for non vascular dementia.

Glucoregulation has greater impact on cognitive performance than macro-vascular disease in men with type 2 diabetes: data from the Caerphilly study.

OBJECTIVE: To compare vascular and glucose related mechanisms of type 2 diabetes on cognitive performance. RESEARCH DESIGN AND METHODS: A cross-sectional observational study of type 2 diabetes defined by non insulin dependant self-report diabetes or fasting blood glucose < or = 7.0 mmol/l of 2205 men eligible for the third phase of the Caerphilly Collaborative Heart Disease Study. Men were aged 55-69 years at time of testing. Tests of cognitive function included NART (crystallised IQ), AH4 (fluid IQ), verbal fluency (executive function) Cambridge Cognitive Examination (CAMCOG) and Mini Mental State Examination (MMSE) (global function), four choice serial reaction time (psychomotor function) and memory. Men with prior stroke were omitted from the analysis. RESULTS: Men with diabetes showed cognitive deficits for verbal fluency, National Adult Reacting Test (NART) and AH4. Adjusting for vascular risk factors had minimal effect. Including blood glucose removed the deficit for verbal fluency and NART but the effect on AH4 score (-2.58; 95% CI: -5.0, -0.1, p = 0.039) was retained. More detailed analyses of AH4 score on men with diabetes showed a curvilinear relationship indicating that men with both low and high glucose levels had worse performance (AH4 = -66 + 80 log(e) glucose - 18 log(e )glucose(2); 95% CI: -29, -6; p=0.002). CONCLUSIONS: These data identify a direct effect of glucose regulation on cognitive performance associated with diabetes in a population sample. These data suggest that an effect of glucose regulation on cognitive performance in diabetes is distinct from any effect of macro-vascular disease.

Is type A behavior really a trigger for coronary heart disease events?

OBJECTIVE: The purpose of this study was to compare chronic with acute mechanisms by which Type A might predict incident coronary heart disease (CHD). METHOD: The study included 2394 men aged 50 to 64 years who were assessed for CHD, Type A behavior, and CHD risk factors. Type A was assessed using the Jenkins Activity Survey (JAS), the Bortner scale, and the Framingham scale. Further examinations were completed at 5 and 9 years for incident CHD. RESULTS: After 9 years, there was no increased risk of CHD associated with any Type A score. Nevertheless, high Bortner scores were associated with increased risk of incident CHD at 5 years and high JAS and Bortner scores were associated with a decreased risk between 5 and 9 years. Further analysis of Type A scores on time to first coronary event found strong inverse associations for all type A scores (JAS = 205 -0.49 months to first event, 95% CI = -0.20, -0.78, p =.001) (Bortner = 176 -0.27 months; 95% CI = -0.10, -0.44; p =.002) (Framingham = 0.44 -0.0011 months; 95% CI = -0.0002, -0.0019; p =.01). CONCLUSIONS: The data show Type A is a strong predictor of when incident coronary heart disease (or coronary event) will occur rather than if it will occur. These findings suggest that Type A increases exposure to potential triggers, rather than materially affecting the process of atherosclerosis.

Advice to eat fish and mood: a randomised controlled trial in men with angina.

People with high intake of fish have lower reported rates of depression and a small trial in psychiatric patients suggested that fish oil supplements reduced episodes of depression and mania. As part of a factorial trial of interventions to reduce mortality in angina 452 men were randomised to advice to eat more fatty fish or no fish advice. Maxepa fish oil capsules were supplied to men who found the fish unpalatable. Fish intake and mood were assessed at baseline and six months. Most men (83%) had mood assessed using the Derogatis Stress Profile at baseline and follow-up. Self reported intake of fish was higher in the fish advice group at six months. There was, however, no difference in depression or anxiety in those allocated to receive fish advice. After controlling for baseline mood, the difference in depression score between those randomised to fish advice and those not was 1.29 (95% CI -0.29 to 2.88) and the difference in anxiety was 0.82 (95% CI -0.57 to 2.22) with positive differences indicating more depression or anxiety in those allocated to the fish arm. This trial provides no evidence that increased fatty fish intake in people without depressive symptoms has any substantial effect on mood.

Vascular disease and cognitive function in older men in the Caerphilly cohort.

OBJECTIVES: Stroke can impair cognitive function, but the associations between other manifestations of vascular disease and cognitive function have not been adequately studied in representative population samples of subjects. We report the associations between cardiac and peripheral vascular disease and cognitive function for a large representative sample of men in Caerphilly, South Wales, UK. DESIGN: The Caerphilly cohort is the basis of on-going studies of vascular disease, of cognitive function and of predictors of these. We have made intensive attempts to identify all cases of vascular disease: myocardial infarction, angina, ECG ischaemia, peripheral vascular disease (intermittent claudication) and stroke. Here we present data on associations between vascular disease and cognitive function. SETTING: The study is based upon a representative population sample of over 1,500 men in South Wales, aged 55-69 years when cognitive function was measured. The men, and hospital and GP notes relating to them, had been repeatedly examined for evidence of vascular disease during the previous ten years. MAIN OUTCOME MEASURES: Standard tests of cognitive function: the AH4, CAMCOG, MMSE and choice reaction time. RESULTS: After the omission of men who had had a stroke, we detected significant associations between cognitive function and the presence of angina, ECG ischaemia, past myocardial infarction and intermittent claudication. The strength of the associations between cognitive function and the various manifestations of vascular disease were similar, and the various cognitive function tests showed effects of similar size. Overall, cardiac and peripheral vascular disease is associated with a significant reduction in cognitive function equivalent to about one sixth of the standard deviation of a number of tests of cognitive function. The size of this effect is roughly equivalent to the decline in cognitive performance over five years of ageing. CONCLUSIONS: Subjects with evidence of cardiac or peripheral vascular disease have on average a significant reduction in cognitive function equivalent to about four or five years of additional age. The effect of long-term, low-dose aspirin on cognitive decline should now be tested.