Tom C. Russ

Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia

OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45–1.80]; men: pooled RR 1.58 [95% CI 1.38–1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86–2.94) in women and 1.73 (95% CI 1.61–1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35–1.73) in women and 1.49 (95% CI 1.31–1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08–1.30]; P < 0.001). CONCLUSIONS Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.

Environmental risk factors for dementia: a systematic review

BackgroundDementia risk reduction is a major and growing public health priority. While certain modifiable risk factors for dementia have been identified, there remains a substantial proportion of unexplained risk. There is evidence that environmental risk factors may explain some of this risk. Thus, we present the first comprehensive systematic review of environmental risk factors for dementia.MethodsWe searched the PubMed and Web of Science databases from their inception to January 2016, bibliographies of review articles, and articles related to publically available environmental data. Articles were included if they examined the association between an environmental risk factor and dementia. Studies with another outcome (for example, cognition), a physiological measure of the exposure, case studies, animal studies, and studies of nutrition were excluded. Data were extracted from individual studies which were, in turn, appraised for methodological quality. The strength and consistency of the overall evidence for each risk factor identified was assessed.ResultsWe screened 4784 studies and included 60 in the review. Risk factors were considered in six categories: air quality, toxic heavy metals, other metals, other trace elements, occupational-related exposures, and miscellaneous environmental factors. Few studies took a life course approach. There is at least moderate evidence implicating the following risk factors: air pollution; aluminium; silicon; selenium; pesticides; vitamin D deficiency; and electric and magnetic fields.ConclusionsStudies varied widely in size and quality and therefore we must be circumspect in our conclusions. Nevertheless, this extensive review suggests that future research could focus on a short list of environmental risk factors for dementia. Furthermore, further robust, longitudinal studies with repeated measures of environmental exposures are required to confirm these associations.

Psychological distress in relation to site specific cancer mortality: pooling of unpublished data from 16 prospective cohort studies.

Objective To examine the role of psychological distress (anxiety and depression) as a potential predictor of site specific cancer mortality. Design Pooling of individual participant data from 16 prospective cohort studies initiated 1994-2008. Setting Nationally representative samples drawn from the health survey for England (13 studies) and the Scottish health survey (three studies). Participants 163u2009363 men and women aged 16 or older at study induction, who were initially free of a cancer diagnosis, provided self reported psychological distress scores (based on the general health questionnaire, GHQ-12) and consented to health record linkage. Main outcome measure Vital status records used to ascertain death from 16 site specific malignancies; the three Scottish studies also had information on cancer registration (incidence). Results The studies collectively contributed an average of 9.5 years of mortality surveillance during which there were 16u2009267 deaths (4353 from cancer). After adjustment for age, sex, education, socioeconomic status, body mass index (BMI), and smoking and alcohol intake, and with reverse causality (by left censoring) and missing data (by imputation) taken into account, relative to people in the least distressed group (GHQ-12 score 0-6), death rates in the most distressed group (score 7-12) were consistently raised for cancer of all sites combined (multivariable adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.48) and cancers not related to smoking (1.45, 1.23 to 1.71), as well as carcinoma of the colorectum (1.84, 1.21 to 2.78), prostate (2.42, 1.29 to 4.54), pancreas (2.76, 1.47 to 5.19), oesophagus (2.59, 1.34 to 5.00), and for leukaemia (3.86, 1.42 to 10.5). Stepwise associations across the full range of distress scores were observed for colorectal and prostate cancer. Conclusion This study contributes to the growing evidence that psychological distress might have some predictive capacity for selected cancer presentations, in addition to other somatic diseases.

Association Between Psychological Distress and Liver Disease Mortality: A Meta-analysis of Individual Study Participants

BACKGROUND & AIMSnRisk factors for cardiovascular disease, such as obesity and hypertension, have been associated with nonalcoholic fatty liver disease. Psychological distress (symptoms of anxiety and depression) is a risk factor for cardiovascular disease, so it might also be associated, directly or indirectly, with liver disease. We investigated the relationship between psychological distress (measured by the 12-item General Health Questionnaire [GHQ]) and liver disease mortality.nnnMETHODSnWe performed a meta-analysis of data from individual participants in 16 prospective studies of the general population in the United Kingdom, initiated from 1994 through 2008. Subjects were assigned to groups based on GHQ score: 0 (no distress), 1-3, 4-6, or 7-12.nnnRESULTSnWe analyzed data from 166,631 individuals (55% women; mean ± SD age, 46.6 ± 18.4 years; range, 16-102 years). During a mean follow-up period of 9.5 years, 17,368 participants died (457 with liver disease). We found a significant increase in liver disease mortality with increase in GHQ score (Ptrend < .001). The age- and sex-adjusted hazard ratio for the highest GHQ score category (ie, 7-12), compared with the 0 score category, was 3.48 (95% confidence interval: 2.68-4.52). After adjustment for health behaviors, socioeconomic status, body mass index, and diabetes, this hazard ratio decreased to 2.59 (95% confidence interval: 1.82-3.68).nnnCONCLUSIONSnBased on a meta-analysis, psychological distress is associated with liver disease mortality, although this finding requires additional analysis. Although one is not likely to cause the other, we provide additional evidence for the deleterious effects of psychological problems on physical health.

Dose-Response Association Between Psychological Distress and Risk of Completed Suicide in the General Population

Elevated suicide rates in people with clinical depression, as indexed by hospitalizations or use of psychiatric outpatient services, are well documented. However, the association between depression across the full range of severity and subsequent suicide risk is unknown. With single-cohort studies insufficiently powered to examine this relation, to our knowledge, we provide the first pooling of individual-level data from a series of large general population–based cohort studies.

Geographical variation in dementia: examining the role of environmental factors in Sweden and Scotland.

Background: This study aimed to estimate the magnitude of geographical variation in dementia rates and suggest explanations for this variation. Small-area studies are scarce, and none has adequately investigated the relative contribution of genetic and environmental factors to the distribution of dementia. Methods: We present 2 complementary small-area hierarchical Bayesian disease-mapping studies using the comprehensive Swedish Twin Registry (n = 27,680) and the 1932 Scottish Mental Survey cohort (n = 37,597). The twin study allowed us to examine the effect of unshared environmental factors. The Scottish Mental Survey study allowed us to examine various epochs in the life course—approximately age 11 years and adulthood. Results: We found a 2- to 3-fold geographical variation in dementia odds in Sweden, after twin random effects—likely to capture genetic and shared environmental variance—were removed. In Scotland, we found no variation in dementia odds in childhood but substantial variation, following a broadly similar pattern to Sweden, by adulthood. Conclusions: There is geographical variation in dementia rates. Most of this variation is likely to result from unshared environmental factors that have their effect in adolescence or later. Further work is required to confirm these findings and identify any potentially modifiable socioenvironmental risk factors for dementia responsible for this geographical variation in risk. However, if these factors do exist and could be optimized in the whole population, our results suggest that dementia rates could be halved.

Data science for mental health: a UK perspective on a global challenge

Data science uses computer science and statistics to extract new knowledge from high-dimensional datasets (ie, those with many different variables and data types). Mental health research, diagnosis, and treatment could benefit from data science that uses cohort studies, genomics, and routine health-care and administrative data. The UK is well placed to trial these approaches through robust NHS-linked data science projects, such as the UK Biobank, Generation Scotland, and the Clinical Record Interactive Search (CRIS) programme. Data science has great potential as a low-cost, high-return catalyst for improved mental health recognition, understanding, support, and outcomes. Lessons learnt from such studies could have global implications.

Geographical Variation in Dementia Mortality in Italy, New Zealand, and Chile: The Impact of Latitude, Vitamin D, and Air Pollution

Background: Dementia risk is reported as being higher in the north compared to the south, which may be related to vitamin D deficiency. If this were the case, an opposite gradient of risk would be observed in the southern hemisphere, but this has not been investigated previously. Methods: We calculated standardised mortality ratios (SMRs) for deaths in 2012 where dementia (Alzheimers disease, vascular or unspecified dementia) was recorded as the underlying cause for 20 regions in Italy, 20 District Health Board areas in New Zealand and 29 Health Service areas in Chile. Results: Dementia SMRs were higher in northern than central or southern Italy. The inverse pattern was seen in women in New Zealand, with rates higher on South Island than North Island. However, dementia risk was raised in eight regions in the north and centre of Chile in both men and women. Conclusions: Geographical variation plays a key role in dementia risk, but patterns vary in men and women. In the northern hemisphere, dementia mortality is higher in the north, but the pattern in the southern hemisphere is more complex.

The Edinburgh Consensus: preparing for the advent of disease-modifying therapies for Alzheimer's disease

ContextThis commentary discusses the implications of disease-modifying treatments for Alzheimer’s disease which seem likely to appear in the next few years and results from a meeting of British experts in neurodegenerative diseases in Edinburgh. The availability of such treatments would help change public and professional attitudes and accelerate engagement with the prodromal and preclinical populations who might benefit from them. However, this would require an updated understanding of Alzheimer’s disease, namely the important distinction between Alzheimer’s disease and Alzheimer’s dementia.ConsensusSince treatments are likely to be most effective in the early stages, identification of clinically relevant brain changes (for example, amyloid burden using imaging or cerebrospinal fluid biomarkers) will be crucial. While current biomarkers could be useful in identifying eligibility for new therapies, trial data are not available to aid decisions about stopping or continuing treatment in clinical practice. Therefore, effective monitoring of safety and effectiveness when these treatments are introduced into clinical practice will be necessary to inform wide-scale use. Equity of access is key but there is a tension between universal access for everyone with a diagnosis of Alzheimer’s disease and specifying an eligible population most likely to respond. We propose the resources necessary for an optimal care pathway as well as the necessary education and training for primary and secondary care.ConclusionThe majority of current services in the UK and elsewhere would not be able to accommodate the specialist investigations required to select patients and prescribe these therapies. Therefore, a stepped approach would be necessary: from innovating sentinel clinical-academic centres that already have capacity to deliver the necessary phase IV trials, through early adoption in a hub and spoke model, to nationwide adoption for true equity of access. The optimism generated by recent and anticipated developments in the understanding and treatment of Alzheimer’s disease presents a great opportunity to innovate and adapt our services to incorporate the next exciting development in the field of dementia.

Pulmonary function as a risk factor for dementia death: an individual participant meta-analysis of six UK general population cohort studies

Background In addition to being associated with all-cause mortality and cardiovascular disease mortality, lung function has been linked with dementia. However, existing studies typically provide imprecise estimates due to small numbers of outcome events and are based on unrepresentative samples of the general population. Methods Individual participant meta-analysis of six cohort studies from the Health Survey for England and the Scottish Health Survey (total N=54u2005671). Dementia-related mortality was identified by mention of dementia on any part of the death certificate (mean follow-up 11.7u2005years). Study-specific Cox proportional hazard models of the association between lung function and dementia-related death were pooled using random effect meta-analysis to produce overall results. Results There was a dose–response association between poorer lung function and a higher risk of dementia-related death (age- and sex-adjusted HR compared to highest quartile of forced expiratory volume in 1u2005s (FEV1), 95% CI: second quartile 1.32, 0.99 to 1.76; third quartile 1.78, 1.30 to 2.43; fourth (lowest) quartile 2.74, 1.73 to 4.32). There was no significant heterogeneity in study-specific estimates (I2=0%). Controlling for height, socioeconomic status, smoking and general health attenuated but did not remove the association (second quartile 1.15, 0.82 to 1.62; third quartile 1.37, 0.96 to 1.94; fourth quartile 2.09, 1.17 to 3.71). Results for forced vital capacity and peak flow were similar. Conclusions In these general population samples, the relation between three measures of lung function and dementia death followed a dose–response gradient. Being in the bottom quartile of lung function was associated with a doubling of the risk.