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Environmental risk factors for dementia are poorly understood. Aluminium and fluorine in drinking water have been linked with dementia but uncertainties remain about this relationship.
In the largest longitudinal study in this context, we set out to explore the individual effect of aluminium and fluoride in drinking water on dementia risk and, as fluorine can increase absorption of aluminium, we also examine any synergistic influence on dementia.
We used Cox models to investigate the association between mean aluminium and fluoride levels in drinking water at their residential location (collected 2005–2012 by the Drinking Water Quality Regulator for Scotland) with dementia in members of the Scottish Mental Survey 1932 cohort who were alive in 2005.
A total of 1972 out of 6990 individuals developed dementia by the linkage date in 2012. Dementia risk was raised with increasing mean aluminium levels in women (hazard ratio per s.d. increase 1.09, 95% CI 1.03–1.15, P < 0.001) and men (1.12, 95% CI 1.03–1.21, P = 0.004). A dose-response pattern of association was observed between mean fluoride levels and dementia in women (1.34, 95% CI 1.28–1.41, P < 0.001) and men (1.30, 95% CI 1.22–1.39, P < 0.001), with dementia risk more than doubled in the highest quartile compared with the lowest. There was no statistical interaction between aluminium and fluoride levels in relation with dementia.
Higher levels of aluminium and fluoride were related to dementia risk in a population of men and women who consumed relatively low drinking-water levels of both.
Anxiety and depression are both important correlates of cognitive function. However, longitudinal studies investigating how they covary with cognition within the same individual are scarce. We aimed to simultaneously estimate associations of between-person differences and within-person variability in anxiety and depression with cognitive performance in a sample of non-demented older people.
Participants in the Lothian Birth Cohort 1921 study, a population-based narrow-age sample (mean age at wave 1 = 79 years, n = 535), were examined on five occasions across 13 years. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS) and cognitive performance was assessed with tests of reasoning, logical memory, and letter fluency. Data were analyzed using two-level linear mixed-effects models with within-person centering.
Divergent patterns were observed for anxiety and depression. For anxiety, between-person differences were more influential; people who scored higher on HADS anxiety relative to other same-aged individuals demonstrated poorer cognitive performance on average. For depression, on the other hand, time-varying within-person differences were more important; scoring higher than usual on HADS depression was associated with poorer cognitive performance relative to the average level for that participant. Adjusting for gender, childhood mental ability, emotional stability, and disease burden attenuated these associations.
The results from this study highlight the importance of addressing both between- and within-person effects of negative mood and suggest that anxiety and depression affect cognitive function in different ways. The current findings have implications for assessment and treatment of older age cognitive deficits.
The present study concerns the relation of mental and bodily characteristics to one another during ageing. The ‘common cause’ theory of ageing proposes that declines are shared across multiple, seemingly-disparate functions, including both physical and intellectual abilities. The concept of ‘reserve’ suggests that healthier cognitive (and perhaps bodily) functions from early in life are protective against the effects of senescence across multiple domains. In three waves of physical and cognitive testing data from the longitudinal Lothian Birth Cohort 1936 (n = 1,091 at age 70 years; n = 866 at 73; n = 697 at 76), we used multivariate growth curve modeling to test the ‘common cause’ and ‘reserve’ hypotheses. Support for both concepts was mixed: although levels of physical functions and cognitive functions were correlated with one another, physical functions did not decline together, and there was little evidence for shared declines in physical and mental functions. Early-life intelligence, a potential marker of system integrity, made a significant prediction of the levels, but not the slopes, of later life physical functions. These data suggest that common causes, which are likely present within cognitive functions, are not as far-reaching beyond the cognitive arena as has previously been suggested. They also imply that bodily reserve may be similar to cognitive reserve in that it affects the level, but not the slope, of ageing-related declines.
The Caltech imaging γ-ray telescope was launched by balloon from Alice Springs, NT, Australia and performed observations of the galactic center during the period 12.62 to 13.00 April 1988 UT. The first coded-aperture images of the galactic center region at energies above 30 keV show a single strong γ-ray source which is located 0.7±0.1° from the galactic nucleus and is tentatively identified as 1E1740.7-2942. If the source is at the distance of the galactic center, it is one of the most luminous objects in the galaxy at energies from 35 to 200 keV.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Tests requiring the pronunciation of irregular words are used to estimate premorbid cognitive ability in patients with clinical diagnoses, and prior cognitive ability in normal ageing. However, scores on these word-reading tests correlate with scores on the Mini-Mental State Examination (MMSE), a widely used screening test for possible cognitive pathology. This study aimed to test whether the word-reading tests’ correlations with MMSE scores in healthy older people are explained by childhood IQ or education.
Wechsler Test of Adult Reading (WTAR), National Adult Reading Test (NART), MMSE scores and information about education were obtained from 1024 70-year-olds, for whom childhood intelligence test scores were available.
WTAR and NART were positively correlated with the MMSE (r ≈ 0.40, p < 0.001). The shared variance of WTAR and NART with MMSE was significantly attenuated by ~70% after controlling for childhood intelligence test scores. Education explained little additional variance in the association between the reading tests and the MMSE.
MMSE, which is often used to index cognitive impairment, is associated with prior cognitive ability. MMSE score is related to scores on WTAR and NART largely due to their shared association with prior ability. Obtained MMSE scores should be interpreted in the context of prior ability (or WTAR/NART score as its proxy).
The analysis of regulations affecting addictive or habitual goods has drawn considerable controversy. Some studies have suggested that such regulations have only small welfare benefits, as consumers value these goods despite health benefits from quitting, while other studies suggest that information or behavioral problems make existing consumption decisions a poor guide to welfare evaluation. We examine potential utility offsets to health benefits of regulations affecting addictive or habitual goods theoretically and empirically. Our analysis focuses on individuals who consume these goods only, ignoring other social costs and benefits. Theoretically, we show the importance of several factors including: money saved in addition to health improvements; differentiating steady-state utility losses from short-term withdrawal costs; lack of utility loss for people dissuaded from starting to consume the good; and accounting for utility consequences of explicit or implicit cost increases. Our empirical analysis considers regulations that affect smoking. To measure the welfare cost of smoking cessation, we divide the population into those with more and less rational smoking behavior and use the valuation of smoking from more rational smokers to impute values of losses for less rational smokers. Our results show that the utility cost of smoking cessation is small relative to the health gains in people for whom withdrawal costs are the main utility loss of quitting, and even among people who have some ongoing loss, the utility offsets represent 20%–25% of the health gains. While marginal smokers induced to quit by regulations can be expected to have low or no steady-state loss, even this higher estimate is far below prevailing estimates of the utility cost of smoking used by the Food and Drug Administration and other analysts.
Epidemiological studies have reported inverse associations between various single healthy diet indices and lower levels of systemic inflammation, but rarely are they examined in the same sample. The aim of the present study was to investigate the potential relationships between biomarkers of systemic inflammation (C-reactive protein (CRP) and fibrinogen) and overall foods (dietary patterns), single foods (fruits and vegetables), and specific nutritive (antioxidants) and non-nutritive (flavonoids) food components in the same narrow-age cohort of older adults. The dietary intake of 792 participants aged 70 years from the Lothian Birth Cohort 1936 was assessed using a 168-item FFQ. Models were adjusted for age, sex, childhood cognitive ability, lifestyle factors and history of disease. Using logistic regression analyses, CRP (normal v. elevated) was favourably associated (at P< 0·05) with the ‘health-aware’ (low-fat) dietary pattern (unstandardised β = (0·200, OR 0·82, 95 % CI 0·68, 0·99) and fruit intake (unstandardised β = (0·100, OR 0·91, 95 % CI 0·82, 0·99), including flavonoid-rich apples (unstandardised β = (0·456, OR 0·63, 95 % CI 0·439, 0·946). Using linear regression analyses, fibrinogen (continuous) was inversely associated (at P< 0·05) with the Mediterranean dietary pattern (standardised β = (0·100), fruit intake (standardised β = (0·083), and combined fruit and vegetable intake (standardised β = (0·084). We observed no association between food components (antioxidant nutrients or specific flavonoid subclasses) and inflammatory markers. In the present cross-sectional study, nutrient-dense dietary patterns were associated with lower levels of systemic inflammation in older people. The results are consistent with dietary guidelines that promote a balanced diet based on a variety of plant-based foods.
People with dementia are extremely vulnerable in hospital and unscheduled
admissions should be avoided if possible.
To identify any predictors of general hospital admission in people with
dementia in a well-characterised national prospective cohort study.
A cohort of 730 persons with dementia was drawn from the Scottish
Dementia Research Interest Register (47.8% female; mean age 76.3 years,
s.d. = 8.2, range 50–94), with a mean follow-up period of 1.2 years.
In the age- and gender-adjusted multivariable model (n =
681; 251 admitted), Neuropsychiatric Inventory score (hazard ratio per
s.d. disadvantage 1.21, 95% CI 1.08–1.36) was identified as an
independent predictor of admission to hospital.
Neuropsychiatric symptoms in dementia, measured using the
Neuropsychiatric Inventory, predict non-psychiatric hospital admission of
people with dementia. Further studies are merited to test whether
interventions to reduce such symptoms might reduce unscheduled admissions
to acute hospitals.
In the above mentioned article by Radakovic et al., a typological error has been found in the Results section under the subheading ‘Systematic review’. At the beginning of the second paragraph, the number ‘166’ should read ‘116’.
That risk factors measured in middle age may not fully explain future
dementia risk implicates exposures acting earlier in life. Height may
capture early-life illness, adversity, nutrition and psychosocial
To investigate the little-explored association between height and
Individual participant meta-analysis using 18 prospective general
population cohort studies with identical methodologies (1994–2008;
n = 181 800).
Mean follow-up of 9.8 years gave rise to 426 and 667 dementia deaths in
men and women respectively. The mean heights were 174.4cm (s.d. = 7.3)
for men and 161.0cm (s.d. = 6.8) for women. In analyses taking into
account multiple covariates, increasing height was related to lower rates
of death from dementia in a dose–response pattern
(P⩽0.01 for trend). There was evidence of a differential
effect by gender (P = 0.016 for interaction). Thus, the
association observed in men (hazard ratio per s.d. decrease in height
1.24, 95% CI 1.11–1.39) was markedly stronger than that apparent in women
(HR = 1.13, 95% CI 1.03–1.24).
Early-life circumstances, indexed by adult height, may influence later
There are several scales used to detect apathy in disease populations. Since apathy is a prevalent symptom in many neurodegenerative diseases, this is an especially important context in which to identify and compare scales.
To provide an overview of apathy scales validated in generic and specific neurodegenerative disease populations, compare validation studies’ methodological quality and the psychometric properties of the validated apathy scales.
A systematic review of literature was conducted of articles published between 1980 and 2013. The final articles selected for review were rated on methodological quality and the psychometric properties of the scales used were interpreted.
Sixteen articles validating apathy scales were included in the review, five in a generic neurodegenerative sample and eleven in specific neurodegenerative samples. The methodological quality of specific studies varied from poor to excellent. The highest quality, which had psychometrically favorable scales, were the dementia apathy interview and rating (DAIR) and the apathy evaluation scale-clinical version (AES-C) in Alzheimer's disease and the Lille apathy rating scale (LARS) in Parkinson's disease. Generic neurodegenerative disease validation studies were of average methodological quality and yielded inconsistent psychometric properties.
Several instruments can be recommended for use in some specific neurodegenerative diseases. Other instruments should either be validated or developed to assess apathy in more generic populations.
We examined the associations between serum cholesterol measures, statin use, and cognitive function measured in childhood and in old age. The possibility that lifelong (trait) cognitive ability accounts for any cross-sectional associations between cholesterol and cognitive performance in older age, seen in observational studies, has not been tested to date.
Participants were 1,043 men and women from the Lothian Birth Cohort 1936 Study, most of whom had participated in a nationwide IQ-type test in childhood (Scottish Mental Survey of 1947), and were followed up at about age 70 years. Serum cholesterol measures included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and cholesterol:HDL cholesterol ratio. Cognitive outcome measures were age 70 IQ (using the same test as at age 11 years), general cognitive ability (g), processing speed, memory, and verbal ability.
Higher TC, higher HDL-C, and lower triglycerides were associated with higher age 70 cognitive scores in most cognitive domains. These relationships were no longer significant after covarying for childhood IQ, with the exception a markedly attenuated association between TC and processing speed, and triglycerides and age 70 IQ. In the fully adjusted model, all conventionally significant (p < 0.05) effects were removed. Childhood IQ predicted statin use in old age. Statin users had lower g, processing speed, and verbal ability scores at age 70 years after covarying for childhood IQ, but significance was lost after adjusting for TC levels.
These results suggest that serum cholesterol and cognitive function are associated in older age via the lifelong stable trait of intelligence. Potential mechanisms, including lifestyle factors, are discussed.
Reports of attitudes to aging from older people themselves are scarce. Which life course factors predict differences in these attitudes is unknown.
We investigated life course influences on attitudes to aging in healthy, community-dwelling people in the UK. Participants in the Lothian Birth Cohort 1936 completed a self-report questionnaire (Attitudes to Aging Questionnaire, AAQ) at around age 75 (n = 792, 51.4% male). Demographic, social, physical, cognitive, and personality/mood predictors were assessed, around age 70. Cognitive ability data were available at age 11.
Generally positive attitudes were reported in all three domains: low Psychosocial Loss, high Physical Change, and high Psychological Growth. Hierarchical multiple regression found that demographic, cognitive, and physical variables each explained a relatively small proportion of the variance in attitudes to aging, with the addition of personality/mood variables contributing most significantly. Predictors of attitudes to Psychosocial Loss were high neuroticism; low extraversion, openness, agreeableness, and conscientiousness; high anxiety and depression; and more physical disability. Predictors of attitudes to Physical Change were: high extraversion, openness, agreeableness, and conscientiousness; female sex; social class; and less physical disability. Personality predictors of attitudes to Psychological Growth were similar. In contrast, less affluent environment, living alone, lower vocabulary scores, and slower walking speed predicted more positive attitudes in this domain.
Older people's attitudes to aging are generally positive. The main predictors of attitude are personality traits. Influencing social circumstances, physical well-being, or mood may result in more positive attitudes. Alternatively, interventions to influence attitudes may have a positive impact on associated physical and affective changes.
Protein deficiency impairs local and systemic immune responses to Heligmosomoides bakeri infection but little is known about their individual and interactive impacts on tissue architecture of maternal lymphoid (thymus, spleen) and visceral (small intestine, kidney, liver, pancreas) organs during the demanding period of lactation. Using a 2×2 factorial design, pregnant CD1 mice were fed a 24% protein sufficient (PS) or a 6% protein deficient (PD) isoenergetic diet beginning on day 14 of pregnancy and were infected with 100 H. bakeri larvae four times or exposed to four sham infections. On day 20 of lactation, maternal organs were examined histologically and serum analytes were assayed as indicators of organ function. The absence of villus atrophy in response to infection was associated with increased crypt depth and infiltration of mast cells and eosinophils but only in lactating dams fed adequate protein. Infection-induced lobular liver inflammation was reduced in PD dams, however, abnormalities in the kidney caused by protein deficiency were absent in infected dams. Bilirubin and creatinine were highest in PD infected mice. Infection-induced splenomegaly was not due to an increase in the lymphoid compartment of the spleen. During lactation, infection and protein deficiency have interactive effects on extra-intestinal pathologies.
We apply a living polymerization theory to describe cooperative string-like particle rearrangement clusters observed in simulations of a coarse-grained polymer melt. The theory quantitatively describes the interrelation between the average string length L, configurational entropy Sconf, and the order parameter for string assembly Φ without free parameters. Combining this theory with the Adam-Gibbs (AG) model allows us to predict the relaxation time τ in a lower temperature T range than accessible by current simulations. In particular, the combined theories suggest a return to Arrhenius behavior near Tg and a low T residual entropy, thus avoiding a Kauzmann ‘entropy crisis’.
We describe the current, 9-spacecraft Interplanetary Network (IPN). The IPN detects about
325 gamma-ray bursts per year, of which about 100 are not localized by any other missions.
We give some examples of how the data, which are public, can be utilized.
Life-course socioeconomic factors may have a role in dementia aetiology but there is a current paucity of studies. Meta-analyses of individual participant data would considerably strengthen this evidence base.
To examine the association between socioeconomic status in early life and adulthood with later dementia death.
Individual participant meta-analysis of 11 prospective cohort studies (1994–2004, n = 86508).
Leaving full-time education at an earlier age was associated with an increased risk of dementia death in women (fully adjusted hazard ratio (HR) for age ⩽14 v. age ⩾16: HR = 1.76, 95% Cl 1.23–2.53) but not men. Occupational social class was not statistically significantly associated with dementia death in men or women.
Lower educational attainment in women was associated with an increased risk of dementia-related death independently of common risk behaviours and comorbidities.