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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.
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.
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.
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.
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.
Evidence from observational studies to date suggests that healthy dietary patterns are associated with better cognitive performance in later life. We examined the extent to which childhood intelligence quotient (IQ) and socioeconomic status account for this association.
Analyses were carried out on 882 participants in the Lothian Birth Cohort 1936 Study. Four dietary patterns were extracted using principal components analysis of a food frequency questionnaire, namely “Mediterranean-style,” “health aware,” “traditional,” and “sweet foods.” Cognitive function was assessed at the age of 70 years, including general (g) cognitive ability, processing speed, memory, and verbal ability.
Before adjustment for childhood IQ and socioeconomic status, the “Mediterranean-style” dietary pattern was associated with significantly better cognitive performance (effect size as partial eta-square (ηp2) range = 0.005 to 0.055), and the “traditional” dietary pattern was associated with poorer performance on all cognitive domains measured in old age (ηp2 = 0.009 to 0.103). After adjustment for childhood IQ (measured at the age of 11 years) and socioeconomic status, statistical significance was lost for most associations, with the exception of verbal ability and the “Mediterranean-style” pattern (National Adult Reading Test (NART) ηp2 = 0.006 and Wechsler Test of Adult Reading (WTAR) ηp2 = 0.013), and the “traditional” pattern (NART ηp2 = 0.035 and WTAR ηp2 = 0.027).
Our results suggest a pattern of reverse causation or confounding; a higher childhood cognitive ability (and adult socioeconomic status) predicts adherence to a “healthy” diet and better cognitive performance in old age. Our models show no direct link between diet and cognitive performance in old age; instead they are related via the lifelong-stable trait of intelligence.
Previous studies have suggested a link between flavonoid intake and better cognitive function in later life but have not been able to control for possible confounding by prior intelligence quotient (IQ). The aim of the present study was to address this issue in a cross-sectional survey of 1091 men and women born in 1936, in whom IQ was measured at age 11 years. At the age of 70 years, participants carried out various neuropsychological tests and completed a FFQ. Associations between test scores and nutrient intake were assessed by linear regression with adjustment for potentially confounding variables. Total fruit, citrus fruits, apple and tea intakes were initially found to be associated with better scores in a variety of cognitive tests, but the associations were no longer statistically significant after adjusting for confounding factors, including childhood IQ. Flavanone intake was initially found to be associated with better scores in verbal fluency (P = 0·003, with standardised regression coefficient 0·10), but, again, the association was no longer statistically significant after adjusting for confounding factors. These findings do not support a role for flavonoids in the prevention of cognitive decline in later life. Studies of diet and cognitive function should include measurement of potential confounding variables, including prior IQ wherever possible.
Background: The Hospital Anxiety and Depression Scale (HADS) is widely used but evaluation of its psychometric properties has produced equivocal results. Little is known about its structure in non-clinical samples of older people.
Methods: We used data from four cohorts in the HALCyon collaborative research program into healthy aging: the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study, and the Lothian Birth Cohort 1921. We used exploratory factor analysis and confirmatory factor analysis with multi-group comparisons to establish the structure of the HADS and test for factorial invariance between samples.
Results: Exploratory factor analysis showed a bi-dimensional structure (anxiety and depression) of the scale in men and women in each cohort. We tested a hypothesized three-factor model but high correlations between two of the factors made a two-factor model more psychologically plausible. Multi-group confirmatory factor analysis revealed that the sizes of the respective item loadings on the two factors were effectively identical in men and women from the same cohort. There was more variation between cohorts, particularly those from different parts of the U.K. and in whom the HADS was administered differently. Differences in social-class distribution accounted for part of this variation.
Conclusions: Scoring the HADS as two subscales of anxiety and depression is appropriate in non-clinical populations of older men and women. However, there were differences between cohorts in the way that individual items were linked with the constructs of anxiety and depression, perhaps due to differences in sociocultural factors and/or in the administration of the scale.
We related geographical variation of ‘probable’ presenile Alzheimer's disease (AD PSD) to exposures to possible risk factors for AD PSD and vascular dementia (VaD) and to geographical differences in survival times after presentation with AD PSD.
We found that an ecological measure of socio-economic deprivation was related to VaD but not to AD PSD. Among men with AD PSD and VaD, specific occupations conveyed no altered risk but having fathers who were coal miners was associated with AD PSD and VaD in offspring. Increased paternal age was associated with AD PSD but only in men. These factors acted independently of one another and did not distinguish between geographical areas of high and low incidence.
The length of survival after presentation with AD PSD distinguished between these areas, and when migration between these areas was taken into account, a plausible multifactorial model of the harmful effects of environment emerged, which acted independently of risk factors acting earlier in life.
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