Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride.
To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water.
A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs.
The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions.
The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.

The Aberdeen birth cohorts of 1921 and 1936 (ABC21 and ABC36) were subjected to IQ tests in 1932 or 1947 when they were aged about 11y. They were recruited between 1997-2001 among cognitively healthy community residents and comprehensively phenotyped in a long-term study of brain aging and health up to 2017. Here, we report associations between baseline cognitive test scores and long-term cognitive outcomes. On recruitment, significant sex differences within and between the ABC21 and ABC36 cohorts supported advantages in verbal ability and learning among the ABC36 women that were not significant in ABC21. Comorbid physical disorders were self-reported in both ABC21 and ABC36 but did not contribute to differences in terms of performance in cognitive tests. When used alone without other criteria, cognitive tests scores which fell below the -1.5 SD criterion for tests of progressive matrices, namely verbal learning, digit symbol and block design, did not support the concept that Mild Cognitive Impairment (MCI) is a stable class of acquired loss of function with significant links to the later emergence of a clinical dementia syndrome. This is consistent with many previous reports. Furthermore, because childhood IQ-type data were available, we showed that a lower cognitive performance at about 64 or 78 y than that predicted by IQ at 11 ± 0.5 y did not improve the prediction of progress to MCI or greater cognitive loss. We used binary logistic regression to explore how MCI might contribute to the prediction of later progress to a clinical dementia syndrome. In a fully adjusted model using ABC21 data, we found that non-amnestic MCI, along with factors such as female sex and depressive symptoms, contributed to the prediction of later dementia. A comparable model using ABC36 data did not do so. We propose that (1) MCI criteria restricted to cognitive test scores do not improve the temporal stability of MCI classifications; (2) pathways towards dementia may differ according to age at dementia onset and (3) the concept of MCI may require measures (not captured here) that underly self-reported subjective age-related cognitive decline.

Conflicting evidence concerning possible harm from mercury (Hg) in regard to offspring cognition if the woman eats fish has prompted this study to examine evidence from a British pre-birth cohort to investigate the relationship between the two.
Pregnant women (median prenatal blood mercury 1.86μg/L) resident in the study area with delivery between April 1991 and December 1992 were followed up and verbal, performance and total intelligence quotient (IQ) of 2062 offspring were measured at age 8. Analysis treated IQ as (a) continuous and (b) the lowest 25% of the distribution. Multiple and logistic regression analyses took account of social and demographic variables. Stratification considered children of fish eaters separately.
Before adjustment, mean full-scale IQ increased with increasing Hg (change with 1SD of Hg=+2.02; 95%CI+1.40,+2.64 IQ points; P <0.0001); after adjustment effect size was reduced although still positive (+0.61;95%CI -0.06,+1.29 IQ points; P=0.073). The adjusted positive relationship was stronger when fish-eating mothers were considered separately (+0.84:95%CI +0.13,+1.56 IQ points; P=0.021) in comparison with the outcomes for non-fish eaters, where the adjusted relationship was negative (-2.22;95%CI -5.00,+0.56 IQ points; P=0.117). The binary outcome showed a similar pattern with the adjusted OR for non-fish-eaters 1.79 (95%CI 1.10,2.93; P=0.019) per SD of Hg, significantly different from that for fish consumers (0.94;95%CI:0.82,1.08)(Pinteraction<0.05). There were no differences between the sexes in the associations, nor did the level of the mother\'s blood selenium change the effect sizes.
The relationship between intrauterine exposure to mercury and offspring IQ appears to be benign provided the mother consumes fish.

the \'triad of impairment\' phenomenon describes the co-occurrence of age-related cognitive, emotional and physical functioning deficits. We investigated how occupational profile and childhood intelligence contribute to the triad of impairment in late life.
we analysed data of a subsample of the Aberdeen Birth Cohort of 1936 (n = 346). Data were collected on participants\' childhood intelligence, late-life cognitive ability, physical functioning, depressive symptoms and main lifetime occupation. We summarised the various occupational and impairment measures into two latent variables, \'occupational profile\' and the \'triad of impairment\'. We used a series of data reduction approaches and structural equation models (SEMs) of increasing complexity to test both the validity of the models and to understand causal relationships between the life-course risks for the triad of impairment.
occupational profile had a significant effect on the triad of impairment independent of childhood intelligence. Childhood intelligence was the predominant influence on the triad of impairment and exerted its effect directly and indirectly via its influence on occupation. The direct effect of childhood intelligence exceeded the independent influence of the occupational profile on impairment by a factor of 1.7-1.8 and was greater by a factor of ∼4 from the indirect pathway (via occupation).
childhood intelligence was the predominant influence on the triad of impairment in late life, independently of the occupational profile. Efforts to reduce impairment in older adults should be informed by a life-course approach with special attention to the early-life environment.

Cognitive reserve is a hypothetical concept introduced to explain discrepancies between severity of clinical dementia syndromes and the extent of dementia pathology. We examined cognitive reserve in a research programme that followed up a non-clinical sample born in 1921 or 1936 and IQ-tested age 11 years in 1932 or 1947. Structural MRI exams were acquired in about 50% of the sample from whom a subsample were recruited into an additional fMRI study. Here, we summarise findings from seven inter-related studies. These support an understanding of cognitive reserve as a balance between positive life course activity-driven experiences and the negative effects of brain pathologies including cerebrovascular disease and total and regional brain volume loss. Hypothesised structural equation models illustrate the relative causal effects of these positive and negative contributions. Cognitive reserve is considered in the context of choice of interventions to prevent dementia and the opposing effects of cerebrovascular disease and Alzheimer like brain appearances.

OBJECTIVE: Carotid intima-media thickness (IMT) is a known precursor to coronary heart disease (CHD) and other relevant health outcomes such as stroke and cognitive impairment. In addition, higher childhood intelligence has been associated with lower risk of coronary heart disease events in later life, although the mechanisms of effect are unclear. We therefore examined the association between childhood intelligence and atherosclerosis using carotid IMT as a marker of the atherosclerotic process.
METHODS: Participants were 412 members of the Newcastle Thousand Families Study, a prospective cohort study of all 1142 births in the city of Newcastle in May and June 1947, who took an IQ test and English and arithmetic tests at age 11 years. Study members participated in a medical examination and lifestyle assessment at age 49-51 years during which IMT was measured using ultrasound techniques.
RESULTS: Individuals with higher childhood IQ score had a lower mean IMT in middle-age. A standard deviation higher score in childhood overall IQ was associated with a 0.053 mm (95% CI -0.102, -0.004) lower IMT in men and a 0.039 mm (95% CI -0.080, -0.002) lower IMT in women. Similar levels of association were found for the English and arithmetic tests. After adjustment for a range of covariates including education, the size of effect was undiminished in men but increased in women.
CONCLUSIONS: In the present study, higher childhood IQ scores were associated with a lower degree of atherosclerosis by middle-age.