Publications by authors named "Singh-Manoux A"
Background: Cerebrovascular reactivity (CVR) is implicated in the progression of dementia, though the underlying mechanisms is not understood. This study examines the relationships between CVR and brain structure and cognitive decline, moderated by mid-life dementia risk.
Method: 163 participants from the Whitehall-II cohort underwent neuropsychological testing and MRI, including T1-weighted, FLAIR, and DTI sequences, at two phases (Phase-I: mean age=68.
Background: The progressive nature of dementia and the complex needs means that people living with dementia require tailored approaches to address their changing care needs over time. These include physical multimorbidity, psychological, behavioural, and cognitive symptoms and possible risks arising from these and helping family caregivers. However, provision of these interventions is highly variable between and within countries, partly due to uncertainty about their efficacy and scarce resources.
View Article and Find Full Text PDFBackground: Data from high-income countries (HICs) suggest a decline in age-specific incidence rates of dementia. However, this has happened primarily in HICs, with low- and middle- income countries (LMICs) facing two main challenges: a higher burden of risk factors and, in general, a faster ageing population. Most people with dementia live in LMICs, and this is set to increase, thus requiring urgent and robust action to prevent, treat and support people with dementia and their families.
View Article and Find Full Text PDFBackground: Our authors from around the world met to summarise the available knowledge, decide which potentially modifiable risk factors for dementia have compelling evidence and create the most comprehensive analysis to date for potentially modifiable risk factors to inform policy, give individuals the opportunity to control their risks and generate research.
Method: We incorporated all risk factors for which we judged there was strong enough evidence. We used the largest recent worldwide meta-analyses for risk factor prevalence and relative risk and if not available the best data.
Background: The 2020 Lancet Commission on dementia prevention, intervention and care estimated that up to 40% of dementia cases could be prevented by tackling 12 potentially modifiable risk factors, namely less education, hearing loss, hypertension, physical inactivity, diabetes, social isolation, excessive alcohol consumption, air pollution, smoking, obesity, traumatic brain injury, depression. As more evidence on risk factors emerges, the Lancet standing commission on dementia met to update evidence on established dementia risk factors and to consider the evidence for other risk factors.
Method: We used a lifecourse approach to understand how to reduce risk or prevent dementia, as many risks operate at different timepoints in the lifespan.
Objective: We hypothesise that subclinical myocardial injury during midlife, indexed by increases in cardiac troponin I, is associated with accelerated cognitive decline, smaller structural brain volume, and higher risk of dementia.
Design: Longitudinal cohort study.
Setting: Civil service departments in London (Whitehall II study).
Background: The ε4 allele of the apolipoprotein E gene (APOE4) plays a role in neurodegeneration and in cardiovascular disease, but findings on its association with mortality are inconsistent. We aimed to examine the association between APOE4 and mortality, and the role of dementia in this association.
Methods: In this pooled analysis, data on White participants aged 45-90 years who underwent APOE genotyping were drawn from two population-based cohorts: the Whitehall II study (UK), which began in 1985 and is ongoing, and the Three-City study (France), initiated in 1999 and ended in 2012.
Background: The contribution of modifiable risk factors to social inequalities in dementia, observed in longitudinal studies, remains unclear. We aimed to quantify the role of cardiovascular health factors, assessed using Life's Essential 8 (LE8) score, in mediating social inequalities in incidence of dementia and, for comparison, in incidence of stroke, coronary heart disease, and mortality.
Methods: In this prospective, population-based cohort study, we collected data from the UK Whitehall II Study and UK Biobank databases.
Background: Obesity is associated with disability but whether age and ageing modify this association remains unclear. We examined whether this association changes between 50 and 90 years, and whether change in disability rates over 14 years differs by body mass index (BMI) categories.
Methods: BMI and ADL-disability data on 28,453 individuals from 6 waves (2004-2018, SHARE study) were used to examine the cross-sectional absolute and relative associations, extracted at age 50, 60, 70, 80, and 90 years using logistic mixed models.
Epidemiological studies suggest lifestyle factors may reduce the risk of dementia. However, few studies have examined the association of diet and waist-to-hip ratio with hippocampus connectivity. In the Whitehall II Imaging Sub-study, we examined longitudinal changes in diet quality in 512 participants and waist-to-hip ratio in 665 participants.
View Article and Find Full Text PDFIntroduction: We first examined the role of age at cardiovascular disease (CVD) onset for incident dementia, and then examined whether lifestyle factors at guideline-recommended levels in individuals with CVD mitigates dementia risk.
Methods: We used population-based data (Whitehall II: n = 10,308/baseline 1985-1988/examinations every 4-5 years). Lifestyle factors (non-smoking, body mass index [BMI], physical activity, diet) were extracted post-CVD.
Background: Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia.
Methods: Obesity (body mass index ≥ 30 kg/m) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70 years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression.
Article Synopsis
- Primordial prevention, focusing on reducing risk factors early on, may help prevent cancer as well as cardiovascular disease, emphasizing the need for a broader health approach.
- A study involving 39,718 participants from three European cohorts found that more ideal cardiovascular health metrics in midlife were linked to a reduced overall cancer risk, including a specific connection to lung cancer.
- The findings suggest that maintaining healthy cardiovascular habits earlier in life could serve as an effective strategy to lower the risk of developing cancer later on.
Article Synopsis
- Current dementia risk scores are not very effective across different ages and regions, prompting the need for a new score.
- Researchers developed the UK Biobank Dementia Risk Score (UKBDRS) using two UK cohorts, identifying key predictors like age, education, and health history.
- The UKBDRS showed strong accuracy in identifying at-risk individuals and outperformed existing dementia risk scores from Australia, Finland, and the UK.
Background: High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals.
Methods: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period.
Importance: The clinical value of current multifactorial algorithms for individualized assessment of dementia risk remains unclear.
Objective: To evaluate the clinical value associated with 4 widely used dementia risk scores in estimating 10-year dementia risk.
Design, Setting, And Participants: This prospective population-based UK Biobank cohort study assessed 4 dementia risk scores at baseline (2006-2010) and ascertained incident dementia during the following 10 years.
Introduction: The association of lipids with dementia remains a subject of debate. Using data from 7,672 participants of the Whitehall II prospective cohort study, we examined whether timing of exposure, length of follow-up, or sex modifies this association.
Methods: Twelve markers of lipid levels were measured from fasting blood and eight among them a further five times.
Article Synopsis
- The global rise in dementia cases highlights the urgent need to address its scale and impact, suggesting that enhancing social participation could play a key role in reducing dementia risk by boosting cognitive reserve and supporting brain health.* -
- Studies indicate that increased social engagement in midlife and late life may lead to a 30-50% lower risk of developing dementia, although this connection might not be entirely causal.* -
- While interventions focused on social participation have shown cognitive benefits, they have not yet demonstrated a clear reduction in dementia risk, prompting discussions on future clinical practices and public health policies for effective dementia prevention.*
Article Synopsis
- Immune system and blood-brain barrier dysfunction may play a role in developing Alzheimer's and other dementias, but the specific causal mechanisms are still unclear.
- Researchers conducted a Mendelian randomization study involving 1,827 related biomarkers, identifying 127 potential causal risk factors linked to amyloid-β, tau, and autoimmunity.
- Results from analyses suggest that treatment with anti-inflammatory methotrexate could reduce the risk of Alzheimer's in high-risk individuals, indicating that autoimmunity could be a modifiable factor in dementia-related diseases.
Background: Alzheimer's disease (AD) is the 5th leading cause of death in people 65 years and older. The ATN classification reflects a biological definition of AD pathology with markers of Aβ deposition (A), pathologic tau (T), and neurodegeneration (N). Little is known about the relationship between ATN status and the risk of mortality, leading us to examine this association in a relatively large population of patients seen at a memory clinic for cognitive disorders.
View Article and Find Full Text PDFBackground: The extent to which education explains variations in sex differences in cognitive function between countries at different levels of economic development is unknown. We examined the role of education in sex differences in four cognitive domains in high- and middle-income countries.
Methods: Analyses were based on 70,846 participants, aged 60 years and older, in cohort studies from a high-income (United States) and four middle-income countries (Mexico, Brazil, China, and India).