Brain maps of general cognitive function and spatial correlations with neurobiological cortical profiles.

In this paper, we attempt to answer two questions: 1) which regions of the human brain, in terms of morphometry, are most strongly related to individual differences in domain-general cognitive functioning ( )? and 2) what are the underlying neurobiological properties of those regions? We meta-analyse vertex-wise -cortical morphometry (volume, surface area, thickness, curvature and sulcal depth) associations using data from 3 cohorts: the UK Biobank (UKB), Generation Scotland (GenScot), and the Lothian Birth Cohort 1936 (LBC1936), with the meta-analytic = 38,379 (age range = 44 to 84 years old). These morphometry associations vary in magnitude and direction across the cortex (|β| range = -0.12 to 0.

Life-course exposure to air pollution and the risk of dementia in the Lothian Birth Cohort 1936.

Background: Air pollution in later life has been associated with dementia; however, limited research has investigated the association between air pollution across the life course, either at specific life periods or cumulatively. The project investigates the association of air pollution with dementia via a life-course epidemiological approach.

Methods: Participants of the Lothian Birth Cohort, born in 1936, provided lifetime residential history in 2014.

The Relationship Between Anxiety, Depression and Cognitive Functioning in Older Adults: An Exploratory Cross-Sectional Analysis of Wave 1 Lothian Birth Cohort 1936 Data.

Objectives: To explore the strength of the association between cognitive functioning and depression and anxiety in older people without dementia.

Methods: An exploratory, cross-sectional analysis of Wave 1 (2004-2007) data from the Lothian Birth Cohort 1936 dataset. Three subgroups were based on Hospital Anxiety and Depression Scale (HADS) subscales: no probable anxiety or depression (N = 592), probable anxiety no depression (N = 122), probable depression with/without anxiety (depression) (N = 30).

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain.

Background: Plasma growth differentiation factor 15 (GDF15) and N-terminal proB-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.

Results: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all P < 0.

Sex-Dependent Effects of Cardiometabolic Health and on Brain Age: A Longitudinal Cohort Study.

Background And Objectives: The aging population is growing faster than all other demographic strata. With older age comes a greater risk of health conditions such as obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging, yet their influence on brain health in females vs males is largely unexplored.

Examining the neurostructural architecture of intelligence: The Lothian Birth Cohort 1936 study.

Examining underlying neurostructural correlates of specific cognitive abilities is practically and theoretically complicated by the existence of the positive manifold (all cognitive tests positively correlate): if a brain structure is associated with a cognitive task, how much of this is uniquely related to the cognitive domain, and how much is due to covariance with all other tests across domains (captured by general cognitive functioning, also known as general intelligence, or 'g')? We quantitatively address this question by examining associations between brain structural and diffusion MRI measures (global tissue volumes, white matter hyperintensities, global white matter diffusion fractional anisotropy and mean diffusivity, and FreeSurfer processed vertex-wise cortical volumes, smoothed at 20mm fwhm) with g and cognitive domains (processing speed, crystallised ability, memory, visuospatial ability). The cognitive domains were modelled using confirmatory factor analysis to derive both hierarchical and bifactor solutions using 13 cognitive tests in 697 participants from the Lothian Birth Cohort 1936 study (mean age 72.5 years; SD = .

Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health.

Background: Epigenetic Scores (EpiScores) for blood protein levels have been associated with disease outcomes and measures of brain health, highlighting their potential usefulness as clinical biomarkers. They are typically derived via penalised regression, whereby a linear weighted sum of DNA methylation (DNAm) levels at CpG sites are predictive of protein levels. Here, we examine 84 previously published protein EpiScores as possible biomarkers of cross-sectional and longitudinal measures of general cognitive function and brain health, and incident dementia across three independent cohorts.

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules.

Motoric cognitive risk syndrome trajectories and incident dementia over 10 years.

Background: Motoric Cognitive Risk (MCR) syndrome is a high-risk state for adverse health outcomes in older adults characterised by measured slow gait speed and self-reported cognitive complaints. The recent addition to the Lothian Birth Cohort 1936 of robust dementia outcomes enabled us to assess the prognostic value of MCR for dementia and explore the various trajectories of participants diagnosed with MCR.

Methods: We classified 680 community-dwelling participants free from dementia into non-MCR or MCR groups at mean [SD] age 76.

Design and Evaluation of Wearable Multimodal RF Sensing System for Vascular Dementia Detection.

Vascular dementia is the second most common form of dementia and a leading cause of death. Brain stroke and brain atrophy are the major degenerative pathologies associated with vascular dementia. Timely detection of these progressive pathologies is critical to avoid brain damage.

Identifying dementia using medical data linkage in a longitudinal cohort study: Lothian Birth Cohort 1936.

Background: The Lothian Birth Cohort 1936 (LBC1936) is a longitudinal study of ageing with well-characterised assessments, but until now, it has relied on self-report or proxies for dementia such as cognitive tests. Our aims were twofold: a) to describe a framework for identifying dementia in a cohort study. b) to report the age-specific incidence and prevalence of all-cause dementia and dementia subtypes in 865 individuals in the LBC1936.

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules.

Anticholinergic burden in middle and older age is associated with lower cognitive function, but not with brain atrophy.

Aims: The aim of this study is to estimate the association between anticholinergic burden, general cognitive ability and various measures of brain structural MRI in relatively healthy middle-aged and older individuals.

Methods: In the UK Biobank participants with linked health-care records (n = 163,043, aged 40-71 at baseline), of whom about 17 000 had MRI data available, we calculated the total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general cognitive ability, 9 separate cognitive domains, brain atrophy, volumes of 68 cortical and 14 subcortical areas and fractional anisotropy and median diffusivity of 25 white-matter tracts.

Socioeconomic status as a risk factor for motoric cognitive risk syndrome in a community-dwelling population: A longitudinal observational study.

Background: Motoric cognitive risk (MCR) is a syndrome characterised by measured slow gait speed and self-reported cognitive complaints. MCR is a high-risk state for adverse health outcomes in older adults, particularly cognitive impairment and dementia. Previous studies have identified risk factors for MCR, but the effect of socioeconomic status has, to date, been insufficiently examined.

Low-level lithium in drinking water and subsequent risk of dementia: Cohort study.

Background: Lithium, a mood stabilizer, is known to exhibit neuroprotective effects in animal models and may have anti-dementia effects.

Aims: We used data from Scottish Mental Survey 1932, a population-based cohort study, to investigate the association between lithium in drinking water and dementia rate in humans.

Method: Lithium levels in drinking water from 285 sampling sites across Scotland dating from 2014 were obtained from the sole public water provider (Scottish Water).

Are neuropsychiatric symptoms a marker of small vessel disease progression in older adults? Evidence from the Lothian Birth Cohort 1936.

Background: Neuropsychiatric symptoms could form part of an early cerebral small vessel disease prodrome that is detectable before stroke or dementia onset. We aimed to identify whether apathy, depression, anxiety, and subjective memory complaints associate with longitudinal white matter hyperintensity (WMH) progression.

Methods: Community-dwelling older adults from the observational Lothian Birth Cohort 1936 attended three visits at mean ages 73, 76, and 79 years, repeating MRI, Mini-Mental State Examination, neuropsychiatric (Dimensional Apathy Scale, Hospital Anxiety and Depression Scale), and subjective memory symptoms.

Predictors of longitudinal cognitive ageing from age 70 to 82 including APOE e4 status, early-life and lifestyle factors: the Lothian Birth Cohort 1936.

Discovering why some people's cognitive abilities decline more than others is a key challenge for cognitive ageing research. The most effective strategy may be to address multiple risk factors from across the life-course simultaneously in relation to robust longitudinal cognitive data. We conducted a 12-year follow-up of 1091 (at age 70) men and women from the longitudinal Lothian Birth Cohort 1936 study.

Prevalence and predictors of Motoric Cognitive Risk syndrome in a community-dwelling older Scottish population: A longitudinal observational study.

Objectives: Motoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia.

Methods: In this longitudinal prospective study, we classified 690 participants (mean [SD] age 76.

Mitigating the impact of air pollution on dementia and brain health: Setting the policy agenda.

Background: Emerging research suggests exposure to high levels of air pollution at critical points in the life-course is detrimental to brain health, including cognitive decline and dementia. Social determinants play a significant role, including socio-economic deprivation, environmental factors and heightened health and social inequalities. Policies have been proposed more generally, but their benefits for brain health have yet to be fully explored.

Life-course exposure to air pollution and biological ageing in the Lothian Birth Cohort 1936.

Background: Exposure to air pollution is associated with a range of diseases. Biomarkers derived from DNA methylation (DNAm) offer potential mechanistic insights into human health differences, connecting disease pathogenesis and biological ageing. However, little is known about sensitive periods during the life course where air pollution might have a stronger impact on DNAm, or whether effects accumulate over time.

Cognitive Change Before Old Age (11 to 70) Predicts Cognitive Change During Old Age (70 to 82).

Identifying predictors of cognitive decline in old age helps us understand its mechanisms and identify those at greater risk. Here, we examined how cognitive change from ages 11 to 70 is associated with cognitive change at older ages (70 to 82 years) in the Lothian Birth Cohort 1936 longitudinal study ( = 1,091 at recruitment). Using latent-growth-curve models, we estimated rates of change from ages 70 to 82 in general cognitive ability () and in three cognitive domains: visuospatial, memory, and processing speed.

Association between anticholinergic burden and dementia in UK Biobank.

Background: Previous studies on the relationship between anticholinergic drugs and dementia have reported heterogeneous results. This variability could be due to different anticholinergic scales and differential effects of distinct classes of drugs.

Methods: Using Cox proportional hazards models, we computed the association between annual anticholinergic burden (AChB) and the risk of dementia in UK Biobank with linked general practitioner prescription records between the years 2000 and 2015 (n = 171,775).

A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.

Inflammation and ageing-related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood-based patterns relate to patterns within the brain and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian Birth Cohort 1936.