Lothian Birth-cohort Studies
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The Lothian birth-cohort studies are two ongoing
cohort studies A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing ...
which primarily involve research into how childhood intelligence relates to intelligence and health in old age. The Lothian Birth Cohort studies of 1921 and 1936 have, respectively, followed up
Lothian Lothian (; ; ) is a region of the Scottish Lowlands, lying between the southern shore of the Firth of Forth and the Lammermuir Hills and the Moorfoot Hills. The principal settlement is the Scottish capital, Edinburgh, while other signific ...
-based participants in the Scottish Mental Surveys of 1932 and 1947 in old age. Scottish Mental Survey data has provided a measure of the intelligence of Lothian Birth Cohort participants at age 11, which has enabled the investigation of how childhood intelligence relates to cognition,
mental health Mental health is often mistakenly equated with the absence of mental illness. However, mental health refers to a person's overall emotional, psychological, and social well-being. It influences how individuals think, feel, and behave, and how t ...
and physical health in old age. Major cognitive ageing findings of the studies have concerned the stability of intelligence from childhood to old age, the influence of genetics on cognitive function and decline, and the role of the brain's
white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...
integrity in successful cognitive ageing. The studies have also been at the vanguard of the field of
cognitive epidemiology Cognitive epidemiology is a field of research that examines the associations between intelligence test scores (IQ scores or extracted ''g''-factors) and health, more specifically morbidity (mental and physical) and mortality. Typically, test scor ...
, which explores how intelligence relates to physical and mental health outcomes. The Lothian Birth Cohort studies are led by
Ian Deary Ian John Deary OBE, FBA, FRSE, FMedSci (born 1954) is a Scottish psychologist (also dual trained as a medical doctor and psychiatrist) known for work in the fields of intelligence, cognitive ageing, cognitive epidemiology, and personality. ...
, the director of the
Centre for Cognitive Ageing and Cognitive Epidemiology Center or centre may refer to: Mathematics *Center (geometry), the middle of an object * Center (algebra), used in various contexts ** Center (group theory) ** Center (ring theory) * Graph center, the set of all vertices of minimum eccentricity ...
at the
University of Edinburgh The University of Edinburgh (, ; abbreviated as ''Edin.'' in Post-nominal letters, post-nominals) is a Public university, public research university based in Edinburgh, Scotland. Founded by the City of Edinburgh Council, town council under th ...
.


Background

The Lothian Birth Cohort (LBC) studies of 1921 (LBC1921) and 1936 (LBC1936) are follow-up studies of, respectively, the Scottish Mental Surveys (SMSs) of 1932 (SMS1932) and 1947 (SMS1947). The Scottish Mental Surveys, which were undertaken by the
Scottish Council for Research in Education The Scottish Council for Research in Education (SCRE) was set up by the Scottish teachers’ union (The Educational Institute of Scotland, EIS) and the Association of Directors of Education in 1928. At that time, there were no similar organisati ...
(SCRE), are the only attempts to date of any country to measure the intelligence of a complete year-of-birth in its population.CCACE (2015). The Scottish Mental Survey 1932 eb page Retrieved from http://www.lothianbirthcohort.ed.ac.uk/index.php?option=com_content&view=article&id=6&Itemid=13 By following up SMS participants in old age, the LBC studies have been able to effectively investigate long-term cognitive ageing and cognitive epidemiology due to the availability of a measure of participants' childhood intelligence. The Moray House Test No. 12, designed by
Godfrey Thomson Sir Godfrey Hilton Thomson FRSE DCL (27 March 1881 – 9 February 1955) was an English educational psychologist known as a critical pioneer in intelligence research. The Godfrey Thomson Unit for Research at Moray College in Edinburgh is name ...
, was used in both Scottish Mental Surveys. It is a valid intelligence test that consists of 75 items of a variety of types including: following directions; word classification; analogies; practical items; reasoning; arithmetic; and spatial items.


Scottish Mental Surveys of 1932 and 1947

The SMS1932 was funded by the
Carnegie Corporation The Carnegie Corporation of New York is a philanthropic fund established by Andrew Carnegie in 1911 to support education programs across the United States, and later the world. Since its founding, the Carnegie Corporation has endowed or othe ...
as part of the International Examination Inquiry. It aimed to find out how many children in Scotland were "mentally deficient" and gather information on the entire distribution of intelligence in Scottish pupils. It was conducted on 1 June 1932, and tested the intelligence of almost all of Scotland's 1921-born population, 87,498 children in all. The SMS1947 was commissioned to test the theory that average intelligence in the United Kingdom was lower in the new generation due to a negative
correlation In statistics, correlation or dependence is any statistical relationship, whether causal or not, between two random variables or bivariate data. Although in the broadest sense, "correlation" may indicate any type of association, in statistics ...
between family size and the intelligence of children. It was carried out on 4 June 1947, and tested the intelligence of 70,805 children, nearly all of Scotland's 1936-born population.


Data rediscovery

The SMS data was rediscovered by Ian Deary and
Lawrence Whalley Lawrence J. Whalley (12 March 1946 – 11 April 2024) was a British psychiatrist who was the Crombie Ross Professor of Mental Health in the University of Aberdeen, from 1992 to 2008. He was later a professor emeritus there, and from 2010 to ...
in the late 1990s.Deary, I. J. (2012). ''An Intelligent Scotland: Professor Sir Godfrey Thomson and the Scottish Mental Surveys'' ecture recording Retrieved from https://www.youtube.com/watch?v=MVGICGmdLiY The data had been in the Charteris Land building of the Moray House School of Education at the University of Edinburgh, which was being rented by the SCRE. Recruitment for the
Aberdeen Aberdeen ( ; ; ) is a port city in North East Scotland, and is the List of towns and cities in Scotland by population, third most populous Cities of Scotland, Scottish city. Historically, Aberdeen was within the historic county of Aberdeensh ...
area-based follow-up studies of the Scottish Mental Surveys, the Aberdeen Birth Cohorts of 1921 and 1936, began in 1997 and 1999 respectively.


Design and aims

A core aim of the LBC studies is to explore causes of different cognitive ageing outcomes. They have also been used to facilitate a variety of psychosocial, medical and genetic investigations. Each wave of data collection typically includes: cognitive tests; socio-demographic information; health behaviours and health status; fitness measures; and physical measures. Metabolic and inflammatory
biomarkers In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
have also been taken in both cohorts. The studies have been funded by a variety of sources, including but not limited to the
Biotechnology and Biological Sciences Research Council Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, is a non-departmental public body (NDPB), and is the largest UK public funder of non-medical bioscience. It predominantly funds science, scient ...
, the Medical Research Council, the Scottish Government's
Chief Scientist Office The Chief Scientist Office is part of the Health and Wellbeing Directorate of the Scottish Government. The Chief Scientist (Health) is currently Professor Dame Anna Dominiczak. See also *Health Science Scotland References External links * ...
,
Age UK Age UK is a registered charity in the United Kingdom, formed on 25 February 2009 and launched on 1 April 2009, as a merging of Age Concern England and Help the Aged. Despite the national merger, many local Age Concern charities decided not to ...
and
Research into Ageing Help the Aged was a United Kingdom based international charity founded in 1961 by Cecil Jackson-Cole and Hugh Faulkner to help disadvantaged older people who were affected by poverty, isolation and neglect. It merged with Age Concern in 2009 to f ...
.


Lothian Birth Cohort 1921

LBC1921 participant recruitment began in 1999. Participants were mainly recruited by tracing SMS1932 participants in the Edinburgh area using the
Community Health Index A community is a social unit (a group of people) with a shared socially-significant characteristic, such as place, set of norms, culture, religion, values, customs, or identity. Communities may share a sense of place situated in a given geogr ...
(CHI), and then asking general practitioners to contact the traced potential LBC participants. The LBC1921 study's main initial aim was to find molecular genetic markers of healthy cognitive ageing. This included the investigation of the influence of the E4
allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
on the
Apolipoprotein E Apolipoprotein E (Apo-E) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular diseases. It is encoded in humans by the gene ''APOE''. Apo-E belongs to a family ...
(''APOE'') gene on cognitive ageing as well as testing the effects of other
candidate gene The candidate gene approach to conducting genetic association studies focuses on associations between genetic variation within pre-specified genes of interest, and Phenotype (clinical medicine), phenotypes or disease states. This is in contrast to ...
s for cognitive ageing. A later research focus was examining relationships involving
single-nucleotide polymorphisms In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...
(SNPs) from genes linked to
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
. The third and fourth waves of data collection were conducted with the main objective of testing the common cause hypothesis of cognitive ageing, which puts forward that age-related declines in physical and cognitive functioning share a common cause.


Lothian Birth Cohort 1936

LBC1936 participant recruitment started in 2004. Potential participants were identified using the CHI and then sent a letter about the study from the Lothian Health Board. The LBC1936 study began with the wider objective of investigating a diverse range of influences on cognitive ageing, including the effects of economic, medical, psychological and social variables. For Wave 2, a specific focus was placed on finding how the white matter of the brain becomes damaged and what relationship white matter damage has with age-related cognitive decline.


Findings

As well as being used to research the topics of major findings outlined below, LBC data has been used in a diverse range of other investigations. For example, LBC1921 participants served as a
control group In the design of experiments, hypotheses are applied to experimental units in a treatment group. In comparative experiments, members of a control group receive a standard treatment, a placebo, or no treatment at all. There may be more than one tr ...
in a study that validated of the use of the
National Adult Reading Test The National Adult Reading Test (NART) is a widely accepted and commonly used method in clinical settings for estimating premorbid intelligence levels of (initially) English-speaking patients with dementia in neuropsychological research and pract ...
as a measure of
premorbid Premorbidity refers to the state of functionality prior to the onset of a disease or illness. It is most often used in relation to psychological function (e.g. premorbid personality or premorbid intelligence), but can also be used in relation to ot ...
cognition in individuals with
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
. LBC1921 data has also been used to find that
facial symmetry Facial symmetry is one specific measure of bodily symmetry. Along with traits such as averageness and youthfulness, it influences judgments of aesthetic traits of physical attractiveness and beauty. For instance, in mate selection, people have be ...
, as measured by
fluctuating asymmetry Fluctuating asymmetry (FA), is a form of biological asymmetry, along with anti-symmetry and direction asymmetry. Fluctuating asymmetry refers to small, random deviations away from perfect bilateral symmetry. This deviation from perfection is thoug ...
, is linked to successful cognitive ageing. Data from both Lothian Birth Cohorts has been used to study changes over time in social class mobility and to find strong rank-order stability of
personality traits In psychology, trait theory (also called dispositional theory) is an approach to the study of human personality. Trait theorists are primarily interested in the measurement of ''traits'', which can be defined as habitual patterns of behavior, thou ...
in old age.


Stability of intelligence

Studies of the LBC1921 have provided the longest-term estimates of the stability of intelligence. They have found that intelligence in childhood is strongly correlated with intelligence in old age, and that this correlation exists because intelligence is highly stable trait, rather than because childhood intelligence is linked to rates of cognitive change during adulthood. The LBC1921 took the Moray House Test at ages 11, 79, 87 and 90, and results at all four sittings were strongly correlated. The raw correlations between test scores at age 11 and at ages 79, 87 and 90 were .66, .51 and .55 respectively, and they rose to .73, .61 and .67 respectively after correction for the restriction of
range Range may refer to: Geography * Range (geographic), a chain of hills or mountains; a somewhat linear, complex mountainous or hilly area (cordillera, sierra) ** Mountain range, a group of mountains bordered by lowlands * Range, a term used to i ...
in the LBC1921 sample. The range restriction-corrected correlation coefficients represent the best estimate of the stability of intelligence across the entire population of SMS1932 participants, and indicate that intelligence is a very stable trait. Even the corrected coefficients may underestimate the strength of the correlation, as the
reliability Reliability, reliable, or unreliable may refer to: Science, technology, and mathematics Computing * Data reliability (disambiguation), a property of some disk arrays in computer storage * Reliability (computer networking), a category used to des ...
of the test is likely below 1.0. Although age 11 intelligence is related to old age intelligence, it has been reported to be unrelated to change in intelligence between ages 79 and 87 in the LBC1921. This finding suggested that childhood intelligence is related to old age intelligence because of the stability of intelligence rather than because it protects against decline in old age. The LBC1936 also re-sat the Moray House Test in old age. In this larger cohort, there was a strong correlation between scores at ages 11 and 70 of .67.


Genetic associations

The most consistent genetic finding from the LBC studies has been that the E4 allele on the ''APOE'' gene, which had previously been known to be a risk factor for late-onset
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
, is also adversely linked to non-pathological cognitive function and change. In an early LBC1921 study, E4 allele status was unrelated to Moray House Test scores at age 11, but at age 80 those with an E4 allele scored lower than those without an E4 allele, indicating that the allele is a risk factor for cognitive decline. Later LBC1921 research found that possession of the E4 allele was associated with greater decline in abstract reasoning and verbal memory, but not verbal fluency, between age 79 and age 87. Additionally, in the LBC1936, the E4 allele has been associated with worse general cognitive ability at age 70, as well as with worse performance on some specific cognitive tests. Genome-wide association (GWA) studies have confirmed the ''APOE'' E4 allele's association with worse cognitive decline and function. A GWA study of longitudinal cohorts, including the LBC1921 and the LBC1936, found that the ''APOE'' E4 allele was associated with deleterious cognitive change. Furthermore, a 2015 meta-analysis of GWA studies in 31 cohorts, including the two Lothian Birth Cohorts, found that the ''APOE'' gene as well as SNPs on the ''APOE''/''
TOMM40 Mitochondrial import receptor subunit TOM40 homolog is a protein which in humans is encoded by the ''TOMM40'' gene. Function ''TOMM40'' codes for a protein that is embedded into outer membranes of mitochondria and is required for the movement ...
'' genomic region were associated with general cognitive ability. Altogether, the ''
HMGN1 Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the ''HMGN1'' gene. Function Chromosomal protein HMG14 and its close analog HMG17 (MIM 163910) bind to the inner side of the nucleosomal DNA, potentially alteri ...
'' gene, 13 SNPs and four candidate genes, including ''APOE'', were
statistically significant In statistical hypothesis testing, a result has statistical significance when a result at least as "extreme" would be very infrequent if the null hypothesis were true. More precisely, a study's defined significance level, denoted by \alpha, is the ...
predictors of general cognitive function. Data from both cohorts was also used, in combination with other data, to establish that intelligence is highly
polygenic A polygene is a member of a group of non- epistatic genes that interact additively to influence a phenotypic trait, thus contributing to multiple-gene inheritance (polygenic inheritance, multigenic inheritance, quantitative inheritance), a type ...
. In addition, LBC1921 and LBC1936 data was used in calculating the first estimate of the
genetic correlation In multivariate quantitative genetics, a genetic correlation (denoted r_g or r_a) is the proportion of variance that two traits share due to genetic causes, the correlation between the genetic influences on a trait and the genetic influences on a d ...
between childhood and old age intelligence in unrelated individuals, which was .62 and therefore indicated that most of the stable
variance In probability theory and statistics, variance is the expected value of the squared deviation from the mean of a random variable. The standard deviation (SD) is obtained as the square root of the variance. Variance is a measure of dispersion ...
in intelligence throughout life is attributable to genes rather than environment. Lothian Birth Cohort data has also been a part of GWA studies for various medical outcomes including cancer, stroke, lung function, arterial pressure and platelet formation.


White matter integrity

Structural
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
brain scans from LBC1936 participants have been used to observe that the integrity of white matter tracts in the brain is linked to cognitive functioning and successful cognitive ageing. In one study, three general
factors Factor (Latin, ) may refer to: Commerce * Factor (agent), a person who acts for, notably a mercantile and colonial agent * Factor (Scotland), a person or firm managing a Scottish estate * Factors of production, such a factor is a resource used ...
of white matter tract integrity, a global trait of the brain,Penke, L., Maniega, S., Bastin, M. et al. Brain white matter tract integrity as a neural foundation for general intelligence. Mol Psychiatry 17, 1026–1030 (2012). https://doi.org/10.1038/mp.2012.66 combined to explain 10% of the variance in general intelligence, and this effect was fully
mediated ''Mediated: How the Media Shapes Your World and the Way You Live in It'' is a non-fiction book by anthropologist Thomas de Zengotita published in 2005 by Bloomsbury about the effect of the media in the Western world. Summary ''Mediated'' aim ...
through processing speed. Later investigation of the associations of specific white matter tracts with '' g'' and specific cognitive abilities found that most specific tract associations were with ''g'' rather than specific abilities, though some associations with specific abilities remained after accounting for associations with ''g''. White matter integrity has also been shown to relate to cognitive change. Specifically, white matter integrity in the
splenium The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental m ...
of the corpus callosum has been found to be a marker of healthy cognitive ageing. Lower
white matter hyperintensity Leukoaraiosis is a particular abnormal change in appearance of white matter near the lateral ventricles. It is often seen in aged individuals, but sometimes in young adults. On MRI, leukoaraiosis changes appear as white matter hyperintense, hype ...
load has also been considered a sign of successful cognitive ageing, because it was associated with higher general cognitive ability and faster processing speed at age 73 after age 11 intelligence was controlled for. Additionally, white matter integrity in some brain areas has been found to be weaker in ''APOE'' E4 allele carriers, and weaker white matter integrity has been shown to partially mediate some of the harmful effects of the E4 allele on cognitive change.


Health, health behaviours and cognitive ageing

In the LBC1921, smoking was linked to greater cognitive decline at age 80. The mean IQ of current smokers was 6.0 points lower than the mean IQ of ex-smokers and 6.5 points lower than the mean IQ of those who had never smoked. Physical fitness, indexed by a general
component Component may refer to: In engineering, science, and technology Generic systems *System components, an entity with discrete structure, such as an assembly or software module, within a system considered at a particular level of analysis * Lumped e ...
extracted from measures of lung function, grip strength and walk time, was associated with successful cognitive ageing at age 79 in the LBC1921. Physical activity has also been associated with successful cognitive ageing in the LBC1936, as it remained associated with age 70 general cognitive ability and processing speed after controlling for intelligence at age 11. One of the strengths of the LBC study designs is that they enable tests of
reverse causation The phrase "correlation does not imply causation" refers to the inability to legitimately deduce a cause-and-effect relationship between two events or variables solely on the basis of an observed association or correlation between them. The idea ...
in associations between intelligence and other variables. Reverse causation is implied if a contemporaneous association in old age is attenuated or eliminated after childhood intelligence is controlled for, which would suggest that the association existed partially or wholly due to the effects of earlier intelligence. Reverse causation has been separately reported for relationships in the LBC1936 between intelligence and each of caffeine consumption,
body mass index Body mass index (BMI) is a value derived from the mass (Mass versus weight, weight) and height of a person. The BMI is defined as the human body weight, body mass divided by the square (algebra), square of the human height, body height, and is ...
, alcohol consumption and
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
.


See also

*
Genetic Studies of Genius The Genetic Studies of Genius, later known as the Terman Study of the Gifted,Holahan, C. K., & Sears, R. R. (1995''The Gifted Group in Later Maturity'' Stanford University Press: Stanford, California. is the oldest and longest-running longitudina ...
* Minnesota Center for Twin and Family Research *
Minnesota Transracial Adoption Study The Minnesota Transracial Adoption Study examined the IQ test scores of 130 black or interracial children adopted by advantaged white families. It has been a focus for controversy in the debate over race and intelligence. The aim of the study wa ...
*
Study of Mathematically Precocious Youth The Study of Mathematically Precocious Youth (SMPY) is a prospective longitudinal survey study of persons (mostly in the United States) identified by scores of 700 or higher on a section of the SAT Reasoning Test before age 13. It is one of the lon ...


References


External links


Lothian Birth Cohorts

CCACE
* {{cite journal , last1=Deary , first1=I. J. , last2=Gow , first2=A. J. , last3=Pattie , first3=A. , last4=Starr , first4=J. M. , title=Cohort Profile: The Lothian Birth Cohorts of 1921 and 1936 , journal=International Journal of Epidemiology , date=1 December 2012 , volume=41 , issue=6 , pages=1576–1584 , doi=10.1093/ije/dyr197 , pmid=22253310 , hdl=20.500.11820/c5fd4b3e-33eb-448a-b766-8994ba950fc9 , hdl-access=free Scottish medical research Society of Scotland Child welfare in Scotland Cohort studies Epidemiological study projects Human development Lothian Population genetics in the United Kingdom Science and technology in Scotland Longitudinal studies