Dementias and childhood associations

Childhood associations of late-life

deficits in cognitive functions

Dorota ChapkoPostdoctoral Research Fellow, Aberdeen Biomedical Imaging Centre

Royal College of General Practitioners, London

Dementias 2017

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BackgroundCognitive functions over the lifespan & cognitive resilience

Maximizing cognitive functions across the lifespan

Aging

Walker SP et al The Lancet 2011

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The Barker’s Hypothesis The Developmental Origins of Health and Disease (DOHaD)

• Low-nutrient intrauterine environment

• Anticipation of limited resources

• Adaptation to suboptimal conditions

• Physiology and morphology reprogramming

• Growing up in the world of plenty

• Mismatch between the environments

• “Compensatory growth”

• Costs: chronic conditions in late-life (DOBHaD)

Barker DJ International Journal of Epidemiology 2002

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The Barker’s Hypothesis Suboptimal intrauterine environment may result in brain dysfunctions in late-life

The brain is extremely vulnerable to a

suboptimal environment in the womb.

Developmental Origins of Behaviour, Health and Disease

(DOBHaD)

Developmental Origins of Health and Disease

(DOHaD)

Giussani, DA Proceedings of the National Academy of Sciences 2011; Van Den Bergh BR Developmental Medicine & Child Neurology 2011

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The Aberdeen Children of the 1950s Study (ACONF)

Life-course determinants of cognitive functions in late-life (n = 12,150)

DATA LINKAGE:

In 2001 over 11,000 of the original

participants were traced followed by

a questionnaire survey with a 63%

response rate.

A subset of > 500 ACONF

participants was recruited in 2010-

2011 as the Aberdeen sample for

Generation Scotland – Scottish

Family Health Study (GS:SFHS).

Analytical

Sample

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MethodsCognitive functions in childhood and mid-life

Cognitive tests routinely used in Aberdeen schools in the 1950s and 1960s:

Cognitive tests at mid-life as part of the Generation Scotland – Scottish Family Health Study:

Batty GD et al Paediatric and Perinatal Epidemiology 2004; Marioni RE et al Behavior Genetics 2014

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Methods

• The relationship between birthweight and cognitive functions from childhood to mid-life based on the repeated measures (at ages 7, 9, 11 and 51-61 years)

• Birth weight categorized into 3 groups:

• Low (< 2.49 kg)

• Normal (2.49 kg ≤ BW < 4.08 kg)

• High (≥ 4.08 kg)

• Cases with complete covariates

• Linear regression:

• Unadjusted

• Adjusted for:

• Childhood: sex, father’s social class, mother’s age

• Mid-life: in addition age at test

Chapko et al. Digital Health 2016

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ResultsBirth Weight – Adjusted Analysis

Cognition

Childhood Coeff. SE P Coeff. SE P

Childhood IQ age 7 (n=431) -11.48 3.74 0.002 -6.01 2.52 0.018



Mid-life Coeff. SE P Coeff. SE P

VerbalFluency (n=391) -2.39 3.26 0.464 0.13 2.26 0.954

MillHillVocabulary (n=389) -1.15 1.22 0.348 -1.30 0.84 0.125

LogicalMemory (n=390) -2.60 1.28 0.044 -1.08 0.89 0.225

DigitSymbol (n=389) -9.66 3.86 0.013 0.86 3.86 0.748

Mean differences in cognitive scores by birthweight group compared with normal

birthweight group (2.49 kg≤BW<4.08 kg) Adjusted

Low Birthweight <2.49 kg High Birthweight ≥ 4.08 kg


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Results Gestational Age – Adjusted Analysis

Cognition

Childhood Coeff. SE P Coeff. SE P




Mid-life Coeff. SE P Coeff. SE P

VerbalFluency (n=391) -3.90 3.26 0.231 -0.43 1.40 0.760

MillHillVocabulary (n=389) -1.06 1.22 0.386 0.07 0.53 0.901

LogicalMemory (n=390) -3.81 1.28 0.003 -0.78 0.55 0.158

DigitSymbol (n=389) -10.31 3.85 0.008 1.95 1.65 0.240

Preterm Birth < 37 weeks Post-term Birth ≥ 42 weeks

Mean differences in cognitive scores by gestational age group compared with birth at

term (term 37 wk 0 d - 41 wk 6 d) Adjusted


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Birth Weight - Conclusions • In this sample, the effect of low birth weight and

preterm birth on cognitive functions lasts until mid-life and is not completely eliminated.

• Infants at the highest risk of poor outcomes were the most affected by cognitive ageing.

• The concurrent low-birth weight & preterm infants were the most disadvantaged and drove the statistical association of adverse cognitive outcomes in mid-life.

• Certain areas of mental function in later life might be differentially affected by poor growth in utero.

• Fluid cognitive abilities, more sensitive to ageing processes, potentially affected the most.


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1936 Aberdeen Birth CohortThe effects of childhood IQ and occupational profile on the triad of impairment in late-life

Chapko et al. Age and Ageing 2016

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1936 Aberdeen Birth CohortChildhood IQ is the predominant influence on the triad of impairment in late-life

• All relationships significant, good model fit

• Childhood IQ had a total standardised regression

weight of .71 of which .58 was direct and .13 indirect

Chapko et al. Age and Ageing 2016

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Cognitive ReserveA form of cognitive resilience

AtrophyWMH

Decline Resilience

Education

Occupation

Max life-time cognition

Murray AD et al Brain 2011; Staff RT et al Brain 2004; Stern Y The Lancet Neurology 2012.

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Cognitive ReserveA form of cognitive resilience

COGNITIVE RESERVE THEORY posits that structural or functional features of the brain allow individuals to maintain normal functioning despite accumulating brain pathology.

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Systematic Literature ReviewLife-course determinants of reserve in cognitive aging

Search

• Databases: Medline, Embase, PsycheInfo

• Strategy: the synonyms of CR

Eligibility

• CR applied to 4 most common dementia types, MCI or healthy aging

• Proper definition of CR in the design; the 3 CR components stated upfront

Screening• Two independent reviewers (D Chapko and R McCormack)

Extraction• Performed by DC, checked by RM

Results• A qualitative synthesis of the results

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Systematic Literature ReviewLife-course determinants of reserve in cognitive aging

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Literature Review Results39 studies out of 9,229 screened records met our inclusion criteria

Future directions:

• specific features of the identified factors such as education, occupation

• interactions between education/occupation/pre-morbid IQ in providing reserve

• other more diverse aspects of early-life environment

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Aberdeen Birth Cohort 1936 Childhood socioeconomic circumstance and brain MRI

Age 68y(2004)

‘+/- Risk’ Cognitive ability

Moray House Test

11y‘Early life’(~1936)Life Stage Adult Life

EducationAdultSEC

Hypertension

HighestQualification

AdultOccupation

Measuredor Historic

SocioeconomicCircumstance

(SEC)

ABC

1936

Data

Paternal Occupation

Staff RT et al. Annals Neurol. 2012: ; 71:653–660.

Cognitive ability

Fluid intelligence

-

Raven’s Progressive

Matrices

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Aberdeen Birth Cohort 1936 Childhood socio-economic status and late-life brain volume measures

Staff RT et al. Annals of Neurology 2012

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Aberdeen Birth Cohort 1936 Childhood socio-economic circumstances and late-life brain pathology

Murray AD et al. PLoS ONE 2014;9(2): e 88969

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CR in Aberdeen Birth Cohort 1936 Murray AD et al., 2011 in Brain

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CR in Aberdeen Birth Cohort 1936

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Summary Results

• Educational attainment, but not occupation,

has a positive effect (b + 0.23) on late life

cognitive ability allowing for childhood

intelligence, WMH and atrophy

• This is greater than the negative impact of

either WMH (b - 0.14) or hippocampal

atrophy (b - 0.20) alone and similar to their

combined effect

Murray AD et al. Brain 2011

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Conclusions

• Brain scan measures of hippocampal atrophy and WMH have negative influence on late life fluid intelligence, allowing for childhood intelligence

• Educational achievement acts as independent contributor to cognitive reserve

• This positive influence enables retention of fluid intelligence in spite of negative influence of brain WMH and lower hippocampal volume

• Subclinical brain pathology balanced by brain experience during life

Murray AD et al. Brain 2011

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Cognitive resilience to ageing brain

Early-life factors are important!

Environment In Utero

Early-life Factors

Mid-life Factors

Late-life Factors

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Policy Implications The importance of brain development and its implications on public policy in low-resource settings

Intrauterine & Early-life Factors

Childhood Cognitive

Trajectories

Late-life Cognition

Mid-life Cognition

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Policy Implications Early Childhood Development and Skills across the Life-course through the Lens of the Developing Brain

Chapko Health, Nutrition and Population Discussion Paper World Bank 2015.

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Acknowledgements

University of Aberdeen:

Prof. Alison Murray

Prof. Corri Black

Dr. Roger Staff

Dr. Chris McNeil

Dr. Anca-Larisa Sandu

Dr. Karen McArdle

Prof. Lawrence Whalley

Dr. Leila Eadie

Ms. Heather Clark

Collaborators:

Joost de Laat

Julieta Trias

Aliza Marcus

Omar Arias

Emanuela Galasso

Sophie Naudeau

Dr. Robin Hill (UoE)

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Acknowledgements

Funders:

Collaborators:

Cohorts:

ACONF 1950s

ABC 1936

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References• Barker, D. J., Eriksson, J. G., Forsen, T., & Osmond, C. (2002). Fetal origins of adult disease: strength of effects and

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• Dorota Chapko, 2015. Early childhood development and cognitive & socio-emotional skills across the life-course through the lens of the developing brain. Health, Nutrition and Population Discussion Paper. World Bank, Washington DC (IO#2086142).

• Chapko D, Staff RT, McNeil CJ, Whalley LJ, Black C, Murray AD (2016). Late life deficits in cognitive, physical and emotional functions, childhood intelligence and occupational profile: A life-course examination of the Aberdeen 1936 Birth Cohort (ABC1936). Age & Ageing.

• Chapko D, Black C, Staff RT, Murray AD 2016. Birth weight and cognitive functions over the life-course in the generation Scotland (GS) subsample of the Aberdeen children of the1950s study (ACONF). Digital Health, 0:1-12.

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Dementias and childhood associations

Health & Medicine

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