The NDA HALCyon research programme: Key findings and implications Diana Kuh

The NDA HALCyon research programme:

Key findings and implicationsDiana Kuh

MRC Unit for Lifelong Health and Ageing

on behalf of the HALCyon study team

NDA & AgeUK Improving later life

London, 11 March 2013

Unit for Lifelong Health and Ageing

Healthy Ageing across the Life Course(www.halcyon.ac.uk, 2008-2012)

HALCyon is a collaborative research programme: • 9 UK cohorts born 1921 to 1958 • Cohort investigators, methodologists and

specialists in ageing and knowledge transfer • To investigate how healthy ageing is

influenced by factors operating across the whole of life

Indicators of healthy ageing being studied:

• Capability: the capacity to undertake the physical and mental tasks of daily living

• Wellbeing: psychological and social

• Underlying biology: physiology and genetics

The Halcyon is a fabled bird identified with the kingfisher. The Halcyon is supposed to have the power to calm the wind & the waves during the winter solstice while it nested on the sea.


Original HALCyon cohorts

Cohort (birth yr/s) Birth Childhood Early Adulthood

Mid Adulthood

Late Adulthood

Lothian (1921)

Hertfordshire Ageing Study (1920-30)

Boyd Orr (1925-37)

Aberdeen (1936)

Hertfordshire Cohort Study (1931-39)

Caerphilly (1920-1934)

ELSA (early 1900s-1952/56)

NSHD (1946)

NCDS (1958)

+ other cohorts now joined: Whitehall II, LASA


Eight integrated work packages


WP1: Life course models of capability Rachel Cooper, Avan Aihie Sayer, Sean Clouston, Ian Deary, Scott Hofer, Marcus Richards, Diana Kuh, Rebecca Hardy,

Includes study of physical and cognitive capability

Common themes •Differences by age & gender

•Lifetime SEP & social roles

•Lifetime body size

•Childhood mental abilities

•Personality traits, lifetime health status & lifestyles

•Relationship between capability & wellbeing


Physiological life course trajectories(adapted from Sheik and Strachan 2004)

Years of life

Leve

l of

ca

pabi

lity

0 10 20 30 40 50 60 70 80 90 1000

10

20

30

40

50

Level below whichlimitations may occur

Adult risk factors

Earl

y lif

e ri

sk f

acto

rs

A

B

C

D

Capability across the life course

“In the broadest sense, problems of growth, development & maturation are as much apart of gerontology as are those of atrophy, degeneration and decline” (Nathan Shock)


Summary hazard ratios of mortality by physical capability (from random effects meta-analyses comparing each quarter of grip strength, walking speed and chair rise time to the highest quarter)

Adjusted for age, sex & body size

[Cooper et al, BMJ 2010;341:c4467]


Age and gender differences in physical capability

Overall (I2 = 91.3% p < .001)

Study

LBC

ELSA

HAS

HCS

NSHD

Mean age (y)

79

66.6

67

66.2

53

N

544

7143

714

2983

2829

-12.62 (-13.90, -11.34)

Regressioncoefficient (95% CI)

-10.07 (-11.51, -8.64)

-12.32 (-12.76, -11.89)

-12.58 (-13.88, -11.29)

-12.24 (-12.90, -11.58)

-15.68 (-16.75, -14.61)

Men stronger Women stronger 0-25 -20 -15 -10 -5 0 5

Difference in mean grip strength (kg)

Gender differences in grip strength (kg)

adj. for age, height & weight• Physical capability declines with age

• Men perform better than women

• Gender difference in grip strength diminishes with increasing age

• Insufficient variation in birth year at any given age to explore cohort differences

[Cooper et al, PLoS One, 2011;6:e27899]

Childhood SEP and physical capability

Father's occupationLothian Birth Cohort 1921

Hertfordshire Ageing Study

Health and Retirement

Caerphilly Study PREHCO project

Boyd Orr

Lothian Birth Cohort 1936

Hertfordshire Cohort Study

ELSA

Aberdeen 1936

Overall (I-squared = 72.3%, p < 0.01)

Study

MF MF MF MMF

M F M

F MF

M F M

F

Sex

79

76

75

7372

71

69

68

66

65

Mean age (y)

-0.26 (-0.47, -0.05)-0.24 (-0.38, -0.10)-0.06 (-0.16, 0.04)-0.01 (-0.14, 0.12)-0.13 (-0.18, -0.09)-0.14 (-0.18, -0.10)-0.06 (-0.09, -0.03)0.05 (-0.03, 0.12)0.01 (-0.05, 0.08)-0.03 (-0.11, 0.05)-0.04 (-0.11, 0.03)-0.12 (-0.26, 0.02)-0.13 (-0.24, -0.02)-0.06 (-0.09, -0.03)-0.04 (-0.11, 0.03)-0.16 (-0.20, -0.12)-0.12 (-0.16, -0.08)-0.04 (-0.15, 0.07)-0.13 (-0.22, -0.04)-0.08 (-0.11, -0.05)

Regression coefficient (95% CI)

Lower SEP=Worse function Better function 0-.4 -.2 .2

Difference in mean walking speed (m/s) comparing lowest with highest SEP

Childhood SEP and physical capability

[Birnie, Cooper et al, PLoS ONE 2011;6:e15564] Adjusted for age


Childhood SEP and physical capability: main findings and implications of systematic review

[Strand et al, Eur J Epidemiol 2011]

• Childhood SEP associated with all physical performance tests

• Modest associations remained with walking speed and chair rise time after adjustment for adult SEP + body size

• Translates into 11% increase in mortality for those most v. least deprived. Impact on QoL likely to be greater

• In depth studies to investigate lifetime pathways


Early growth and later physical capability

Systematic reviews:• Strong evidence that

birth weight associated with later grip strength after adj. for height

• Less evidence for infant body size/growth

In depth NSHD studies:• Pubertal growth

associated with midlife grip strength

• Pre-pubertal growth associated with better physical performance in boys

[Dodds et al, J Nutr Health Aging, 2012


Men (n=5085)lowest234highest

Women (n=4676)lowest234highest

BMI categorised by quintiles

0.80 (-0.70, 2.29)1.02 (-0.46, 2.50)0-3.82 (-5.30, -2.34)-6.96 (-9.58, -4.34)

3.31 (1.11, 5.51)2.41 (0.25, 4.56)0-2.27 (-4.46, -0.07)-11.36 (-15.17, -7.55)

Regression coefficient(95% CI)

poorer performance better performance -20 -10 0 10

Body size, strength and physical performance [Hardy et al, PLoS One, in press]

• Greater adiposity is associated with worse performance on all 3 tests, esp. in highest 2/5ths of BMI

• Low grip strength is associated with worse performance, esp. in lowest fifth

• Effects of adiposity & poor strength on physical performance generally stronger in women than men

Walking speed (cm/s) by fifths of BMI

NOTE: Weights are from random effects analysis

MenLBC21 (n=229)HAS (n=169)HCS (n=766)ELSA (n=2166)Overall (I-squared = 85.1%, p = 0.000)

WomenLBC21 (n=312)HAS (n=118)HCS (n=1029)ELSA (n=2643)Overall (I-squared = 84.2%, p = 0.000)

Study

1.49 (0.81, 2.18)0.61 (0.29, 0.94)0.44 (0.31, 0.57)0.80 (0.66, 0.93)0.72 (0.44, 1.01)

1.98 (1.18, 2.77)0.55 (0.02, 1.08)0.77 (0.41, 1.13)1.38 (1.21, 1.55)1.12 (0.62, 1.62)

Regression coefficient(95% CI)

poorer performance better performance0-1 1 2 3

Mean difference in walking speed (cm/s) per unit increase in grip strength


HPA axis and physical capability

• Across 4 HALCyon cohorts and 2 other studies a larger diurnal drop in cortisol was associated with faster walking and chair rise speed (but little evidence of associations with grip strength or standing balance) (Gardner et al, Psychoneuroendocrinology, 2012)

• In CaPS higher cortisol levels associated with faster walking speed and a smaller diurnal drop was associated with slower walking speed (Gardner et al, IJE 2012)

• the ability to mount a good stress-induced response may be a marker of a more reactive and healthier HPA axis (Ben-Shlomo et al., OUP in press).

[Gardner et al, Psychoneuroendocrinology, 2012]


Grip strengthLBC1921HCSNSHD

Overall (I2 = 70.8%, p = 0.03)

Chair rise speedHCSNSHD

Overall (I2 = 63.3%, p = 0.10)

Study

23013981809

9001744

N

86.673.263.6

73.263.6

Mean age (y)

1.97 (0.94, 3.00)0.69 (0.27, 1.11)0.51 (0.14, 0.88)

0.86 (0.29, 1.42)

1.15 (0.63, 1.67)0.61 (0.24, 0.98)

0.85 (0.32, 1.37)

Effect estimate (95% CI)

0 1 2 3Change in mean WEMWBS score per 1SD

increase in physical capability

Physical capability and subsequent wellbeing[Cooper et al, submitted]

• Higher levels of physical capability were modestly associated with higher levels of subsequent mental wellbeing (as measured by the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS))

•Adjustment for age, gender, socioeconomic position, living alone, health status and neuroticism attenuated these associations


Other HALCyon systematic reviews & cross cohort studies

• Midlife fluid cognition associated with childhood cognition & level of education (Clouston, IJE 2013)

• Little evidence for a dynamic relationship between physical & cognitive capability (Clouston, Epi Reviews, 2013)

• Only 7 studies of change in fluid cognition with change in physical function• Findings not sufficiently strong or consistent to support a common cause

mechanism• Operationalisation & measurement challenges limit comparability

• Genetic variants & physical & cognitive capability (Alfred 2011, 2012, 2013)• No consistent evidence, across HALCyon cohorts of associations between

physical capability & common polymorphisms (e.g.TERT, ACTN3)

• Telomere length & physical & cognitive capability (Gardner, under review)• Weak and inconsistent evidence of associations between change in telomere

length and physical or cognitive capability


HALCyon is related to other cross cohort networks

• Measurement & Modelling of Function Across the Life Course (FALCon): Prof Rebecca Hardy (LHA)

• IALSA: Prof Scott Hofer (Victoria)• 25 longitudinal ageing studies in 8 countries, focus

on health & cognition

• Cohorts & Longitudinal Studies Enhancement Resources (CLOSER): Prof Jane Elliot• 9 UK longitudinal studies, to maximise use, value

and impact of longitudinal studies

• :Prof Aroon Hingorani• 11 UK cohort studies using cardiometabochip for

applied & translational genomic studies


A life course approach to healthy ageing (Kuh et al, Oxford University Press, forthcoming)

Focus on key components of healthy ageing:• Physical & cognitive capability, & wellbeing (individual)

• Musculoskeletal, vascular, metabolic, neuroendocrine, biomarkers, epigenetics, genetics, (body system, cellular, molecular)

• Physical activity, diet and area-based characteristics (healthy living)

• Investigate change with age• Review the evidence from cohort studies of risk and protective factors from

early life onwards that affect these outcomes. Based on research from HALCyon & other cross cohort studies

• Life course methods for studying healthy ageing• Design of life course studies • Analytical approaches • Modelling repeat exposures• Narratives, individual biographies & other qualitative approaches

• Implications for research and policy


Translational framework for public health research (Ogilvie et al. 2009)


Making use of HALCyon findings: academic investigatorsHALCyon has become a well recognised brand

• 43 HALCyon articles published, in press or under review.

• 60+ HALCyon presentations presentations

• 9 workshops/conferences complete

• Oxford HALCyon symposium April 2010

• 1st International Meeting of HALCyon, FALCon, IALSA June 2010

• Narrative and mixed methods research for the study of healthy ageing November 2010

• Pooling cohorts – the challenges of different dietary assessment methods. Cambridge, June 10th 2011

• 2nd International Meeting of HALCyon, FALCon, IALSA June 2011

• World Congress of Epidemiology HALCyon symposium, August 2011

• Epigenomic studies in Cohorts. 14th September 2011. WT conference on Epigenomics of Common Disease. Hinxton.

• Gerontological Society of America, HALCyon/IALSA symposium

• Society for Social Medicine HALCyon day. Sept 2012


Making use of HALCyon findings: academic investigators (2)

• A life course approach to healthy ageing. OUP book proposal approved based on HALCyon project. To be published Spring 2014.

• Provided a model for data sharing and integrative research for UK cohorts that is being copied by other consortia (e.g. UCLEB)

• Funding for continuing HALCyon network and research being sought elsewhere, in collaboration with IALSA (NIH)

• This will allow HALCyon and other bona fide scientists to make continuing and best use of the HALCyon datasets


Making use of HALCyon findings: general public

• HALCyon website

• HALCyon podcasts on Youtube (to be updated at the end of programme?)

• Glossy brochure summarising findings in ‘A life course approach to healthy ageing.’ (OUP book) To be published at the end of 2013. Puts HALCyon findings in the context of other research.

• NDA conference in Autumn 2013

• Links to AgeUK initiatives


Making use of HALCyon findings: policy makers and practitioners

• HALCyon interactive model of knowledge transfer

• Specific opportunities: e.g. Evidence to the Birmingham Commission on Healthy Ageing. Feb 2013; Liverpool initiative October 2013

Principles of a life course approach to healthy ageing • Promotion of healthy ageing needs to start early in life and continue

across life• maximise the level of peak function achieved by maturity • modifying the age at onset and rate of functional decline

• Identify early markers of an accelerated trajectory of functional decline or worsening longitudinal risk factor profiles • Can simple and regular performance assessments be used by

practitioners to identify those most vulnerable to accelerated ageing? Can suitable thresholds be identified? Do the different tests provide added value?


Interventions to promote healthy ageing should:

• Start in the womb and continue across life

• Enable best early nurturing environments

• Take advantage of times of heightened physiological or behavioural plasticity during later biological and social transitions e.g.

• Adolescence• Pregnancy, becoming a parent• Menopause, retirement

Focus on interventions at key life stages: e.g.• to tackle obesity and excessive weight gain (Foresight report)• to promote physical activity and the maintenance of

independence (e.g. Life Study)• to promote healthy environments and tackle social inequalities

• Integrated services, vertically as well as horizontally• Evaluate interventions to ensure use of good practice models


HALCyon study team

Diana Kuh, Avan Aihie Sayer, Yoav Ben-Shlomo, Ian Day, Ian Deary, Jane Elliott, Catharine Gale, James Goodwin,Rebecca Hardy, Alison Lennox, Marcus Richards, Thomasvon Zglinicki, Cyrus Cooper, Panos Demakakos, JohnGallacher, Scott Hofer, Richard Martin, Gita Mishra, Chris Power, Paul Shiels, Humphrey Southall, John Starr, Andrew Steptoe, Kate Tilling, Geraldine McNeill, Leone Craig, CarmenMartin-Ruiz

Tamuno Alfred, Paula Aucott, Sean Clouston, RachelCooper, Mike Gardner, Emily Murray, Zeinab Mulla, SamParsons, Vicky Tsipouri

plus a Knowledge Transfer Steering Group and 19 national andinternational collaborators


www.halcyon.ac.uk


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The NDA HALCyon research programme: Key findings and implications Diana Kuh

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