Coupled change in brain white matter integrity and fluid intelligence in

later life

Stuart J. RitchieCentre for Cognitive Ageing and

Cognitive EpidemiologyThe University of Edinburgh

stuart.ritchie@ed.ac.uk@StuartJRitchie

Age-related cognitive decline

Salthouse (2004) Curr Direct Psych Sci, p. 141

The disconnected mind

• Geschwind (1965), Brain (parts I and II)

• White matter lesions may cause agnosias, aphasias, apraxias

• What about age-related cognitive decline?

• Regional volumes; white matter lesions; diffusion tensor imaging variables

• “…at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak.” (p. 753)

Charlton et al. (2010)

• 84 adults aged 55-91 (M = 71)• n = 73 with DTI variables across 2

years• Measures of working memory,

executive function, processing speed– Only working memory shows sig.

decline

• Sig. decline in white matter integrity• White matter change correlated with

working memory change (r = .35, p = .004)

Lövdén et al. (2014)

• Sample of very old adults (aged 81-103)

• n = 40 with 2 waves of DTI and cognitive testing

• Strong change-change correlations found (but large 95% CIs)

Lothian Birth Cohort 1936

• Born in 1936, tested in Scottish Mental Survey in 1947

• Followed up from 2004 onwards as a study of ageing

• Follow-up testing:– n = 1,091 at mean age 70;– n = 866 at mean age 73; – n = 697 at mean age 76.

• DT-MRI scans (1.5T):– n = 731 at age 73;– n = 488 at age 76.

Cognitive Domains

• Tests completed at age 70, 73, & 76• Fluid intelligence ( gf )– Matrix Reasoning, Block Design, Digit Span

Backwards, Letter-Number Sequencing (all WAIS)

• Processing speed– Digit-Symbol Substitution (WAIS), Symbol

Search (WAIS), Simple & Choice Reaction Time, Inspection Time

• Memory– Logical Memory, Verbal Paired Associates,

Spatial Span (all WMS)

DT-MRI

• Fractional anisotropy (FA; non-randomness of water molecule movement) calculated using a diffusion tensor

From Chanraud et al. (2010), Neuropsychol. Rev.

Tractography• General FA calculated (age 73 and age

76) from 12 white matter tracts across the brain

Cross-sectional work

• Penke et al. (2010), J Neurosci

• n = 132

• Penke et al. (2012), Mol Psych: 10% of variance in general intelligence explained by general factor of white matter integrity– FA + other variables (MD,

MTR)

Age-related FA decline

Kochunov et al. (2012) Neurobiol. Aging, p. 17

Hypotheses

1. (FA will correlate at baseline with performance in each of the cognitive domains)

2. FA and each of the cognitive domains will decline from age 73 to age 76

3. Decline in FA will correlate with decline in cognitive performance (fluid intelligence and processing speed, but not necessarily memory)

Latent Difference Score model

y[1] = (1*y[0]) + (1*Δy)

Results: Level-Level

.

Results: Level-Change

Results: Change-change

*

Conclusions

• Decline in white matter integrity is associated with decline in fluid intelligence from age 73 to age 76 (p = 0.011)– Very large, narrow-age longitudinal sample– More complex & appropriate modeling technique than in

previous work– But also higher-IQ and healthier than general population

• No such correlation for declines in memory (expected) or processing speed (unexpected)

• Longer time window needed for more power to detect change-change correlations?

• Best evidence to date for “the disconnected mind” underlying age-related cognitive decline?

Next up for diffusion MRI

• Covariates– APOE genotype; lifestyle factors; childhood

IQ

• Other white matter integrity factors– And measures of white matter lesions

• And other DTI techniques (e.g. TBSS)• In more detail: anterior vs. posterior

tracts – which age faster?• Connectomic/graph theory measures• Wait 3 more years........

*Extra bonus stuff*

• New analysis: brain volumes• Same LDS model, but for brain volume

(total volume or grey/white matter volumes)

• Sig. vol. decline between 73 and 76 (all p < .001):– Total Brain Volume: -.07 SDs/year (-6.4ml/year)– Grey Matter: -.07 SDs/year–White Matter: -.10 SDs/year

Brain volume conclusions

• Grey and white matter do not decline together

• No predictions for subsequent decline in any cognitive domain

• Brain volume declines are correlated with speed decline

• Smaller, borderline correlations for gf

• No differences between grey and white matter coupled change

Thanks• LBC1936 participants• Ian Deary• Mark Bastin• Simon Cox• Elliot Tucker-Drob• Laura Engelhardt• David Alexander Dickie• Susana Muñoz Maniega• Maria Valdés Hernández• Joanna Wardlaw

• Funders:

stuart.ritchie@ed.ac.uk