White matter hyperintensities are common in midlife and already associated with cognitive decline

d’Arbeloff, Tracy; Elliott, M.; Knodt, Annchen R.; Melzer, Tracy R.; Keenan, Rāwiri; Ireland, David; Ramrakha, Sandhya; Poulton, Richie; Anderson, Tim; Caspi, Avshalom; Moffitt, Terrie E.; Hariri, Ahmad R.

doi:10.1093/braincomms/fcz041

Cited by 67 publications

(51 citation statements)

References 22 publications

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“…This question is rarely assessed in young and/or middle-aged adults, and results are contrasted [7][8][9][10][11][12][13]. While one previous study did not find any significant relationship between WMH and cognition in a group of cognitively unimpaired individuals including both young and middle-aged adults (i.e., from 20 to 60 years old) [8], more recent studies showed a negative association between total WMH and cognition in samples including both middle-aged and older participants (i.e., aged from 40 to 75 years old) [9][10][11][12][13]. We did not find the age group to affect the relationships between WMH and executive functions, suggesting that this effect is not limited to a specific age group but existed across the entire adult lifespan.…”

Section: Discussionmentioning

confidence: 99%

“…Statistical analyses were performed using the R software version 3.5.2, 2018 (R Core Team, www.R-project.org ). In models where WMH were included as dependent variables, due to the non-normal distribution of WMH, raw WMH values (+ 0.01 to avoid zeros) were log-transformed as usually performed [ 5 , 13 , 42 ].…”

Section: Methodsmentioning

confidence: 99%

“…In models where WMH were included as dependent variables, due to the non-normal distribution of WMH, raw WMH values (+ 0.01 to avoid zeros) were logtransformed as usually performed [5,13,42]. Table S1).…”

Section: Statistical Analysesmentioning

confidence: 99%

“…There is converging evidence for a relationship between increased WMH and decreased cognitive performance, mostly for executive functions, attention, and processing speed, even in older adults with normal cognition [1,2]. In contrast, only a few studies have investigated the prevalence and regional specificity of WMH in young and middle-aged adults [3][4][5][6][7] or their link with cognition [7][8][9][10][11][12][13], and findings are contrasted. Overall, they showed a non-linear increase in WMH with age, with a steeper increase from the fifth or sixth decade [4,7].…”

Section: Introductionmentioning

confidence: 99%

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White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition

Garnier‐Crussard¹,

Bougacha²,

Wirth³

et al. 2020

Alz Res Therapy

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Background White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. Methods One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). Results WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition. Conclusion WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition

Garnier‐Crussard¹,

Bougacha²,

Wirth³

et al. 2020

Alz Res Therapy

View full text Add to dashboard Cite

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“…To identify and extract the total volume of white matter hyperintensities (WMH), T1-weighted and FLAIR images for each participant were processed with the UBO Detector, a cluster-based, fully-automated pipeline with established out-of-sample performance, and high reliability in our data (test-retest ICC = 0.87). 60,61 The resulting WMH probability maps were thresholded at 0.7, which is the suggested standard. WMH volume is measured in Montreal Neurological Institute (MNI) space, thus removing the influence of differences in brain volume on WMH volume.…”

Section: Structural Mrimentioning

confidence: 99%

Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy

Elliott

Caspi

Houts

et al. 2021

Preprint

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All humans age, but some age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between biological aging and indicators of future frailty risk in the Dunedin cohort of 1037 infants born the same year and followed to age 45. Participants' Pace of Aging was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, hepatic, immune, dental, and pulmonary systems across ages 26, 32, 38, and 45 years, in 2019. Participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearance, and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports.

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Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk

Wang,

Sims,

Ackley

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONCancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD).METHODSIn the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed‐effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers.RESULTSCancer history was associated with smaller mean hippocampal volume (b = ‐19 mm3, 95% CI = ‐36, ‐1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = ‐0.004 mm, 95% CI = ‐0.007, ‐0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.DISCUSSIONSome brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk.HIGHLIGHTS We found no evidence of an inverse association between cancer history and ADRD‐related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

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White matter hyperintensities are common in midlife and already associated with cognitive decline

Cited by 67 publications

References 22 publications

White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition

White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition

Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk

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