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

Abstract

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.

Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer’s disease

“…All participants took part in a larger multimodal imaging study of early-stage AD (“Imagerie Multimodale de la maladie d’Alzheimer à un stade Précoce”, IMAP+) conducted in Caen (France). The subset of cognitively normal participants was included in our earlier study on WMH in IMAP+ [ 3 ]. Inclusion and exclusion criteria of the IMAP+ cohort are detailed in our previous publications [ 3 , 22 , 23 ].…”

“…The subset of cognitively normal participants was included in our earlier study on WMH in IMAP+ [ 3 ]. Inclusion and exclusion criteria of the IMAP+ cohort are detailed in our previous publications [ 3 , 22 , 23 ]. Briefly, participants were all aged ≥ 50 years, had at least 7 years of education, and had no history of alcoholism, drug abuse, head trauma, or psychiatric disorders.…”

“…Processing of FLAIR scans is described in detail in our previous publication [ 3 ]. Briefly, WMH probability maps were computed using lesion prediction algorithm (LPA) as implemented in the lesion segmentation toolbox (LST) (version 2; https://www.applied-statistics.de/lst.html ) for SPM ( www.statistical-modelling.de/lst.html ) [ 32 ] based on T1 and FLAIR images.…”

“…White matter hyperintensities (WMH), as quantified using fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), are recognized as a marker of cerebrovascular disease [ 1 ] that is robustly associated with age [ 2 , 3 ] as well as cardiovascular risk factors [ 4 , 5 ]. The presence of WMH is also related to lower cognitive performance [ 6 , 7 ] and increased risk of clinical Alzheimer’s disease (AD) ([ 8 , 9 ], for review see [ 10 ]), suggesting an involvement of WM damage in AD pathogenesis.…”

Semi-Supervised Learning in Medical MRI Segmentation: Brain Tissue with White Matter Hyperintensity Segmentation Using FLAIR MRI

“…Larger WMH regions are associated with an accelerated cognitive decline and increased risk for AD [4]. Recent studies suggest that WMH plays a role in AD's clinical symptoms and there is synergistic contribution of both medial temporal lobe atrophy and WMH on cognitive impairment and dementia severity [5]. Patients with mild cognitive impairment or early AD had concurrent WMH, which indicates a more significant cognitive dysfunction than those with a low WMH burden [5].…”