Abstract
BackgroundWhite 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.MethodsOne 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).ResultsWMH 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.ConclusionWMH 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.
Highlights
White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance
Systolic blood pressure (SBP), Diastolic blood pressure (DBP), and Glycated hemoglobin (HbA1C) were positively associated with global and regional WMH in model 1, i.e., higher WMH were associated with higher SBP, DBP, or HbA1C
Temporal, and occipital WMH were positively associated with Cortical β-amyloid (Aβ) in model 1, i.e., higher WMH in these regions were associated with higher Aβ load, but this association was not found in model 2 (Table 2)
Summary
White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. White matter hyperintensities (WMH), visible on T2weighted MRI scans, are frequent in the elderly population, being in patients with cognitive impairment and in cognitively unimpaired adults older than 60 years old. 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. Further assessments of WMH in young and middle-aged adults, and of their clinical relevance, seem of particular interest to improve our understanding of their impact, and eventually design and monitor prevention interventions
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