Brain atrophy associations with white matter lesions in the ageing brain: the Lothian Birth Cohort 1936

Objective Cerebral atrophy and white matter lesions (WMLs) are common in older people with common risk factors, but it is unclear if they are related. We investigated whether and to what degree they are related in deep and superficial structures using both volumetric and visual ratings.
Methods The intracranial, total brain tissue (TBV), cerebrospinal fluid (CSF), ventricular superficial subarachnoid space (SSS), grey matter, normal-appearing white matter, WMLs, and combined CSF, venous sinuses and dural volumes were measured. WMLs were also rated using the Fazekas scale.
Results Amongst 672 adults (mean age 73 ± 1years), WMLs were associated with global brain atrophy (TBV, β = −0.43mm^{3, P < 0.01) and specifically with deep (ventricular enlargement, β = 0.10mm3, P = 0.03) rather than superficial (SSS, β = 0.09mm3, P = 0.55) atrophy. A 1mm3 increase in WML volume was associated with a 0.43mm3 decrease in TBV and 0.10mm3 increase in ventricular volume. WMLs were associated with combined CSF + Venous Sinuses + Meninges volumes, but not CSF volume alone. Some of the associations were attenuated after correcting for vascular risk factors. The associations were similar for visually scored WMLs.}

Conclusion WMLs are associated with brain atrophy, primarily with deep brain structures. Measures of brain atrophy should include all intracranial structures when assessing brain shrinkage.

Key Points • Increasing age-related white matter lesions (WML) are modestly associated with brain atrophy. • Most associated atrophy affects deep structures (white matter, basal ganglia, etc.). • This is true whether WMLs are assessed volumetrically or visually scored. • Precise evaluation of brain atrophy requires assessment of all intracranial tissues.