Association of white matter hyperintensity burden and cognitive performance in young‐aged, middle‐aged and old‐aged participants: Results of the population‐based 1000BRAINS study

Abstract

AbstractBackgroundSome individuals seem less susceptible to the effect of high white matter hyperintensity (WMH) load on cognition reflecting differences in individual cognitive reserve (CR). Little is known about young‐ or middle‐aged participants. The aim of the present study was to examine (1) the effect of WMH on global cognition in three different age groups and (2) if education (as proxy for CR) moderates this association.MethodWe included 707 healthy participants (18‐85 years) without evidence of cardiovascular/neurological disease (young‐aged: 18‐44 years (Ø33.5±6.7): n = 108; middle‐aged: 45‐65 years (Ø57.9±5.5): n = 341; old‐aged: >65 years (Ø72.0±4.1): n = 258) from the population‐based 1000BRAINS study. An extensive cognitive assessment was conducted. The sum of all cognitive domain z‐scores defined the global score. Education was classified according to the International Standard Classification of Education as total years of formal education, combining school and vocational training. Magnetic resonance imaging (MRI) was carried out on a 3‐Tesla‐MR‐scanner (Tim‐TRIO, Siemens Medical Systems, Erlangen, Germany). WMH volume was determined using the Brain‐Intensity‐Abnormality‐Classification‐Algorithm. The associations of global cognition as outcome with WMH volume (in cm3) as predictor were analyzed using linear models (PROCESS v4.1 macro for SPPS) stratified by age group resulting in regression coefficient b with 95% confidence intervals (CI; adjusted for age, sex, depression, diabetes mellitus). To examine moderation effects of education, all models contained an interaction term (WMH x education).ResultHigher WMH volume was associated with lower global cognition in middle‐aged participants (b:‐0.27 (‐0.52 to ‐0.03, all reported results are fully adjusted). This effect was moderated by education (interaction term: b:‐0.07 (‐0.014 to ‐0.01)). In the young‐aged group, the association between WMH load and cognition was ‐1.27 (‐3.30 to 0.77). No association was found in the old‐aged group (b: ‐0.03 (‐0.20 to 0.14)).ConclusionHigher WMH load was associated with lower cognitive performance only in middle‐aged participants and was moderated to a small degree by education. Overall, the influence of WMH on global cognition in our cohort of healthy participants seems limited. Future analyses will focus on specific cognitive domains that might be more vulnerable to higher WMH load and will examine participants with certain cardiovascular risk profile.