Longitudinal brain ageing after stroke: a marker for neurodegeneration and its relevance for upper limb motor outcome.

Brain age, as distinct from chronological age, may reveal post-stroke recovery mechanisms, but longitudinal studies tracking brain age are lacking. We explored longitudinal change of brain age post-stroke and its relation to upper limb sensorimotor outcome. T₁-weighted MRI at baseline (∼3 weeks) and follow-up (3-7 months) post-stroke was used to estimate brain age. Difference to chronological age was calculated as brain age gap (BAG). Grey and white matter changes and lesion location related to increased brain ageing were investigated, controlling for lesion volume. Association between BAG change and upper limb sensorimotor outcome was studied using linear mixed effects regression. Totally, 114 stroke patients with arm/hand hemiparesis were pooled from three studies. BAG significantly increased from baseline to follow-up, a period of ∼6 months, by a mean of 3.62 years (t = -7.31; P < 0.001). Voxel-based morphometry showed that high BAG change was related to reduced grey and white matter volume ipsilesionally, extending beyond the stroke lesion. Voxel-based lesion symptom mapping showed that lesion to thalamocortical projections, internal capsule and corona radiata related to accelerated brain ageing. BAG change was significantly associated with motor outcomes in the sub-acute to chronic phase, as expressed by Fugl-Meyer assessment (β = -5.62, SE = 2.81, t = -2.00, P = 0.05), maximum grip strength (β = -0.14, SE = 0.04, t = -3.36, P = 0.001) and dexterity assessment (β = -0.09, SE = 0.04, t = -2.17, P = 0.03). We demonstrate increased brain ageing within the first few months post-stroke. This secondary neurodegeneration was negatively related to motor outcome. Brain age may be a valid whole-brain probe of individual secondary post-stroke degeneration, relevant for predicting recovery and identifying targets of neural plasticity.