Background and Purpose
Post-stroke cognitive impairment (PSCI) is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates.
Methods
One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set-shifting (TMT-B-A difference, proportion, quotient scores and TMT-B set-shifting errors). The TMT was administered to two overt ischemic stroke cohorts from a multinational study: (i) a chronic stroke cohort (N=61) and (ii) an acute-sub-acute stroke cohort (N=45). Volumetric quantification of ischemic stroke and White Matter HyperIntensities (WMH) was done on MRI, along with ratings of involvement of cholinergic projections, using the previously published Cholinergic Hyperintensities Projections Scale (CHIPS). Damage to the superior longitudinal fasciculus (SLF), which co-localizes with some cholinergic projections, was also documented.
Results
Multiple linear regression analyses were completed. While larger infarcts (β=0.37, p<0.0001) were associated with slower processing speed, CHIPS severity (β=0.39, p<0.0001) was associated with all metrics of set shifting. Left SLF damage, however, was only associated with the difference score (β=0.17, p=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set shifting errors also had greater CHIPS severity.
Conclusions
In this multinational stroke cohort study, damage to lateral cholinergic pathways and the SLF emerged as significant neuroanatomical correlates for executive deficits in set shifting.
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