Selective neuronal changes in prefrontal cortex of post-stroke dementia and ageing-related dementias

Introduction:Over 30% of stroke survivors develop poststroke dementia (PSD). The precise pathological sub-strates associated with PSD are unknown. Besides cog-nitive abnormalities involving memory, executivedysfunction is a key feature of dementia associated withcerebrovascular disease or vascular dementia (VaD).Three separate yet interconnecting circuits controlexecutive function: the dorsolateral Prefrontal Cortex(dlPFC), Anterior Cingulate Cortex (ACC) and theOrbitofrontal Cortex (OFC). Pyramidal neuronal projec-tions form connections between regions of these circuitsand any cellular changes may induce dysfunctionalcircuits leading to executive dysfunction in PSD.Material and methods:Pyramidal neuronal density andvolume were assessed from cortical layers III and V in10 cases from each group using 3D stereological meth-odology. Thirtylm Nissl sections from the prefrontalcortex were analysed from the CogFAST stroke survi-vors cohort aged>75 years, who developed PSD orremained stable as post-stroke non-demented (PSND).To evaluate disease mechanisms, these groups werecompared with Alzheimer’s disease (AD), vascular dis-ease (VaD), and Mixed AD and VaD dementias, andelderly controls. Results:We found decreases (P<0.05) in pyramidalneuronal volumes in layers III and V in the dementedgroups compared to control and PSND groups in dlPFC.No changes in neuronal volumes were evident in eitherOFC or ACC. However, neuronal densities were notaltered between PSD and PSND groups in any of thethree frontal regions.Conclusions:These findings suggest selective effects andreduced neuronal volumes rather than densities indlPFC are associated with dementia and executive dys-function in PSD.