Hippocampal neuronal densities and volumes in ageing related dementias and post-stroke survivors

Introduction: Around 30% of stroke survivors develop dementia, which can develop as delayed post-stroke dementia (PSD) months after the fi rst event. The mecha-nisms involved in PSD are unknown, however there is evidence that hippocampal neurodegeneration may be related to medial temporal lobe atrophy, and neuron loss has been associated with cognitive decline. We hypothe-sised that PSD may be due to neurodegeneration, and compared hippocampal neuronal densities and volumes in stroke survivors who developed PSD and those who maintained normal cognition (PSND).Material and methods: We used unbiased 3D stereological methods to quantify pyramidal neuronal volumes and densi-ties in hippocampal subfi elds CA1 and CA2, known to be differentially vulnerable in ischaemic and neurodegenerative processes. Cases from the prospective Cognitive Function After Stroke (CogFAST) study were assigned into ‘non-demented’ (PSND) and ‘demented’ (PSD) stroke survivor groups based on their fi nal cognitive status. These were com-pared against Alzheimer’s disease (AD), vascular dementia (VaD), mixed AD and VaD, dementia with Lewy bodies (DLB) and similar aged control groups. In total we assessed n = 93 cases and n = 14 controls with age range 64 to 96 years.Results: Neuron density was reduced in CA1 in PSND, AD, VaD and mixed dementia groups relative to controls (p < 0.05). However, there was a reduction in neuronal volumes in AD, VaD, mixed dementia and DLB groups (p < 0.05) in CA1 and CA2 as well as in PSD when CA1 and CA2 data were combined (p < 0.05). PSND survivors had greater neuronal volume than dementia groups in CA1 and CA2 (p < 0.05, VaD CA2 p = 0.08). There were no differences in neuronal volume between ND stroke survivors and controls (CA1 or CA2 p < 0.4). Neuronal volumes were positively correlated with cognitive test scores (CAMCOG) in CA1 and CA2 (p < 0.05). Conclusions: These results suggest that reduced neuronal volume is an important pathological substrate for demen-tia after stroke in elderly survivors.