Cognitive state following mild stroke: A matter of hippocampal mean diffusivity

Abstract

The hippocampus is known to play a vital role in learning and memory and was demonstrated as an early imaging marker for Alzheimer's disease (AD). However, its role as a predictor for mild cognitive impairment and dementia following stroke is unclear. The main purpose of this study was to examine the associations between hippocampal volume, mean diffusivity (MD) and connectivity and cognitive state following stroke. Eighty three consecutive first ever mild to moderate stroke or transient ischemic attack (TIA) survivors from our ongoing prospective TABASCO (Tel Aviv Brain Acute Stroke Cohort) study underwent magnetic resonance imaging scans within 7 days of stroke onset. Hippocampal volume was measured from T1 weighted images, hippocampal mean diffusivity was calculated from diffusion tensor imaging and connectivity was calculated from resting state fMRI. Global cognitive assessments were evaluated during hospitalization and 6 and 12 months later using a computerized neuropsychological battery. Multiple linear regression analysis was used to test which of the hippocampi measurements best predict cognitive state. All three imaging parameters were significantly correlated to each other (|r's| >0.3, P's < 0.005), and with cognitive state 6 and 12 months after the event. Multiple regression analyses demonstrated the predictive role of hippocampal mean diffusivity (β = -0.382, P = 0.026) on cognitive state, above and beyond that of volume and connectivity of this structure. To our knowledge, the combination of hippocampal volume, mean diffusivity and connectivity in first ever post stroke or TIA patients has not yet been considered in relation to cognitive state. The results demonstrate the predictive role of hippocampal mean diffusivity, suggesting that these changes may precede and contribute to volumetric and connectivity changes in the hippocampi, potentially serving as a marker for early identification of patients at risk of developing cognitive impairment or dementia.

Genetic and environmental influences on mean diffusivity and volume in subcortical brain regions

“…The meta-analysis by Clerx et al (Clerx, et al, 2012) of 55 DTI studies comprising 2,791 individuals has shown that the effect sizes of hippocampus MD are larger than those for hippocampus volume when predicting individuals with MCI (Clerx, et al, 2012). Similar conclusions have been made with respect to stroke patients (Kliper, et al, 2016), and to Parkinson’s disease (PD), where again hippocampus MD better predicts memory scores in PD patients (Carlesimo, et al, 2010). In terms of other regions, putamen MD is another good discriminator of individuals who develop PD (Peran, et al, 2010).…”

“…Among reports investigating the strength of association between volume and MD at subcortical ROIs, most have focused on mild cognitive impairment (Fellgiebel and Yakushev, 2011; Muller, et al, 2007), Alzheimer’s disease (Cherubini, et al, 2010; Kantarci, et al, 2005), and stroke (Kliper, et al, 2015). Two studies, each based on small case-control designs (Kantarci, et al, 2005; Kliper, et al, 2015), have reported large significant correlations between hippocampus volume and MD. In contrast, one report based on a large sample of elderly, non-demented subjects by den Heijer et al (den Heijer, et al, 2012) found no correlation between hippocampus volume and MD.…”

Post-stroke dementia – a comprehensive review

“…Results from the SMART-MR study suggested that the interaction between brain atrophy and white matter hyperintensities or infarcts could aggravate cognitive decline [75]. There is evidence of the role of hippocampal mean diffusivity in the post-stroke cognitive state, above and beyond that of volume and connectivity of this structure [76]. …”

Transient Ischemic Attack and Minor Stroke

“…7 Similarly, changes in hippocampal mean diffusivity and hippocampal connectivity predict cognitive state at 6 and 12 months after a mild stroke. 8 Structural and functional changes, including these subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks are also seen in the course of Alzheimer disease, 9 suggesting that TIA or minor stroke possibly induce a long-term neurodegenerative process.…”