Severity of Lesions Involving the Cortical Cholinergic Pathways May Be Associated With Cognitive Impairment in Subacute Ischemic Stroke

Abstract

Purpose: Impairment of cortical cholinergic pathways (CCP) is an important risk factor for chronic vascular cognitive impairment. However, this phenomenon has rarely been studied in post-stroke cognitive impairment (PSCI). We investigated the relationship between PSCI and CCP lesions assessed by structural magnetic resonance imaging (MRI).Patients and methods: We prospectively enrolled 103 patients within 7 days of ischemic stroke onset. CCP was measured by the cholinergic pathways hyperintensities scale (CHIPS), which semiquantitatively grades MR lesions strategically located on the CCP identified in human brains. We also measured other MRI parameters, including the location and volumes of acute infarcts, cerebral microbleeds, medial temporal lobe atrophy, and white matter lesions. Neuropsychological assessments were performed using the 60-min modified vascular dementia battery (VDB) at 3 months after the index stroke, and PSCI was defined according to VDB as well as ADL.Results: Of all 103 patients, 69 men (67.0%) and 34 women (33.0%) with a mean age of 57.22 ± 12.95 years, 55 patients (53.4%) were judged to have PSCI at 3 months, including 43 (41.7%) patients with PSCI-no dementia and 12 (11.7%) patients with poststroke dementia. According to the VBD assessment, the most commonly impaired cognitive domain was visuomotor speed (27.2%) followed by verbal memory (25.2%). Univariate analysis showed that patients with PSCI were older; had higher informant questionnaire on cognitive decline in the elderly (IQCODE) scores; had more frequent previous stroke history and atrial fibrillation; and had higher CHIPS scores, more severe white matter lesions, and medial temporal lobe atrophy. PSCI patients also had higher depression scores at 3 months. In the multivariate regression analysis, age, IQCODE score, CHIPS score, and Hamilton depression rating scale score were independent predictors of PSCI. Ordinal regression analysis for risk factors of poor functional outcomes revealed that IQCODE scores and cognitive function status were related to mRS score at 3 months after stroke.Conclusion: In patients with early subacute ischemic stroke, the severity of lesions involving the CCP may be associated with cognitive impairment at 3 months.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1800014982.

Resveratrol Preconditioning Mitigates Ischemia-Induced Septal Cholinergic Cell Loss and Memory Impairments

“…The central cholinergic system is vital for learning and memory processes and disturbances in cholinergic signaling have been associated with several neurological disorders, 5 including cerebral ischemia. 24–26 While earlier studies have shown that MCA occlusion promotes the deafferentiation of cholinergic fibers from the BF, 26 this is the first study to examine cell survival within distinct BF nuclei after FCI, in which we observed cholinergic cell loss within the ipsilateral MSN/DB following tMCAo in rodents. Notably, the MSN/DB functions as a central hub for information processing where it sends/receives projections to/from various cortical and limbic structures (Figure 2B) such as the cingulate and retrosplenial cortices, hippocampal formation, amygdala, and hypothalamus.…”

Traditional Chinese Medicine for Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis

“…Third, PSCI often impairs everyday activities and affects neurological recovery ( Hoffmann et al, 2011 ). Previous studies indicate that PSCI may be accompanied by obvious mental disorders ( Zhong et al, 2021 ), and poor mental status may be associated with higher mortality ( Robinson and Jorge, 2016 ) and affect cognitive recovery ( Medeiros et al, 2020 ). Therefore, more attention needs to be paid to psychological symptoms as well as cognitive function after stroke.…”

Predictors of post-stroke cognitive impairment using acute structural MRI neuroimaging: A systematic review and meta-analysis

“…Fifteen studies (N=11,060), measured CMB (Supplement 8). 19,[21][22][23]25,26,[28][29][30][31]34,36,39,41,42 The harvest plot shows an association between presence of CMB and PSD but not PSCI (Figure 2). Two studies were suitable for meta-analysis, finding association between presence of CMB and PSCI/PSD (2 studies, N=9151, OR a =1.36, 95%CI=1.08-1.70, I 2 =0%, P=0.009) 25,26 .…”

“…Twenty-one stroke-populations (78%) excluded patients with pre-stroke cognitive impairment and/ or dementia. [16][17][18][20][21][22][24][25][26][27][28][29]31,[33][34][35][36][37][38][39]41 MRI was performed at various times from admission to 30 days. Full demographic and vascular risk factors for each stroke population are presented in Supplement 4.…”

“…We summarized data on associations between neuroimaging features and PSCI or PSD from 23 stroke populations in the harvest plot, [15][16][17][18][19][20][21][23][24][25][26]28,[30][31][32][34][35][36][37][38][39]41,42 excluding two studies that only reported associations with specific cognitive domains 22,29 and two studies which reported acute stroke features that did not align with our pre-specified classifications. 27,33 Atrophy 10 studies (N = 1475) measured global and/or localized atrophy (Supplement 6).…”