Long-term cognitive and neurovascular changes after carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) has been associated with both cognitive decline and improvement, but the underlying neurovascular mechanisms are unclear. The aim of this study was to investigate the relationship between neurovascular indices and cognitive changes after CEA. METHODS: We studied 55 patients with severe (≥70%) symptomatic or asymptomatic carotid stenosis before and six months after CEA. A wide array of neuropsychological tests was arranged in eight cognitive domains and cognitive functions specific to hemisphere ipsilateral to operation. Differences in cognitive performance between patients and 38 matching healthy controls were studied with linear mixed models. Neurovascular functioning and microembolic signals were assessed with transcranial Doppler ultrasound of the middle cerebral artery. Associations between neurovascular indices and cognitive change were assessed with linear regression analyses. RESULTS: On group level, the CEA patients improved more than controls in working memory, whereas no cognitive deterioration was detected. Also on individual level, improvement was most frequently observed in working memory. Worse preoperative cerebrovascular reactivity was related with improvement in cognitive functions of the ipsilateral hemisphere. Low preoperative pulsatility index was associated with improvement in executive functioning and ipsilateral cognitive functions. Poorer preoperative blood flow velocity associated with improvement in complex attention. Microembolic signals were rare. CONCLUSION: The present findings suggest that CEA may have beneficial long-term effects on cognition. These effects may specifically involve patients with impaired preoperative circulatory adaptive mechanisms.

Retinal vessel diameters and microvascular abnormalities in patients with carotid stenosis before and 6 months after carotid endarterectomy: A prospective study.

PURPOSE: To assess retinal findings in patients with severe carotid stenosis (CS) before and after carotid endarterectomy (CEA) compared to those in controls. METHODS: This study is based on 70 patients (male 81%, mean age 69) scheduled for CEA in Helsinki University Hospital and 41 healthy nonmedicated controls (male 76%, mean age 68). Our examinations included fundus photographs. Semi-automated software (Vesselmap, Imedos) served for evaluation of central retinal arterial equivalent (CRAE) and venular equivalent (CRVE), and arterio-venous ratio (AVR) in both eyes. We assessed fundus photographs to subjectively grade microvascular abnormalities in the ipsilateral eyes including focal arteriolar narrowing and irregularities, arteriolar wall reflex, arterio-venous crossing signs and arteriolar and venular tortuosity in the macula. RESULTS: CRAE was similar in the ipsi-and contralateral eyes of our patients, and similar to that of the controls both pre- and postoperatively. Preoperatively, we observed higher CRVE in the patients' ipsilateral than in their contralateral eyes (222 vs. 217 µm, p = 0.009), and likewise higher than in controls' eyes (222 vs. 214 µm, p = 0.024). CRVE decreased postoperatively in the patients' ipsilateral eyes (222 vs. 217 µm, p = 0.037). Among the microvascular abnormalities, arteriolar and venular tortuosity in the macula showed higher grades in the patients than in the controls preoperatively (p = 0.035 and p = 0.043), but not postoperatively (p = 0.15 and p = 0.10). CONCLUSIONS: CRVE decreased after CEA, showing that venules constrict after the mechanical hindrance of blood flow is removed. Higher grades in arteriolar and venular tortuosity in the macula, a potential ocular biomarker of CS, subsided after CEA.

Differential Cognitive Functioning and Benefit From Surgery in Patients Undergoing Coronary Artery Bypass Grafting and Carotid Endarterectomy.

Background: Stenosing atherosclerosis in both coronary and carotid arteries can adversely affect cognition. Also their surgical treatments, coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA), are associated with cognitive changes, but the mechanisms of cognitive decline or improvement may not be the same. This study was designed to compare the cognitive profile and outcome in patients undergoing surgical treatment for coronary or carotid disease. Methods: A total of 100 CABG patients and 44 CEA patients were recruited in two previously reported studies. They were subjected to a comprehensive neuropsychological examination prior to surgery and in the acute (3-8 days) and stable (3 months) phase after operation. A group of 17 matched healthy controls were assessed with similar intervals. We used linear mixed models to compare cognitive trajectories within six functional domains between the CABG, CEA and control groups. Postoperative cognitive dysfunction (POCD) and improvement (POCI) were determined with the reliable change index method in comparison with healthy controls. Results: Before surgery, the CEA patients performed worse than CABG patients or healthy controls in the domains of executive functioning and processing speed. The CABG patients exhibited postoperative cognitive dysfunction more often than the CEA patients in most cognitive domains in the acute phase but had regained their performance in the stable phase. The CEA patients showed more marked postoperative improvement in executive functioning than the CABG group in the acute phase, but the difference did not reach significance in the stable phase. Conclusion: Our findings suggest that anterior cerebral dysfunction in CEA patients impairs preoperative cognition more severely than global brain dysfunction in CABG patients. However, CEA may have more beneficial effects on cognition than CABG, specifically in executive functions mainly operated by the prefrontal lobes. In addition, the results underline that POCD is a heterogeneous condition and dependent on type of revascularization surgery.

Flicker-induced retinal vascular dilation in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy: a prospective study.

PURPOSE: Retinal vascular function was assessed in patients with carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) and in controls at a six-month interval. METHODS: We studied 68 patients (81% male, mean age 69) and 41 healthy non-medicated controls (77%, 68) from March 2015 to December 2018. Our ophthalmological examination included flicker-induced arteriolar and venular measurements with a Dynamic Vessel Analyser in both eyes. RESULTS: At baseline, flicker-induced arteriolar and venular dilation was reduced in the ipsilateral eyes of the patients compared with dilation in the controls (arteriolar 1.0% versus 2.6%, p = 0.001 and venular 2.2% versus 2.8%, p = 0.049). These differences subsided after CEA. In patients' ipsilateral eyes, flicker-induced arteriolar dilation was borderline postoperatively (preoperative 1.0% versus postoperative 1.6%, p = 0.06), whereas venular dilation increased (2.2% versus 2.8%, p = 0.025). We found various tentative associations with the change in flicker-induced dilations after CEA, but not with the preoperative dilations. CONCLUSIONS: Postoperative recovery of the reduced flicker-induced arteriolar and venular dilatation in the ipsilateral eye shows that, after CEA, the activity-dependent vascular reactivity of haemodynamically compromised retinal tissue can improve.

Ocular signs of carotid stenosis in ipsi- and contralateral eyes before and after carotid endarterectomy: a prospective study.

PURPOSE: We describe hypoperfusion-related and embolic ocular signs of carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) in a CS population. METHODS: We enrolled prospectively 70 CEA patients (81% male, mean age 69) and 41 non-medicated control subjects (76%, 68), from March 2015 to December 2018, assessing intraocular pressure (IOP), best-corrected visual acuity (BCVA) in logMAR units and performing a bio-microscopy examination. RESULTS: Main index symptoms included amaurosis fugax (Afx) (29, 41%) and hemispheric TIA (17, 24%), and 17 (24%) were asymptomatic. Of the 70, 17 patients (24%, 95% CI 16-36) showed ocular signs of CS. Of four embolic (Hollenhorst plaques) findings, one small macular plaque disappeared postoperatively. Four had hypoperfusion, that is ocular ischaemic syndrome (OIS), requiring panretinal photocoagulation: one for multiple mid-peripheral haemorrhages, two for iris neovascularization and one for neovascular glaucoma (NVG); only the NVG proved irreversible. Nine (de novo in three) showed mild OIS, that is only few mid-peripheral haemorrhages, ranging pre- /postoperatively in ipsilateral eyes from one to eleven (median two)/ one to two (median one), and in contralateral eyes from three to nine (median five)/ one to six (median three). Pre- and postoperative median BCVA was 0 or better, and mean IOP was normal, except in the NVG patient. Temporary visual impairment from 0 to 0.3 occurred in one eye soon after CEA due to ocular hyperperfusion causing macular oedema. CONCLUSIONS: Ocular signs of CS are common in CEA patients, ranging from few mid-peripheral haemorrhages to irreversible NVG. Clinicians should be aware of these signs in detecting CS.

Subfoveal choroidal thickness in ipsi- and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy: a prospective study.

PURPOSE: To compare subfoveal choroidal thickness (SFCT) and associated clinical variables in patients with carotid stenosis (CS) before and 6 months after carotid endarterectomy (CEA). METHODS: The prospective non-randomized Helsinki Carotid Endarterectomy Study - Brain and Eye Sub-sTudy included seventy patients (81% male, mean age 69 years) and 40 control subjects (77% male, 68 years), from March 2015 to December 2018. Ophthalmological examination included SFCT measured with enhanced-depth imaging-optical coherence tomography. Carotid stenosis (CS) was more severe (≥70% stenosis in 92%) ipsilateral to the CEA than contralaterally (<50% stenosis in 74%; p < 0.001). RESULTS: At baseline, patients had thinner mean SFCT than control subjects in both eyes (ipsilateral, 222 versus 257 µm and contralateral, 217 versus 258 µm, p ≤ 0.005). At follow-up, SFCT did not change in ipsi- and contralateral eyes compared to baseline in patients (p = 0.68 and p = 0.77), or in control subjects (p = 0.59 and p = 0.79). Patients with coronary artery disease had thinner mean SFCT versus those without it in ipsilateral eyes before CEA (200 versus 233 µm, p = 0.027). In ipsilateral eyes of patients before CEA, thinner SFCT and ocular signs of CS, plaque and hypoperfusion related findings combined, were associated (p = 0.036), and the best-corrected visual acuity, measured in logMAR, increased with increasing SFCT (r = -0.25; p = 0.046). CONCLUSIONS: Subfoveal choroidal thickness (SFCT) is thinner in patients with CS without association between SFCT and the grade of CS. Unchanged SFCT after CEA suggests, that choroidal vessels in severe CS are unable to react to increased blood flow. Bilaterally thin SFCT could be considered as yet another sign of CS.

Postoperative cognitive change after cardiac surgery predicts long-term cognitive outcome.

OBJECTIVES: Postoperative cognitive dysfunction (POCD) is a common consequence of coronary artery bypass grafting. However, domain-specific associations between postoperative changes and long-term performance are poorly known. The aim of this study was to investigate whether domain-specific cognitive changes after cardiac surgery predict long-term cognitive outcome. MATERIALS AND METHODS: We assessed 100 patients (86 men, mean age 60) before coronary artery bypass grafting, with re-examinations after one week, three months, and a mean of 6.7 years. The extensive neuropsychological test battery was organized into seven functional cognitive domains. Cognitive decline and improvement were defined with the reliable change index derived from 17 matching healthy controls. Analyses were adjusted for baseline cognitive performance, age, gender, education and cardiovascular risks factors. RESULTS: On group level, one week after surgery 71% patients showed cognitive decline and 9% improvement in any functional domain, as compared to preoperative results. Three months postsurgery, decline was observed in 47% and improvement in 25% of patients. Executive functioning was the most sensitive domain to both decline and improvement. Postoperative dysfunction predicted long-term cognitive deterioration six years after operation, particularly in the domain of executive functioning. CONCLUSIONS: POCD after coronary artery bypass grafting is an essential risk factor for long-term deterioration and an indication for neuropsychological follow-up. Assessment of change in executive functioning after coronary artery bypass grafting may help to identify patients at risk for unfavorable long-term outcome.

Cognitive Dysfunction and Mortality After Carotid Endarterectomy.

Background: Carotid endarterectomy (CEA) has been associated with both postoperative cognitive dysfunction (POCD) and improvement (POCI). However, the prognostic significance of postoperative cognitive changes related to CEA is largely unknown. The aim of this study was to examine the associations between postoperative cognitive changes after CEA and long-term survival. Methods: We studied 43 patients 1 day before CEA as well as 4 days and 3 months after surgery with an extensive neuropsychological test array, and followed them for up to 14 years. POCD and POCI relative to baseline were determined with the reliable change index derived from 17 healthy controls. Associations between POCD/POCI and mortality within the patient group were studied with Cox regression analyses adjusted for confounders. Results: POCD in any functional domain was evident in 28% of patients 4 days after surgery and in 33% of patients 3 months after surgery. POCI was shown in 23% of patients at 4 days and in 44% of patients at 3 months. POCD at 3 months was associated with higher long-term mortality (hazard ratio 5.0, 95% CI 1.8-13.9, p = 0.002) compared with patients with no cognitive decline. Conclusions: Our findings suggest that POCD in a stable phase, 3 months after CEA predicts premature death. Evaluation of postoperative cognitive changes is essential, and POCD in a stable phase after CEA should prompt scrutiny of underlying factors and better adherence to therapies to prevent recurrences and to promote early intervention in imminent deterioration.

Word semantics is processed even without attentional effort.

We examined the attentional modulation of semantic priming and the N400 effect for spoken words. The aim was to find out how the semantics of spoken language is processed when attention is directed to another modality (passive task), to the phonetics of spoken words (phonological task), or to the semantics of spoken words (word task). Equally strong behavioral priming effects were obtained in the phonological and the word tasks. A significant N400 effect was found in all tasks. The effect was stronger in the word and the phonological tasks than in the passive task, but there was no difference in the magnitude of the effect between the phonological and the word tasks. The latency of the N400 effect did not differ between the tasks. Although the N400 effect had a centroparietal maximum in the phonological and the word tasks, it was largest at the parietal recording sites in the passive task. The effect was more pronounced at the left than right recording sites in the phonological task, but there was no laterality effect in the other tasks. The N400 effect in the passive task indicates that semantic priming occurs even when spoken words are not actively attended. However, stronger N400 effect in the phonological and the word tasks than in the passive task suggests that controlled processes modulate the N400 effect. The finding that there were no differences in the N400 effect between the phonological and the word tasks indicates that the semantics of attended spoken words is processed regardless of whether semantic processing is relevant for task performance.

Separate neural processes for retrieval of voice identity and word content in working memory.

Working memory for voice identity and words was studied to investigate whether the neural system underlying extralinguistic and linguistic information processing is dissociated and whether the possible differences in the distribution of activity are related to specific periods of working memory tasks. Separate analyses of task-related activations evoked during the encoding, maintenance, and recognition periods of the memory tasks were performed. During the voice task, the superior temporal, ventral prefrontal and medial frontal cortices were activated in comparison with the control task whereas the word task produced activation in the occipital, parietal, and dorsal prefrontal areas. Direct contrasts between different periods of the tasks indicated that the ventral prefrontal cortex and the right superior temporal sulcus/gyrus were more activated during recognition than encoding and maintenance periods in the voice compared with the word task. In contrast, the right supramarginal gyrus was more active during the recognition than encoding period in the word compared with the voice task. The results suggest that dissociable neural substrates are recruited for processing of linguistic and extralinguistic information during the recognition period of a working memory task.