Patient-Reported Postoperative Neuropsychological Deterioration After Heart Valve Replacement and Coronary Artery Bypass Grafting.

Background: Postoperative cognitive decline (POCD) after cardiosurgical interventions are well described through objective psychometric tests. However, a patient's subjective perception is essential to clinical assessment and quality of life. This study systematically evaluated patient-reported POCD between subjects undergoing coronary artery bypass grafting and heart valve replacement. Methods: This study was a multicentre, prospective questionnaire survey conducted at the cardiac surgery departments at the Kerckhoff Clinic in Bad Nauheim and the University Hospital in Giessen, Germany. We included patients undergoing elective coronary artery bypass grafting (CABG), aortic valve replacement (AVR), mitral valve replacement or reconstruction (MVR), and combined surgery (CABG + valve replacement [VR]) with extracorporeal circulation. The Hospital Anxiety and Depression Scale, the Cognitive Failures Questionnaire (CFQ) for Self-assessment (CFQ-S), and the external assessment (CFQ-foreign [F]) were completed preoperatively, as well as at 3 and 12 months postoperatively. Results: A total of 491 patients were available for analyses (CABG = 182, AVR = 134, MVR = 93, CABG + VR = 82). POCD and postoperative depression increase (PODI) were observed for each surgical procedure. (At the 3-month follow-up: CFQ-S [CABG = 7.1%, AVR = 3.7%, MVR = 9.7%, CABG + VR = 9.8%]; CFQ-F [CABG = 9.9%, AVR = 9.7%, MVR = 9.7%, CABG + VR = 15.9%]; PODI [CABG = 7.7%, AVR = 9.7%, MVR = 6.5%, CABG + VR = 8.5%]. At the 12-month follow-up: CFQ-S [CABG = 6.6%, AVR = 7.5%, MVR = 15.1%, CABG + VR = 7.3%]; CFQ-F [CABG = 7.1%, AVR = 14.9%, MVR = 10.8%, CABG + VR = 9.8%]; PODI [CABG = 10.4%, AVR = 11.2%, MVR = 6.5%, CABG + VR = 4.9%]). No significant between-group effects were observed for the CFQ-S, CFQ-F, or the Hospital Anxiety and Depression Scale. Conclusions: For clinicians, paying attention to patients' self-reported experiences of reduced cognitive function and symptoms of depression following cardiac surgery is important. Such reporting is an indication that interventions such as cognitive training or psychotherapy should be considered.

Contexte: Le déclin cognitif postopératoire (DCPO) à la suite d'interventions de chirurgie cardiaque est bien décrit par des évaluations psychométriques objectives. Cependant, la perception subjective du patient est essentielle à l'évaluation clinique et à la qualité de vie. Cette étude visait à évaluer de façon systématique le DCPO déclaré par le patient chez des sujets ayant subi un pontage aortocoronarien ou une chirurgie valvulaire. Méthodologie: Cette étude prospective multicentrique par questionnaire a été menée aux services de chirurgie cardiaque de la clinique Kerckhoff de Bad Nauheim et de l'hôpital universitaire de Giessen, en Allemagne. Elle a porté sur des patients ayant subi un pontage aortocoronarien (PAC), un remplacement valvulaire aortique (RVA), un remplacement ou une reconstruction de la valvule mitrale (RVM) ou une chirurgie combinée (PAC et remplacement valvulaire [RV]) avec circulation extracorporelle, en situation non urgente. L'échelle d'évaluation de l'anxiété et de la dépression à l'hôpital (HADS), le questionnaire d'auto-évaluation des déficits cognitifs (CFQ-S) et le questionnaire d'évaluation externe des déficits cognitifs (CFQ-F) ont été remplis avant l'intervention chirurgicale, ainsi que 3 et 12 mois après la chirurgie. Résultats: Au total, les résultats de 491 patients étaient disponibles aux fins d'analyses (PAC = 182, RVA = 134, RVM = 93, PAC et RV = 82). Des cas de DCPO et une augmentation postopératoire des symptômes de dépression (APOD) ont été observés après chacune des interventions chirurgicales. (Lors du suivi après 3 mois : DCPO selon le CFQ-S [PAC = 7,1 %, RVA = 3,7 %, RVM = 9,7 %, PAC + RV = 9,8 %]; DCPO selon le CFQ-F [PAC = 9,9 %, RVA = 9,7 %, RVM = 9,7 %, PAC + RV = 15,9 %]; APOD [PAC = 7,7 %, RVA = 9,7 %, RVM = 6,5 %, PAC + RV = 8,5 %]. Lors du suivi après 12 mois : DCPO selon le CFQ-S [PAC = 6,6 %, RVA = 7,5 %, RVM = 15,1 %, PAC + RV = 7,3 %]; DCPO selon le CFQ-F [PAC= 7,1 %, RVA = 14,9 %, RVM = 10,8 %, PAC+ RV = 9,8 %]; APOD [PAC = 10,4 %, RVA = 11,2 %, RVM = 6,5 %, PAC + RV = 4,9 %]). Aucun effet intergroupe significatif n'a été observé relativement aux questionnaires CFQ-S et CFQ-F ou à l'échelle HADS. Conclusions: Il est important que les cliniciens portent attention aux déclarations des patients en ce qui concerne la diminution des fonctions cognitives et les symptômes de dépression à la suite d'une chirurgie cardiaque. De telles déclarations sont une indication que des interventions comme l'entraînement cognitif ou la psychothérapie doivent être envisagées.

TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumulation, leading to lipid droplet formation and upregulation of Perilipin-2 (PLIN2) expression after hypoxia. Knockdown of TREM2 results in increased lipid synthesis (PLIN2, SOAT1) and decreased cholesterol clearance and lipid hydrolysis (LIPA, ApoE, ABCA1, NECH1, and NPC2), further impacting microglial phenotypes. In these lipid droplet-rich microglia, the TGF-ß1/Smad2/3 signaling pathway is downregulated, driving microglia towards a pro-inflammatory phenotype. Meanwhile, in a neuron-microglia co-culture system under hypoxic conditions, we found that microglia lost their protective effect against neuronal injury and apoptosis when TREM2 was knocked down. Under in vivo conditions, TREM2 knockdown mice express lower TGF-ß1 expression levels and a lower number of anti-inflammatory M2 phenotype microglia, resulting in increased cerebral infarct size, exacerbated neuronal apoptosis, and aggravated neuronal impairment. Our work suggests that TREM2 attenuates stroke-induced neuroinflammation by modulating the TGF-ß1/Smad2/3 signaling pathway. TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases.

TGF-ß1 Decreases Microglia-Mediated Neuroinflammation and Lipid Droplet Accumulation in an In Vitro Stroke Model.

Hypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-ß1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-ß1 patterns under such conditions, a TGF-ß1 siRNA and an exogenous recombinant TGF-ß1 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-ß1 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-ß1 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-ß1 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-ß1 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-ß1 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions.

Twelve-month follow-up effects of cognitive training after heart valve surgery on cognitive functions and health-related quality of life: a randomised clinical trial.

OBJECTIVES: Postoperative cognitive decline (POCD) or decreased health-related quality of life (HQL) have been reported after cardiac surgery. A previous investigation showed beneficial effects of postoperative cognitive training on POCD and HQL 3 months after heart surgery. Here, we present the 12-month follow-up results. METHODS: This bicentric, 1:1 randomised and treatment-as-usual controlled trial included elderly patients scheduled for elective heart valve surgery. The training consisted of paper-and-pencil-based exercises practising multiple cognitive functions for 36 min/day 6 days/week over a period of 3 weeks. Neuropsychological tests and questionnaires assessing HQL (36-Item Short Form Health Survey (SF-36)) and cognitive failures in daily living (Cognitive Failures Questionnaire) were performed presurgery and 12 months after training. RESULTS: Twelve months post training, the training group (n=30) showed improvements in HQL compared with the control group (n=28), especially in role limitations due to physical health (U=-2.447, p=0.015, η2=0.109), role limitations due to emotional problems (U=-2.245, p=0.025, η2=0.092), pain (U=-1.979, p=0.049, η2=0.068), average of all SF-36 factors (U=-3.237, p<0.001, η2=0.181), health change from the past year to the present time (U=-2.091, p=0.037, η2=0.075), physical component summary (U=-2.803, p=0.005, η2=0.138), and mental component summary (U=-2.350, p=0.018, η2=0.095). Furthermore, the training group (n=19) showed an improvement compared with the control group (n=27) in visual recognition memory (U=-2.137, p=0.034, η2=0.099). POCD frequency was 22% (n=6) in the control group and 11% (n=2) in the training group (χ²(1) =1.06, p=0.440; OR=2.43, 95% CI 0.43 to 13.61). CONCLUSION: In conclusion, postoperative cognitive training shows enhancing effects on HQL in cardiac surgery patients after 12 months.

The impact of postoperative cognitive training on health-related quality of life and cognitive failures in daily living after heart valve surgery: A randomized clinical trial.

BACKGROUND: Heart surgery is a risk factor for objectively and subjectively assessable postoperative cognitive decline (POCD), which is relevant for everyday life. The aim of this study was to investigate whether early postoperative cognitive training has an impact on health-related quality of life and cognitive failures in daily living after cardiac surgery. METHODS: The study was a two-arm, randomized, controlled, outcome-blinded trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation (ECC). Recruitment took place at the Departments of Cardiac Surgery of the Kerckhoff Clinic in Bad Nauheim (Germany) and the University Hospital in Giessen (Germany). The patients were randomized (1:1 ratio) to either a paper-and-pencil-based cognitive training group or a control group. We applied the Short Form Health Survey (SF-36) and the Cognitive Failures Questionnaire (CFQ) prior to surgery and 3 months after the cognitive training. Data were analyzed in a per-protocol fashion. RESULTS: Three months after discharge from rehabilitation, the training group (n = 31) showed improvement in health-related quality of life compared to the control group (n = 29), especially in role limitations due to emotional problems (U = -2.649, p = .008, η2  = 0.121), energy and fatigue (F[2.55] = 5.72, p = .020, η2  = 0.062), social functioning (U = -2.137, p = .033, η2  = 0.076), the average of all SF-36 factors (U = -2.374, p = .018, η2  = 0.094), health change from the past year to the present time (U = -2.378, p = .017, η2  = 0.094), and the mental component summary (U = -2.470, p = .013, η2  = 0.102). CONCLUSION: As our cognitive training has shown beneficial effects, this intervention could be a promising method to enhance health-related quality of life after cardiac surgery.

Increasing preoperative cognitive reserve to prevent postoperative delirium and postoperative cognitive decline in cardiac surgical patients (INCORE): Study protocol for a randomized clinical trial on cognitive training.

Introduction: Postoperative delirium (POD) and postoperative cognitive decline (POCD) can be observed after cardiosurgical interventions. Taken together, these postoperative neurocognitive disorders (PNCDs) contribute to increased morbidity and mortality. Preoperative risk factors of PNCD, such as decreased neuropsychometric performance or decreased cognitive daily activities, can be interpreted as reduced cognitive reserve. This study aims to build up cognitive reserves to protect against the development of PNCD through preoperative, home-based, cognitive training. Methods: The planned research project is a monocentric, two-arm randomized controlled intervention study involving 100 patients undergoing elective cardiac surgery with extracorporeal circulation. Patients will be assigned to a training group or control group. The intervention involves a standardized, paper-and-pencil-based cognitive training that will be performed by the patients at home for ~40 min per day over a preoperative period of 2-3 weeks. The control group will receive neither cognitive training nor a placebo intervention. A detailed assessment of psychological functions will be performed ~2-3 weeks before the start of training, at the end of the training, during hospitalization, at discharge from the acute clinic, and 3 months after surgery. The primary objective of this study is to investigate the interventional effect of preoperative cognitive training on the incidence of POD during the stay in the acute clinic, the incidence of POCD at the time of discharge from the acute clinic, and 3 months after surgery. Secondary objectives are to determine the training effect on objective cognitive functions before the surgery and subjective cognitive functions, as well as health-related quality of life 3 months after surgery. Discussion: Should it become evident that the use of our cognitive training can both reduce the incidence of POCD and POD and improve health-related quality of life, this intervention may be integrated into a standardized prehabilitation program.

Visual Hallucinations following Coronary Artery Bypass Grafting: A Prospective Study.

Background and Objectives: After major heart surgery, some patients report visual hallucinations that cannot be attributed to psychosis or delirium. This study aimed to investigate the hallucination incidence in patients after coronary artery bypass grafting with (on-pump) and without (off-pump) extracorporeal circulation. Materials and Methods: A total of 184 consecutive patients listed for elective on- or off-pump coronary artery bypass grafting were prospectively enrolled into the study. Preoperative baseline investigations 24-48 h before surgery (t0) and postoperative follow-up 24-48 h (t1) and 5-6 days (t2) after surgery included cognitive testing and a clinical visual acuity test (Landolt rings). Patients reporting visual hallucinations were interviewed using a structured survey to record the type, timing, duration, and frequency of their hallucinations. All the patients received a neurological examination and cranial magnetic resonance imaging if indicated. Results: Of the patients in the sample, 155 patients underwent on-pump bypass surgery, and 29 patients received off-pump surgery. Of these, 25 patients in the on-pump group, but none in the off-pump group, reported transient visual hallucinations (p = 0.020), which could not be attributed to stroke, delirium, psychosis, migraine, or severely impaired vision. Significant correlations were observed for the occurrence of visual hallucinations and the amount of nicotine consumption and aortic clamp/extracorporeal circulation time. Conclusions: Transient visual hallucinations occur in a noticeable proportion of patients after on-pump heart surgery. Knowledge of the phenomenon's benignity is important for patients to prevent anxiety and uncertainty and for treating physicians to avoid unnecessary medication and drug-induced delirium.

Effects of postoperative cognitive training on neurocognitive decline after heart surgery: a randomized clinical trial.

OBJECTIVES: Following cardiac surgery, postoperative cognitive decline (POCD) is a common complication that can impair the quality of life and increase mortality. The aim of this study was to investigate whether early postoperative cognitive training can decrease POCD after cardiac surgery. METHODS: The study was a multi-centred, two-arm, randomized (1:1 ratio), controlled trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation. Recruitment took place at the Department of Cardiac Surgery of the Kerckhoff-Clinic in Bad Nauheim (Germany) and the University-Hospital in Giessen (Germany). The patients were randomized to either a paper-and-pencil-based cognitive training group or a standard rehabilitation care control group. The cognitive training started 1 week after surgery and lasted about 3 weeks until discharge from rehabilitation. To detect POCD, neuropsychological functions were assessed prior to surgery, upon discharge from rehabilitation (primary outcome), and 3 months after discharge (secondary outcome). Data were primarily analysed in a per-protocol fashion. RESULTS: The frequency of POCD at discharge from rehabilitation (training group, n = 37; control group, n = 44) was 50% in the control group and 19% in the training group (χ2[1] = 8.45, P = 0.004; odds ratio = 4.29, 95% confidence interval [1.56-11.80]). Three months after the cognitive training (training group, n = 33; control group, n = 34), POCD frequency was 29% in the control group and 6% in the training group (χ2[1] = 6.21, P = 0.013; odds ratio = 6.46, 95% confidence interval [1.29-32.28]). CONCLUSIONS: Since our cognitive training showed beneficial effects, it could be a promising method to prevent POCD.

Neuroprotective effects of dynamic bubble trap use in patients undergoing pulmonary endarterectomy: a two-arm randomized controlled trial.

BACKGROUND: During cardiosurgical procedures that use extracorporeal circulation (ECC), a variety of neurological complications can occur, and postoperative cognitive deficits remain an unsolved problem. Among the sources of these complications are intraoperatively detectable cerebral microemboli, which mainly consist of air. This study's purpose was to assess neuroprotective effects of reducing these gaseous microemboli using a dynamic bubble trap (DBT) in patients undergoing pulmonary endarterectomy (PEA) for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Patients undergoing PEA were randomly assigned to receive either a DBT (n=47) or no additional device (controls, n=46) during ECC. Neuropsychological testing was performed before and 3 months after PEA. The primary endpoint was cognitive improvement in the DBT group (n=29) compared with the control group (n=42). As secondary endpoint, ischemic brain micro-lesions were analyzed on postoperative days 6 through 10 using diffusion-weighted magnetic resonance imaging (MRI). RESULTS: Analysis of interaction effects revealed improved performance in visual long-term memory (P=0.008, η2=0.099), verbal long-term memory (P=0.030, η2=0.067), verbal short-term memory (P=0.014, η2=0.083), and attention and processing speed (P=0.043, η2=0.056) from pre- to post-testing in the DBT group compared to control group. In MRI, postoperative ischemic micro-lesions could only be detected in one patient; another patient suffered a severe bihemispheric embolic stroke. CONCLUSIONS: DBT positively influences memory function after PEA. This effect is most likely caused by the reduction of gaseous microemboli. TRIAL REGISTRATION: This study is registered in the German Clinical Trials Register, ID: DRKS00021499.

Validation of the German Version of Functional Oral Intake Scale (FOIS-G) for Flexible Endoscopic Evaluation of Swallowing (FEES).

The Functional Oral Intake Scale (FOIS) is the most frequently used scale for the evaluation of functional oral intake by dysphagia patients. FOIS was validated using data from Videofluoroscopic Swallowing Study (VFSS). Until now, a validated German version of FOIS for Flexible Endoscopic Evaluation of Swallowing (FEES) is lacking. The aim of this study was a cross-cultural validation of the German version of FOIS (FOIS-G) for FEES. The translation of the original FOIS was carried out according to the Translation, Review, Adjudication, Pretesting, Documentation (TRAPD) translation methodology. For the validation process, six experienced language therapists (SLT) retrospectively analyzed charts of 93 stroke patients. Inclusion criteria were comprised of stroke, clinical examination by an SLT within 24 h of admission, and FEES within 72 h of admission. The validity was calculated by comparison with Modified Rankin Scale (MRS), Barthel Index (BI), the Penetration-Aspiration-Scale (PAS), and a water swallow test. Spearman rank correlation of all paired raters ranged from rs = 0.96 to rs = 0.99, and percentage agreement ranged from 81 to 94%. The overall agreement between all raters was calculated by Fleiss kappa (0.83) (s.e. 0.02). There is a significant correlation between the BI and the MRS with the FOIS-G (rs = 0.301, p = 0.003 for BI; rs = - 0.366, p < 0.001 for MRS), between the PAS and the FOIS-G (rs = - 0.758, p < 0.001), as well as between the 70 ml-water-test and the FOIS-G (rs = 0.470, p < 0.001). FOIS-G is a valid instrument for the evaluation of the functional oral intake of food and liquids in dysphagia patients.

Epileptic seizure discharges in patients after open chamber cardiac surgery-a prospective prevalence pilot study using continuous electroencephalography.

PURPOSE: Patients undergoing cardiac surgery often develop delirium which increases the risk of postoperative morbidity and leads to a reduced quality of life. Retrospective studies show a higher incidence of delirium in patients with seizures. However, these studies do not systematically detect subclinical seizures, so the incidence of seizures after cardiac surgery remains speculative. The objective of this study is to determine the prevalence of electrographic seizures after elective open-chamber cardiac surgery. METHODS: This prospective, blinded, monocentric, observational study investigated patients scheduled for elective open-chamber valve reconstruction or replacement. Anaesthesia, surgery and postoperative treatment were standardized and not influenced by the presented observation. After surgery, all patients arrived at the ICU, and EEG monitoring started within the first hour. EEG recording was continuously performed for up to 24 h, and the results were independently analysed by two blinded EEG board-certified neurologists. RESULTS: 100 patients were included. Abnormal EEG patterns were present in 33% of patients, and 9% of all patients showed electrographic seizures. The main EEG activity at the beginning of each recording was suppressed or showed a burst-suppression pattern, and at the end of recording, all patients had an alpha/theta rhythm. An association between electrographic seizures and delirium was found (pχ2 < 0.01). CONCLUSION: This study reveals a surprisingly high incidence of abnormal EEG patterns and electrographic seizures in patients undergoing open-chamber cardiac surgery. As electrographic seizures are associated with the incidence of delirium, this finding is a relevant phenomenon in the post-cardiac surgery ICU population.

Decreasing postoperative cognitive deficits after heart surgery: protocol for a randomized controlled trial on cognitive training.

BACKGROUND: The occurrence of postoperative cognitive deficits, especially after heart surgery, has been demonstrated in several studies. These deficits can clearly be noticed by the patients and by their close relatives in daily life. Furthermore, postoperative cognitive deficits can decrease quality of life in social functioning and earning capacity. The aim of this study is to investigate whether early postoperative cognitive training can reduce subjective and objective postoperative cognitive deficits. METHODS: The proposed study is a multicenter, two-arm, randomized controlled trial involving 144 elderly patients undergoing elective heart-valve surgery with extracorporeal circulation. Patients will be assigned to either a training group or a control group. The intervention involves paper-and-pencil-based cognitive training, which is conducted for 36 min over a period of 18 days. The training starts about 1 week after surgery and is carried out during the hospitalized rehabilitation phase. The control group will not receive cognitive training or a placebo intervention. A detailed assessment of psychological functions and health-related quality of life prior to surgery at discharge from rehabilitation and 3 and 12 months after discharge will be performed. The primary outcome of this trial is the training effect on objective cognitive functions at discharge from rehabilitation. Secondary outcomes are the training effect on objective and subjective cognitive functions (3 and 12 months after discharge), depression, health-related quality of life, and the impact of perioperative cerebral ischemia on the training effect. Perioperative cerebral ischemia will be measured with postoperative magnetic resonance imaging including diffusion-weighted sequences. DISCUSSION: Should it be shown that our cognitive training can improve postoperative cognitive deficits and quality of life, one possibility could be to integrate this intervention into early rehabilitation. Furthermore, we hope that the investigation of perioperative ischemia by diffusion-weighted magnetic resonance imaging will improve our understanding of neurobiological factors influencing the course of postoperative cognitive plasticity. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00015512. Retrospectively registered on 21 September 2018.

Age-Related Effects of the Apolipoprotein E Gene on Brain Function.

The apolipoprotein E (ApoE) ɛ4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE ɛ4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4±4.6 years, 25 ɛ4 carriers) and old (n = 40; age 66.1±7.0 years, 20 ɛ4 carriers) participants. A cross-sectional factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype-related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in ɛ4 carriers. The increased BOLD response in old ɛ4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the ɛ4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young ɛ4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age.

Recognition memory is associated with altered resting-state functional connectivity in people at genetic risk for Alzheimer's disease.

The apolipoprotein E ε4 (ApoE ε4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE ε4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50-80 years old), of which 20 carried the ε4 allele. All participants underwent resting-state functional magnetic resonance imaging (fMRI), high-resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting-state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE ε4 carriers performed significantly poorer than non-carriers in wordlist recognition and cued recall. Furthermore, ε4 carriers showed increased connectivity relative to ε4 non-carriers between the PCC seed region and left-hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting-state connectivity in the left MTG in ε4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross-links between DMN core areas and cortical areas involved in memory processing.