Mechanisms Of Cognitive Deficits Research Articles

Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study.

This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this case‒control 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for TreatmentResponseandResistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICSConsensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27%female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serineracemase and serine-hydroxymethyltransferase1, and higher levels of the glutamate-cysteinetransporter3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteinetransporter3 levels only in responders; this association was disrupted in the treatmentresistant group. Treatmentresistantpatients and limitedresponders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials.

Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19.

Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds and infection) alter cellular structures and physiologic processes within the neurovascular unit and contribute to cognitive dysfunction. COVID-19 has posed significant complications during acute and convalescent stages in multiple organ systems, including the brain. Cognitive impairment is a prevalent complication in COVID-19 patients, irrespective of severity of acute SARS-CoV-2 infection. Moreover, overwhelming evidence from in vitro, preclinical and clinical studies has reported SARS-CoV-2-induced pathologies in components of the neurovascular unit that are associated with cognitive impairment. Neurovascular unit disruption alters the neurovascular coupling response, a critical mechanism that regulates cerebromicrovascular blood flow to meet the energetic demands of locally active neurons. Normal cognitive processing is achieved through the neurovascular coupling response and involves the coordinated action of brain parenchymal cells (i.e. neurons and glia) and cerebrovascular cell types (i.e. endothelia, smooth muscle cells and pericytes). However, current work on COVID-19-induced cognitive impairment has yet to investigate disruption of neurovascular coupling as a causal factor. Hence, in this review, we aim to describe SARS-CoV-2's effects on the neurovascular unit and how they can impact neurovascular coupling and contribute to cognitive decline in acute and convalescent stages of the disease. Additionally, we explore potential therapeutic interventions to mitigate COVID-19-induced cognitive impairment. Given the great impact of cognitive impairment associated with COVID-19 on both individuals and public health, the necessity for a coordinated effort from fundamental scientific research to clinical application becomes imperative. This integrated endeavour is crucial for mitigating the cognitive deficits induced by COVID-19 and its subsequent burden in this especially vulnerable population.

Theta and gamma hippocampal–neocortical oscillations during the episodic-like memory test: Impairment in epileptogenic rats

Cortical oscillations in different frequency bands have been shown to be intimately involved in exploration of environment and cognition. Here, the local field potentials in the hippocampus, the medial prefrontal cortex (mPFC), and the medial entorhinal cortex (mEC) were recorded simultaneously in rats during the execution of the episodic-like memory task. The power of theta (~4–10 Hz), slow gamma (~25–50 Hz), and fast gamma oscillations (~55–100 Hz) was analyzed in all structures examined. Particular attention was paid to the theta coherence between three mentioned structures. The modulation of the power of gamma rhythms by the phase of theta cycle during the execution of the episodic-like memory test by rats was also closely studied. Healthy rats and rats one month after kainate-induced status epilepticus (SE) were examined. Paroxysmal activity in the hippocampus (high amplitude interictal spikes), excessive excitability of animals, and the death of hippocampal and dentate granular cells in rats with kainate-evoked SE were observed, which indicated the development of seizure focus in the hippocampus (epileptogenesis). One month after SE, the rats exhibited a specific impairment of episodic memory for the what-where-when triad: unlike healthy rats, epileptogenic SE animals did not identify the objects during the test. This impairment was associated with the changes in the characteristics of theta and gamma rhythms and specific violation of theta coherence and theta/gamma coupling in these structures in comparison with the healthy animals. We believe that these disturbances in the cortical areas play a role in episodic memory dysfunction in kainate-treated animals. These findings can shed light on the mechanisms of cognitive deficit during epileptogenesis.

Decreased Peripheral BDNF Levels and Cognitive Impairment in Late-Life Schizophrenia.

Objectives: There are relatively few studies on mechanisms of cognitive deficits in late-life schizophrenia (LLS). Brain-derived neurotrophic factor (BDNF), as an important neuroplastic molecule, has been reported to be involved in neurocognitive impairment in schizophrenia. This study aimed to examine whether peripheral BDNF levels were associated with cognitive deficits in LLS, which has not been explored yet.Methods: Forty-eight LLS patients and 45 age-matched elderly controls were recruited. We measured all participants on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for cognition and serum BDNF levels. Psychopathological symptoms in patients were assessed by the Positive and Negative Syndrome Scale (PANSS).Results: The levels of BDNF in LLS patients were significantly lower than those in healthy controls (8.80 ± 2.30 vs. 12.63 ± 5.08 ng/ml, p < 0.001). The cognitive performance of LLS patients was worse than that of the controls on RBANS total score and scores of immediate memory, attention, language, and delayed memory (all p ≤ 0.005). BDNF was positively associated with attention in LLS patients (r = 0.338, p = 0.019).Conclusion: Our findings suggest that older patients with schizophrenia exhibit lower BDNF levels and more cognitive deficits than older controls, supporting the accelerated aging hypothesis of schizophrenia. Moreover, decreased BDNF is related to attention deficits, indicating that BDNF might be a candidate biomarker of cognitive impairments in LLS patients.

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease.

This study provides crucial information that could be helpful in the development of new or repurposing of existing therapies for the treatment of cognitive deficit in individuals with sickle cell disease (SCD). Its impact is in demonstrating for the first time that neuroinflammation and along with abnormal neuroplasticity are among the underlying mechanism of cognitive and behavioral deficits in SCD and that drugs such as minocycline which targets these pathophysiological mechanisms could be repurposed for the treatment of this life altering complication of SCD.

Radiotherapy and Its Impact on the Nervous System of Cancer Survivors.

Radiotherapy is routinely used for the treatment of nearly all brain tumors, but it may lead to progressive and debilitating impairments of cognitive function. The growing evidence supports the fact that radiation exposure to CNS disrupts diverse cognitive functions including learning, memory, processing speed, attention and executive functions. The present review highlights the types of radiotherapy and the possible mechanisms of cognitive deficits and neurotoxicity following radiotherapy. The review summarizes the articles from Scopus, PubMed, and Web of science search engines. Radiation therapy uses high-powered x-rays, particles, or radioactive seeds to kill cancer cells, with minimal damage to healthy cells. While radiotherapy has yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side effects from the treatment, which can lead to dose reduction or even cessation of treatment. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities; however, neuroinflammation is widely considered as one of the major mechanisms responsible for radiotherapy-induced toxicities. The present study reviews the different types of radiotherapy available for the treatment of various types of cancers and their associated neurological complications. It also summarizes the doses of radiations used in the variety of radiotherapy, and their early and delayed side effects. Special emphasis is given to the effects of various types of radiations or late side effects on cognitive impairments.

Association of schizophrenia polygenic risk score with data-driven cognitive subtypes: A six-year longitudinal study in patients, siblings and controls

Cross-sectional studies have shown that the polygenic risk score for schizophrenia (PRSSCZ) may influence heterogeneity in cognitive performance although evidence from family-based longitudinal study is limited. This study aimed to identify trajectories of cognitive function and assess whether the PRSSCZ is associated with baseline cognitive performance and predicted six-year trajectories. We included 1119 patients with a schizophrenia spectrum disorder, and 1059 unaffected siblings and 586 unrelated controls who are eligible at baseline. Genotype data were collected at baseline, whereas clinical and sociodemographic data were collected at baseline, three and six years. Group-based trajectory modeling was applied on a weighted standardized composite score of general cognition to unravel cognitive subtypes and explore trajectories over time. We followed a standard procedure to calculate the polygenic risk score. A random-effects ordinal regression model was used to investigate the association between PRSSCZ and cognitive subtypes. Five cognitive subtypes with variable trajectories were found in patients, four in siblings and controls, and six in all combined samples. PRSSCZ significantly predicted poor cognitive trajectories in patients, siblings and all samples. After Bonferroni correction and adjustment for non-genetic factors, only the results in all combined sample remained significant. Cognitive impairment in schizophrenia is heterogeneous and may be linked with high PRSSCZ. Our finding confirmed at least in all combined samples the presence of genetic overlap between schizophrenia and cognitive function and can give insight into the mechanisms of cognitive deficits.

Investigation of Psychiatric and Neuropsychological Correlates of Default Mode Network and Dorsal Attention Network Anticorrelation in Children.

The default mode network (DMN) and dorsal attention network (DAN) demonstrate an intrinsic "anticorrelation" in healthy adults, which is thought to represent the functional segregation between internally and externally directed thought. Reduced segregation of these networks has been proposed as a mechanism for cognitive deficits that occurs in many psychiatric disorders, but this association has rarely been tested in pre-adolescent children. The current analysis used data from the Adolescent Brain Cognitive Development study to examine the relationship between the strength of DMN/DAN anticorrelation and psychiatric symptoms in the largest sample to date of 9- to 10-year-old children (N = 6543). The relationship of DMN/DAN anticorrelation to a battery of neuropsychological tests was also assessed. DMN/DAN anticorrelation was robustly linked to attention problems, as well as age, sex, and socioeconomic factors. Other psychiatric correlates identified in prior reports were not robustly linked to DMN/DAN anticorrelation after controlling for demographic covariates. Among neuropsychological measures, the clearest correlates of DMN/DAN anticorrelation were the Card Sort task of executive function and cognitive flexibility and the NIH Toolbox Total Cognitive Score, although these did not survive correction for socioeconomic factors. These findings indicate a complicated relationship between DMN/DAN anticorrelation and demographics, neuropsychological function, and psychiatric problems.

Immediate and delayed decrease of long term potentiation and memory deficits after neonatal intermittent hypoxia

Apnea of prematurity is a common clinical condition that occurs in premature infants and results in intermittent hypoxia (IH) to brain and other organs. While short episodes of apnea are considered of no clinical significance, prolonged apnea with bradycardia and large oxygen desaturation is associated with adverse neurological and cognitive outcome. The mechanisms of cognitive deficits in IH are poorly understood. We hypothesized that brief but multiple episodes of severe oxygen desaturation accompanied by bradycardia may affect early and late synaptic plasticity and produce long-term cognitive deficits.C57BL/6 mouse pups were exposed to IH paradigm consisting of alternating cycles of 5% oxygen for 2.5 min and room air for 5–10 min, 2 h a day from P3 to P7. Long term potentiation (LTP) of synaptic strength in response to high frequency stimulation in hippocampal slices were examined 3 days and 6 weeks after IH. LTP was decreased in IH group relative to controls at both time points. That decrease was associated with deficits in spatial memory on Morris water maze and context fear conditioning test. Hypomyelination was observed in multiple gray and white matter areas on in vivo MRI using micromolecule proton fraction and ex vivo diffusion tensor imaging. No difference in caspase labeling was found between control and IH groups.We conclude that early changes in synaptic plasticity occurring during severe episodes of neonatal IH and persisting to adulthood may represent functional and structural substrate for long term cognitive deficits.

Types and mechanisms of cognitive deficits in childhood epilepsy

Many human studies on cognition have focused on infants, preschool, and school age children. This period is characterized by peak hippocampal and cortical regional development, as well as myelinogenesis, dendritogenesis, and synaptogenesis. The presence of epilepsy and its treatment during the period of maximal white-matter growth might result in impairment in spatial learning, memory processes and other aspects of cognition. Several variables are associated with cognitive impairment in epilepsy, which includes maternal-related, seizure-related and medication-related variables. Paroxysmal seizures and electroencephalography epileptic discharges may cause transient, persistent or progressive cognitive impairment. Transient disruption of cognitive processing may occur with paroxysmal epileptic activity. Repeated seizure activity selectively impairs myelin accumulation, consumes, and reduces hippocampal plasticity available for information processing. High doses of antiepileptic drugs (AEDs) and polypharmacy are also significant risks for cognitive impairment with AEDs. AEDs produce global changes in the excitation levels in the central nervous system and often lead to cognitive deficits. In utero exposure to AEDs may cause defects in neuronal proliferation and migration and increase apoptosis. Although the immature brain has increased vulnerability to seizures but appears to be more “resistant” to the damaging affect of epilepsy than does the mature brain, however, if sufficiently long, a seizure can result in damage at any age. Cognitive impairment even if trivial may adversely affect the child's psychosocial functioning in daily life by interference with educational skills and learning tasks. To conclude, understanding the mechanisms underlying cognitive impairment with epilepsy and AEDs raise important clinical and research implications and recommendations.

Intracellular chloride accumulation: a possible mechanism for cognitive deficits in Down syndrome.

A study involving a mouse model of Down syndrome and analysis of human postmortem brain samples indicates that hippocampal GABAA receptor signaling in Down syndrome may be excitatory. This advance promises new clinical applications in Down syndrome.

Targeting α7 nicotinic acetylcholine receptors: a future potential for neuroprotection from traumatic brain injury.

Traumatic brain injury (TBI) poses a significant socioeconomic burden in the world. The long lasting consequences in cognitive impairments are often underreported and its mechanisms are unclear. In this perspective, cholinergic dysfunction and therapeutic strategy targeting this will be reviewed. Novel agents that can target specific subtype of acetylcholine receptors have been developed over the recent years and are at various stages of development, which include AR-R 17779, GTS-21, SSR-180711A, AR-{"type":"entrez-nucleotide","attrs":{"text":"R17779","term_id":"771389","term_text":"R17779"}}R17779, and PNU-282987. A detailed review on this topic has been previously published (Shin and Dixon, 2015).

Obesity Elicits Interleukin 1-Mediated Deficits in Hippocampal Synaptic Plasticity

Adipose tissue is a known source of proinflammatory cytokines in obese humans and animal models, including the db/db mouse, in which obesity arises as a result of leptin receptor insensitivity. Inflammatory cytokines induce cognitive deficits across numerous conditions, but no studies have determined whether obesity-induced inflammation mediates synaptic dysfunction. To address this question, we used a treadmill training paradigm in which mice were exposed to daily training sessions or an immobile belt, with motivation achieved by delivery of compressed air on noncompliance. Treadmill training prevented hippocampal microgliosis, abolished expression of microglial activation markers, and also blocked the functional sensitization observed in isolated cells after ex vivo exposure to lipopolysaccharide. Reduced microglial reactivity with exercise was associated with reinstatement of hippocampus-dependent memory, reversal of deficits in long-term potentiation, and normalization of hippocampal dendritic spine density. Because treadmill training evokes broad responses not limited to the immune system, we next assessed whether directly manipulating adiposity through lipectomy and fat transplantation influences inflammation, cognition, and synaptic plasticity. Lipectomy prevents and fat transplantation promotes systemic and central inflammation, with associated alterations in cognitive and synaptic function. Levels of interleukin 1β (IL1β) emerged as a correlate of adiposity and cognitive impairment across both the treadmill and lipectomy studies, so we manipulated hippocampal IL1 signaling using intrahippocampal delivery of IL1 receptor antagonist (IL1ra). Intrahippocampal IL1ra prevented synaptic dysfunction, proinflammatory priming, and cognitive impairment. This pattern supports a central role for IL1-mediated neuroinflammation as a mechanism for cognitive deficits in obesity and diabetes.

Association between reduced expression of hippocampal glucocorticoid receptors and cognitive dysfunction in a rat model of traumatic brain injury due to lateral head acceleration

Expression of hippocampal glucocorticoid receptors (GRs) and spatial learning and memory were observed in rat model of diffuse traumatic brain injury (TBI) due to lateral head acceleration with an aim at investigating the relation between GRs expression and cognitive deficits. Immunohistochemical staining, Western blotting, and RT-PCR indicated that down-regulation of GRs expression occurred in the hippocampus among TBI-rats which demonstrated reduced performance of learning and memory in Morris water maze. As the GRs expression bounced up, the cognitive function approached to normal. It is concluded that reduced expression of hippocampal GRs was closely associated with learning and memory deficits in TBI-rats. Hippocampal GRs was involved in the biochemical mechanisms of cognitive deficits after TBI.

Impaired cognition in bipolar I disorder: The roles of the serotonin transporter and brain-derived neurotrophic factor

Studies have proposed that cognitive deficits are present in a variety of mood states in bipolar disorder (BD). The goal of this study was to find the cognitive deficits in euthymic BD patients and to further explore possible underlying mechanisms of the deficits. Thirty-three healthy controls (HCs) and twenty-three euthymic BD type I patients were recruited. Single photon emission computed tomography (SPECT) with (123)I-ADAM was used to image the serotonin transporter (SERT). Ten milliliters of venous blood was drawn for the measurement of brain derived neurotrophic factor (BDNF). Cognitive functions were tested included attention, memory, and executive function. We found that the SERT availability in both the midbrain and striatal regions was decreased in the BD patients compared with the HCs; however, the BDNF were not different between the two groups. There was no correlation between the SERT availability and the BDNF. Interestingly, there were statistically significant differences in sub-items of the facial memory test and the Wisconsin Card Sorting Test between the BD patients and the HCs, which showed that there was a cognitive deficit in the BD patients. However, the overall deficits in cognition were not significantly correlated with the SERT availability or the BDNF. The effect of medications on cognitive function and BDNF should be considered. We replicated previous findings that showed cognitive deficits in euthymic BD patients. However, the underlying mechanism of cognitive deficits in euthymic BD patients cannot be entirely explained by SERT and BDNF.

Cognitive Neuroscience of Aging: Linking Cognitive and Cerebral Aging

Back to table of contents Previous article Next article Book ForumFull AccessCognitive Neuroscience of Aging: Linking Cognitive and Cerebral AgingDAN G. BLAZER, M.D., PH.D., DAN G. BLAZERSearch for more papers by this author, M.D., PH.D., Durham, N.C.Published Online:1 Mar 2006https://doi.org/10.1176/appi.ajp.163.3.560AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Psychiatry today is firmly grounded in the neurosciences, such as the genetics, molecular biology, anatomy, and physiology of the brain. It is less aware of (and less grounded in) the significant advances in the cognitive sciences, such as attention, perception, and memory. Nevertheless, psychiatry has applied the cognitive sciences through its psychotherapeutic approaches, especially the cognitive/behavioral therapies. Yet the neurosciences and the cognitive sciences are now evolving into the “transdisciplinary” discipline of cognitive neuroscience. And the construct of transdisciplinary is critical to understanding this evolution. Rather than neuroscientists and cognitive scientists simply working in parallel or even working together on the same project (what we typically think of as interdisciplinary), a new “transdiscplinary” breed of scientists is emerging. This new breed of scientists tends to focus upon the extremities of the life cycle—childhood and late life—primarily because both cognitive and neuroanatomical/neurophysiological changes occur at a faster rate during these stages than during the majority of adulthood (and therefore can be effectively studied over a briefer interval). This discipline potentially could become a key basic science of geriatric psychiatry.In this edited volume, which seeks to become a handbook of the new transdisciplinary field of the cognitive neuroscience of aging, a group of international investigators present the basics of this emerging discipline. In my view, they easily accomplish their goal. The book is divided into four main sections. The first section reviews the main neuroimaging methods, documenting, for example, age-related decline in both post- and presynaptic dopamine markers. This decline is associated with age-related cognitive decline (it is not just acetylcholine). The second section focuses upon basic cognitive processes. With aging, frontal and hippocampal structures that are central to higher-order cognition show decreases in volume, yet these decreases do not map directly onto decreases in basic functions such as attention and memory (the brain, even in later life, exhibits significant plasticity).The third section focuses upon clinical and applied issues. One area that has received much attention in recent years is the degree to which cognitive exercises (e.g., learning a novel task such as playing chess) might delay or even prevent the onset of cognitive decline in later life. Though few seriously believe that such exercises can absolutely prevent the dementing disorders, such exercises could be protective. Evidence is emerging that such exercises can be minimally effective in later life but are much more effective earlier in life. Nevertheless, recent and more refined studies suggest that certain types of deficits are more prominent in later life (production versus processing deficits) and that interventions may be targeted toward those deficits. In the final section, a group of investigators propose a series of models that can be applied to the cognitive neuroscience of aging. These models emphasize that the brain is an open system and that lifespan cognitive development is a dynamic, cumulative process that shapes the neurocognitive representation of ongoing interactions with the environment and sociocultural contexts through experience. In other words, neural mechanisms not only feed up to cognition and behavior, cognition and behavior feed down to basic neurobiology.Psychiatrists will perhaps be disappointed because foundational psychological constructs to our field are not explored, such as emotion, motivation, and temperament. We must remember, however, that the cognitive neuroscience of aging has developed to explore the association between the cognition and the neuroscience. The cognitive sciences, although neglected in our studies, are critical to the psychological well-being of our patients.Reprints are not available; however, Book Forum reviews can be downloaded at http://ajp.psychiatryonline.org.Edited by Roberto Cabeza, Lars Nyberg, and Denise Park. New York, Oxford University Press, 2004, 408 pp, $69.50 FiguresReferencesCited byDetailsCited ByRole of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease22 September 2020 | Experimental Biology and Medicine, Vol. 246, No. 1 Volume 163Issue 3 March 2006Pages 560-561 Metrics PDF download History Published online 1 March 2006 Published in print 1 March 2006

Alcoholism, Aging, and Cognition: A Review of Evidence for Shared or Independent Impairments

Little is known about the combined effects of aging and alcoholism on cognitive function, in spite of the potential importance of this knowledge. Studies reported to date have focused on whether aging and alcoholism have shared mechanisms (i.e., the premature aging hypothesis) or independent mechanisms. Most have concluded that the effects of aging and alcoholism on cognition operate through independent mechanisms. However, there are reasons to doubt this conclusion. Many of the studies were not optimally designed to discover shared mechanisms because they used a limited range of ages, included several different groups in their analyses, or had low statistical power. Furthermore, interpretation of the patterns of main effects and interactions between aging and alcoholism is not straightforward. Assumptions must be made about the nature of the impairments in order to interpret the data. This review uses several theories of cognitive aging as an organizing heuristic for interpreting the extant data on aging, cognition, and alcoholism. Some potential shared mechanisms for cognitive deficits in aging and alcoholism are identified, such as information processing speed and proactive interference in working memory. In contrast, some potential independent mechanisms are also identified, such as decay from working and long-term memory. These mechanisms should be used as a base to guide necessary further research.

Unrecognized cognitive impairment in cardiac rehabilitation patients.

To determine the prevalence of unrecognized brain dysfunction accompanying chronic severe cardiac disease, we examined 20 clinically stable consecutive admissions to a cardiac rehabilitation service who were free of known stroke or dementia. Age range was 47 to 85 years (mean +/- SEM, 72.5 +/- 2.1 years), the male: female ratio was 10:10. Multiple cognitive deficits including significant memory impairment and disorientation were present in eight patients (40%), and seven of these eight patients were unable to administer their own medications reliably. An additional six patients (30%) showed milder impairments. One patient was found to be normal after neurological examination, four showed evidence of a single brain lesion, and 15 of 20 (75%) had multiple neurological abnormalities suggesting multifocal brain disease. The mechanism of cognitive deficits in cardiac patients is unclear, and it may be related to multiple infarcts, or acute or chronic hypoxic damage secondary to arrhythmias, cardiac failure, or small vessel disease of the brain. The term "circulatory dementia" is proposed to describe patients with vascular disease and non-Alzheimer type dementia. Patients with cardiac disease should undergo cognitive screening, as early identification of patients at risk of progressive intellectual loss may allow early use of preventive therapy.