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Biomedical subjects

Andrew J Saykin

Publications and source records attributed to Andrew J Saykin.

30 records · Page 2Linked to original sources

Contribution of organizational strategy to verbal learning and memory in adults with attention-deficit/hyperactivity disorder.

Statistical mediation modeling was used to test the hypothesis that poor use of a semantic organizational strategy contributes to verbal learning and memory deficits in adults with attention-deficit/hyperactivity disorder (ADHD). Comparison of 28 adults with ADHD and 34 healthy controls revealed lower performance by the ADHD group on tests of verbal learning and memory, sustained attention, and use of semantic organization during encoding. Mediation modeling indicated that state anxiety, but not semantic organization, significantly contributed to the prediction of both learning and delayed recall in the ADHD group. The pattern of findings suggests that decreased verbal learning and memory in adult ADHD is due in part to situational anxiety and not to poor use of organizational strategies during encoding.

Adult↗

Working memory deficits after traumatic brain injury: catecholaminergic mechanisms and prospects for treatment -- a review.

PRIMARY OBJECTIVE: To review the neural circuitry and neurochemistry of working memory and outline the evidence for working memory deficits after traumatic brain injury, and the evidence for the use of catecholaminergic agents in the amelioration of these deficits. Current knowledge gaps and research needs are identified. MAIN OUTCOMES AND RESULTS: Impairments in working memory are a core component of the cognitive deficits associated with traumatic brain injury. Recent progress in understanding the neural circuitry and neurochemistry of working memory suggests that catecholamines play a central role in the activation and regulation of working memory and thus lays a framework in which to consider the use of catecholaminergic agents (dopaminergic and alpha-2 adrenergic agonists) in the treatment of specific cognitive deficits after traumatic brain injury. CONCLUSIONS: The combined methods of cognitive neuroscience, functional brain imaging and neuropharmacology are proposed as an excellent method for studying working memory deficits. A strong rationale exists for the targeted use of catecholaminergic agonists in the treatment of working memory deficits after traumatic brain injury.

Adrenergic alpha-Agonists↗

Apathy in schizophrenia: reduced frontal lobe volume and neuropsychological deficits.

OBJECTIVE: Apathy is a common negative symptom in schizophrenia. The authors investigated neuropsychological performance and regional brain volumes in schizophrenia patients with high versus low levels of apathy. METHOD: Schizophrenia patients with low apathy levels (N=18) and high apathy levels (N=20) and 12 healthy comparison subjects completed neuropsychological testing as well as magnetic resonance imaging scanning to obtain lobar volumes after total intracranial volume was controlled. RESULTS: The high apathy group scored lower than comparison subjects on rapid visuomotor sequencing and verbal learning/recall. The high apathy group had lower performance IQ scores than the low apathy and comparison groups. Only the high apathy group showed significantly reduced bilateral frontal lobe volumes relative to comparison subjects; both schizophrenia patient groups showed bilateral temporal lobe volume reductions. CONCLUSIONS: The present findings are consistent with studies in other disorders showing frontal lobe involvement in apathy.

Adult↗

Neurologic injury associated with CABG surgery: outcomes, mechanisms, and opportunities for improvement.

Neurologic injuries, whether subtle or overt, are a major source of morbidity secondary to coronary artery bypass graft (CABG) surgery. A comprehensive review of research in the area of neurologic injury is provided. We conclude this article by providing insight regarding areas requiring further investigation in order to reduce sustainably the risk of these iatrogenic events among patient undergoing CABG surgery.

Clinical Trials as Topic↗

The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy.

PURPOSE: The primary purpose of this study was to compare the neuropsychological performance of long-term survivors of breast cancer and lymphoma treated with standard dose chemotherapy who carried the epsilon 4 allele of the Apolipoprotein E (APOE) gene to those who carry other APOE alleles. PATIENTS AND METHODS: Long-term survivors (mean=8.8+/-4.3 years post-treatment) of breast cancer (N=51, age=55.9+/-8.8) or lymphoma (N=29, age=55.8+/-11.6) who had been treated with standard-dose chemotherapy completed a standardized battery of neuropsychological and psychological tests. Survivors were also classified into two groups based on the presence (N=17) or absence (N=63) of at least one epsilon 4 allele of APOE. RESULTS: Analysis of covariance, controlling for age, gender, education, diagnosis, and WRAT-3 reading subtest (a proxy measure of baseline IQ), indicated that survivors with at least one epsilon 4 allele scored significantly lower in the visual memory (p<0.03) and the spatial ability (p<0.05) domains and tended to score lower in the psychomotor functioning (p<0.08) domain as compared to survivors who did not carry an epsilon 4 allele. No group differences were found on depression, anxiety, or fatigue. CONCLUSIONS: The results of this study provide preliminary support for the hypothesis that the epsilon 4 allele of APOE may be a potential genetic marker for increased vulnerability to chemotherapy-induced cognitive decline.

Adult↗

Mild cognitive impairment: conceptual issues and structural and functional brain correlates.

Mild cognitive impairment (MCI) is a prevalent condition among older adults that carries a high risk of progression to Alzheimer's disease or other dementias. Given the potential for delaying or preventing the onset of dementia, efforts aimed at early detection and early intervention are important. The current paper reviews the conceptualization and diagnosis of MCI, assessment of memory complaints and deficits in the elderly, as well as recent research on the neurobiological basis of the disorder, including neurochemical, structural, and functional neuroimaging findings.

Aged↗

Mechanisms of chemotherapy-induced cognitive disorders: neuropsychological, pathophysiological, and neuroimaging perspectives.

Recent studies have indicated the frequent occurrence of neuropsychologic deficits and cognitive complaints after systemic cancer chemotherapy. Most early reports were retrospective, but prospective longitudinal studies are underway. Although the available evidence suggests a fairly diffuse pattern of changes, memory and executive functions could be preferentially affected. Preliminary data also suggest that some individuals might be more vulnerable than others, leading to investigation of genetic and other risk factors. The greatest gap in our knowledge regarding chemotherapy-related cognitive changes is a lack of understanding of the mechanism or mechanisms that account for the observed changes. Several pathophysiological candidates include direct neurotoxic effects leading to atrophy of cerebral gray matter (GM) and/or demyelination of white matter (WM) fibers, secondary immunologic responses causing inflammatory reactions, and microvascular injury. Altered neurotransmitter levels and metabolites could constitute an additional mechanism related to neurotoxic effects. Advanced brain imaging techniques can directly or indirectly assess many of these mechanisms, but to date there has been very limited application of these tools. Morphometric magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are noninvasive techniques that could yield important complementary data regarding the nature of neural changes after chemotherapy. Electrophysiological studies and targeted molecular imaging with positron emission tomography (PET) could also provide unique information. We review the minimal imaging data available at present and also note studies of other brain disorders or treatment effects that might serve as a model for imaging chemotherapy-induced changes. Large-scale prospective studies are needed to help isolate the pathophysiological mechanisms underlying the cognitive deficits associated with chemotherapy.

Antineoplastic Agents↗

Intact motor imagery in chronic upper limb hemiplegics: evidence for activity-independent action representations.

Four experiments were undertaken to examine the effects of chronic hemiplegia on the ability to internally represent actions involving either the paralyzed (contralesional) or relatively unaffected (ipsilesional) limb. An experimental group of chronic, densely hemiplegic patients was compared with controls who experienced nearly full recovery from an initially dense hemiparesis. All participants suffered cerebral vascular accidents that spared sites in premotor and parietal areas directly involved in representing upper limb actions. Despite chronic limb immobility, hemiplegic patients performed all four tasks at a high level of accuracy and showed no differences in their ability to represent actions of the contralesional versus ipsilesional limbs. On tasks that involved representing actions of the hands and lower arms, hemiplegic patients were as accurate as recovered controls. Hemiplegic patients were, however, less accurate than controls on a task that involved representing actions of either upper arm. Overall, chronic hemiplegics performed more accurately for decisions based on their contralesional limbs: a "hemiplegic advantage" that may be related to an ongoing focus on planning and/or imagining currently impossible movements. These findings reveal a dissociation between the ability to internally "represent" versus "produce" manual actions. Further, they demonstrate that internal action representations can be robust to even years of limb disuse.

Aged↗

Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma.

PURPOSE: The primary purpose of this study was to compare the neuropsychologic functioning of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only. PATIENTS AND METHODS: Long-term survivors (5 years postdiagnosis, not presently receiving cancer treatment, and disease-free) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast cancer: n = 35, age, 59.1 +/- 10.7 years; lymphoma: n = 36, age, 55.9 +/- 12.1 years) or local therapy only (breast cancer: n = 35, age, 60.6 +/- 10.5 years; lymphoma: n = 22, age, 48.7 +/- 11.7 years) completed a battery of neuropsychologic and psychologic tests (Center for Epidemiological Study-Depression, Spielberger State-Trait Anxiety Inventory, and Fatigue Symptom Inventory). RESULTS: Multivariate analysis of variance, controlling for age and education, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on the battery of neuropsychologic tests compared with those treated with local therapy only (P <.04), particularly in the domains of verbal memory (P <.01) and psychomotor functioning (P <.03). Survivors treated with systemic chemotherapy were also more likely to score in the lower quartile on the Neuropsychological Performance Index (39% v 14%, P <.01) and to self-report greater problems with working memory on the Squire Memory Self-Rating Questionnaire (P <.02). CONCLUSION: Data from this study support the hypothesis that systemic chemotherapy can have a negative impact on cognitive functioning as measured by standardized neuropsychologic tests and self-report of memory changes. However, analysis of the Neuropsychological Performance Index suggests that only a subgroup of survivors may experience long-term cognitive deficits associated with systemic chemotherapy.

Adult↗

Functional magnetic resonance imaging: emerging clinical applications.

Functional magnetic resonance imaging (fMRI) is a relatively new and noninvasive method of functional brain mapping. Functional MRI is increasingly being applied to the study of neuropsychiatric disorders, including schizophrenia, Alzheimer's disease, traumatic brain injury, and others. Particularly noteworthy are findings related to plasticity in the adult human brain. Despite the promise of fMRI for improving the conceptualization, assessment, and treatment of neuropsychiatric disorders, important technical and scientific issues remain. Future research will address integrating fMRI with other emerging neuroimaging techniques.

Brain↗

Breast cancer chemotherapy-related cognitive dysfunction.

Cognitive side effects of systemic chemotherapy have become an increasing concern among breast cancer survivors, their families, and health care professionals. A growing body of research supports the hypothesis that chemotherapy can produce long-term cognitive changes in at least a subgroup of cancer survivors. We review evidence implicating systemic chemotherapy as the cause of cognitive changes; describe the limitations due to lack of longitudinal studies and gaps in knowledge (ie, no clear mechanism by which chemotherapy can produce cognitive changes has been proposed); discuss possible factors like age, intelligence quotient/education, and psychological, genetic, and hormonal factors that might increase risk for chemotherapy-induced cognitive changes; and outline future directions for research. Such future research includes large-scale, longitudinal studies of pretreatment neuropsychological assessments, use of imaging techniques and the development of animal models to study the mechanisms of chemotherapy-induced changes in cognitive functioning, and the development of interventions to prevent or reduce the negative cognitive effects of chemotherapy

Antineoplastic Combined Chemotherapy Protocols↗

Executive dysfunction following traumatic brain injury: neural substrates and treatment strategies.

Executive dysfunction is among the most common and disabling aspects of cognitive impairment following traumatic brain injury (TBI), and may include deficits in reasoning, planning, concept formation, mental flexibility, aspects of attention and awareness, and purposeful behavior. These impairments are generally attributed to frontal systems dysfunction, due either to direct insult to the frontal lobes or to disruption of their connections to other brain regions. Evaluation of executive deficits typically includes neuropsychological assessment, though adjunctive interviews can be critical in detecting subtle dysexecutive symptoms that may not be apparent on standardized testing. Rehabilitation programs emphasizing cognitive-behavioral approaches to the retraining of planning and problem-solving skills can be effective in ameliorating identified executive deficits. In addition, pharmacological approaches may be useful in addressing aspects of executive dysfunction. This review summarizes the nature of executive deficits following TBI, their neuroanatomical substrates, selected assessment and treatment strategies, and recent research findings and trends.

Brain Injuries↗