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5 Examining the Cognitive, Vascular, and Lifestyle Profiles of Older Adults with Late-Onset Epilepsy
- Anny Reyes, Emily L. Johnson, Carrie R. McDonald
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 793-794
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Objective:
Older adults represent the fastest-growing population of individuals with epilepsy with an incidence that peaks after age 65. Patients with late-onset epilepsy (LOE) have a multitude of risk factors for accelerated cognitive and brain aging, including vascular and metabolic risk factors. Despite this, there are few studies investigating the cognitive profiles of older adults with LOE, a neglected area in aging research. We examine the cognitive profiles of older adults with LOE and determine the contribution of demographic and vascular risk factors to impairment.
Participants and Methods:Participants were part of the Atherosclerosis Risk in Communities Study (ARIC) and the incidence of epilepsy was identified using ARIC hospitalization records and Centers for Medicare and Medicaid Services claims data from 1991 to 2015. Approximately 1.8% of the participants with sufficient Medicare coverage data were classified as having LOE (LOE n=281; Non-LOE n=9808). Vascular, lifestyle, and cognitive data were obtained from the ARIC Neurocognitive Study (ARIC-NCS) which consisted of three visits since 2011. Participants with ARIC-NCS visits completed after the onset of seizures were included in the final sample. Non-LOE participants with normal cognition (Black: n=603 and White: n=2543 participants independently) were used to generate z-scores across tests of language, memory, executive function, and processing speed/attention. Impairment was defined as <1.5 standard deviations below the mean of the normative sample. Stepwise regressions were conducted to examine the contribution of demographic (age, race, sex, education) and vascular risk factors (hypertension, diabetes, hyperlipidemia, obesity, smoking) to cognitive performance.
Results:Average age of first seizure of all LOE participants (n=281) was 76.23 (SD=6.24), 55.9% female, 30.7% Black/African American, and the majority had either a college (28.1%) or high school degree (26%). Fifty-six LOE participants had ARIC-NCS visits after the onset of seizures (average age=79.84, SD=5.17, 57.1% female, 32.1% Black). Approximately 67.9% of the sample had at least one vascular risk factor with 81.5% having hypertension, 37% diabetes, 26.4% hyperlipidemia, 20.4% obesity (BMI>30), and 4.5% current smoker. The most frequently impaired domains were language (naming=29.7%; animal fluency=20%; letter fluency=30%) and memory (prose immediate recall=18.4%; prose delayed recall=44.7%; word delayed recall=19.4%). Higher education was associated with better naming (b=0.801, p=0.040). Female sex (b=-0.799, p=0.017) and lower education levels (b=0.418, p=0.050) were associated with poorer immediate prose recall. Older age was associated with poorer delayed prose recall (b=-0.191, p=0.036). Hypertension was associated with worse digit span backward (b=-0.942, p=0.002).
Conclusions:In older adults with LOE, language and memory were the most commonly impaired cognitive domains, similar to studies in early onset epilepsy. Vascular risk factors were prevalent among LOE and hypertension was associated with worse working memory. Further, important demographic factors (sex, education, and age) were associated with the extent of cognitive impairment. Characterizing cognitive profiles in LOE and determining the contribution of demographic and vascular factors to impairment could help to identify patients at risk for future cognitive decline and/or the development of LOE itself, as well as interventions aimed at reducing the risk of further decline.
28 Challenges to Lateralizing Visual Memory Dysfunction in TLE Patients
- Chantal Muller-Cohn, Carrie McDonald, Amanda Gooding, Marc Norman
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 29-30
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Objective:
Neuropsychological assessment is an essential part of presurgical evaluation for epilepsy patients with refractory temporal lobe epilepsy. Evaluations assist in localizing and lateralizing epileptogenic focal points and identifying possible risks for cognitive decline following surgery. Researchers and clinicians consistently find that verbal memory dysfunction is an accurate indicator of left temporal lobe epilepsy (TLE) through verbal measures such as the CVLT-II. Although visual memory structures are assumed to be in the right (nondominant) hemisphere, visual memory assessments have not been reliable in identifying right TLE. It is hypothesized that assessments to test visual memory are confounded by verbal cueing to assist in visual learning. To account for this, researchers have identified that comparing verbal and visual score asymmetries does accurately differentiate left and right TLE patients. This study aimed to determine if verbalvisual asymmetry using the CVLT-II and BVMT-R accurately identifies left and right TLE relative weaknesses potentially associated with epileptogenic regions.
Participants and Methods:As part of a pre-surgical neuropsychological evaluation, 37 well-characterized medically refractory TLE patients (18 right TLE; 19 left TLE) were administered the Brief Visuospatial Memory Test-Revised to evaluate visuospatial memory and the CVLT-II to evaluate verbal memory. A multivariate analysis of variance was used to compare RTLE and LTLE group performances on BVMT-R delay recall subscales, using T-scores. Then memory asymmetry scores were calculated by converting CVLT-II verbal delay memory scores to T-scores and subtracting BVMT-R delayed recall T-score from the verbal memory T-score. An independent samples t-test was used to compare asymmetry scores between the groups.
Results:There were no significant differences between patients with RTLE and LTLE for BVMT-R Delay [F(2,34) = 0.11, p = .895]. There was not a significant difference when accounting for verbal-visual asymmetry (t (35) = 0.422, p = 0.675, d = 12.566) between left (M = -2.42, SD = 13.82) and right side (M = -4.17, SD = 11.09).
Conclusions:The BVMT-R did not identify nondominant hemisphere dysfunction in this sample of 18 right TLE patients. Because visual memory performance did not inform lateralization, we investigated the usefulness of memory asymmetry. Inconsistent with our hypothesis, verbal-visual memory asymmetry scores did not differentiate RTLE from LTLE in this sample. These findings add to existing findings that the BVMT-R may not be able to identify visuospatial memory dysfunction in epilepsy. Additionally, these data indicate the inability to assess for visuospatial memory even when accounting for verbal abilities in epilepsy patients. Future research should consider alternate visuospatial measures for the evaluation of epilepsy patients.
1 Network Efficiency as Structural Reserve: Pre- And Post-Operative Associations Between Network Organization and Memory in Temporal Lobe Epilepsy
- Alena Stasenko, Erik Kaestner, Donatello Arienzo, Adam Schadler, Carrie R McDonald
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 306-307
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Objective:
Memory impairment is a common comorbidity in individuals with temporal lobe epilepsy (TLE). Further, in medication-resistant epilepsy the frontline option, neurosurgical epileptogenic zone destruction, places memory at significant risk. Research has highlighted that TLE causes whole-brain network efficiency disruption, but it is not established how this may explain pre- and post-surgical cognition. Here we examine whether white matter structural network organization predicts pre-operative memory function and/or risk for post-operative memory decline.
Participants and Methods:Patients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-operative sample included 51 individuals with left TLE (L-TLE), 52 with right TLE (R-TLE), and 57 healthy controls who underwent T1- and diffusion-weighted MRI (dMRI), and neuropsychological tests of verbal and visual memory. Forty-four patients (n=21 L-TLE) subsequently underwent temporal lobe surgery (36 anterior temporal lobectomy; 7 stereotactic laser amygdalohippocampectomy; 1 amygdalohippocampectomy) and completed post-operative memory testing. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory, focusing on network integration (path length) and specialization (transitivity). In the preoperative dataset, first we compared TLE versus controls with analysis of covariance (ANCOVAs) controlling for age. Next, linear regressions examined the association between memory scores and network efficiency between L-TLE, R-TLE and controls. In the post-operative sample, bivariate correlations examined the association between pre- to post-operative memory change and 1) global network efficiency and 2) asymmetry of mesial temporal efficiency (i.e., local efficiency of the hippocampal, parahippocampal, and entorhinal nodes). Finally, efficiency metrics were entered into stepwise regressions along with established predictors of memory decline.
Results:Compared to controls, TLE showed longer path length (p < .05; ηp2 = .03) and lower transitivity (p = .01; ηp2 = .04). Pre-operatively, better verbal learning and memory were associated with both shorter path length (β = -0.23 to -0.32; psadjusted < .05) and increased transitivity (β = 0.20 to 0.31; psadjusted < .05). These associations were greater in L-TLE than R-TLE (i.e., a significant interaction; β = -0.29 to 0.25; psadjusted <.05). Post-operatively, global metrics predicted decline on list learning for LTLEs (rs = -.57 to .58; ps < .01), and were marginal on list recall (rs = -.42 to .40; ps < .10). Leftward asymmetry of mesial temporal local efficiency predicted greater decline across most verbal memory measures for L-TLE (rs -.47 to -59; psadjusted <.05), but not R-TLE. Asymmetry of mesial network efficiency uniquely explained at least 20 to 43% of the variance in list learning, recall, and story learning for L-TLE, outperforming hippocampal asymmetry and preoperative score (psadjusted <.05).
Conclusions:Our findings suggest that global white matter network abnormalities contribute to verbal memory impairment pre-operatively and vulnerability to decline post-operatively in L-TLE. Asymmetry of a predefined mesial temporal sub-network may help predict post-operative memory function following left temporal lobe surgery, such that greater efficiency in the to-beresected mesial temporal network may be an important risk factor for decline. Our findings extend the importance of network approaches in TLE to include the relationships between neurobiological networks and memory function.
2 Cross Cultural Application of the International Classification of Cognitive Disorders in Epilepsy (IC CoDE) Cognitive Phenotypes in People with Temporal Lobe Epilepsy in India
- Urvashi Shah, Shivani Rajeshree, Anny Reyes, Aparna Sahu, Mayuri Kalika, Sangeeta Ravat, Robyn Busch, Mayu Fujikawa, Victoria Ives-Deliperi, Sallie Baxendale, Bruce Hermann, Carrie McDonald
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 307-308
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To apply the new IC-CoDE cognitive diagnostic taxonomy (Norman et al., 2020) to a large cohort of people with temporal lobe epilepsy (TLE) in India. The IC-CoDE taxonomy of cognitive diagnoses for 1,409 Englishspeaking adults with TLE from seven epilepsy centres in the U.S. has been published (McDonald et al., 2022). Initial results suggest that the IC-CoDE produces stable cognitive phenotypes across centres; however, its international applicability, including the suggested impairment cut-off needs to be considered across cultures and languages to avoid misclassification. The aim of this study was to apply the IC-CoDE to a population, outside of the U.S., diverse in language representation (i.e., bi/multi-lingual), assessment tools, normative data, and educational and cultural backgrounds to determine whether the same cognitive phenotypes and their relative frequencies would emerge.
Participants and Methods:Data from 549 adults with TLE (mean age=27.14 (8.04), 60.47% males) from a tertiary referral hospital in Mumbai, India who had undergone a comprehensive neuropsychological evaluation (minimum two tests in at least 4 of the 5 cognitive domains: memory, language, executive function, attention/processing speed and visuospatial) were analysed using the ICCoDE criteria. The base rate of impairment for individual tests was calculated using a cutoff of 1.5 standard deviations (S.D.) below the normative mean. The cognitive diagnostic criteria were applied, and the distribution and base rate of cognitive phenotypes was compared to the published taxonomy data from the U.S. (McDonald et al., 2022).
Results:In comparison to the U.S. cohort, the India group was relatively younger, lower in the education level, had a younger age at seizure onset and a shorter duration of the epilepsy. Application of the IC-CoDE taxonomy using a 1.5 S.D. cutoff revealed an Intact cognitive profile in 48% of patients, Single Domain impairment in 32%, Bi Domain impairment in 15% and Generalised impairment in 5%. These findings were mostly comparable to percentages reported in the U.S. cohorts with Intact profile (47%; c2= 0.158, p=0.690), Single Domain (29%; c2= 46.26, p<0.01), Bi Domain (16%; c2= 0.298, p=0.585) and Generalised (8%; c2= 5.347, p=0.021) impairment. However, the most common impairment in the Single Domain group for the bi/multilingual India population was Memory (38%) followed by Attention (20%) and then Language (13%), diverging from the distribution in the U.S. data with maximum impairment in Language (49%) followed by Memory (32%) in the Single Domain Group.
Conclusions:These findings demonstrate that the IC-CoDE can be applied internationally, and the broad taxonomy of cognitive diagnosis holds even in a culturally, linguistically diverse population. Differences in rates of impairments across specific domains emerged with language relatively preserved in the India bi/multilingual population, and memory more frequently impaired than observed in the multi-centre U.S. sample. These findings may reflect differences in demographics, rates of bi/multilingualism, normative data, language tools, or underlying neuropathology, which should be further explored to determine their impact on cognitive profiles.
25 High-resolution MRI Reveals Selective Patterns of Hippocampal Subfield Atrophy in Focal Epilepsy
- Adam Schadler, Erik Kaestner, Alena Stasenko, Christine N. Smith, Catherine Tallman, Nigel P. Pedersen, Shahin Hakimian, Michelle S. Kim, Daniel J Peterson, Thomas J. Grabowski, Daniel L. Drane, Carrie R. McDonald
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 25-26
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Hippocampal pathology is a consistent feature in persons with temporal lobe epilepsy (TLE) and a strong biomarker of memory impairment. Histopathological studies have identified selective patterns of cell loss across hippocampal subfields in TLE, the most common being cellular loss in the cornu ammonis 1 (CA1) and dentage gyrus (DG). Structural neuroimaging provides a non-invasive method to understand hippocampal pathology, but traditionally only at a whole-hippocampal level. However, recent methodological advances have enabled the non-invasive quantification of subfield pathology in patients, enabling potential integration into clinical workflow. In this study, we characterize patterns of hippocampal subfield atrophy in patients with TLE and examine the associations between subfield atrophy and clinical characteristics.
Participants and Methods:High-resolution T2 and T1-weighted MRI were collected from 31 participants (14 left TLE; 6 right TLE; 11 healthy controls [HC], aged 18-61 years). Reconstructions of hippocampal subfields and estimates of their volumes were derived using the Automated Segmentation of Hippocampal Subfields (ASHS) pipeline. Total hippocampal volume was calculated by combining estimates of the subfields CA1-3, DG, and subiculum. To control for variations in head size, all volume estimates were divided by estimates of total brain volume. To assess disease effects on hippocampal atrophy, hippocampi were recoded as either ipsilateral or contralateral to the side of seizure focus. Two sample t-tests at a whole-hippocampus level were used to test for ipsilateral and contralateral volume loss in patients relative to HC. To assess whether we replicated the selective histopathological patterns of subfield atrophy, we carried out mixed-effects ANOVA, coding for an interaction between diagnostic group and hippocampal subfield. Finally, to assess effects of disease load, non-parametric correlations were performed between subfield volume and age of first seizure and duration of illness.
Results:Patients had significantly smaller total ipsilateral hippocampal volume compared with HC (d=1.23, p<.005). Contralateral hippocampus did not significantly differ between TLE and HC. Examining individual subfields for the ipsilateral hemisphere revealed significant main-effects for group (F(1, 29)=8.2, p<0.01), subfields (F(4, 115)=550.5, p<0.005), and their interaction (F(4, 115)=8.1, p<0.001). Post-hoc tests revealed that TLE had significantly smaller volume in the ipsilateral CA1 (d=-2.0, p<0.001) and DG (d = -1.4, p<0.005). Longer duration of illness was associated with smaller volume of ipsilateral CA2 (p=-0.492, p<0.05) and larger volume of contralateral whole-hippocampus (p=0.689, p<0.001), CA1 (p=0.614, p < 0.005), and DG (p=0.450, p<0.05).
Conclusions:Histopathological characterization after surgery has revealed important associations between hippocampal subfield cell loss and memory impairments in patients with TLE. Here we demonstrate that non-invasive neuroimaging can detect a pattern of subfield atrophy in TLE (i.e., CA1/DG) that matches the most common form of histopathologically-observed hippocampal sclerosis in TLE (HS Type 1) and has been linked directly to both verbal and visuospatial memory impairment. Finally, we found evidence that longer disease duration is associated with larger contralateral hippocampal volume, driven by increases in CA1 and DG. This may reflect subfield-specific functional reorganization to the unaffected brain tissue, a compensatory effect which may have important implications for patient function and successful treatment outcomes.
4 Preoperative International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) Phenotype is Associated with Postoperative Memory Decline Following Temporal Lobectomy
- Kayela Arrotta, Bruce P Hermann, Carrie R McDonald, Anny Reyes, Sallie Baxendale, Robyn Busch
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 310-311
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Objective:
The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is a new consensus-based taxonomy that classifies patients into one of four cognitive phenotypes (i.e., cognitively intact, single-domain impairment, bi-domain impairment, generalized impairment). The IC-CoDE has been effectively applied to patients with temporal lobe epilepsy (TLE), but little is known about the relationship between pre-operative cognitive phenotype and post-operative cognitive outcome following epilepsy surgery. The purpose of this study was to examine whether the IC-CoDE classifications are related to memory decline following surgery for TLE.
Participants and Methods:347 patients (ages 16-66; 57% female) with pharmacoresistant TLE completed comprehensive pre- and post-surgical neuropsychological assessments. Patients were classified into IC-CoDE phenotypes based on pre-surgical pattern of cognitive impairment using a threshold of >1.5 standard deviations (SD) below the normative mean. Change scores were calculated from delay trial scores of the following memory tests: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from the Wechsler Memory Scale - Third Edition (WMS-III). Cutoffs were applied using epilepsy-specific reliable change indices and patients were classified within the ‘decline’ group if they experienced significant decline on any of the three memory measures.
Results:The distribution of IC-CoDE phenotypes in our sample were as follows: 57% intact, 29% single-domain, 10% bi-domain, and 5% generalized impairment. 108 patients (31%) demonstrated post-surgical memory decline. Patients who underwent dominant temporal lobectomy were more likely to show post-surgical memory decline compared to non-dominant temporal lobectomy. However, there was no significant difference in phenotype distribution between patients who underwent left versus right-sided resections; thus, analyses were conducted on the entire sample to increase power. Chi-square analyses revealed unique patterns of post-surgical memory decline across phenotypes, X2 = 8.79, p = .032. There was a significantly higher proportion of patients with memory decline in the single-domain phenotype (39%) and this was followed by the bi-domain phenotype (33%) and the intact phenotype (29%). In contrast, patients with generalized impairment were unlikely to show memory decline (.06%). Within the single domain impaired phenotype, there were no differences between the specific domains impaired and memory decline. Logistic regression model was also significant; after controlling for surgery side, the IC-CoDE phenotypes significantly predicted the likelihood of a patient experiencing post-surgical memory decline; X2 = 8.18, p = .043.
Conclusions:In addition to the IC-CoDE providing a useful cognitive classification scheme in epilepsy, the IC-CoDE phenotypes appear helpful in identifying those at risk for post-operative memory decline. Previous literature has suggested that those with better pre-surgical cognition are generally at highest risk for cognitive decline. Our results generally follow this trend, but interestingly, patients with single domain impairment were at the highest risk of memory decline, even above those in the cognitively intact group. Future studies are important to confirm this pattern in other samples and examine additional contributing factors and underlying mechanisms that may influence risk of memory decline across these cognitive phenotypes.
Impaired Behavioral Pattern Separation in Refractory Temporal Lobe Epilepsy and Mild Cognitive Impairment
- Sanam J. Lalani, Anny Reyes, Erik Kaestner, Shauna M. Stark, Craig E.L. Stark, David Lee, Leena Kansal, Jerry J. Shih, Christine N. Smith, Brianna M. Paul, Carrie R. McDonald
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- Journal of the International Neuropsychological Society / Volume 28 / Issue 6 / July 2022
- Published online by Cambridge University Press:
- 03 June 2021, pp. 550-562
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Objective:
Episodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI.
Method:Patients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST). Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test—Second Edition scores, and MST performance were tested in the TLE group.
Results:Patients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance.
Conclusion:Memory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.
Central Nervous System Manifestations of COVID-19: A Critical Review and Proposed Research Agenda
- Kelsey C. Hewitt, David E. Marra, Cady Block, Lucette A. Cysique, Daniel L. Drane, Michelle M. Haddad, Emilia Łojek, Carrie R. McDonald, Anny Reyes, Kara Eversole, Dawn Bowers
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- Journal of the International Neuropsychological Society / Volume 28 / Issue 3 / March 2022
- Published online by Cambridge University Press:
- 16 April 2021, pp. 311-325
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Objective:
On March 11, 2020, the World Health Organization declared an outbreak of a new viral entity, coronavirus 2019 (COVID-19), to be a worldwide pandemic. The characteristics of this virus, as well as its short- and long-term implications, are not yet well understood. The objective of the current paper was to provide a critical review of the emerging literature on COVID-19 and its implications for neurological, neuropsychiatric, and cognitive functioning.
Method:A critical review of recently published empirical research, case studies, and reviews pertaining to central nervous system (CNS) complications of COVID-19 was conducted by searching PubMed, PubMed Central, Google Scholar, and bioRxiv.
Results:After considering the available literature, areas thought to be most pertinent to clinical and research neuropsychologists, including CNS manifestations, neurologic symptoms/syndromes, neuroimaging, and potential long-term implications of COVID-19 infection, were reviewed.
Conclusion:Once thought to be merely a respiratory virus, the scientific and medical communities have realized COVID-19 to have broader effects on renal, vascular, and neurological body systems. The question of cognitive deficits is not yet well studied, but neuropsychologists will undoubtedly play an important role in the years to come.
Developmental mechanisms in the prodrome to psychosis
- Elaine F. Walker, Hanan D. Trotman, Sandra M. Goulding, Carrie W. Holtzman, Arthur T. Ryan, Allison McDonald, Daniel I. Shapiro, Joy L. Brasfield
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- Development and Psychopathology / Volume 25 / Issue 4pt2 / November 2013
- Published online by Cambridge University Press:
- 17 December 2013, pp. 1585-1600
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Psychotic disorders continue to be among the most disabling and scientifically challenging of all mental illnesses. Accumulating research findings suggest that the etiologic processes underlying the development of these disorders are more complex than had previously been assumed. At the same time, this complexity has revealed a wider range of potential options for preventive intervention, both psychosocial and biological. In part, these opportunities result from our increased understanding of the dynamic and multifaceted nature of the neurodevelopmental mechanisms involved in the disease process, as well as the evidence that many of these entail processes that are malleable. In this article, we review the burgeoning research literature on the prodrome to psychosis, based on studies of individuals who meet clinical high risk criteria. This literature has examined a range of factors, including cognitive, genetic, psychosocial, and neurobiological. We then turn to a discussion of some contemporary models of the etiology of psychosis that emphasize the prodromal period. These models encompass the origins of vulnerability in fetal development, as well as postnatal stress, the immune response, and neuromaturational processes in adolescent brain development that appear to go awry during the prodrome to psychosis. Then, informed by these neurodevelopmental models of etiology, we turn to the application of new research paradigms that will address critical issues in future investigations. It is expected that these studies will play a major role in setting the stage for clinical trials aimed at preventive intervention.
Are Empirically-Derived Subtypes of Mild Cognitive Impairment Consistent with Conventional Subtypes?
- Lindsay R. Clark, Lisa Delano-Wood, David J. Libon, Carrie R. McDonald, Daniel A. Nation, Katherine J. Bangen, Amy J. Jak, Rhoda Au, David P. Salmon, Mark W. Bondi
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- Journal of the International Neuropsychological Society / Volume 19 / Issue 6 / July 2013
- Published online by Cambridge University Press:
- 03 April 2013, pp. 635-645
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Given the importance of identifying dementia prodromes for future treatment efforts, we examined two methods of diagnosing mild cognitive impairment (MCI) and determined whether empirically-derived MCI subtypes of these diagnostic methods were consistent with one another as well as with conventional MCI subtypes (i.e., amnestic, non-amnestic, single-domain, multi-domain). Participants were diagnosed with MCI using either conventional Petersen/Winblad criteria (n = 134; >1.5 SDs below normal on one test within a cognitive domain) or comprehensive neuropsychological criteria developed by Jak et al. (2009) (n = 80; >1 SD below normal on two tests within a domain), and the resulting samples were examined via hierarchical cluster and discriminant function analyses. Results showed that neuropsychological profiles varied depending on the criteria used to define MCI. Both criteria revealed an Amnestic subtype, consistent with prodromal Alzheimer's disease (AD), and a Mixed subtype that may capture individuals in advanced stages of MCI. The comprehensive criteria uniquely yielded Dysexecutive and Visuospatial subtypes, whereas the conventional criteria produced a subtype that performed within normal limits, suggesting its susceptibility to false positive diagnostic errors. Whether these empirically-derived MCI subtypes correspond to dissociable neuropathologic substrates and represent reliable prodromes of dementia will require additional follow-up. (JINS, 2013, 19, 1–11)
A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children
- TONY J. SIMON, JOEL P. BISH, CARRIE E. BEARDEN, LIJUN DING, SAMANTHA FERRANTE, VY NGUYEN, JAMES C. GEE, DONNA M. McDONALD–McGINN, ELAINE H. ZACKAI, BEVERLY S. EMANUEL
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- Development and Psychopathology / Volume 17 / Issue 3 / September 2005
- Published online by Cambridge University Press:
- 01 November 2005, pp. 753-784
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We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in “frontal” attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-O-methyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development.
We thank the children and families that participated in our studies and the staff of the 22q and You Center at the Children's Hospital of Philadelphia. This work was supported by grants from the NIH (R01HD42974 and R01HD46159) and the Philadelphia Foundation to T.J.S., Grant PO1DC02027 to B.S.E., and Grant M01-RR00240 to the Children's Hospital of Philadelphia.
Is impairment in set-shifting specific to frontal-lobe dysfunction? Evidence from patients with frontal-lobe or temporal-lobe epilepsy
- CARRIE R. MCDONALD, DEAN C. DELIS, MARC A. NORMAN, EVELYN S. TECOMA, VICENTE J. IRAGUI-MADOZ
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- Journal of the International Neuropsychological Society / Volume 11 / Issue 4 / July 2005
- Published online by Cambridge University Press:
- 01 July 2005, pp. 477-481
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Frontal-lobe epilepsy (FLE), temporal-lobe epilepsy (TLE), and matched-control subjects were administered the Trail Making Test (TMT) of the Delis-Kaplan Executive Function System (D-KEFS; Delis et al., 2001), which assesses set-shifting on a visuomotor sequencing task. Results indicated that patients with FLE were impaired in both speed and accuracy on the switching condition relative to patients with TLE and controls. The two patient groups did not differ from controls on the four baseline conditions of the test, which assess visual scanning, motor speed, number sequencing, and letter sequencing. In addition, seizure-related variables (i.e., age of seizure onset, duration of epilepsy, and seizure frequency) failed to correlate with set-shifting performance in patients with FLE. These results suggest that patients with FLE can be reliably distinguished from those with TLE and control subjects on set-shifting as measured by the DKEFS TMT. (JINS, 2005, 11, 477–481.)
Semantic priming in patients with right frontal lobe lesions
- CARRIE R. MCDONALD, RUSSELL M. BAUER, J. VINCENT FILOTEO, LAURA GRANDE, STEVEN N. ROPER, ROBERT J. BUCHANAN, ROBIN GILMORE
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- Journal of the International Neuropsychological Society / Volume 11 / Issue 2 / March 2005
- Published online by Cambridge University Press:
- 11 April 2005, pp. 132-143
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Patients with unilateral, right frontal lobe damage (N = 13) and matched controls (N = 20) performed a task of lexical ambiguity resolution in order to explore the contribution of right frontal regions to lexical-semantic priming. Word triplets consisting of balanced homographs were presented to participants in four conditions: concordant, discordant, neutral, and unrelated. Controls demonstrated facilitation for concordant meanings of homographs, as evidenced by their faster reaction times in the concordant relative to the unrelated (baseline) condition, as well as a lack of facilitation for the discordant meaning relative to the neutral and concordant conditions. Results in patients with right frontal lobe damage differed depending on the site of the lesion. Patients with lesions restricted to the right medial frontal lobe only showed facilitation in the neutral condition, while those with lesions encroaching upon the right dorsolateral region demonstrated facilitation of both discordant and concordant meanings relative to the baseline condition. These results support a role for the right frontal lobe in semantic priming and suggest possible specialization within the right prefrontal cortex for the processing of lexical-semantic information. (JINS, 2005, 11, 132–143.)