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The Mini-mental State Examination (MMSE) is a commonly used screening tool for cognitive impairment. Lenient scoring of spatial orientation errors (SOEs) on the MMSE is common and negatively affects its diagnostic utility. We examined the effect of lenient SOE scoring on MMSE classification accuracy in a consecutive case series of 103 older adults (age 60 or above) clinically referred for neuropsychological evaluation. Lenient scoring of SOEs on the MMSE occurred in 53 (51.4%) patients and lowered the sensitivity by 7% to 18%, with variable gains in specificity (0% to 11%) to psychometrically operationalized cognitive impairment. Results are consistent with previous reports that lenient scoring is widespread and attenuates the sensitivity of the MMSE. Given the higher clinical priority of correctly detecting early cognitive decline over specificity, a warning against lenient scoring of SOEs (on the MMSE and other screening tools) during medical education and in clinical practice is warranted.
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Disfunção Cognitiva , Orientação Espacial , Humanos , Idoso , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Empatia , Disfunção Cognitiva/diagnóstico , Testes NeuropsicológicosRESUMO
Prospective memory (PM) is the accurate execution of an intention in the future. PM may be negatively impacted by negative affect, but the underlying mechanisms remain unclear. Rumination may increase the frequency of task-irrelevant thoughts, which deplete attentional capacity and reduce performance. To date, no studies have examined state and trait rumination on an online measure of PM. The present study examined the effects of state and trait rumination on an event-based, focal PM task embedded within a one-back task over multiple sessions. 95 non-depressed adults (18-53 years) completed measures of state/trait rumination, mood, and PM on at least two occasions. Using multi-level modelling, we found that a derived measure of trait rumination, but not an established trait rumination survey, nor negative mood, predicted poorer PM accuracy. These novel findings demonstrate that trait rumination may partially underlie the association between negative affect & PM in a non-clinical sample, and highlight the potential of online methods to study PM.
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BACKGROUND: Individuals differ in how they remember the past: some richly re-experience specific details of past episodes, whereas others recall only the gist of past events. Little research has examined how such trait mnemonics, or lifelong individual differences in memory capacities, relate to cognitive aging. We specifically examined trait episodic autobiographical memory (AM, the tendency to richly re-experience episodic details of past events) in relation to complaints of everyday cognitive functioning, which are known to increase with age. Although one might predict that individuals reporting higher trait-level episodic AM would be resistant to age-related decline in everyday function, we made the opposite prediction. That is, we predicted that those with lower trait-level episodic AM would be better equipped with compensatory strategies, practiced throughout the lifespan, to cope with age-related memory decline. Those with higher trait-level episodic AM would have enhanced sensitivity to age-related cognitive changes due to their tendency to rely on their perceived above-average memory function. METHODS: We tested these predictions in 959 older adults aged 50-93 using online subjective and objective measures of memory and cognitive function. Our key measures of interest were the Survey of Autobiographical Memory, a measure of autobiographical memory abilities; and the Cognitive Failures Questionnaire, a measure of everyday cognitive function. RESULTS: In keeping with our prediction, we found that complaints of day-to-day memory slips and errors (normally elevated with age) remained stable or even decreased with age among those reporting lower trait-level episodic AM, whereas those reporting higher trait-level episodic AM reported the expected age-related increase in such errors. This finding was specific to episodic AM and not observed for other autobiographical memory capacities (e.g., semantic, spatial). It was further unaccounted for by response bias or objectively assessed cognitive abilities. CONCLUSIONS: Congenitally low trait-level episodic AM may paradoxically confer a functional advantage in aging. This could be due to well-developed non-episodic strategies not present in those with higher abilities, who are more sensitive to age-related memory decline attributable to medial temporal lobe changes. Our findings emphasize the importance of considering individual differences when studying cognitive aging trajectories.
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Memória Episódica , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Cognição , Humanos , Transtornos da Memória/diagnóstico , Rememoração MentalRESUMO
The precise roles of the hippocampus (HPC) and medial prefrontal cortex (mPFC) in initially constructing imagined events remains unclear. HPC activity during imagination may be modulated by mnemonic load, given its role in working memory for complex materials, and/or by the semantic relatedness (i.e. congruency) between items and their context. MPFC activation may track with congruency or mnemonic load, given the role of ventral mPFC in schema processing and the dorsal mPFC in working memory for social information. Sixteen healthy adults (M ageâ¯=â¯22.3) underwent an event construction task, wherein participants were provided with a context and item words and imagined an event, forming as many inter-item associations as possible among the items. The stimuli varied by set size and by normatively-defined congruence (normative congruency) to explore their effects on HPC and mPFC activity and functional connectivity. We observed HPC connectivity during event construction in general, whereas dorsal mPFC connectivity occurred during imagining only at higher set sizes. Moreover, anterior hippocampal activity correlated positively with increasing coherence between items during imagining, suggesting that the anterior HPC is sensitive to the relational demands of constructing a novel event. Parahippocampal, hippocampal, temporal pole, and mPFC activity tracked only with individual differences in subjective ratings of congruency of imagined events, which may contribute to construction by retrieving existing schema-related information. Collectively, these findings provide new insights into the factors that modulate HPC and mPFC activity when constructing mental simulations.
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Hipocampo/fisiologia , Imaginação/fisiologia , Rede Nervosa/fisiologia , Córtex Pré-Frontal/fisiologia , Pensamento/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Rede Nervosa/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: There is a high prevalence of depressive and anxiety disorders in multiple sclerosis (MS), a disease 2.5 times more frequent in females. Contrary to the general population, in whom studies have demonstrated higher rates of depression and anxiety in females, little is known about the impact of gender on psychiatric sequelae in MS patients. OBJECTIVES: We conducted a retrospective study to try to clarify this uncertainty. METHODS: Demographic, illness-related and behavioral variables were obtained from a neuropsychiatric database of 896 patients with a confirmed diagnosis of MS. Symptoms of depression and anxiety were obtained with the Hospital Anxiety and Depression Scale (HADS). Gender comparisons were undertaken and predictors of depression and anxiety sought with a linear regression analysis. RESULTS: HADS data were available for 711 of 896 (79.35%) patients. Notable gender differences included a higher frequency of primary progressive MS in males (p = 0.002), higher HADS anxiety scores in females (p < 0.001), but no differences in HADS depression scores. CONCLUSION: In MS, gender influences the frequency of anxiety only. This suggests that the etiological factors underpinning anxiety and depression in MS are not only different from one another, but also in the case of depression, different from those observed in general population samples.
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Transtornos de Ansiedade/psicologia , Ansiedade/psicologia , Depressão/psicologia , Transtorno Depressivo/psicologia , Esclerose Múltipla/psicologia , Adulto , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Bases de Dados Factuais , Depressão/epidemiologia , Transtorno Depressivo/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores SexuaisRESUMO
A growing body of evidence suggests that the hippocampus contributes to performance (or is implicated) in non-memory domains from perception to problem solving. In a previous study we found that hippocampal contribution to exemplar generation in a fluency task was determined jointly by the open-endedness of the task and its ability to elicit episodic memories (Sheldon and Moscovitch (2012) Hippocampus 22:1451-1466). In the current study, we extend these observations by exploring the role of the hippocampus in generative, goal-directed open-ended thought in patients with medial temporal lobe (MTL) amnesia on a free association task (think of words as they come to mind). Patients and control participants were asked to associate freely for one minute to cue words that varied in the open-endedness of the responses they elicited (greater for low- than high-frequency words), and in the ease with which episodic memories were evoked (greater for high imageable than low imageable words). As predicted, MTL amnesia patients generated fewer words than control participants when cues were highly imageable and low in frequency, but performed equivalently to them in the other conditions. These results support our prediction that the hippocampus contributes to free association, and possibly more generally to other generative tasks that are open-ended, creative, or that elicit the use of contextual and likely episodic memories in order to derive relevant information.
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Amnésia/fisiopatologia , Aprendizagem por Associação/fisiologia , Rememoração Mental/fisiologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologia , Adulto , Amnésia/patologia , Distribuição de Qui-Quadrado , Feminino , Lateralidade Funcional/fisiologia , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , VocabulárioRESUMO
OBJECTIVE: To avoid misdiagnosing mild cognitive impairment (MCI), knowledge of the multivariate base rates (MVBRs) of low scores on neuropsychological tests is crucial. Base rates have typically been determined from normative population samples, which may differ from clinically referred samples. The current study addresses this limitation by calculating the MVBR of low or high cognitive scores in older adults who presented to a memory clinic experiencing subjective cognitive decline but were not diagnosed with MCI. METHOD: We determined the MVBRs on the Kaplan-Baycrest Neurocognitive Assessment for 107 cognitively healthy older adults (M age = 75.81), by calculating the frequency of patients producing n scores below or above different cut-off values (i.e., 1, 1.5, 2.0, 2.5 SD from the mean), stratifying by education and gender. RESULTS: Performing below or above cut-off was common, with more stringent cut-offs leading to lower base rates (≥1 low scores occurred in 84.1% of older adults at -1 SD, 55.1% at -1.5 SD, and 39.3% at -2 SD below the mean; ≥1 high scores occurred in 80.4% of older adults at +1 SD, 35.5% at +1.5 SD, and 16.8% at +2 SD above the mean). Higher education was associated with varying base rates. Overall, the MVBR of obtaining a low cognitive test score was higher in this clinic sample, compared with prior studies of normative samples. CONCLUSIONS: MVBRs for clinically referred older adults experiencing memory complaints provide a diagnostic benefit, helping to prevent attributing normal variability to cognitive impairment and limiting false positive diagnoses.
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Disfunção Cognitiva , Humanos , Idoso , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , EscolaridadeRESUMO
OBJECTIVES: The diagnostic entity of mild cognitive impairment (MCI) is heterogeneous, highlighting the need for data-driven classification approaches to identify patient subgroups. However, these approaches can be strongly determined by sample characteristics and selected measures. Here, we applied a cluster analysis to an MCI patient database from a neuropsychology clinic to determine whether the inclusion of patients with MCI with vascular pathology would result in a different classification of subgroups. METHODS: Participants diagnosed with MCI (n = 166), vascular cognitive impairment-no dementia (n = 26), and a group of older adults with subjective cognitive concerns but no objective impairment (n = 144) were assessed using a full neuropsychological battery and other clinical measures. Cognitive measures were analyzed using a hierarchical cluster analysis and then a k-means approach, with resulting clusters compared on a range of demographic and clinical variables. RESULTS: We found a 4-factor solution: a cognitively intact cluster, a globally impaired cluster, an amnestic/visuospatial impairment cluster, and a mild, mixed-domain cluster. Interestingly, group differences in self-reported multilingualism emerged in the derived clusters that were not observed when comparing diagnostic groups. CONCLUSIONS: Our results were generally consistent with previous studies using cluster analysis in MCI. Including patients with primarily cerebrovascular disease resulted in subtle differences in the derived clusters and revealed new insights into shared cognitive profiles of patients beyond diagnostic categories. These profiles should be further explored to develop individualized assessment and treatment approaches.
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Disfunção Cognitiva , Humanos , Idoso , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Análise por Conglomerados , AutorrelatoRESUMO
Problem Gambling (PG) represents a serious problem for affected individuals, their families and society in general. Previous approaches to understanding PG have been confined to only a subset of the psychobiological factors influencing PG. We present a model that attempts to integrate potential causal factors across levels of organization, providing empirical evidence from the vast literature on PG and complimentary literatures in decision-making and addiction. The model posits that components are arranged systematically to bias decisions in favor of either immediately approaching or avoiding targets affording the opportunity for immediate reward. Dopamine, Testosterone and Endogenous Opioids favor immediate approach, while Serotonin and Cortisol favor inhibition. Glutamate is involved in associative learning between stimuli and promotes the approach response through its link to the DA reward system. GABA functions to monitor performance and curb impulsive decision-making. Finally, while very high levels of Norepinephrine can induce arousal to an extent that is detrimental to sound decision-making, the reactivity of the Norepinephrine system and its effects of Cortisol levels can shift the focus towards long-term consequences, thereby inhibiting impulsive decisions. Empirical evidence is provided showing the effects of each component on PG and decision-making across behavioural, neuropsychological, functional neuroimaging and genetic levels. Last, an effect size analysis of the growing pharmacotherapy literature is presented. It is hoped that this model will stimulate multi-level research to solidify our comprehension of biased decision-making in PG and suggest pharmacological and psychological approaches to treatment.
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Comportamento Aditivo/psicologia , Tomada de Decisões , Jogo de Azar/psicologia , Modelos Psicológicos , Autoimagem , Autoeficácia , Comportamento Aditivo/classificação , Comportamento Aditivo/diagnóstico , Feminino , Jogo de Azar/classificação , Jogo de Azar/diagnóstico , Humanos , Controle Interno-Externo , Masculino , Poder Psicológico , Reprodutibilidade dos Testes , Assunção de Riscos , Comportamento SocialRESUMO
BACKGROUND: Web-based research allows cognitive psychologists to collect high-quality data from a diverse pool of participants with fewer resources. However, web-based testing presents unique challenges for researchers and clinicians working with aging populations. Older adults may be less familiar with computer usage than their younger peers, leading to differences in performance when completing web-based tasks in their home versus in the laboratory under the supervision of an experimenter. OBJECTIVE: This study aimed to use a within-subjects design to compare the performance of healthy older adults on computerized cognitive tasks completed at home and in the laboratory. Familiarity and attitudes surrounding computer use were also examined. METHODS: In total, 32 community-dwelling healthy adults aged above 65 years completed computerized versions of the word-color Stroop task, paired associates learning, and verbal and matrix reasoning in 2 testing environments: at home (unsupervised) and in the laboratory (supervised). The paper-and-pencil neuropsychological versions of these tasks were also administered, along with questionnaires examining computer attitudes and familiarity. The order of testing environments was counterbalanced across participants. RESULTS: Analyses of variance conducted on scores from the computerized cognitive tasks revealed no significant effect of the testing environment and no correlation with computer familiarity or attitudes. These null effects were confirmed with follow-up Bayesian analyses. Moreover, performance on the computerized tasks correlated positively with performance on their paper-and-pencil equivalents. CONCLUSIONS: Our findings show comparable performance on computerized cognitive tasks in at-home and laboratory testing environments. These findings have implications for researchers and clinicians wishing to harness web-based testing to collect meaningful data from older adult populations.
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In this study we attempted to replicate the classification accuracy of the newly introduced Forced Choice Recognition trial (FCR) of the Rey Complex Figure Test (RCFT) in a clinical sample. We administered the RCFTFCR and the earlier Yes/No Recognition trial from the RCFT to 52 clinically referred patients as part of a comprehensive neuropsychological test battery and incentivized a separate control group of 83 university students to perform well on these measures. We then computed the classification accuracies of both measures against criterion performance validity tests (PVTs) and compared results between the two samples. At previously published validity cutoffs (≤16 & ≤17), the RCFTFCR remained specific (.84-1.00) to psychometrically defined non-credible responding. Simultaneously, the RCFTFCR was more sensitive to examinees' natural variability in visual-perceptual and verbal memory skills than the Yes/No Recognition trial. Even after being reduced to a seven-point scale (18-24) by the validity cutoffs, both RCFT recognition scores continued to provide clinically useful information on visual memory. This is the first study to validate the RCFTFCR as a PVT in a clinical sample. Our data also support its use for measuring cognitive ability. Replication studies with more diverse samples and different criterion measures are still needed before large-scale clinical application of this scale.
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Memória , Reconhecimento Psicológico , Cognição , Humanos , Testes NeuropsicológicosRESUMO
Normal aging is typically associated with reduced ability to reconstruct the spatiotemporal context of past events, a core component of episodic memory. However, little is known about our ability to remember the order of events comprising extended real-world experiences and how this ability changes with age. We leveraged the richness and structure of a museum exhibit to address this question. Three months after visiting the exhibit, 141 adults aged 18-84 completed a test of spatiotemporal order memory and old/new recognition using pictures from the exhibit and similar lures, from which measures of associative and item memory were derived. Order discrimination accuracy was modulated by interitem order and distance in younger and older adults, extending findings from recognition of laboratory stimuli at short delays to remote real-world experiences. In contrast to established findings from laboratory-based assessments, we observed a significant effect of aging on item memory driven by increased lure susceptibility, but no age-related reduction in spatiotemporal associative memory. These findings present novel insights into different components of memory for real-world experiences at naturalistic timescales and across the lifespan. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Aprendizagem por Associação/fisiologia , Memória Episódica , Adulto , Idoso , Envelhecimento , Feminino , Humanos , Masculino , Transtornos da Memória , Rememoração Mental , Pessoa de Meia-Idade , Adulto JovemRESUMO
Anxiety-like behaviors emerge with repeated exposure to and short-term withdrawal from cocaine. The stress-related neuropeptide, corticotropin-releasing factor (CRF), has been implicated in the anxiogenic effects of cocaine withdrawal, as well as in some of the long-lasting effects of cocaine. One objective of the present experiments was to determine whether repeated exposures to cocaine, under conditions that induce anxiety in the initial withdrawal period, would induce longer-lasting anxiogenic responses. A second objective was to determine whether any such effects would be potentiated by CRF. In Experiment 1, animals were injected once daily for 7 days with cocaine (30 mg/kg, i.p.) or saline in the home cages and, after a 10-day drug-free period, were given an i.c.v. injection of CRF (0.5 or 5.0 micro g) or vehicle, followed by a 5-min test for anxiety in the elevated plus maze or light-dark transition apparatus. In Experiment 2, animals were given the cocaine or saline injections in a distinct environment. At test, they were placed in the distinct environment after the CRF (0.5 micro g) or vehicle injection and were subsequently tested for anxiety. Cocaine produced enhanced levels of anxiety when pre-exposures were given in a distinct environment, but not when they were given in the home cage. In neither case did cocaine differentially alter anxiety-like responses to CRF. The results suggest that a "reminder" of the drug experience, such as re-exposure to cocaine-paired contextual cues, may be necessary to induce elevated levels of anxiety after the initial withdrawal period. In addition, although the results do not rule out a role for endogenous CRF in lasting cocaine-induced anxiogenic responses, they suggest that an increased sensitivity of CRF receptors to the peptide is not responsible for the effect.
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Ansiedade/induzido quimicamente , Cocaína/farmacologia , Hormônio Liberador da Corticotropina/administração & dosagem , Animais , Ansiedade/tratamento farmacológico , Hormônio Liberador da Corticotropina/uso terapêutico , Escuridão , Injeções Intraventriculares , Luz , Masculino , Ratos , Ratos WistarRESUMO
Cognitive impairment affects approximately 40-70% of MS patients. As management of MS typically begins with, and is co-ordinated by neurologists, they are often the first to raise concerns about a patient's cognitive functioning. However, it is not known how accurate the neurological examination is in identifying cognitive impairment. To this end, we conducted a retrospective chart review of 97 MS patients referred by neurologists for neuropsychological assessment based on suspected cognitive impairment. Patients were classified as globally-impaired or intact according to failure on 2 or more of 11 cognitive indices comprising the MACFIMS, a recommended neuropsychological battery for MS. Neurologists' accuracy was not significantly different from chance, Χ(2)=1.25, p=0.26, with 44.3% of patients with suspected cognitive impairment showing global impairment on objective testing. Cognitively intact patients when compared to those who were impaired had higher levels of education and were less likely to have mood disturbances. These findings indicate the clinical interview and standard neurological examination are not sufficiently sensitive to detect cognitive impairment in MS, and suggest the need for a brief, accurate cognitive screen to complement routine clinical evaluation.
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Transtornos Cognitivos/complicações , Transtornos Cognitivos/diagnóstico , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Exame Neurológico , Testes Neuropsicológicos , Adulto , Escolaridade , Feminino , Humanos , Entrevistas como Assunto , Masculino , Transtornos do Humor/complicações , Neurologia , Médicos , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: A subset of patients with multiple sclerosis (MS) smoke cannabis to relieve symptoms including spasticity and pain. Recent evidence suggests that smoking cannabis further impairs cognition in people with MS and is linked to impaired functional brain changes. No such association, however, has been reported between cannabis use and structural brain changes, hence the focus of the present study. METHODS: Twenty patients with MS who smoke cannabis for symptom relief, and 19 matched non-cannabis-smoking MS patients were given the Brief Repeatable Neuropsychological Battery and structural MRI scans. Images were segmented into gray matter and white matter, and subsequently analysed with Partial Least Squares, a data-driven multivariate technique that explores brain-behaviour associations. RESULTS: In both groups, the Partial Least Squares analysis yielded significant correlations between cognitive scores and both gray matter (33% variance, p < .0001) and white matter (17% variance, p < .05) volume. Gray matter volume in the thalamus, basal ganglia, medial temporal, and medial prefrontal regions, and white matter volume in the fornix correlated with cognitive deficits. Crucially, the analysis indicated that brain volume reductions were associated with more extensive cognitive impairment in the cannabis versus the non-cannabis MS group. INTERPRETATION: These results suggest that cannabis use in MS results in more widespread cognitive deficits, which correlate with tissue volume in subcortical, medial temporal, and prefrontal regions. These are the first findings demonstrating an association between cannabis use, cognitive impairment and structural brain changes in MS patients.
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Transtornos Cognitivos/fisiopatologia , Substância Cinzenta/patologia , Maconha Medicinal/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/patologia , Substância Branca/patologia , Adulto , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/etiologia , Substância Cinzenta/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Dor/tratamento farmacológico , Dor/etiologia , Substância Branca/efeitos dos fármacosRESUMO
The neural underpinnings of cognitive dysfunction in mild traumatic brain injury (TBI) are not fully understood. Consequently, patient prognosis using existing clinical imaging is somewhat imprecise. Single photon emission computed tomography (SPECT) is a frequently employed investigation in this population, notwithstanding uncertainty over the clinical utility of the data obtained. In this study, subjects with mild TBI underwent (99m)Tc-ECD SPECT scanning, and were administered a brief battery of cognitive tests and self-report symptom scales of concussion and emotional distress. Testing took place 2 weeks (n=84) and 1 year (n=49) post-injury. Multivariate analysis (i.e., partial least squares analysis) revealed that frontal perfusion in right superior frontal and middle frontal gyri predicted poorer performance on the Stroop test, an index of executive function, both at initial and follow-up testing. Conversely, SPECT scans categorized as normal or abnormal by radiologists did not differentiate cognitively impaired from intact subjects. These results demonstrate the clinical utility of SPECT in mild TBI, but only when data are subjected to blood flow quantification analysis.
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Lesões Encefálicas/diagnóstico , Transtornos Cognitivos/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Concussão Encefálica , Cognição , Função Executiva , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Teste de StroopRESUMO
BACKGROUND: Numerous studies have shown decreased perfusion in the prefrontal cortex following mild traumatic brain injury (mTBI). However, similar hypoperfusion can also be observed in depression. Given the high prevalence of depressive symptoms following mTBI, it is unclear to what extent depression influences hypoperfusion in TBI. METHODS: Mild TBI patients without depressive symptoms (mTBI-noD, n = 39), TBI patients with depressive symptoms (mTBI-D, n = 13), and 15 patients with major depressive disorder (MDD), but no TBI were given 99m T-ECD single-photon emission computed tomography (SPECT) scans within 2 weeks of injury. All subjects completed tests of information processing speed, complex attention, and executive functioning, and a self-report questionnaire measuring symptoms of psychological distress. Between-group comparisons of quantified SPECT perfusion were undertaken using univariate and multivariate (partial least squares) analyses. RESULTS: mTBI-D and mTBI-noD groups did not differ in terms of cerebral perfusion. However, patients with MDD showed hypoperfusion compared to both TBI groups in several frontal (orbitofrontal, middle frontal, and superior frontal cortex), superior temporal, and posterior cingulate regions. The mTBI-D group showed poorer performance on a measure of complex attention and working memory compared to both the mTBI-noD and MDD groups. CONCLUSION: These results suggest that depressive symptoms do not affect SPECT perfusion in the sub-acute phase following a mild TBI. Conversely, MDD is associated with hypoperfusion primarily in frontal regions.