Executive dysfunction contributes to verbal encoding and retrieval deficits in posterior cortical atrophy.
ABSTRACT: Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome that typically presents with predominant visual and spatial impairments. The early diagnostic criteria specify a relative sparing of functioning in other cognitive domains, including executive functions, language, and episodic memory, yet little is known of the cognitive profile of PCA as the disease progresses. Studies of healthy adults and other posterior cortical lesion patients implicate posterior parietal and temporal regions in executive functions of working memory and verbal fluency, both of which may impact episodic memory. Relatively little has been reported about these cognitive functions in PCA, and to our knowledge there has not yet been a study of the impact of such deficits on memory function in PCA. We sought to examine PCA patients' performance on tests of executive function and the associations to verbal episodic memory encoding, storage, and delayed recall. Nineteen individuals with PCA underwent neuropsychological and neuroimaging evaluations as part of a comprehensive clinical assessment. We developed a novel consensus rating method-the Neuropsychological Assessment Rating (NAR) scale-to grade the severity of test performance impairments in selected cognitive domains and subdomains. Hypothesis-driven analyses demonstrated relative deficits in working memory and lexical-semantic retrieval. Preliminary analyses suggested associations between both deficits and atrophy in the left-hemisphere inferior parietal lobule. These executive deficits were also associated with impairments in verbal encoding and delayed recall, but not with recognition discriminability. We conclude that deficits in verbal executive functions impact verbal episodic memory in PCA. Our findings also support theories emphasizing the role of the posterior parietal cortex in supporting executive and lexical-semantic contributions to verbal episodic memory.
Project description:Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum--22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.
Project description:Both episodic memory and executive function are impaired in amnestic mild cognitive impairment (aMCI) subjects, but it is unclear if these impairments are independent or interactive. The present study aimed to explore the relationship between episodic memory deficits and executive function deficits, and the underlying functional mechanisms in aMCI subjects. Thirty-one aMCI subjects and 27 healthy subjects underwent neuropsychological tests and multimodal magnetic resonance imaging (MRI) scans. Hippocampal networks and medial prefrontal cortex (MPFC) networks were identified based on resting-sate functional MRI (fMRI) data. AMCI subjects displayed lower episodic memory scores and executive function scores than control subjects, and the episodic memory scores were positively correlated with the executive function scores in aMCI subjects. Brain network analyses showed an interaction between the hippocampal networks and the MPFC networks, and the interaction was significantly associated with the episodic memory scores and the executive function scores. Notably, aMCI subjects displayed higher functional connectivity (FC) of the right hippocampal network with the right prefrontal cortex than did control subjects, but this difference disappeared when controlling for the MPFC networks. Furthermore, the effects of the MPFC networks on the hippocampal networks were significantly associated with the episodic memory scores in aMCI subjects. The present findings suggested that the episodic memory deficits in aMCI subjects could be partially underpinned by the modulation of the MPFC networks on the hippocampal networks.
Project description:<h4>Objective</h4>Neurocognitive studies of HIV typically target executive functions dependent on frontostriatal circuitry. The integrity of medial temporal systems has received considerably less attention despite high hippocampal viral load. Studies also predominately involve HIV+ men, though HIV+ women may be at increased risk for cognitive dysfunction due to the high prevalence of psychosocial/mental health problems and lower educational attainment. Our aim was to conduct a preliminary investigation of episodic memory and its neural correlates in HIV-infected and at-risk uninfected women.<h4>Methods</h4>Participants included 54 HIV+ and 12 HIV- women (mean age = 43 years; 86% African American) recruited from the Chicago site of the Women's Interagency HIV Study. Participants completed standardized tests of verbal and visual episodic memory, working memory, and executive function. A subset of 11 women also underwent functional MRI during a delayed verbal episodic memory task.<h4>Results</h4>HIV serostatus predicted significantly lower immediate and delayed verbal episodic memory, working memory, and visual memory. Preliminary neuroimaging findings revealed group differences in bilateral hippocampal function, with HIV+ women showing decreased activation during encoding and increased activation during delayed recognition. These alterations correlated with worse episodic verbal memory.<h4>Conclusions</h4>Verbal episodic memory deficits are evident in HIV+ women and may be associated with hippocampal dysfunction at both encoding and retrieval.
Project description:Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel-based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age- and education-matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole-brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome.
Project description:The recently discovered hexanucleotide repeat expansion, C9ORF72, has been shown to be among the most common cause of familial behavioural variant frontotemporal dementia (bvFTD) and to be present in a significant minority of apparently sporadic cases. While mounting evidence points to prominent episodic memory dysfunction in bvFTD cases, recent reports have also suggested an amnestic profile in C9ORF72 mutation carriers. No study to date, however, has formally characterised the extent to which episodic memory is impaired in C9ORF72 mutation versus sporadic cases, or the underlying neural substrates of such deficits. We conducted a comparison of C9ORF72 (n = 8) and sporadic (n = 15) bvFTD cases using a battery of verbal and visual episodic memory tasks, and contrasted their performance with that of Alzheimer's disease (AD, n = 15) and healthy older control (n = 15) participants. Behaviourally, the two bvFTD groups displayed comparable episodic memory profiles, irrespective of task administered, with prominent impairments evident relative to Controls. Whole-brain voxel-based morphometry analyses revealed distinct neural correlates of episodic memory dysfunction in each patient group. Widespread atrophy in medial prefrontal, medial and lateral temporal cortices correlated robustly with episodic memory dysfunction in sporadic bvFTD cases. In contrast, atrophy in a distributed set of regions in the frontal, temporal, and parietal lobes including the posterior cingulate cortex, was implicated in episodic memory dysfunction in C9ORF72 cases. Our results demonstrate that while episodic memory is disrupted to the same extent irrespective of genetic predisposition in bvFTD, distinct neural changes specific to each patient group are evident. The involvement of medial and lateral parietal regions in episodic memory dysfunction in C9ORF72 cases is of particular significance and represents an avenue of considerable interest for future studies.
Project description:The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients' overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications.
Project description:Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV + ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy.HIV, ALC, HIV + ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times.HIV, ALC, and HIV + ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV + ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all 3 clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV + ALC, age was a unique predictor of Episodic Memory Composite score.Disease-specific and disease-overlapping patterns of impairment in HIV, ALC, and HIV + ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging.
Project description:Developmental coordination disorder (DCD) is a neurodevelopmental disorder affecting primarily motor skills, but attentional and executive impairments are common in affected individuals. Moreover, the presence of neurodevelopmental comorbidities is frequent in this population, which certainly influences the cognitive profile of the children concerned. Previous studies have reported deficits in visuospatial/nonverbal and planning tasks. This systematic review of the literature aims to determine if impairments can be found in other attentional and executive functions as well. The type of cognitive tasks, the tasks' modality (verbal/nonverbal), and the influence of comorbid disorders on attentional and executive profiles are systematically considered. Forty-one studies were identified through the PubMed/Medline and PsycINFO databases according to pre-established eligibility criteria. The results reveal weaknesses in inhibitory control, working memory, planning, nonverbal fluency, and general executive functioning in children with DCD. The presence of comorbid disorders seemingly contributes to the verbal working memory difficulties findings. This review contributes to a better understanding of the cognitive impairments in DCD and of the needs of children with this disorder, allowing to optimize practitioners' therapeutic interventions.
Project description:<b>Background:</b> Verbal fluency (VF) has been associated with several cognitive functions, but the cognitive processes underlying verbal fluency deficits in Multiple Sclerosis (MS) are controversial. Further knowledge about VF could be useful in clinical practice, because these tasks are brief, applicable, and reliable in MS patients. In this study, we aimed to evaluate the cognitive processes related to VF and to develop machine-learning algorithms to predict those patients with cognitive deficits using only VF-derived scores. <b>Methods:</b> Two hundred participants with MS were enrolled and examined using a comprehensive neuropsychological battery, including semantic and phonemic fluencies. Automatic linear modeling was used to identify the neuropsychological test predictors of VF scores. Furthermore, machine-learning algorithms (support vector machines, random forest) were developed to predict those patients with cognitive deficits using only VF-derived scores. <b>Results:</b> Neuropsychological tests associated with attention-executive functioning, memory, and language were the main predictors of the different fluency scores. However, the importance of memory was greater in semantic fluency and clustering scores, and executive functioning in phonemic fluency and switching. Machine learning algorithms predicted general cognitive impairment and executive dysfunction, with F1-scores over 67-71%. <b>Conclusions:</b> VF was influenced by many other cognitive processes, mainly including attention-executive functioning, episodic memory, and language. Semantic fluency and clustering were more explained by memory function, while phonemic fluency and switching were more related to executive functioning. Our study supports that the multiple cognitive components underlying VF tasks in MS could serve for screening purposes and the detection of executive dysfunction.
Project description:This study aims to investigate the relationship between executive function and verbal memory and to explore the underlying neuroanatomical correlates in 358 individuals with amnestic mild cognitive impairment (MCI) and 222 healthy controls (HCs). The MCI participants were divided into 2 groups (high vs. low) based on executive function task performance. Results demonstrated that although both MCI groups were impaired on all memory measures relative to HCs, MCI individuals with higher executive function (HEF) demonstrated better verbal memory performance than those with lower executive function (LEF), particularly on measures of learning. The 2 MCI groups did not differ in mesial temporal morphometric measures, but the MCI LEF group showed significant thinning in dorsolateral prefrontal and posterior cingulate cortices bilaterally compared with the MCI HEF and HCs. Further, thickness in numerous regions of frontal cortex, and bilateral posterior cingulate, was significantly associated with memory performance in all MCI participants above and beyond the contribution of the mesial temporal regions known to be associated with episodic memory. Overall, these results demonstrate the importance of evaluating executive function in individuals with MCI to predict involvement of brain areas beyond the mesial temporal lobe.