Deficits In Specific Cognitive Domains Research Articles

Post-stroke cognitive impairment remains highly prevalent and disabling despite state-of-the-art stroke treatment.

State-of-the-art stroke treatment significantly reduces lesion size and stroke severity, but it remains unclear whether these therapeutic advances have diminished the burden of post-stroke cognitive impairment (PSCI). In a cohort of patients receiving modern state-of-the-art stroke care including endovascular therapy, we assessed the frequency of PSCI and the pattern of domain-specific cognitive deficits, identified risk factors for PSCI, and determined the impact of acute PSCI on stroke outcome. In this prospective monocentric cohort study, we examined patients with first-ever anterior circulation ischemic stroke without pre-stroke cognitive decline, using a comprehensive neuropsychological assessment ⩽10 days after symptom onset. Normative data were stratified by demographic variables. We defined PSCI as at least moderate (<1.5 standard deviation) deficits in ⩾2 cognitive domains. Multivariable regression analysis was applied to define risk factors for PSCI. We analyzed 329 non-aphasic patients admitted from December 2020 to July 2023 (67.2 ± 14.4 years old, 41.3% female, 13.1 ± 2.7 years of education). Although most patients had mild stroke (median National Institutes of Health Stroke Scale (NIHSS) 24 h = 1.00 (0.00; 3.00); 87.5% with NIHSS ⩽ 5), 69.3% of them presented with PSCI 2.7 ± 2.0 days post-stroke. The most severely and often affected cognitive domains were verbal learning, episodic memory, executive functions, selective attention, and constructive abilities (39.1%-51.2% of patients), whereas spatial neglect was less frequent (18.5%). The risk of PSCI was reduced with more years of education (odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.23-0.99) and right hemisphere lesions (OR = 0.47, 95% CI = 0.26-0.84), and increased with stroke severity (NIHSS 24 h, OR = 4.19, 95% CI = 2.72-6.45), presence of hyperlipidemia (OR = 1.93, 95% CI = 1.01-3.68), but was not influenced by age. After adjusting for stroke severity and depressive symptoms, acute PSCI was associated with poor functional outcome (modified Rankin Scale > 2, F = 13.695, p < 0.001) and worse global cognition (Montreal Cognitive Assessment (MoCA) score, F = 20.069, p < 0.001) at 3 months post-stroke. Despite modern stroke therapy and many strokes having mild severity, PSCI in the acute stroke phase remains frequent and associated with worse outcome. The most prevalent were learning and memory deficits. Cognitive reserve operationalized as years of education independently protects post-stroke cognition.

IC3 protocol: a longitudinal observational study of cognition after stroke using novel digital health technology

IntroductionStroke is a major cause of death and disability worldwide, frequently resulting in persistent cognitive deficits among survivors. These deficits negatively impact recovery and therapy engagement, and their treatment is...

A - 106 Predicting Depression in Individuals with Parkinson's Disease Using the Repeatable Battery for the Assessment of Neuropsychological Status.

This study investigates whether deficits in specific cognitive domains predict depression in individuals with Parkinson's disease. Neurocognitive domains are measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Affective symptoms are measured by the Personality Assessment Inventory (PAI). A simultaneous hierarchical multiple regression with three univariately predicting RBANS indices was used to predict the PAI Depression Scale. Participants were individuals diagnosed with Parkinson's disease who underwent neuropsychological evaluation as candidates for deep brain stimulation procedures. The sample included 31 participants, between ages 41 to 75, with a mean age of 61.29. Twenty-seven were male and four were female. Twenty-six were white, one was African-American, one was Hispanic, one was Asian, two were not racially identified. The model was significant with a large effect size, R2 = 0.444, F(3,27) = 7.177, p < 0.001, indicating Attention, Visuospatial/constructional, and Immediate Memory RBANS indices accounted for 44% of the variation found in depression as measured by the PAI. Attention had 15% of unique variance accounting for one third of the 44% predicted by the regression model. Visuospatial/constructional had 9% unique variance, indicating that approximately 20% of the model variance is in common between the predictors and depression. The analysis found a significant negative correlation between depression and cognitive deficits, supporting the hypothesis that cognitive deficits in one or more of the RBANS domains predicts depression in individuals with Parkinson's disease.

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease

Backgroundand Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. IntroductionParkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. Material and methodsWe retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. ResultsParticipants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. ConclusionWe found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Peripheral inflammation is associated with impairments of inhibitory behavioral control and visual sensorimotor function in psychotic disorders.

Elevated markers of peripheral inflammation are common in psychosis spectrum disorders and have been associated with brain anatomy, pathology, and physiology as well as clinical outcomes. Preliminary evidence suggests a link between inflammatory cytokines and C-reactive protein (CRP) with generalized cognitive impairments in a subgroup of individuals with psychosis. Whether these patients with elevated peripheral inflammation demonstrate deficits in specific cognitive domains remains unclear. To examine this, seventeen neuropsychological and sensorimotor tasks and thirteen peripheral inflammatory and microvascular markers were quantified in a subset of B-SNIP consortium participants (129 psychosis, 55 healthy controls). Principal component analysis was conducted across the inflammatory markers, resulting in five inflammation factors. Three discrete latent cognitive domains (Visual Sensorimotor, General Cognitive Ability, and Inhibitory Behavioral Control) were characterized based on the neurobehavioral battery and examined in association with inflammation factors. Hierarchical clustering analysis identified cognition-sensitive high/low inflammation subgroups. Among persons with psychotic disorders but not healthy controls, higher inflammation scores had significant associations with impairments of Inhibitory Control (R2=0.100, p-value=2.69e-4, q-value=0.004) and suggestive associations with Visual Sensorimotor function (R2=0.039, p-value=0.024, q-value=0.180), but not with General Cognitive Ability (R2=0.015, p-value=0.162). Greater deficits in Inhibitory Control were observed in the high inflammation patient subgroup, which represented 30.2% of persons with psychotic disorders, as compared to the low inflammation psychosis subgroup. These findings indicate that inflammation dysregulation may differentially impact specific neurobehavioral domains across psychotic disorders, particularly performance on tasks requiring ongoing behavioral monitoring and control.

Comparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18–86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

Self-paced Multi-view Learning for CT-based severity assessment of COVID-19

Prior studies for the task of severity assessment of COVID-19 (SA-COVID) usually suffer from domain-specific cognitive deficits. They mainly focus on visual cues based on single cognitive functions but fail to reconcile the valuable information from other alternative views. Inspired by the cognitive process of radiologists, this paper shifts naturally from single-symptom measurements to a multi-view analysis, and proposes a novel Self-paced Multi-view Learning (SPML) framework for automated SA-COVID. Specifically, the proposed SPML framework first comprehensively aggregates multi-view contexts in lung infection with different measure paradigms, i.e., Global Feature Branch, Texture Feature Branch, and Volume Feature Branch. In this way, multiple-perspective clues are taken into account to reflect the most essential pathological manifestation on CT images. To alleviate small-sample learning problems, we also introduce an optimization with self-paced learning strategy to cognitively increase the characterization capabilities of training samples by learning from simple to complex. In contrast to traditional batch-wise learning, a pure self-paced way can further guarantee the efficiency and accuracy of SPML when dealing with small and biased samples. Furthermore, we construct a well-established SA-COVID dataset that contains 300 CT images with fine annotations. Extensive experiments on this dataset demonstrate that SPML consistently outperforms the state-of-the-art baselines. The SA-COVID dataset is publicly released at https://github.com/YishuLiu/SA-COVID.

Cholinergic systems, attentional-motor integration, and cognitive control in Parkinson's disease.

Dysfunction and degeneration of CNS cholinergic systems is a significant component of multi-system pathology in Parkinson's disease (PD). We review the basic architecture of human CNS cholinergic systems and the tools available for studying changes in human cholinergic systems. Earlier post-mortem studies implicated abnormalities of basal forebrain corticopetal cholinergic (BFCC) and pedunculopontine-laterodorsal tegmental (PPN-LDT) cholinergic projections in cognitive deficits and gait-balance deficits, respectively. Recent application of imaging methods, particularly molecular imaging, allowed more sophisticated correlation of clinical features with regional cholinergic deficits. BFCC projection deficits correlate with general and domain specific cognitive deficits, particularly for attentional and executive functions. Detailed analyses suggest that cholinergic deficits within the salience and cingulo-opercular task control networks, including both neocortical, thalamic, and striatal nodes, are a significant component of cognitive deficits in non-demented PD subjects. Both BFCC and PPN-LDT cholinergic projection systems, and striatal cholinergic interneuron (SChI), abnormalities are implicated in PD gait-balance disorders. In the context of experimental studies, these results indicate that disrupted attentional functions of BFCC and PPN-LDT cholinergic systems underlie impaired gait-balance functions. SChI dysfunction likely impairs intra-striatal integration of attentional and motor information. Thalamic and entorhinal cortex cholinergic deficits may impair multi-sensory integration. Overt degeneration of CNS systems may be preceded by increased activity of cholinergic neurons compensating for nigrostriatal dopaminergic deficits. Subsequent dysfunction and degeneration of cholinergic systems unmasks and exacerbates functional deficits secondary to dopaminergic denervation. Research on CNS cholinergic systems dysfunctions in PD requires a systems-level approach to understanding PD pathophysiology.

Impaired neurovascular coupling and cognitive deficits in anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently identified autoimmune disorder with heterogeneous neurological, psychiatric, and cognitive manifestations. The NMDAR is a key signaling node for neurovascular coupling, the mechanism by which cerebral blood perfusion is enhanced to meet local metabolic requirements from increased neuronal activity. Therefore, anti-NMDAR encephalitis may disrupt neurovascular coupling and induce cognitive deficits. This study examined neurovascular coupling and cognitive function in anti-NMDAR encephalitis patients to identify prognostic biomarkers, reveal potential pathogenic mechanisms, and provide clues to possible therapeutic strategies. In this study, twenty-three anti-NMDAR encephalitis patients and thirty healthy controls received neuropsychological testing and multimodal magnetic resonance imaging (MRI). Cerebral blood flow (CBF) was calculated from arterial spin labeling, and regional homogeneity (ReHo) was computed from functional MRI. Pearson's correlation coefficients between CBF and ReHo were calculated to obtain neurovascular coupling. At the whole gray matter level, CBF‒ReHo coupling was reduced in patients compared to healthy controls. At the regional level, CBF‒ReHo was significantly lower among patients in the precentral gyrus, frontal gyrus, insula, cuneus, inferior parietal lobe, supramarginal gyrus, angular gyrus, precuneus, temporal gyrus, and temporal pole. Reduced CBF‒ReHo in the left superior medial frontal gyrus of patients was significantly correlated with a deficit in verbal inhibition control, and the reduced CBF‒ReHo in the left insula was significantly correlated with impaired executive function. In conclusion, anti-NMDAR encephalitis is associated with both global and regional disruptions in neurovascular coupling that may in turn lead to deficits in specific cognitive domains.

Post-Stroke Cognitive Impairment is Frequent After Infra-Tentorial Infarct

Background and purposePost-stroke cognitive impairment is a common and well-known consequence of supra-tentorial infarct, but its prevalence and severity after infra-tentorial infarct is unclear. We compared the frequencies and prognostic value of domain-specific cognitive deficits after supra-tentorial and infra-tentorial infarct. MethodsIn a consecutive cohort of patients with first-ever stroke (N = 244) admitted to Helsinki University Hospital, 37 patients had an infra-tentorial infarct. Patients were assessed with a comprehensive neuropsychological examination 3 months post-stroke covering 9 cognitive domains and functional disability was assessed at 15 months with the modified Rankin Scale. ResultsThere were no statistically significant differences between the frequencies of cognitive deficits in patients with infra-tentorial vs supra-tentorial infarct. Altogether 73% of patients with infra-tentorial infarct and 82% of patients with supra-tentorial infarct had impairment in at least one cognitive domain. Further 42% of patients with infra-tentorial infarct and 47% of those with supra-tentorial infarct had deficits in 3 or more cognitive domains. In patients with infra-tentorial infarct, visuo-constructional deficits were significantly associated with functional disability at 15 months (OR 9.0, 95%CI 1.3–62.5, p = 0.027). In patients with supratentorial infarct, executive deficits (OR 2.9, 95%CI 1.5–5.8, p = 0.002) and visuo-constructional deficits (OR 2.9, 95%CI 1.5–5.7, p = 0.001) showed associations with functional disability at 15 months. ConclusionCognitive deficits are as common in patients with infra-tentorial infarct as in those with supra-tentorial infarct, and it is important to recognize them to meet the needs of rehabilitation.

Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery.

To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation. Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear. Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines. Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery. The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

Impaired Executive Function and Depression as Independent Risk Factors for Reported Delirium Symptoms: An Observational Cohort Study Over 8 Years.

BackgroundAcute medical illnesses, surgical interventions, or admissions to hospital in older individuals are frequently associated with a delirium. In this cohort study, we investigated the impact of specific cognitive domains and depression before the occurrence of delirium symptoms in an 8-year observation of older non-hospitalized individuals.MethodsIn total, we included 807 participants (48–83 years). Deficits in specific cognitive domains were measured using the CERAD test battery, and depressive symptoms were measured using Beck Depression Inventory and the Geriatric Depression Scale (GDS) before the onset of a delirium. Delirium symptoms were retrospectively assessed by a questionnaire based on the established Nursing Delirium Screening Scale.ResultsFifty-eight of eight hundred seven participants (7.2%) reported delirium symptoms over the 8-year course of the study. Sixty-nine percent (n = 40) of reported delirium symptoms were related to surgeries. In multivariate regression analysis, impaired executive function was an independent risk factor (p = 0.034) for the occurrence of delirium symptoms. Furthermore, age (p = 0.014), comorbidities [captured by the Charlson Comorbidity Index (CCI)] (p < 0.001), and depression (p = 0.012) were significantly associated with reported delirium symptoms.ConclusionEspecially prior to elective surgery or medical interventions, screening for impaired executive function and depression could be helpful to identify patients who are at risk to develop delirium symptoms.

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease

Backgroundand Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. IntroductionParkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. Material and methodsWe retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. ResultsParticipants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. ConclusionWe found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Executive Functioning in Extreme Obesity: Contributions from Metabolic Status, Medical Comorbidities, and Psychiatric Factors.

Extreme obesity has been associated with cognitive deficits across the lifespan and may be a risk factor for dementia in later life. However, the relationship between obesity and domain-specific cognitive deficits is complicated by a body of literature that often fails to adequately account for medical and psychiatric conditions frequently co-occurring with extreme obesity. The present study included a cross-sectional evaluation of adults with extreme obesity (n=117) compared to lean control (n=46) participants on a brief cognitive battery using the NIH Toolbox and Rey Auditory Verbal Learning Test. Specifically, this study evaluated measures of executive functioning, attention, processing speed, learning, and memory while accounting for many common obesity-related medical and psychiatric comorbidities with known cognitive effects. Results revealed group differences with lower performances on measures of executive functioning, processing speed, and learning (ps<0.01) for participants with obesity. Reduced executive functioning was associated with abdominal obesity and medication use (ps<0.01) and together contributed significantly to overall modeling of cognition in individuals with obesity. Individuals with extreme obesity in this sample showed lower cognitive performance on measures of executive functioning, processing speed, and learning compared to lean controls. Abdominal obesity was associated with executive functioning deficits independent of many common medical and psychiatric factors.

MANAGEMENT OF ENDOCRINE DISEASE Subclinical hypothyroidism in children.

Subclinical hypothyroidism (SH) is biochemically defined as serum TSH levels above the upper limit of the reference range in the presence of normal free T4 (FT4) concentrations. While there is a general agreement to treat subjects with serum TSH levels above 10 mU/L, the management of mild form (TSH concentrations between 4.5 and 10 mU/L) is still a matter of debate. In children, mild SH is often a benign and remitting condition and the risk of progression to overt thyroid dysfunction depends on the underlying condition, being higher in the autoimmune forms. The major concern is to establish whether SH in children should always be considered an expression of mild thyroid dysfunction and may deserve treatment. Current data indicate that children with mild SH have normal linear growth, bone health and intellectual outcome. However, slight metabolic abnormalities and subtle deficits in specific cognitive domains have been reported in children with modest elevation of TSH concentration. Although these findings are not sufficient to recommend levothyroxine treatment for all children with mild SH, they indicate the need for regular monitoring to ensure early identification of children who may benefit from treatment. In the meanwhile, the decision to initiate therapy in children with mild SH should be based on individual factors.

Does Hearing Loss in the Elderly Individuals Conform to Impairment of Specific Cognitive Domains?

It is well known that age-related hearing loss (ARHL) is strongly associated with dementia. Different hypotheses have been considered to explain this link, including sensorial deprivation, the reduction in cognitive reserve, and the presence of shared pathological pathways (microvascular damage of the brain). We carried out a study of the audiological and neuropsychological characteristics of a sample of hearing impaired but cognitively healthy individuals (HIH). The aim of our study was to carefully outline the neuropsychological profile of the patients in order to verify whether hearing loss correlated with deficits in specific cognitive domains. Episodic memory is affected by the presence of hearing loss, while semantic competences, syntactic, and grammar skills seem not to be affected. Furthermore, some audiological features linked to the intelligibility of spoken words can predict the presence of executive dysfunction; the same does not apply to memory impairment. In HIH, executive functions are widely employed in maintaining an acceptable level of comprehension of spoken language; consequently, other cognitive domains and instrumental abilities in HIH are not properly supported. Thus, it is arguable that programs of hearing rehabilitation for HIH could restore the allocation of attentional resources to the functioning of other cognitive domains.

Longitudinal progression of grey matter atrophy in non-amnestic Alzheimer's disease.

Recent models of Alzheimer's disease progression propose that disease may be transmitted between brain areas either via local diffusion or long-distance transport via white matter fibre pathways. However, it is unclear whether such models are applicable in non-amnestic Alzheimer's disease, which is associated with domain-specific cognitive deficits and relatively spared episodic memory. To date, the anatomical progression of disease in non-amnestic patients remains understudied. We used longitudinal imaging to differentiate earlier atrophy and later disease spread in three non-amnestic variants, including logopenic-variant primary progressive aphasia (n = 25), posterior cortical atrophy (n = 20), and frontal-variant Alzheimer's disease (n = 12), as well as 17 amnestic Alzheimer's disease patients. Patients were compared to 37 matched controls. All patients had autopsy (n = 7) or CSF (n = 67) evidence of Alzheimer's disease pathology. We first assessed atrophy in suspected sites of disease origin, adjusting for age, sex, and severity of cognitive impairment; we then performed exploratory whole-brain analysis to investigate longitudinal disease spread both within and outside these regions. Additionally, we asked whether each phenotype exhibited more rapid change in its associated disease foci than other phenotypes. Finally, we investigated whether atrophy was related to structural brain connectivity. Each non-amnestic phenotype displayed unique patterns of initial atrophy and subsequent neocortical change that correlated with cognitive decline. Longitudinal atrophy included areas both proximal to and distant from sites of initial atrophy, suggesting heterogeneous mechanisms of disease spread. Moreover, regional rates of neocortical change differed by phenotype. Logopenic-variant patients exhibited greater initial atrophy and more rapid longitudinal change in left lateral temporal areas than other groups. Frontal-variant patients had pronounced atrophy in left insula and middle frontal gyrus, combined with more rapid atrophy of left insula than other non-amnestic patients. In the medial temporal lobes, non-amnestic patients had less atrophy at their initial scan than amnestic patients, but longitudinal rate of change did not differ between patient groups. Medial temporal sparing in non-amnestic Alzheimer's disease may thus be due in part to later onset of medial temporal degeneration than in amnestic patients rather than different rates of atrophy over time. Finally, the magnitude of longitudinal atrophy was predicted by structural connectivity, measured in terms of node degree; this result provides indirect support for the role of long-distance fibre pathways in the spread of neurodegenerative disease. 10.1093/brain/awz091_video1 awz091media1 6041544065001.

Orientation and verbal fluency in the English Longitudinal Study of Ageing: modifiable risk factors for falls?

To determine the relationship between falls and deficits in specific cognitive domains in older adults. An analysis of the English Longitudinal Study of Ageing (ELSA) cohort. United Kingdom community-based. 5197 community-dwelling older adults recruited to a prospective longitudinal cohort study. Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models. Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65-0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96-1.00; p = 0.05) remained significant for predicting recurrent falls. The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall.

Altered Neural Dynamics during a Flanker Attention Task in Patients with Type 1 Diabetes

Background: Patients with type 1 diabetes appear to have deficits in specific cognitive domains, particularly in attention and executive function (1). In this study, we used magnetoencephalography (MEG; 2), a noninvasive functional neuroimaging method, to identify neuronal changes in attention processing in otherwise healthy young adults with type 1 diabetes during euglycemia. Methods: Adults with type 1 diabetes and no micro- or macro-vascular complications (N = 38) completed a visual selective attention task during MEG. A demographically-matched control group without type 1 diabetes was used for comparison. Each trial began with a fixation cross presented centrally, followed by a row of 5 arrows. Participants were asked to respond regarding the direction of the middle arrow (right index finger for left, right middle finger for right) and ignore the flanking arrows that were presented in either the same (congruent condition) or opposite direction (incongruent condition). All MEG data was processed following standard protocols (3), and the resulting images of functional brain activity were examined statistically. Results: While no differences in reaction time or accuracy were found between groups, patients recruited a more widespread network of task relevant brain regions compared to controls, particularly the prefrontal cortex and anterior cingulate. Patients had a greater alpha increase from baseline in the anterior cingulate (p &amp;lt; .01), an important brain region in attention, and in the prefrontal cortex (p &amp;lt; .01) as compared to controls, likely reflecting compensatory mechanisms at play. Conclusions: These results indicate that type 1 diabetes affects neural activity in attention networks of patients who are otherwise healthy and without major comorbidities, reflecting the recruitment of compensatory neural responses to complete task goals. Disclosure C.M. Embury: None. T.J. McDermott: None. A.I. Wiesman: None. K. Brau: None. C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Merck &amp; Co., Inc.. Advisory Panel; Self; Medscape. A. Drincic: None. T.W. Wilson: None.

218. Top-Down or Bottom-Up? Comparison of Two Computer-Assisted Modalities of Cognitive Remediation Therapy for Schizophrenia

Abstract Cognitive remediation (CRT) designed to improve cognitive function in patients with schizophrenia has shown significant efficacy. Our study was designed to compare 2 computerized CRT programs for improving memory and problem-solving skills in patients with schizophrenia. Each intervention uses a specific theoretical rationale: a top down approach (CogPack), training a broad range of cognitive features and a bottom up approach (PositScience), which targets the discrimination ability in perceptual systems. Goals of this study were (1) to perform a noninferiority comparison of the effects of the two programs in patients with chronic schizophrenia and (2) to examine whether the addition of a social cognition remediation intervention, Mind Reading, would further improve social function outcomes over each intervention alone. Both CRT treatments were administered during a 12-week training period. Stable patients with DSM 5 schizophrenia who received either inpatient or outpatient clinical services were recruited. Patients were evaluated on a standardized battery of neuropsychological assessments (MCCB), social emotion measures, auditory and visual discrimination tasks, and a brief assessment of functional skills (PSP) and clinical symptoms (PANSS) at screening and at end point. 64 subjects were randomized as follows: (1) COGPACK Alone (n = 17), (2) PositScience Brain Fitness Alone (n = 14), (3) COGPACK + Mind Reading (Social cognition program; n = 19), (4) PositScience Brain Fitness + Mind Reading (n = 14). For the initial comparison and due to the small sample size, all subjects receiving COGPACK (n = 36), and all subjects receiving PositScience (n = 28) were each combined. Significant improvements from baseline were found in the COGPACK-treated patients for working memory and attention/vigilance. PositScience-treated patients showed significant improvements from baseline in working memory ( = .046) and visual learning ( = .048). Comparison of differential treatment effects found that patients treated with COGPACK + Mind Reader were significantly more benefited than patients treated with PositScience or COGPACK alone ( = .044). Changes in total PANSS ( = .453, = .049) and PSP ( = .466, = .045) scores were correlated with improvement in the MindReader combined groups (PositScience + Mind Reader and COGPACK + Mind Reader). COGPACK or PositScience was associated with intervention specific improvements in working memory and attention/vigilance, and working memory and visual learning respectively. Cognitive improvement in the Mind Reader augmented groups was associated with changes in psychopathology and functional outcomes. Patients with deficits in specific cognitive domains may benefit differentially from a bottom up versus a top down approach and may therefore be assigned to a specific “deficit associated” program within a personalized therapeutic approach.