White matter atrophy and cognitive dysfunctions in neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM.     

Higher Education Moderates the Effect of T2 Lesion Load and Third Ventricle Width on Cognition in Multiple Sclerosis

Background

Previous work suggested greater intellectual enrichment might moderate the negative impact of brain atrophy on cognition. This awaits confirmation in independent cohorts including investigation of the role of T2-lesion load (T2-LL), which is another important determinant of cognition in MS. We here thus aimed to test this cognitive reserve hypothesis by investigating whether educational attainment (EA) moderates the negative effects of both brain atrophy and T2-LL on cognitive function in a large sample of MS patients.

Methods

137 patients participated in the study. Cognition was assessed by the “Brief Repeatable Battery of Neuropsychological Tests.” T2-LL, normalized brain volume (global volume loss) and third ventricle width (regional volume loss) served as MRI markers.

Results

Both T2-LL and atrophy predicted worse cognition, with a stronger effect of T2-LL. Higher EA (as assessed by years of education) also predicted better cognition. Interactions showed that the negative effects of T2-LL and regional brain atrophy were moderated by EA.

Conclusions

In a cohort with different stages of MS, higher EA attenuated the negative effects of white matter lesion burden and third ventricle width (suggestive of thalamic atrophy) on cognitive performance. Actively enhancing cognitive reserve might thus be a means to reduce or prevent cognitive problems in MS in parallel to disease modifying drugs.     

Modeling of Cognitive Impairment by Disease Duration in Multiple Sclerosis: A Cross-Sectional Study

Background/Aims

Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS) are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years.

Methods

1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD) and severe cognitive impairment as below 2SD for age and education matched healthy population norms.

Results

Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p = 0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p = 0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p = 0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years.

Conclusions

The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.     

Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

Objectives

Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline.

Methods

121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points.

Results

Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up.

Conclusions

The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease.     

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD.     

The effects of hormone therapy on cognition in breast cancer

The use of hormonal therapies for the treatment of breast cancer is common, yet few studies have examined the possible cognitive effects. Several regions of the brain, important in memory and cognition, are rich in oestrogen receptors. As a result, the long-term use of anti-oestrogens may have potential consequences for cognition. This project aims to establish whether significant cognitive deficit exists in women receiving hormone therapy for breast cancer and to develop a cognitive package that is sensitive to the potential effects of oestrogen deficiency on cognition. Cognitive assessments measured a range of memory and attention functions in patient and control groups to identify whether cognitive impairment, if apparent, occurs at a widespread or function specific level. Ninety-four patients from the anastrozole, tamoxifen and combined (ATAC) trial and 35 non-cancer controls were assessed. Groups did not differ significantly in age or estimated full-scale intelligence. The patient group did not differ from controls on measures of working memory, attention and visual memory but was significantly impaired compared to the control group on measures of verbal memory (P=0.026) and processing speed (P=0.032). Cognitive performance in the patient group was not significantly related to length of time on trial or measures of psychological morbidity. As more and more hormonal agents are used in clinical trials of both adjuvant and preventive settings it is of vital importance that any potentially deleterious effects on cognitive function are measured adequately. Preliminary results from this study suggest that anti-oestrogen therapy may cause a specific deficit in verbal memory that corroborates the links between oestrogen levels and verbal memory often reported in studies of the cognitive benefits of hormone replacement therapy.     

Cognitive Functioning in Patients with Bipolar Disorder: Association with Depressive Symptoms and Alcohol Use

Background

Cognitive dysfunction is clearly recognized in bipolar patients, but the degree of impairment varies due to methodological factors as well as heterogeneity in patient populations. The goal of this study was to evaluate cognitive functioning in bipolar patients and to assess its association with depressive symptoms. Post hoc the relationship with lifetime alcohol use disorder was explored.

Methodology/Principal Findings

The study included 110 bipolar patients and 75 healthy controls. Patients with severe depressive symptoms, (hypo)manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating. Patients were euthymic (n = 46) or with current mild (n = 38) or moderate (n = 26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients, most prominent in executive functioning (effect size; ES 0.49) and speed of information processing (ES 0.47). Depressive symptoms were associated with dysfunction in psychomotor speed (adjusted beta 0.43; R² 7%), speed of information processing (adjusted beta 0.36; R² 20%), attentional switching (adjusted beta 0.24; R² 16%) and the mean score (adjusted beta 0.23; R² 24%), but not with verbal and visual memory and executive functioning. Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains. Comorbid lifetime alcohol use (n = 21) was not associated with cognitive dysfunction.

Conclusions/Significance

Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder.     

Cognitive Reserve in Young and Old Healthy Subjects: Differences and Similarities in a Testing-the-Limits Paradigm with DSST

Cognitive reserve (CR) is understood as capacity to cope with challenging conditions, e.g. after brain injury or in states of brain dysfunction, or age-related cognitive decline. CR in elderly subjects has attracted much research interest, but differences between healthy older and younger subjects have not been addressed in detail hitherto. Usually, one-time standard individual assessments are used to characterise CR. Here we observe CR as individual improvement in cognitive performance (gain) in a complex testing-the-limits paradigm, the digit symbol substitution test (DSST), with 10 repeated measurements, in 140 younger (20–30 yrs) and 140 older (57–74 yrs) healthy subjects. In addition, we assessed attention, memory and executive function, and mood and personality traits as potential influence factors for CR. We found that both, younger and older subjects showed significant gains, which were significantly correlated with speed of information processing, verbal short-term memory and visual problem solving in the older group only. Gender, personality traits and mood did not significantly influence gains in either group. Surprisingly about half of the older subjects performed at the level of the younger group, suggesting that interindividual differences in CR are possibly age-independent. We propose that these findings may also be understood as indication that one-time standard individual measurements do not allow assessment of CR, and that the use of DSST in a testing-the-limits paradigm is a valuable assessment method for CR in young and elderly subjects.     

The impact of early adversity and education on genetic and brain morphological predictors of cognitive ability

Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known about how these factors combine and interact to explain this variation in cognition. To address this, we modelled the relationship between common genetic variation, grey matter volume, early life adversity and education and cognitive ability in a UK Biobank sample of N = 5237 individuals using structural equation modelling. We tested the hypotheses that total grey matter volume would mediate the association between genetic variation and cognitive ability, and that early life adversity and educational attainment would moderate this relationship. Common genetic variation, grey matter volume and early life adversity were each significant predictors in the model, explaining ~15% of variation in cognitive ability. Contrary to our hypothesis, grey matter volume did not mediate the relation between genetic variation and cognition performance. Neither did early life adversity or educational attainment moderate this relation, although educational attainment was observed to moderate the relationship between grey matter volume and cognitive performance. We interpret these findings in terms of the modest explanatory value of currently estimated polygenic scores accounting for variation in cognitive performance (~5%), making potential mediating and moderating variables difficult to confirm.     

The relationship between IGF-I concentration, cognitive function and quality of life in adults with Prader-Willi syndrome

Mental retardation is one of the clinical characteristics of Prader-Willi syndrome (PWS) and in part of the patients growth hormone deficiency is demonstrable. Cognitive function seems to be influenced by insulin-like growth factor I (IGF-I); however, little is known about cognitive function in relation to IGF-I levels in PWS adults. The aim of the present study was to evaluate cognitive function in adult PWS patients in comparison to healthy siblings and to investigate whether there is a correlation between cognitive function and IGF-I levels. Anthropometric measurements, IGF-I levels, quality of life (QoL), Appetite Assessment Score, IQ (GIT and Raven) and cognitive function (by four subtests of the Cambridge Neuropsychological Automated Testing Battery, CANTAB) were evaluated in PWS patients and their healthy siblings served as control group. PWS patients had significantly lower IGF-I levels, IQ and QoL when compared to controls. Reaction times were longer and performance was worse on CANTAB subtests in PWS adults. IGF-I on one hand and IQ, Appetite Assessment Score and cognitive performance on the other hand seem to be correlated in PWS patients. In conclusion, IGF-I levels, IQ and QoL are significantly lower in PWS subjects when compared to healthy siblings. In PWS adults, temporal as well as prefrontal cognitive functions are impaired. Higher IGF-I levels appear to be related to better intellectual skills and faster temporal memory processing in PWS patients.     

Estimating Premorbid Cognitive Abilities in Low-Educated Populations

Objective

To develop an informant-based instrument that would provide a valid estimate of premorbid cognitive abilities in low-educated populations.

Methods

A questionnaire was drafted by focusing on the premorbid period with a 10-year time frame. The initial pool of items was submitted to classical test theory and a factorial analysis. The resulting instrument, named the Premorbid Cognitive Abilities Scale (PCAS), is composed of questions addressing educational attainment, major lifetime occupation, reading abilities, reading habits, writing abilities, calculation abilities, use of widely available technology, and the ability to search for specific information. The validation sample was composed of 132 older Brazilian adults from the following three demographically matched groups: normal cognitive aging (n = 72), mild cognitive impairment (n = 33), and mild dementia (n = 27). The scores of a reading test and a neuropsychological battery were adopted as construct criteria. Post-mortem inter-informant reliability was tested in a sub-study with two relatives from each deceased individual.

Results

All items presented good discriminative power, with corrected item-total correlation varying from 0.35 to 0.74. The summed score of the instrument presented high correlation coefficients with global cognitive function (r = 0.73) and reading skills (r = 0.82). Cronbach''s alpha was 0.90, showing optimal internal consistency without redundancy. The scores did not decrease across the progressive levels of cognitive impairment, suggesting that the goal of evaluating the premorbid state was achieved. The intraclass correlation coefficient was 0.96, indicating excellent inter-informant reliability.

Conclusion

The instrument developed in this study has shown good properties and can be used as a valid estimate of premorbid cognitive abilities in low-educated populations. The applicability of the PCAS, both as an estimate of premorbid intelligence and cognitive reserve, is discussed.     

An Investigation of Emotion Recognition and Theory of Mind in People with Chronic Heart Failure

Objectives

Cognitive deficits are common in patients with chronic heart failure (CHF), but no study has investigated whether these deficits extend to social cognition. The present study provided the first empirical assessment of emotion recognition and theory of mind (ToM) in patients with CHF. In addition, it assessed whether each of these social cognitive constructs was associated with more general cognitive impairment.

Methods

A group comparison design was used, with 31 CHF patients compared to 38 demographically matched controls. The Ekman Faces test was used to assess emotion recognition, and the Mind in the Eyes test to measure ToM. Measures assessing global cognition, executive functions, and verbal memory were also administered.

Results

There were no differences between groups on emotion recognition or ToM. The CHF group’s performance was poorer on some executive measures, but memory was relatively preserved. In the CHF group, both emotion recognition performance and ToM ability correlated moderately with global cognition (r = .38, p = .034; r = .49, p = .005, respectively), but not with executive function or verbal memory.

Conclusion

CHF patients with lower cognitive ability were more likely to have difficulty recognizing emotions and inferring the mental states of others. Clinical implications of these findings are discussed.     

Macrophage inhibitory cytokine‐1 is associated with cognitive impairment and predicts cognitive decline – the Sydney Memory and Aging Study

Higher levels of macrophage inhibitory cytokine‐1, also known as growth differentiation factor 15 (MIC‐1/GDF15), are associated with adverse health outcomes and all‐cause mortality. The aim of this study was to examine the relationships between MIC‐1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70–90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C‐reactive protein, tumor necrosis factor‐α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC‐1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross‐sectional associations were found between MIC‐1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC‐1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC‐1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC‐1/GDF15 cutoff values associated with cognitive decline and showed that a MIC‐1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC‐1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship.     

Cognitive functioning of adults with Noonan syndrome: a case–control study

Noonan syndrome (NS) is a genetic disorder characterised by short stature, facial dysmorphia, congenital heart defects and mildly lowered intellectual abilities. Research has mainly focused on genetic and somatic aspects, while intellectual and cognitive functioning has been documented scarcely. Also, to date studies have been primarily performed in children. This is the first study in which functioning within the major cognitive domains is systematically evaluated in a group of adults with NS and compared with a control group. Extensive neuropsychological assessment, including the domains intelligence, speed of information processing, memory (working memory, immediate recall and delayed recall), executive function and visuoconstruction, was performed in a sample of 42 patients with NS and 42 healthy controls, matched on age, sex and education level. In addition, subjective cognitive complaints were assessed with self‐report questionnaires. On the domain speed of information processing patients performed worse than controls (P < 0.05). Furthermore, except for slightly better results on delayed recall in the patients with NS (P < 0.05), none of the other cognitive domains showed between‐group differences. On the questionnaires, patients reported substantially more complaints about their own cognitive abilities than controls (P < 0.05). A lowered speed of information processing and relatively intact functioning in other cognitive domains characterises the cognitive profile of adult patients, in contrast to previous findings in children with NS, who seem to have more generalised cognitive deficits.     

Brief International Cognitive Assessment for MS (BICAMS): international standards for validation

ABSTRACT: An international expert consensus committee recently recommended a brief battery of tests for cognitive evaluation in multiple sclerosis. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory. Recognizing that resources for validation will vary internationally, the committee identified validation priorities, to facilitate international acceptance of BICAMS. Practical matters pertaining to implementation across different languages and countries were discussed. Five steps to achieve optimal psychometric validation were proposed. In Step 1, test stimuli should be standardized for the target culture or language under consideration. In Step 2, examiner instructions must be standardized and translated, including all information from manuals necessary for administration and interpretation. In Step 3, samples of at least 65 healthy persons should be studied for normalization, matched to patients on demographics such as age, gender and education. The objective of Step 4 is test-retest reliability, which can be investigated in a small sample of MS and/or healthy volunteers over 1-3 weeks. Finally, in Step 5, criterion validity should be established by comparing MS and healthy controls. At this time, preliminary studies are underway in a number of countries as we move forward with this international assessment tool for cognition in MS.     

Intelligence May Moderate the Cognitive Profile of Patients with ASD

BackgroundThe intelligence of individuals with Autism Spectrum Disorder (ASD) varies considerably. The pattern of cognitive deficits associated with ASD may differ depending on intelligence. We aimed to study the absolute and relative severity of cognitive deficits in participants with ASD in relation to IQ.MethodsA total of 274 children (M age = 12.1, 68.6% boys) participated: 30 ASD and 22 controls in the below average Intelligence Quotient (IQ) group (IQ<85), 57 ASD and 54 controls in the average IQ group (85<IQ<115) and 41 ASD and 70 controls in the above average IQ group (IQ>115). Matching for age, sex, Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and VIQ-PIQ difference was performed. Speed and accuracy of social cognition, executive functioning, visual pattern recognition and basic processing speed were examined per domain and as a composite score.ResultsThe composite score revealed a trend significant IQ by ASD interaction (significant when excluding the average IQ group). In absolute terms, participants with below average IQs performed poorest (regardless of diagnosis). However, in relative terms, above average intelligent participants with ASD showed the most substantial cognitive problems (particularly for social cognition, visual pattern recognition and verbal working memory) since this group differed significantly from the IQ-matched control group (p < .001), whereas this was not the case for below-average intelligence participants with ASD (p = .57).ConclusionsIn relative terms, cognitive deficits appear somewhat more severe in individuals with ASD and above average IQs compared to the below average IQ patients with ASD. Even though high IQ ASD individuals enjoy a certain protection from their higher IQ, they clearly demonstrate cognitive impairments that may be targeted in clinical assessment and treatment. Conversely, even though in absolute terms ASD patients with below average IQs were clearly more impaired than ASD patients with average to above average IQs, the differences in cognitive functioning between participants with and without ASD on the lower end of the IQ spectrum were less pronounced. Clinically this may imply that cognitive assessment and training of cognitive skills in below average intelligent children with ASD may be a less fruitful endeavour. These findings tentatively suggest that intelligence may act as a moderator in the cognitive presentation of ASD, with qualitatively different cognitive processes affected in patients at the high and low end of the IQ spectrum.     

Deficits in Executive and Memory Processes in Delusional Disorder: A Case-Control Study

Objective

Delusional disorder has been traditionally considered a psychotic syndrome that does not evolve to cognitive deterioration. However, to date, very little empirical research has been done to explore cognitive executive components and memory processes in Delusional Disorder patients. This study will investigate whether patients with delusional disorder are intact in both executive function components (such as flexibility, impulsivity and updating components) and memory processes (such as immediate, short term and long term recall, learning and recognition).

Methods

A large sample of patients with delusional disorder (n = 86) and a group of healthy controls (n = 343) were compared with regard to their performance in a broad battery of neuropsychological tests including Trail Making Test, Wisconsin Card Sorting Test, Colour-Word Stroop Test, and Complutense Verbal Learning Test (TAVEC).

Results

When compared to controls, cases of delusional disorder showed a significantly poorer performance in most cognitive tests. Thus, we demonstrate deficits in flexibility, impulsivity and updating components of executive functions as well as in memory processes. These findings held significant after taking into account sex, age, educational level and premorbid IQ.

Conclusions

Our results do not support the traditional notion of patients with delusional disorder being cognitively intact.     

Deterioration in Motor Function Over Time in Older Adults With Type 2 Diabetes is Associated with Accelerated Cognitive Decline

Objective: Type 2 diabetes (T2D) is associated with motor impairments and a higher dementia risk. The relationships of motor decline with cognitive decline in T2D older adults has rarely been studied. Using data from the Israel Diabetes and Cognitive Decline study (N = 892), we examined associations of decline in motor function with cognitive decline over a 54-month period.Methods: Motor function measures were strength (handgrip) and gait speed (time to walk 3 m). Participants completed a neuropsychologic battery of 13 tests transformed into z-scores, summarized into 4 cognitive domains: episodic memory, attention/working memory, executive functions, and language/semantic categorization. The average of the 4 domains’ z-scores defined global cognition. Motor and cognitive functions were assessed in 18-months intervals. A random coefficients model delineated longitudinal relationships of cognitive decline with baseline and change from baseline in motor function, adjusting for sociodemographic, cardiovascular, and T2D-related covariates.Results: Slower baseline gait speed levels were significantly associated with more rapid decline in global cognition (P = .004), language/semantic categorization (P = .006) and episodic memory (P = .029). Greater decline over time in gait speed was associated with an accelerated rate of decline in global cognition (P = .050), attention/working memory (P = .047) and language/semantic categorization (P<.001). Baseline strength levels were not associated with cognitive decline but the rate of declining strength was associated with an accelerated decline in executive functions (P = .025) and language/semantic categorization (P = .006).Conclusion: In T2D older adults, the rate of decline in motor function, beyond baseline levels, was associated with accelerated cognitive decline, suggesting that cognitive and motor decline share common neuropathologic mechanisms in T2D.     

The Role of Cognitive Factors in Predicting Balance and Fall Risk in a Neuro-Rehabilitation Setting

IntroductionThere is a consistent body of evidence supporting the role of cognitive functions, particularly executive function, in the elderly and in neurological conditions which become more frequent with ageing. The aim of our study was to assess the role of different domains of cognitive functions to predict balance and fall risk in a sample of adults with various neurological conditions in a rehabilitation setting.MethodsThis was a prospective, cohort study conducted in a single centre in the UK. 114 participants consecutively admitted to a Neuro-Rehabilitation Unit were prospectively assessed for fall accidents. Baseline assessment included a measure of balance (Berg Balance Scale) and a battery of standard cognitive tests measuring executive function, speed of information processing, verbal and visual memory, visual perception and intellectual function. The outcomes of interest were the risk of becoming a faller, balance and fall rate.ResultsTwo tests of executive function were significantly associated with fall risk, the Stroop Colour Word Test (IRR 1.01, 95% CI 1.00–1.03) and the number of errors on part B of the Trail Making Test (IRR 1.23, 95% CI 1.03–1.49). Composite scores of executive function, speed of information processing and visual memory domains resulted in 2 to 3 times increased likelihood of having better balance (OR 2.74 95% CI 1.08 to 6.94, OR 2.72 95% CI 1.16 to 6.36 and OR 2.44 95% CI 1.11 to 5.35 respectively).ConclusionsOur results show that specific subcomponents of executive functions are able to predict fall risk, while a more global cognitive dysfunction is associated with poorer balance.     

Neurodegenerative properties of chronic pain: cognitive decline in patients with chronic pancreatitis

Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance), use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions) were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients.