Letter Digit Substitution Test Research Articles

Is empathy correlated to patients’ level of cognitive impairment in schizophrenia?

IntroductionEmpathy, which refers to the ability to understand and share the thoughts and feelings of others, may be compromised in schizophrenia (SCZ). Yet the relationship between empathy and neurocognitive functioning remains unclear.ObjectivesTo explore whether cognitive and affective empathy are associated with the neurocognitive functioning in SCZ.MethodsFifty-eight outpatients with stable SCZ completed the Questionnaire of Cognitive and Affective Empathy (QCAE) comprising five subscales intended to assess cognitive and affective components of empathy. They also completed a neurocognitive battery comprising the following tests: the Hopkins Verbal Learning Test–Revised (HVLT-R), the Letter Digit Substitution Test (LDST), the Stroop Test (ST), the “Double Barrage” of Zazzo (DBZ), the Modified Card Sorting Test (MCST), Verbal Fluency (VF), the Trail Making Test-Part A (TMT-A) and the Digit Span (DS).ResultsBetter affective and cognitive empathy correlated with better performance in the ST (less hesitations and less errors). Patients with better cognitive empathy performed better in the MCST (more categories achieved; P = 0.029) and in the LDST (more substitutions per minute; P = 0.031).ConclusionsOur results bolster support for the presence of an association between NF and the decreased cognitive and affective empathy in schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Correlation between childhood trauma and cognitive impairment in patients with schizophrenia

IntroductionAbusive childhood experiences are claimed to be more prevalent in people with schizophrenia (SCZ) than in the general population. The exposure to childhood trauma can have adverse effects on cognitive function.ObjectivesTo investigate whether there is a relationship between childhood trauma (CT) and cognitive functioning in patients with SCZ.MethodsFifty-eight outpatients with stable SCZ were recruited. The participants completed the Childhood Trauma Questionnaire retrospectively assessing five types of childhood trauma (emotional, physical and sexual abuse, and emotional and physical neglect). They also completed a neurocognitive battery comprising the following tests: the Hopkins Verbal Learning Test–Revised (HVLT-R), the Letter Digit Substitution Test (LDST), the Stroop Test (ST), the “Double Barrage” of Zazzo (DBZ), the Modified Card Sorting Test (MCST), the Verbal Fluency (VF), the Trail Making Test-Part A (TMT-A) and the Digit Span (DS).ResultsThe patients with a history of physical abuse (P = 0.03) or emotional neglect (P = 0.07) performed worse at the delayed recall of the HVLT-R. A history of emotional neglect was also correlated to a significantly worse performance in theTMT-A (P < 0.0001), while physical abuse was correlated to worse DS (P = 0.015). High emotional abuse scores were significantly correlated to poorer efficiency in DBZ (P = 0.025).ConclusionsThe results need replication, but underline the necessity of investigating biological and psychosocial mechanisms underlying these subjects’ cognitive impairment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Are neurocognition and facial emotion recognition related in schizophrenia?

IntroductionPatients with schizophrenia (SCZ) show impairments in many social cognition domains including facial emotion recognition (FER). The existence of a relationship association between FER and neurcognitive functioning (NF) remains uncertain.ObjectivesTo investigate the association between ToM functioning and neurocognitive functioning in SCZ.MethodsFER was evaluated in 58 patients with stable schizophrenia with a newly validated FER task constructed from photographs of the face of a famous Tunisian actress representing the Ekman's six basic emotions. They also completed a neurocognitive battery comprising the following tests: the Hopkins Verbal Learning Test–Revised (HVLT-R), the Letter Digit Substitution Test (LDST), the Stroop Test (ST), the “Double Barrage” of Zazzo (DBZ), the Modified Card Sorting Test (MCST), Verbal Fluency (VF), the Trail Making Test-Part A (TMT-A) and the Digit Span (DS).ResultsPatients who performed better in the FER task had better performance in the VF task (P = 0.001) and in the immediate recall of the HVLT-R (P = 0.021). No correlations were found with the other neurocognitive tests.ConclusionsOur results suggest that FER represents an autonomous cognitive function which does not necessarily require good NF.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Do patients with better neuro-cognition have better theory of mind?

IntroductionTheory of mind (ToM) has repeatedly been shown to be compromised in many patients with schizophrenia (SCZ). By contrast, the association between ToM deficits and neuro-cognitive functioning (NF) remains uncertain.ObjectivesTo investigate the association between ToM functioning and neuro-cognitive functioning in SCZ.MethodsFifty-eight outpatients with stable SCZ completed the intention-inferencing task (IIT), in which the ability to infer a character's intentions from 28 short comic strip stories is assessed. They also completed a neuro-cognitive battery comprising the following tests: the Hopkins Verbal Learning Test–Revised (HVLT-R), the Letter Digit Substitution Test (LDST), the Stroop Test (ST), the “Double Barrage” of Zazzo (DBZ), the Modified Card Sorting Test (MCST), Verbal Fluency (VF), the Trail Making Test-Part A (TMT-A) and the Digit Span (DS).ResultsThe performance in the IIT significantly correlated with performance in some neuro-cognitive tests including efficiency in DBZ, number of uncorrected mistakes in ST, number of correct categories in MCST and the time needed to succeed the TMT-A. No correlations were found between performance in the ITT and in memory tasks (HVLT-R and DS).ConclusionsToM may rely on some neuro-cognitive functions (mainly attention and executive functioning). Elucidating the exact relationship between ToM and NF may be useful as both are targeted in specific psychotherapeutic interventions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Association between Blood Omega-3 Index and Cognition in Typically Developing Dutch Adolescents.

The impact of omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) on cognition is heavily debated. In the current study, the possible association between omega-3 LCPUFAs in blood and cognitive performance of 266 typically developing adolescents aged 13–15 years is investigated. Baseline data from Food2Learn, a double-blind and randomized placebo controlled krill oil supplementation trial in typically developing adolescents, were used for the current study. The Omega-3 Index was determined with blood from a finger prick. At baseline, participants finished a neuropsychological test battery consisting of the Letter Digit Substitution Test (LDST), D2 test of attention, Digit Span Forward and Backward, Concept Shifting Test and Stroop test. Data were analyzed with multiple regression analyses with correction for covariates. The average Omega-3 Index was 3.83% (SD 0.60). Regression analyses between the Omega-3 Index and the outcome parameters revealed significant associations with scores on two of the nine parameters. The association between the Omega-3 Index and both scores on the LDST (β = 0.136 and p = 0.039), and the number of errors of omission on the D2 (β = −0.053 and p = 0.007). This is a possible indication for a higher information processing speed and less impulsivity in those with a higher Omega-3 Index.

Mild deficits in attentional control in patients with the IGSF1 deficiency syndrome.

Male patients with the X-linked IGSF1 deficiency syndrome are characterized by central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency and occasionally transient partial growth hormone deficiency. Thyroid hormone plays a vital role in brain development and functioning, and while most patients receive adequate replacement therapy starting shortly after birth, it is unknown whether this syndrome is accompanied by long-term impaired cognitive functioning. We therefore assessed cognitive functioning in male patients with IGSF1 deficiency. Fifteen adult male patients with IGSF1 deficiency participated in neuropsychological assessment of executive functioning and memory, and completed validated questionnaires on health-related quality of life (HRQoL), mood and fatigue. Results were compared to data from previous studies by our department: 54 healthy controls (76 for the attention task) for the test battery and 191 healthy controls for the questionnaires. All patients had central hypothyroidism, and twelve were treated with levothyroxine. Patients performed worse than controls in tasks that required attentional control (Trail Making Test, Letter-Digit Substitution Test, and Sustained Attention to Response Task) (all P < 0·001). Memory was unaffected. In addition, patients reported more mental fatigue and reduction of activity (Multidimensional Fatigue Inventory) (both P < 0·01), while HRQoL and mood reports were not different from controls. Age at the start of replacement therapy and current thyroxine levels were not related to outcome. Adult male patients with IGSF1 deficiency exhibit mild deficits in attentional control on formal testing. This finding was not related to the age at start of replacement therapy, or current levothyroxine treatment.

Executive function, but not memory, associates with incident coronary heart disease and stroke.

To evaluate the association of performance in cognitive domains executive function and memory with incident coronary heart disease and stroke in older participants without dementia. We included 3,926 participants (mean age 75 years, 44% male) at risk for cardiovascular diseases from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with Mini-Mental State Examination score ≥24 points. Scores on the Stroop Color-Word Test (selective attention) and the Letter Digit Substitution Test (processing speed) were converted to Z scores and averaged into a composite executive function score. Likewise, scores of the Picture Learning Test (immediate and delayed memory) were transformed into a composite memory score. Associations of executive function and memory were longitudinally assessed with risk of coronary heart disease and stroke using multivariable Cox regression models. During 3.2 years of follow-up, incidence rates of coronary heart disease and stroke were 30.5 and 12.4 per 1,000 person-years, respectively. In multivariable models, participants in the lowest third of executive function, as compared to participants in the highest third, had 1.85-fold (95% confidence interval [CI] 1.39-2.45) higher risk of coronary heart disease and 1.51-fold (95% CI 0.99-2.30) higher risk of stroke. Participants in the lowest third of memory had no increased risk of coronary heart disease (hazard ratio 0.99, 95% CI 0.74-1.32) or stroke (hazard ratio 0.87, 95% CI 0.57-1.32). Lower executive function, but not memory, is associated with higher risk of coronary heart disease and stroke. Lower executive function, as an independent risk indicator, might better reflect brain vascular pathologies.

Diet and cognitive decline at middle age: the role of antioxidants.

To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, β-carotene, lutein, flavonoids and lignans) and cognitive decline at middle age, analyses were performed on data from the population based Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002). Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive function was assessed with a neuropsychological test battery, consisting of the 15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter Digit Substitution Test. Scores on global cognitive function, memory, processing speed, and cognitive flexibility were calculated. In regression analyses, quintiles of antioxidant intake were associated with change in cognitive domain scores. Results showed that higher lignan intake was linearly associated with less decline in global cognitive function (P= 0.01), memory (P< 0.01) and processing speed (P= 0.04), with about two times less declines in the highest v. the lowest quintile. In the lowest quintile of vitamin E intake, decline in memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive decline in the highest lutein intake group was greater than in the lowest intake group (P< 0.05). Higher flavonoid intake was associated with greater decline in cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were not associated with cognitive decline. We conclude that within the range of a habitual dietary intake, higher intake of lignans is associated with less cognitive decline at middle age.

Cognition, structural brain changes and complicated grief. A population-based study.

Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study. The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter-Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test - immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms. Compared with no-grief participants, participants with complicated grief had lower scores for the Letter-Digit Substitution Test [Z-score -0.16 v. 0.04, 95% confidence interval (CI) -0.36 to -0.04, p = 0.01] and Word Fluency Task (Z-score -0.15 v. 0.03, 95% CI -0.35 to -0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI -37.6 to -0.10, p = 0.04). Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.

Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia.

We aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of MAPT (microtubule-associated protein tau) or GRN (progranulin) mutations. In this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk of frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, structural MRI, and fMRI. We used voxel-based morphometry and tract-based spatial statistics for voxel-wise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsular, anterior midcingulate, and posterior cingulate cortices. Carriers (n = 39) and noncarriers (n = 36) had similar neuropsychological performance, except for lower Letter Digit Substitution Test scores in carriers. Worse performance on Stroop III, Rivermead Behavioral Memory Test, and Happé Cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy in the right uncinate fasciculus was found in carriers compared with controls. Reductions in functional connectivity between anterior midcingulate cortex and frontoinsula and several other brain regions were found in carriers compared with controls and correlated with higher age in carriers, but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found, except for a small cluster of higher volume in the precentral gyrus in carriers. This study demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.

T2* MRI of minimal hepatic encephalopathy and cognitive correlates in vivo

To evaluate regional brain iron deposition in minimal hepatic encephalopathy (MHE) patients using T2*-weighted gradient-echo imaging and to explore the relationship between T2* MR changes and cognitive performance. Forty hepatitis-B virus (HBV)-related cirrhotic patients and 22 age-, sex-, and education-matched healthy controls were included in this study. Of the patients, twenty eight patients were diagnosed with MHE. All subjects were administered Number Connection Test-A (NCT-A), Letter Digit Substitution Test (LDST), Rey-Osterrieth Complex Figure Test (RCFT), and the Mini-Mental State Examination (MMSE). T2*-weighted gradient-echo images were acquired using 3 Tesla MRI. Phase values (putative iron levels) in the frontal-basal ganglia-thalamocortical circuits were measured. Spearman correlation and multiple linear regression analysis were performed. MHE patients exhibited significantly prolonged NCT-A time and decreased LDST, RCFT immediate and delayed recall scores. Significant decreases of phase values in the bilateral putamen were detected in MHE patients compared to without MHE patients and controls. Multiple linear regression analysis confirmed significant correlations between the phase values in the putamen and right frontal white matter and cognitive performances by MHE patients. Decreased phase values in the frontal cortical-basal ganglial circuits independently contribute to cognitive impairments in MHE patients.

Do apolipoprotein E genotype and educational attainment predict the rate of cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging Study.

We investigated suspected longitudinal interaction effects of apolipoprotein E (APOE) genotype and educational attainment on cognitive decline in normal aging. Our sample consisted of 571 healthy, nondemented adults aged between 49 and 82 years. Linear mixed-models analyses were performed with four measurement time points: baseline, 3-year, 6-year, and 12-year follow-up. Covariates included age at baseline, sex, and self-perceived physical and mental health. Dependent measures were global cognitive functioning (Mini-Mental State Examination; Folstein, Folstein, & McHugh, 1975), Stroop performance (Stroop Color-Word Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006a), set-shifting performance (Concept Shifting Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006b), cognitive speed (Letter-Digit Substitution Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006c), verbal learning (Verbal Learning Test: Sum of five trials; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2005), and long-term memory (Verbal Learning Test: Delayed recall). We found only faint evidence that older, high-educated carriers of the APOE-ε4 allele (irrespective of zygosity) show a more pronounced decline than younger, low-educated carriers and noncarriers (irrespective of educational attainment). Moreover, this outcome was confined to concept-shifting performance and was especially observable between 6- and 12-year follow-ups. No protective effects of higher education were found on any of the six cognitive measures. We conclude that the combination of APOE-ε4 allele and high educational attainment may be a risk factor for accelerated cognitive decline in older age, as has been reported before, but only to a very limited extent. Moreover, we conclude that, within the cognitive reserve framework, education does not have significant protective power against age-related cognitive decline.

The Letter Digit Substitution Test: Demographic Influences and Regression-Based Normative Data for School-Aged Children

The Letter Digit Substitution Test (LDST) was administered to a sample of N=296 healthy children (aged between 8.03 and 15.87). The aim of the present study was to evaluate the impact of age, gender, and parental educational level on LDST performance and to establish demographically corrected normative data. The results showed that the relationship between age and LDST performance was curvilinear (i.e., improvements in test performance were more pronounced for younger children than for older children) and was moderated by gender (i.e., the gender differences were small at younger ages but increased as a function of age, with girls outperforming boys). Moreover, children who had parents with a higher level of education outperformed their counterparts who had parents with a lower level of education. Regression-based normative LDST data were established, and an automatic scoring program was provided.

New Measures of Masked Text Recognition in Relation to Speech-in-Noise Perception and Their Associations With Age and Cognitive Abilities

In this research, the authors aimed to increase the analogy between Text Reception Threshold (TRT; Zekveld, George, Kramer, Goverts, & Houtgast, 2007) and Speech Reception Threshold (SRT; Plomp & Mimpen, 1979) and to examine the TRT's value in estimating cognitive abilities that are important for speech comprehension in noise. The authors administered 5 TRT versions, SRT tests in stationary (SRT(STAT)) and modulated (SRT(MOD)) noise, and 2 cognitive tests: a reading span (RSpan) test for working memory capacity and a letter-digit substitution test for information-processing speed. Fifty-five adults with normal hearing (18-78 years, M = 44 years) participated. The authors examined mutual associations of the tests and their predictive value for the SRTs with correlation and linear regression analyses. SRTs and TRTs were well associated, also when controlling for age. Correlations for the SRT(STAT) were generally lower than for the SRT(MOD.) The cognitive tests were correlated to the SRTs only when age was not controlled for. Age and the TRTs were the only significant predictors of SRT(MOD). SRT(STAT) was predicted by level of education and some of the TRT versions. TRTs and SRTs are robustly associated, nearly independent of age. The association between SRTs and RSpan is largely age dependent. The TRT test and the RSpan test measure different nonauditory components of linguistic processing relevant for speech perception in noise.

DNA methylation and cognitive functioning in healthy older adults

Long-term supplementation with folic acid may improve cognitive performance in older individuals. The relationship between folate status and cognitive performance might be mediated by changes in methylation capacity, as methylation reactions are important for normal functioning of the brain. Although aberrant DNA methylation has been implicated in neurodevelopmental disorders, the relationship between DNA methylation status and non-pathological cognitive functioning in human subjects has not yet been investigated. The present study investigated the associations between global DNA methylation and key domains of cognitive functioning in healthy older adults. Global DNA methylation, defined as the percentage of methylated cytosine to total cytosine, was measured in leucocytes by liquid chromatography-MS/MS, in 215 men and women, aged 50-70 years, who participated in the Folic Acid and Carotid Intima-Media Thickness (FACIT) study (clinical trial registration number NCT00110604). Cognitive performance was assessed by means of the Visual Verbal Word Learning Task, the Stroop Colour-Word Interference Test, the Concept Shifting Test, the Letter-Digit Substitution Test and the Verbal Fluency Test. Using hierarchical linear regression analyses adjusted for age, sex, level of education, alcohol consumption, smoking status, physical activity, erythrocyte folate concentration and 5,10-methylenetetrahydrofolate reductase 677C→T genotype, we found that global DNA methylation was not related to cognitive performance on any of the domains measured. The present study results do not support the hypothesis that global DNA methylation, as measured in leucocytes, might be associated with cognitive functioning in healthy older individuals.

Recurrent pain is associated with decreased selective attention in a population-based sample

Studies which have examined the impact of pain on cognitive functioning in the general population are scarce. In the present study we assessed the predictive value of recurrent pain on cognitive functioning in a population-based study (N=1400). Furthermore, we investigated the effect of pain on cognitive functioning in individuals with specific pain complaints (i.e. back pain, gastric pain, muscle pain and headache). Cognitive functioning was assessed using the Stroop Color-Word Interference test (Stroop interference), the Letter-Digit-Substitution test (LDST) and the Visual Verbal learning Task (VVLT). Pain was measured with the COOP/WONCA pain scale (Dartmouth Primary Care Cooperative Information Project/World Organization of National Colleges, Academies, and Academic Associations of General Practice /Family Physicians). We controlled for the effects of age, sex, level of education and depressive symptoms. It was demonstrated that pain had a negative impact on the performance on the Stroop interference but not on the VVLT and the LDST. This indicates that subjects who reported extreme pain had more problems with selective attention and were more easily distracted. Effects were in general larger in the specific pain groups when compared to the associations found in the total group. Implications of these findings are discussed.The experience of recurrent pain has a negative influence on selective attention in a healthy population.

Depressive Symptoms and Cognitive Decline in Community‐Dwelling Older Adults

To examine the temporal association between depressive symptoms and cognitive functioning and estimate the effect measure modification of the apolipoprotein E (APOE) epsilon4 allele on this relationship. Prospective cohort study. General community. Population-based sample of 598 cognitively intact older adults aged 60 and older, with re-assessments after 3 (N=479) and 6 years (N=412). Depressive symptoms (Symptom Checklist) and neurocognitive functioning (memory, Visual Verbal Learning Test; attention, Stroop Color-Word Test; processing speed, Letter Digit Substitution Test; general cognition, Mini-Mental State Examination). Longitudinal associations were assessed using linear mixed models. The risk for cognitive impairment, no dementia (CIND) was examined using logistic regression. Adjusting for age, sex, education, and baseline cognition, the rate of change in memory z-scores was 0.00, -0.11, -0.20, and -0.37 for those in the lowest (reference group), second, third, and highest depressive symptom quartiles at baseline, respectively (P<.001 for highest vs lowest quartile). The odds ratios for developing CIND with amnestic features were 1.00, 0.87, 0.69, and 2.98 for the four severity groups (P=.05 for highest vs lowest quartile). Associations were strongest for those with persistent depressive symptoms, defined as high depressive symptoms at baseline and at least one follow-up visit. Results were similar for processing speed and global cognitive function but were not as strong for attention. No APOE interaction was observed. Depression and APOE act independently to increase the risk for cognitive decline and may provide targets for prevention and early treatment.

Subtle Cognitive Impairments in Patients with Long-Term Cure of Cushing’s Disease

Active Cushing's disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushing's disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushing's disease. Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning. We included 74 patients cured of Cushing's disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education. Compared with NFMA patients, patients cured from Cushing's disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushing's disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushing's disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushing's disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients. Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing's disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids.

Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up

Our previous study on cognitive functioning among 195 patients with low-grade glioma (LGG) a mean of 6 years after diagnosis suggested that the tumour itself, rather than the radiotherapy used to treat it, has the most deleterious effect on cognitive functioning; only high fraction dose radiotherapy (>2 Gy) resulted in significant added cognitive deterioration. The present study assesses the radiological and cognitive abnormalities in survivors of LGG at a mean of 12 years after first diagnosis. Patients who have had stable disease since the first assessment were invited for follow-up cognitive assessment (letter-digit substitution test, concept shifting test, Stroop colour-word test, visual verbal learning test, memory comparison test, and categoric word fluency). Compound scores in six cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed) were calculated to detect differences between patients who had radiotherapy and patients who did not have radiotherapy. White-matter hyperintensities and global cortical atrophy were rated on MRI scans. 65 patients completed neuropsychological follow-up at a mean of 12 years (range 6-28 years). 32 (49%) patients had received radiotherapy (three had fraction doses >2 Gy). The patients who had radiotherapy had more deficits that affected attentional functioning at the second follow-up, regardless of fraction dose, than those who did not have radiotherapy (-1.6 [SD 2.4] vs -0.1 [1.3], p=0.003; mean difference 1.4, 95% CI 0.5-2.4). The patients who had radiotherapy also did worse in measures of executive functioning (-2.0 [3.7] vs -0.5 [1.2], p=0.03; mean difference 1.5, 0.2-2.9) and information processing speed (-2.0 [3.7] vs -0.6 [1.5], p=0.05; mean difference 0.8, 0.009-1.6]) between the two assessments. Furthermore, attentional functioning deteriorated significantly between the first and second assessments in patients who had radiotherapy (p=0.25). In total, 17 (53%) patients who had radiotherapy developed cognitive disabilities deficits in at least five of 18 neuropsychological test parameters compared with four (27%) patients who were radiotherapy naive. White-matter hyperintensities and global cortical atrophy were associated with worse cognitive functioning in several domains. Long-term survivors of LGG who did not have radiotherapy had stable radiological and cognitive status. By contrast, patients with low-grade glioma who received radiotherapy showed a progressive decline in attentional functioning, even those who received fraction doses that are regarded as safe (</=2 Gy). These cognitive deficits are associated with radiological abnormalities. Our results suggest that the risk of long-term cognitive and radiological compromise that is associated with radiotherapy should be considered when treatment is planned. Kaptein Fonds; Schering Plough.

Consuming Functional Foods Enriched with Plant Sterol or Stanol Esters for 85 Weeks Does Not Affect Neurocognitive Functioning or Mood in Statin-Treated Hypercholesterolemic Individuals1–3

Recent animal and human studies have shown that plant sterols and stanols, which are used as functional food ingredients to lower increased LDL cholesterol concentrations, pass the blood-brain barrier. Whether this affects neurocognitive functioning and mental well-being in humans has, to our knowledge, never been investigated. The aim of the present study was therefore to examine the effects of long-term plant sterol or stanol consumption on neurocognitive functioning and mood in a randomized, double-blind, placebo-controlled dietary intervention trial. To this end, hypercholesterolemic individuals, aged 43–69 y, receiving stable statin treatment were randomly assigned to an 85-wk supplementation with margarines enriched with plant sterol esters (2.5 g/d), plant stanol esters (2.5 g/d), or placebo. At baseline and at the end of the intervention period, all participants underwent a cognitive assessment. In addition, subjective cognitive functioning and mood were assessed by means of questionnaires (Cognitive Failure Questionnaire and depression subscale of the Symptom Checklist 90, respectively). Long-term supplementation with plant sterol or stanol esters did not affect cognitive performance (memory, simple information processing speed, complex information processing speed, Letter-Digit Substitution test performance), subjective cognitive functioning, or mood. In conclusion, the present results indicate that long-term use of plant sterols or stanols at recommended intakes of 2.5 g/d does not affect neurocognitive functioning or mood in hypercholesterolemic individuals receiving statin treatment.