Motor dysfunction influence on executive functioning in manifest and premanifest Huntington's disease

Motor disturbances can be present in both manifest and premanifest Huntington's disease (HD). We aimed to investigate the role of motor functioning on executive functioning to better understand the progression of cognitive dysfunction in HD. Forty patients with manifest HD, 21 patients with premanifest HD, and a group of 28 controls were tested twice with a 1‐year interval. For the Symbol Digit Modalities Test and the Figure Fluency Test, extra conditions were designed to measure motor involvement. Subtraction of this motor score from the original test score resulted in isolation of the cognitive component. Groups were compared on motor, cognitive, and original test scores using multilevel regression analysis. Manifest patients had lower baseline scores of 0.53 standard deviations (SD) on the original Symbol Digit Modalities Test (P = 0.03) and 0.71 SD on the motor isolation part (P = 0.006), and they showed a deterioration of 0.47 SD over 1 year of follow‐up on the original Symbol Digit Modalities Test (P = 0.001) compared with controls. Premanifest patients had lower baseline scores of 0.67 SD on the Symbol Digit Modalities motor part (P = 0.008) and deterioration of 0.48 SD on the original (P = 0.001) and cognitive isolation (P = 0.02) parts. Secondary analyses revealed that the premanifest deterioration resulted from the close‐to‐predicted‐onset group. Motor disturbances have a negative influence on performance on the Symbol Digit Modalities Test. Isolation of the cognitive component of this test revealed cognitive deterioration in the premanifest group only, caused by deteriorating scores for patients who were close to their predicted clinical disease onset. The Figure Fluency Test did not prove sensitive to cognitive change. © 2014 International Parkinson and Movement Disorder Society     

Transient and executive function working memory in schizophrenia

Transient working memory requires attention and temporary storage of information, whereas executive function working memory requires additional mental manipulation of that information. Working memory impairment is common in schizophrenia patients, but only some studies have found differential impairment in executive function working memory compared to transient working memory. We measured both types of working memory using the Digit Span forward (DF) and backward (DB) tasks in a large sample of schizophrenia patients (n=267) and normal comparison subjects (n=82); in the patients, we also examined associations between performance on the Digit Span tasks and Letter-Number Sequencing (LNS), a putative executive function working memory test. Compared to healthy subjects, the schizophrenia patients showed impairment in the medium effect size range on both DF (d=-0.55) and DB (d=-0.68). DB scores predicted LNS performance, whereas DF scores did not. Worse negative symptoms were associated with worse performance on DF, DB and LNS. These results do not reflect differential executive function working memory dysfunction in schizophrenia, but appear to support transient and executive function working memory as separable constructs.     

精神分裂症伴迟发性运动障碍认知功能的对照研究

目的 了解慢性精神分裂症TD患者是否存在认知功能损害。方法 符合持续性TD诊断标准且年龄低于65岁的慢性精神分裂症患者纳入TD组,对照组为同期住院慢性精神分裂症患者。其性别与TD组配对,年龄、文化程度、目前抗精神病药物各类分别与TD组匹配。两组患者认知功能测验包括:韦氏成人智力量表(WAIS-RC)、韦氏记忆量表(WMS)及威期康星卡片分类测验(WCST)。结果 WAIS-RC测验TD组和对照组语言智商、作业智商、总智商成绩无显著差异,但数字广度、数字符合测验TD组得分明显低于对照组。WMS测验结果显示TD组顺数数、累积、背数测验得分明显低于对照组,TD组记忆商数较低。WCST测验结果显示:两组持续错误数无差异,TD组总反应数、正确数、随机错误数、分类完成数的成绩均关于对照组。二元变量相关分析显示:AIMS得分与记忆商数、总反应数、正确数、随机错误数、分类完成数相关。多元逐步回归分析显示:文化程度、TD、年龄是影响患者认知功能的主要因素。结论 有无TD的慢性精神分裂症患者的智商无显著差异;TD患者存在记忆损害,特别是工作记忆损害;TD患者额叶执行功能差于无TD者;除文化程度、年龄外,TD对患者的认知功能损害有影响。     

Cognitive correlates of cortical cholinergic denervation in Parkinson’s disease and parkinsonian dementia

We recently reported findings that loss of cortical acetylcholinesterase (AChE) activity is greater in parkinsonian dementia than in Alzheimer’s disease (AD). In this study we determined cognitive correlates of in vivo cortical AChE activity in patients with parkinsonian dementia (PDem, n = 11), Parkinson’s disease without dementia (PD, n = 13), and in normal controls (NC, n = 14) using N–[¹¹C]methyl–piperidin–4–yl propionate ([¹¹C]PMP) AChE positron emission tomography (PET). Cortical AChE activity was significantly reduced in the PDem (–20.9%) and PD (–12.7 %) subjects (P < 0.001) when compared with the control subjects. Analysis of the cognitive data within the patient groups demonstrated that scores on the WAIS-III Digit Span, a test of working memory and attention, had most robust correlation with cortical AChE activity (R = 0.61, p < 0.005). There were also significant correlations between cortical AChE activity and other tests of attentional and executive functions, such as the Trail Making and Stroop Color Word tests. There was no significant correlation between cortical AChE activity and duration of motor disease (R = –0.01, ns) or severity of parkinsonian motor symptoms (R = 0.14, ns). We conclude that cortical cholinergic denervation in PD and parkinsonian dementia is associated with decreased performance on tests of attentional and executive functioning. Supported by grants from the Department of Veterans Affairs, National Institute of Aging (Alzheimer Disease Research Center, AG05133), and The Scaife Family Foundation, Pittsburgh, PA, USA.     

Executive function impairment in community elderly subjects with questionable dementia

BACKGROUND: The neurocognitive profile of community-dwelling Chinese subjects with 'questionable' dementia was studied. METHODS: One hundred and fifty-four ambulatory Chinese subjects were recruited from local social centers for the elderly. Each subject was examined using the Clinical Dementia Rating (CDR), the Cantonese version of the Mini-Mental State Examination (CMMSE), the Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Category Verbal Fluency Test (CVFT), digit and visual span tests, and the Cambridge Neurological Inventory. The neurocognitive profile of nondemented subjects (CDR 0) was compared with that of subjects with 'questionable' dementia (CDR 0.5). RESULTS: Subjects with 'questionable' dementia were older, and had lower educational levels and global cognitive assessment scores than the controls (CMMSE and ADAS-Cog; t tests, p < 0.001). In addition, they also had significantly lower scores in delayed recall, reverse span, verbal fluency tests and worse performance in complex motor tasks related to executive function (Mann-Whitney tests, p < 0.001). Logistic regression analysis revealed that ADAS-Cog, CVFT, and reverse visual span were significant predictors for the CDR of 'questionable' dementia. CONCLUSION: Aside from memory impairment, executive function deficits were also present in subjects with 'questionable' dementia. To identify groups cognitively at risk for dementia, concomitant assessments of memory and executive function are suggested.     

原发性失眠患者认知功能改变及其影响因素分析

目的:探讨原发性失眠患者认知功能改变及其影响因素.方法:对40例失眠患者(失眠组)和48例正常睡眠者(对照组)进行匹兹堡睡眠质量指数(Pittsburgh SleepQuality Index,PSQI)、情景记忆测试和蒙特利尔认知评估(Montreal cognitive assessment,MoCA)测验.结果:失眠者MoCA测试的总分(t=3.24,p=0.002)、命名(t=3.17,p=0.002)成绩较对照组差,即刻记忆(t=3.33,p=0.001)、延迟回忆(t=6.05,p=0.001)成绩较对照组差.不同失眠程度的被试在命名(F=7.56,p=0.001)、 语言(F=3.22,p=0.045)、 总分(F=6.72,p=0.002)、延迟记忆(F=8.41,p=0.001)、延迟回忆(F=22.67,p=0.001)差异显著.且原发性失眠患者的年龄与MoCA总分、即刻记忆、延迟回忆和延迟再认功能相关有统计学意义,受教育年限与MoCA总分、视空间与执行功能、命名、注意、语言、抽象等功能相关有统计学意义.结论:原发性失眠患者存在认知功能损害;且失眠程度越严重,认知功能损害范围越广,程度越重.     

The relationship of recency discrimination to explicit memory and executive functioning.

Recency discrimination has been conceptualized as an executive ability by some investigators and as an aspect of episodic memory by others. We compared the performance of 261 neurologically healthy adults on a recency discrimination task (RDT) with their performance on measures of executive functioning and explicit memory. Mean z-transformed raw scores were used to construct indices of visual and verbal explicit memory, fluency, and executive functioning. Analyses revealed that RDT performance correlated more closely with visual (r = 0.32; p < 0.001) and verbal memory (r = 0.25; p < 0.001) than with fluency (r = 0.16; p < 0.05) and executive functioning (r = 0.13; p < 0.05). These findings suggest that recency discrimination might be better understood as an aspect of episodic memory that is subserved primarily by hippocampal and medial temporal structures than as an executive function that is subserved primarily by prefrontal cortex.     

Cognitive correlates of brain MRI subcortical signal hyperintensities in non-demented elderly

OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) subcortical gray and capsular (SGCH) and white matter hyperintensities (WMH) and cognitive functions in non-demented community dwelling elderly. METHODS: The severity of SGCH and WMH on proton density and T2 MR images in 16 subjects was scored using the semi-quantitative rating scale of Scheltens et al. (1993). A limited series of cognitive tests selected a priori were then correlated with severity of SGCH and WMH. RESULTS: Analysis demonstrated that severity of SGCH was inversely related to performance on the Digit Span (R = -0.64, p < 0.01) and the Stroop Color Word Tests (R = -0.64, p < 0.01). Severity of WMH was related to worsening performance on the Trail Making Test (R = 0.67, p < 0.005). CONCLUSIONS: These findings indicate that severity of WMH is negatively related to more pure executive cognitive functions, specifically set shifting, while severity of SGCH is inversely related to more basic functions of attention and working memory.     

Insomnia and daytime neuropsychological test performance in older adults

Objectives/BackgroundThere is good documentation of the impact of insomnia on daytime cognitive function based on self-reports, but not on neuropsychological test performance. The study investigated the association of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA) complaints with daytime domain-specific neuropsychological performance in older adults.Participants/MethodsParticipants were 859 older adults (mean 71.9 years) in the Singapore Longitudinal Ageing Studies. They were interviewed and assessed at community-based eldercare activity centres and completed a sleep survey questionnaire and a battery of neuropsychological tests (Digit span, Rey Auditory Verbal Learning Test, Story memory, Brief Visuospatial Memory Test-Revised, Color Trails Test (1 and 2), Block design, and Verbal fluency).ResultsInsomnia complaints were present in 18.0% (n = 155) of participants. Controlling for the presence of other insomnia complaints, psychosocial and medical variables, and depression, EMA was independently and significantly associated with worse executive functioning (p = 0.031). DIS and DMS were not independently associated with poorer performance on any cognitive domain.ConclusionThe association of EMA among older adults with decreased executive functioning and underlying mechanistic factors should be further investigated.     

Brief assessment of cognition in schizophrenia: validation of the Japanese version

This preliminary study was performed to test the reliability and validity of the Brief Assessment of Cognition in Schizophrenia (BACS) as an assessment tool in a Japanese-language version (BACS-J). The subjects for the present study were 30 outpatients with chronic schizophrenia. Each subject gave written informed consent to participate in the research. Cronbach's alpha for the BACS-J was 0.77. The BACS-J composite score was significantly correlated with all primary measures of BACS-J (verbal memory, working memory, motor speed, verbal fluency, attention, and executive function). All BACS-J primary measures and the composite score were significantly correlated between two assessments. The mean score of the Digit Sequencing Task and composite score on the second assessment were significantly larger than those on the first assessment. All BACS-J primary measures except the Symbol Coding Task were significantly correlated with relevant standard neurocognitive tests. Also, the BACS-J composite score was significantly correlated with all standard neurocognitive tests except the Continuous Performance Test. A principal components analysis with varimax rotation resulted in a three-factor solution (executive function and memory; motor speed and general cognitive functions; and working memory). This preliminary study indicates that the BACS-J is a reliable and practical scale to evaluate cognitive function.     

Trail making test errors and executive function in schizophrenia and depression

The Trail Making Test (TMT) frequently is used as a measure of executive cognitive function. However, traditional use of test completion time as the primary outcome score does not give the more detailed information on cognitive processes that analysis of test-taking errors may provide. The present study compared TMT performance of three groups: patients with schizophrenia, patients with major depression, and healthy control participants (n = 30 for each group). Three operationally defined error types were examined: (a) tracking, (b) perseverative, and (c) proximity. Although both patient groups were slower than the healthy control group, only the schizophrenia group made significantly more errors, particularly tracking errors, suggesting a greater degree of cognitive disorganization. Within-group analysis of a larger group of schizophrenia patients (n = 84) revealed that TMT time was most strongly associated with the Withdrawal-Retardation factor of the Brief Psychiatric Rating scale. In contrast, TMT errors were most strongly associated with the Conceptual Disorganization factor. Comparisons of TMT scores and other cognitive tests showed moderate to high associations with tests of working memory, psychomotor speed, and executive function. Stepwise regression analysis revealed an independent association between Digit Cancellation and Part B Time, indicating a unique contribution of visuomotor scanning to performance. In contrast, Part B errors were uniquely associated with the Verbal Series Attention Test and the Token Test, tests of mental tracking and executive-mediated working memory, respectively. These findings demonstrate the utility of TMT error analysis in revealing cognitive deficits not traditionally captured using completion time as the sole outcome variable.     

Early onset Alzheimer's disease is associated with a distinct neuropsychological profile

Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.     

Increase in Number of Depression Symptoms Over Time is Related to Worse Cognitive Outcomes in Older Adults With Type 2 Diabetes

ObjectiveOlder adults with type 2 diabetes (T2D) are at increased risk for depression, cognitive decline, and dementia compared to those without T2D. Little is known about the association of simultaneous changes in depression symptoms and cognitive decline over time.MethodsSubjects (n=1021; mean age 71.6 [SD=4.6]; 41.2% female) were initially cognitively normal participants of the Israel Diabetes and Cognitive Decline study who underwent evaluations of depression and cognition approximately every 18 months. Cognitive tests were summarized into four cognitive domains: episodic memory, attention/working memory, executive functions, and semantic categorization. The average of the z-scores of the four domains defined global cognition. Depression symptoms were assessed using the Geriatric Depression Scale, 15-item version. We fit a random coefficients model of changes in depression and in cognitive functions, adjusting for baseline sociodemographic and cardiovascular variables.ResultsHigher number of depression symptoms at baseline was significantly associated with lower baseline cognitive scores in global cognition (estimate = ?0.1175, SE = 0.021, DF = 1,014, t = ?5.59; p < 0.001), executive functions (estimate = ?0.186, SE = 0.036, DF = 1,013, t = ?5.15; p = <0.001), semantic categorization (estimate = ?0.155, SE = 0.029, DF = 1,008, t = ?5.3; p < 0.001), and episodic memory (estimate = ?0.08165, SE = 0.027, DF = 1,035, t = ?2.92; p = 0.0036), but not with rate of decline in any cognitive domain. During follow-up, a larger increase in number of depression symptoms, was associated with worse cognitive outcomes in global cognition (estimate = ?0.1053, SE = 0.027, DF = 1,612, t = ?3.77; p = 0.0002), semantic categorization (estimate = ?0.123, SE = 0.036, DF = 1,583, t = ?3.36; p = 0.0008), and in episodic memory (estimate = ?0.165, SE = 0.055, DF = 1,622, t = ?3.02; p = 0.003), but the size of this effect was constant over time.ConclusionIn elderly with T2D, increase in depression symptoms over time is associated with parallel cognitive decline, indicating that the natural course of the two conditions progresses concurrently and suggesting common underlying mechanisms".     

Neuropsychological comparison of Alzheimer's disease and dementia with lewy bodies

BACKGROUND/AIMS: The present study examined the patterns of memory and cognitive performance associated with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: A battery of standardized neuropsychological tests was administered to individuals with these disorders as well as to a group of cognitively intact controls. The battery included measures of memory (learning, recall and recognition), language, visuospatial ability, psychomotor speed, executive functioning and mood. All subjects (n = 115) were evaluated at a memory disorder clinic and were diagnosed based on published criteria. RESULTS: The controls outperformed both dementia groups on all cognitive measures. With respect to memory, the DLB group scored significantly higher than the AD group on measures of word list free recall and recognition (p < or = 0.001). In other cognitive domains, the AD group performed significantly better than the DLB group on constructional praxis, sustained attention, phonemic fluency, spatial judgment, psychomotor speed and working memory (all p < or = 0.01). CONCLUSION: These findings support the usefulness of memory and other cognitive test score patterns as in distinguishing AD from DLB, particularly in mild to moderately demented populations that may not present with hallmark symptomology.     

Neuropsychological and neuroradiological correlates in Huntington''s disease.

Measurements of cortical and subcortical atrophy were made on CT scans of 34 patients with Huntington's disease. Significant correlations were found between the bicaudate ratio (BCR) and an eye movement scale (r = 0.44, p less than 0.01), and activities of daily living scale (r = 0.57, p less than 0.001) and the Mini-Mental State Exam (r = 0.49, p less than 0.01). No correlations were found between BCR values and severity of chorea or voluntary motor impairment. A detailed neuropsychological evaluation of 18 Huntington's disease patients showed significant correlations between the BCR and Symbol Digit Modalities test (r = 0.65, p less than 0.01), and parts A (r = 0.72, p less than 0.001) and B (r = 0.80, p less than 0.0001) of the Trail Making Test. These data support work in primates that demonstrates the role of the caudate nucleus in cognitive and oculomotor functions, but not in motor control (which is governed by putamino-subthalamic systems). The specific cognitive skills correlated with caudate atrophy in Huntington's disease are those reported in primate work to be served by the frontal-caudate loop system: eye movements, conceptual tracking, set shifting and psychomotor speed.     

Influence of seasonal variation in mood and behavior on cognitive test performance among young adults

Background: Seasonal variations in mood and behavior are common among the general population and may have a deteriorating effect on cognitive functions. Aims: In this study the effect of seasonal affective disorder (SAD-like symptoms) on cognitive test performance were evaluated in more detail. Methods: The data were derived from the study Mental Health in Early Adulthood in Finland. Participants (n = 481) filled in a modified Seasonal Pattern Assessment Questionnaire (SPAQ) and performed cognitive tests in verbal and visual skills, attention and general intelligence. Results: SAD-like symptoms, especially regarding the seasonal variations in weight and appetite, had a significant effect on working memory (Digit Span Backward, P = 0.008) and auditory attention and short-term memory (Digit Span Forward, P = 0.004). The seasonal variations in sleep duration and mood had an effect on auditory attention and short-term memory (Digit Span Forward, P = 0.02 and P = 0.0002, respectively). The seasonal variations in social activity and energy level had no effect. Conclusions: Seasonal changes in mood, appetite and weight have an impairing effect on auditory attention and processing speed. If performance tests are not to repeated in different seasons, attention needs to be given to the most appropriate season in which to test.     

Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder

Kulkarni S, Jain S, Janardhan Reddy YC, Kumar KJ, Kandavel T. Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder.
Bipolar Disord 2010: 12: 647–656. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. Methods: We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. Results: Unaffected siblings performed poorly on the Tower of London test (TOL), the Rey’s auditory verbal learning test (RAVLT), and the Rey’s complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). Conclusions: Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.     

The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan.

OBJECTIVE: Age-associated decline in gray matter brain volume and cognitive function in healthy adults has been reported in the literature. The goal of the current study is to examine the relationship between age-related changes in regional gray matter volumes and cognitive function in a large, cross-sectional sample of healthy adults across the lifespan. METHODS: Magnetic resonance imaging and cognitive assessment were conducted on 148 adults aged 21-76 years. Multiple regression analyses examining the effect of age were performed on magnetic resonance image-derived gray matter brain volumes and standardized cognitive summary scores of attention and executive function. Regression was also performed to test the effect of age, gray matter volumes, and their interaction on the prediction of cognitive performance. RESULTS: Age significantly predicted performance on tests of attention (F [1, 146]=50.97, p <0.01, R2=0.26) and executive function (F [1, 146]=126.19, p <0.01, R2=0.46) and gray matter volumes for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and putamen (F [2, 145]=45.34-23.96, p <0.01-0.02). Lateral frontal (beta=-1.53, t=-2.16, df=131, p <0.03) and orbital frontal (beta=1.24, t=2.08, df=131, p <0.04) regions significantly predicted performance on tests of attention. Lateral frontal (beta=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age and lateral frontal volume (beta=3.76, t=2.49, df=131, p <0.02) significantly predicted executive function. CONCLUSIONS: The findings confirm age-associated decline in cognitive function and gray matter volumes, particularly in anterior cortical brain regions. Furthermore, the association between lateral frontal gray matter volume and the ability to successfully plan, organize, and execute strategies varies as a function of age across the healthy adult lifespan.     

The kynurenine pathway and cognitive performance in community-dwelling older adults. The Hordaland Health Study

IntroductionTryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults.MethodsThis cross-sectional study included 2174 participants aged 70–72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner’s regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5′phosphate, sex and smoking were considered as potential confounders.ResultsHigher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β −0.08, p = 0.001) and COWAT (β −0.08, p = 0.001), but not with DST (β −0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β −0.07; p = 0.001; COWAT: β −0.06, p = 0.010; DST: β −0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition.ConclusionHigher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language.     

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study

OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.