Moving on with (social) cognition in idiopathic cervical dystonia.

OBJECTIVE: Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients. METHOD: In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy). RESULTS: CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC. CONCLUSIONS: The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

Neural Substrates of Psychomotor Speed Deficits in Cerebral Small Vessel Disease: A Brain Disconnectome Mapping Study.

It remains unknown which factors influence how brain disconnectivity derived from White Matter Hyperintensity (WMH) lesions leads to psychomotor speed dysfunction, one of the earliest and most common cognitive manifestations in the cerebral Small Vessel Disease (cSVD) population. While the burden of WMH has been strongly linked to psychomotor speed performance, the effect that different locations and volumes of WMH may have on cSVD-related cognitive impairment remains unclear. Therefore, we aimed to explore (1) whether global WMH, deep WMH (DWMH), and periventricular (PVWMH) volumes display different psychomotor speed associations; (2) whether tract-specific WMH volume shows stronger cognitive associations compared with global measures of WMH volume; (3) whether specific patterns of WMH location lead to different degrees of disconnectivity. Using the BCBToolkit, we investigated which pattern of distribution and which locations of WMH lesion result in impaired psychomotor speed in a well-characterized sample (n = 195) of cSVD patients without dementia. Two key findings emerge from our study. First, global (and not tract-specific) measures of WMH volume were associated with psychomotor speed performance. Second, disconnection maps revealed the involvement of callosal tracts, association and projection fibers, and frontal and parietal cortical brain areas related to psychomotor speed, while the lesion location influenced such associations. In conclusion, psychomotor deficits are affected differently by WMH burden and topographic distribution through brain disconnection in non-demented cSVD patients.

Processing speed in temporal lobe epilepsy. A scoping review.

BACKGROUND: Impaired processing speed (PS) can affect patients with temporal lobe epilepsy (TLE). However, it is usually considered a nonspecific clinical feature and is not measured, but this raises lexical and methodological problems. This review aims to evaluate the existing terminology and assessment methods of PS in patients with TLE. METHODS: A scoping review was conducted based on the extended guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The electronic literature search was conducted on Medline-PubMed, American Psychological Association-PsycINFO, Elton Bryson Stephens Company, and Google Scholar, using the keywords "temporal lobe epilepsy" and "speed" or "slowing" plus "processing," "cognitive," "psychomotor," or "mental." Peer-reviewed articles published before December 2022 were analyzed if they were in English, including patients older than 14 years and at least one neuropsychological measure, reported original research focused on PS and had the selected keywords in the title, keywords, and abstract. RESULTS: Seven articles published between December 2004 and September 2021 were selected. The terms "processing speed," "psychomotor speed," and "information processing speed," based on similar theoretical constructs, were the most frequently used. Assessment methods included non-computerized or paper-and-pencil tests (WAIS-III Digit Symbol and Symbol Search subtests, Purdue Pegboard and Grooved Pegboard Tests, Trail Making Test and Stroop Color-Word Test) and computerized tests (Sternberg Memory Scanning Test, Pattern Comparison Processing Speed, Computerized Visual Searching). In some studies, impairment was associated with white and gray matter damage in the brain, independent of clinical and treatment variables. CONCLUSION: Clinical research on TLE has focused inconsistently on PS. Different evaluation terms and methods have been used while referring to similar theoretical constructs. These findings highlight a gap between the clinical importance of PS and its assessment. Studies are needed to share terms and tools among clinical centers and clarify the position of PS in the TLE phenotype.

Statins, Enzyme CoQ10 Supplement Use, and Cognitive Functioning.

OBJECTIVE: The current study assessed the effects of statin and CoQ10 supplement use on changes in cognitive functioning in the Wisconsin Registry for Alzheimer's Prevention study. METHODS: 1,573 subjects were administered medical histories, the Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Wechsler Memory Scale, Logical Memory subtest, and the Trail Making Test, Parts A (TMT-A) and B (TMT-B) 3-4 times over 5-10 years. RESULTS: Linear mixed models did not yield significant effects for statin or CoQ10 supplement use on changes in mental status, learning and memory, psychomotor speed, and cognitive flexibility. CONCLUSIONS: Statin and/or CoQ10 supplement use was not associated with neuropsychological test performance in the Wisconsin Registry for Alzheimer's Prevention study.

Free testosterone is related to aspects of cognitive function in women with and without polycystic ovary syndrome.

Evidence suggests impairment in aspects of cognitive function in women with polycystic ovary syndrome (PCOS). Direct effects of raised testosterone levels associated with PCOS are a potential mechanism. We aimed to explore the relationship between testosterone levels and cognitive functioning in women. Women with a range of testosterone levels, including women with PCOS, were recruited. Depressive and anxiety symptoms were measured by self-report. Participants underwent a comprehensive battery of cognitive tests assessing psychomotor speed, visuospatial learning and memory, verbal learning and memory, and executive function. Free testosterone serum levels were assessed. All measures were completed at the same time point. Correlation analysis (Spearman's Rho) was used to explore associations between free testosterone and cognitive test variables. Eighty-one women were recruited, with 40 meeting diagnostic criteria for PCOS. Free testosterone was normally distributed, with significant overlap between women with PCOS and controls. Mean depressive and anxiety symptoms were in the mild range. Higher free testosterone levels were significantly correlated with poorer performance on measures assessing psychomotor speed and visuospatial learning. These significant correlations remained after adjusting for confounders (premorbid verbal IQ, depressive, and anxiety symptoms). Higher free testosterone levels in women were associated with poorer cognitive function, specifically psychomotor speed and visuospatial learning. Women with PCOS and raised free testosterone levels may experience impairment in these aspects of cognitive function which are not accounted for by mood or anxiety symptoms.

Differential Cognitive Performance in Females and Males with Regular Cannabis Use.

OBJECTIVES: Preclinical and clinical studies suggest that males and females may be differentially affected by cannabis use. This study evaluated the interaction of cannabis use and biological sex on cognition, and the association between observed cognitive deficits and features of cannabis use. METHODS: Cognitive measures were assessed in those with regular, ongoing, cannabis use (N = 40; 22 female) and non-using peers (N = 40; 23 female). Intelligence, psychomotor speed, and verbal working memory were measured with the Wechsler Abbreviated Scale of Intelligence, Digit Symbol Test, and Digit Span and Hopkins Verbal Learning Test, respectively. Associations between cognitive measures and cannabis use features (e.g., lifetime cannabis use, age of initiation, time since last use of cannabis, recent high-concentration tetrahydrocannabinoid exposure) were also evaluated. RESULTS: No main effects of group were observed across measures. Significant interactions between group and biological sex were observed on measures of intelligence, psychomotor speed, and verbal learning, with greatest group differences observed between males with and without regular cannabis use. Psychomotor performance was negatively correlated with lifetime cannabis exposure. Female and male cannabis use groups did not differ in features of cannabis use. CONCLUSIONS: Findings suggest that biological sex influences the relationship between cannabis and cognition, with males potentially being more vulnerable to the neurocognitive deficits related to cannabis use.

Associations of individual and structural socioeconomic status with cognition and mental distress in pharmacoresistant focal epilepsy.

OBJECTIVE: Epilepsy is often associated with low socioeconomic status (SES). People with epilepsy (PWE) also suffer from cognitive dysfunction and mental distress. In the general population, these constraints are related to individual and structural SES. However, in PWE, cognitive dysfunction and mental distress have been mainly attributed to biological factors such as brain lesions or pharmacological treatment, whereas comprehensive studies on possible social determinants are missing. Here, we study associations of individual and structural SES with cognition and mental distress in PWE. METHODS: We retrospectively studied 340 adult patients with pharmacoresistant focal epilepsy from Berlin treated at a tertiary epilepsy center. Individual SES (education, employment, and income), structural SES (social index of district and neighborhood), and their interactions were examined. Associations between social variables and verbal learning, psychomotor speed, and mental distress were analyzed with multiple regression analyses, controlling for demographic and medical variables and intelligence. RESULTS: Our sample had lower educational levels and lived more frequently in low SES neighborhoods compared to the general population of Berlin. Thirty percent showed reduced verbal learning, 31% had deficits in psychomotor speed, and 20% revealed significant mental distress. Lower structural SES was related to lower psychomotor speed (ΔR2 = 0.9%) and higher mental distress (ΔR2 = 1.6%). Employment was related to verbal learning (ΔR2 = 0.7%) and psychomotor speed (ΔR2 = 1.2%). Income and education were linked to mental distress (ΔR2 = 5%). Neighborhood and individual SES covered more than half of the explained variance in mental distress. Furthermore, interactions between individual and structural SES were identified. CONCLUSION: We confirm cognitive deficits, significant mental distress, and individual and structural social disadvantage in PWE. Our findings indicate that individual and structural SES are related to cognitive and emotional well-being beyond demographic and medical characteristics. As a clinical implication, individual and structural SES should be considered when interpreting neuropsychological findings.

Methanol Poisoning as an Acute Toxicological Basal Ganglia Lesion Model: Evidence from Brain Volumetry and Cognition.

BACKGROUND: Acute methanol poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of methanol poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of methanol poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of methanol poisoning and the volume of the brain structures that are selectively vulnerable to methanol. METHODS: We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute methanol poisoning during methanol mass poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software. RESULTS: In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01). CONCLUSIONS: Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in methanol poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in methanol poisoning.

Is Low Psychomotor Speed a Marker of Brain Vulnerability in Late Life? Digit Symbol Substitution Test in the Prediction of Alzheimer, Parkinson, Stroke, Disability, and Depression.

BACKGROUND: Dementia, stroke, depression, and disability are frequent in late life and are major causes of quality of life disruption and family burden. Even though each of these disorders relies on specific pathogenic processes, a common clinical manifestation is psychomotor slowing. OBJECTIVE: We assessed the relevance of a simple marker of low psychomotor speed in predicting several brain outcomes: dementia, Alzheimer's disease (AD), Parkinson's disease (PD), stroke, depressive symptoms, and disability in activities of daily living (ADL) and instrumental ADL (IADL). METHODS: PAQUID is a population-based study involving 3,777 individuals aged 65 or older prospectively followed-up with repeated clinical evaluations. After 10 years, 437 participants developed dementia, 333 developed AD, 71 developed PD, 207 reported incident stroke, 404 developed disability in ADL, 994 in IADL, and 494 developed depressive symptomology. Psychomotor speed was measured with the digit symbol substitution test (DSST). Cox proportional hazards models controlled for several confounders assessed the risk of incident outcomes. RESULTS: Participants with low DSST performance had increased risk of incident all-type dementia (hazard ratio [HR] 3.41, p < 0.0001) and AD-type dementia (HR 3.18, p < 0.0001). Higher risk for PD (HR 2.98, p = 0.04), IADL (HR 1.82, p < 0.0001), ADL disability (HR 1.95, p = 0.001), depressive symptoms (HR 1.53, p = 0.03), and a statistical trend for stroke (HR 1.88, p = 0.09) was also found. CONCLUSION: Low psychomotor speed is associated with an increased risk of developing various brain outcomes: dementia, AD, PD, disability, depressive symptoms, and marginally stroke. Low psychomotor speed may be the consequence of a number of discrete cerebral abnormalities and could be considered as a marker of brain vulnerability. In clinical practice, a low score in DSST should be seen as a warning sign of possible negative evolution.

[The association between paid or voluntary employment and neuropsychological test performance at an older age]. / Langer doorwerken: wellicht zo slecht nog niet? Een pilotstudie naar de relatie tussen werkzaam zijn en cognitief functioneren op latere leeftijd.

Studies have convincingly shown that both physical and mental activity are positively associated with cognitive task performance in aging. Little is known, however, about whether still being employed or doing volunteer work, which obviously engages physical and/or mental activity, is similarly associated with cognitive ability at an older age. The current study explored this relationship in 28 volunteers aged sixty years and older. Participants completed a neuropsychological test battery, and data regarding the number of working hours (paid and voluntary) per week were collected. A total of 28 participants were included, 13 of whom worked three or more hours per week. As a group, these active participants achieved better episodic memory, sustained attention and psychomotor speed results. This study shows that older people who are still working demonstrate better neuropsychological task performance. An important question for future research concerns the causality of this relationship.

Inflammatory markers are associated with decreased psychomotor speed in patients with major depressive disorder.

Previous data have demonstrated that administration of inflammatory cytokines or their inducers leads to altered basal ganglia function associated with reduced psychomotor speed. Decreased psychomotor speed, referred to clinically as psychomotor retardation, is a cardinal symptom of major depressive disorder (MDD) and has been associated with poor antidepressant treatment response. We therefore examined the association between plasma inflammatory markers and psychomotor speed in ninety-three un-medicated patients with MDD. Psychomotor speed was assessed by a range of neuropsychological tests from purely motor tasks (e.g. movement latency and finger tapping) to those that involved motor activity with increasing cognitive demand and cortical participation (e.g. Trails A and Digit Symbol Substitution Task (DSST)). Linear regression analyses were performed to determine the relationship of inflammatory markers and psychomotor task performance controlling for age, race, sex, education, body mass index, and severity of depression. MDD patients exhibited decreased psychomotor speed on all tasks relative to normative standards. Increased IL-6 was associated with decreased performance on simple and choice movement time tasks, whereas MCP-1 was associated with decreased performance on the finger tapping task and DSST. IL-10 was associated with increased performance on the DSST. In an exploratory principle component analysis including all psychomotor tasks, IL-6 was associated with the psychomotor speed factor. Taken together, the data indicate that a peripheral inflammatory profile including increased IL-6 and MCP-1 is consistently associated with psychomotor speed in MDD. These data are consistent with data demonstrating that inflammation can affect basal ganglia function, and indicate that psychomotor speed may be a viable outcome variable for anti-inflammatory therapies in depression and other neuropsychiatric disorders with increased inflammation.

The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder.

OBJECTIVE: The aim of the present study was to characterize the neurocognitive effects of lithium in bipolar disorder to inform clinical and research approaches for further investigation. METHODS: Key words pertaining to neurocognition in bipolar disorder and lithium treatment were used to search recognized databases to identify relevant literature. The authors also retrieved gray literature (e.g., book chapters) known to them and examined pertinent articles from bibliographies. RESULTS: A limited number of studies have examined the effects of lithium on neurocognition in bipolar disorder and, although in some domains a consistent picture emerges, in many domains the findings are mixed. Lithium administration appears to reshape key components of neurocognition - in particular, psychomotor speed, verbal memory, and verbal fluency. Notably, it has a sophisticated neurocognitive profile, such that while lithium impairs neurocognition across some domains, it seemingly preserves others - possibly those vulnerable to the effects of bipolar disorder. Furthermore, its effects are likely to be direct and indirect (via mood, for example) and cumulative with duration of treatment. Disentangling the components of neurocognition modulated by lithium in the context of a fluctuating and complex illness such as bipolar disorder is a significant challenge but one that therefore demands a stratified and systematic approach, such as that provided by the Lithium Battery. CONCLUSIONS: In order to delineate the effects of lithium therapy on neurocognition in bipolar disorder within both research and clinical practice, a greater understanding and measurement of the relatively stable neurocognitive components is needed to examine those that indeed change with lithium treatment. In order to achieve this, we propose a Lithium Battery-Clinical and a Lithium Battery-Research that can be applied to these respective settings.

Two Novel Psychomotor Tasks in Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. METHODS: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; p<.001). RESULTS: The INPH group demonstrated slower performance on SDT (p<.001) and made a greater number of errors on both tasks (p<.001). Combined Time/Error scores revealed poorer performance in the INPH group for original-LTT (p<.001), modified-LTT (p ≤ .001) and SDT (p<.001). CONCLUSIONS: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools.

Mental slowing in relation to epilepsy and antiepileptic medication.

OBJECTIVES: Slowing of the central information-processing speed (CIPS) is frequently observed in epilepsy as a consequence of epileptic seizures and/or antiepileptic drugs (AEDs). A variety of neuropsychological tests are used to asses this 'mental slowing,' but it is highly questionable whether the different tasks measure the same cognitive process. Also, it remains unspecified to which degree the various tasks are sensitive to seizure- or treatment-related factors, or both. METHODS: We used an open clinical non-comparative study design. The sample consisted of adult patients with cryptogenic localization-related epilepsy who performed different cognitive measures of CIPS and psychomotor speed (PmS). Clinical data about their seizures and antiepileptic drug treatment were collected from an electronic patient database. RESULTS: Eighty patients were included. CIPS tasks mutually correlated significantly, but did not correlate with measures of PmS (finger tapping and reaction time). Also, the CIPS tasks were differently affected by treatment and seizure effects. Processing of complex information is affected by tonic-clonic seizures, while less complex tasks are more sensitive for AED effects. CONCLUSIONS: CIPS tasks are mainly measuring central processing, and the psychomotor component of these tasks is negligible. We propose a psychometric continuum on which PmS and CIPS tasks are ordered with ascending complexity. The model shows that the tasks are affected differently by seizures, treatment, age, and education level. In neuropsychological practice, this continuum can be helpful in the detection of treatment and seizure effects on the CIPS in epilepsy.

The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. METHODS: Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. RESULTS: Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05-0.27; I(2) = 46%) and delayed recall (SMD 0.24; 95% CI 0.15-0.34; I(2) = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. CONCLUSIONS: Available evidence suggests that antidepressants have a significant positive effect on psychomotor speed and delayed recall.

Age-related increases in basal ganglia glutamate are associated with TNF, reduced motivation and decreased psychomotor speed during IFN-alpha treatment: Preliminary findings.

Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate turnover by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit 1) and after 4weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly greater increase in glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior.

Lap time variation and executive function in older adults: the Baltimore Longitudinal Study of Aging.

BACKGROUND: poor cognitive and motor performance predicts neurological dysfunction. Variable performance may be a subclinical indicator of emerging neurological problems. OBJECTIVE: examine the cross-sectional association between a clinically accessible measure of variable walking and executive function. METHODS: older adults aged 60 or older from the Baltimore Longitudinal Study of Aging (n = 811) with data on the 400-m walk test and cognition. Based on ten 40-m laps, we calculated mean lap time (MLT) and variation in time across ten 40-m laps (lap time variation, LTV). Executive function tests assessed attention and short-term memory (digit span forward and backward), psychomotor speed [Trail Making Test (TMT) part A] and multicomponent tasks requiring cognitive flexibility [TMT part B, part B-A (Delta TMT) and digit symbol substitution test (DSST)]. Multivariate linear regression analysis examined the cross-sectional association between LTV and executive function, adjusted for MLT, age, sex and education, as well as the LTV × MLT interaction. RESULTS: the LTV was univariately associated with all executive function tests except digit span (P < 0.001); after adjustment, the association with TMT part A remained (standardised ß = 0.142, P = 0.002). There was an interaction between MLT and LTV; among fast walkers, greater LTV was associated with a greater Delta TMT (ß for LTV × MLT = -1.121, P = 0.016) after adjustment. CONCLUSION: at any walking speed, greater LTV is associated with psychomotor slowing. Among persons with faster walking speed, variation is associated with worse performance on a complex measure of cognitive flexibility. A simple measure of variability in walking time is independently associated with psychomotor slowing.

Clinical predictors of individual cognitive fluctuations in patients undergoing hemodialysis.

BACKGROUND: Cognitive impairment in hemodialysis (HD) patients is frequent and mediated by several factors. It is unclear which patients are more susceptible to cognitive variations around the dialysis cycle and which clinical factors may play a mediator role. We aimed to answer these issues by investigating intraindividual changes within the dialysis cycle. STUDY DESIGN: Cross-sectional observational study with repeated measures. SETTING & PARTICIPANTS: 47 HD patients and 40 controls without kidney disease, both without history of neurologic disease. PREDICTORS: Dialysis vintage, disease duration, vascular risk factors, comorbidity index score, intradialytic weight change, frequency of hypotensive episodes, and biochemical levels (hemoglobin, leukocytes, urea, creatinine, sodium, and potassium). Covariates included demographics (age, education, and sex). OUTCOMES & MEASUREMENTS: Significant individual deterioration in attention and executive functions (phasic and intrinsic alertness, Stroop test, and Trail Making Test) after dialysis, as measured by a regression-based reliable change method. Regression models were used to identify clinical predictors of individual cognitive decline after dialysis. RESULTS: After dialysis, patients primarily showed prolonged reaction times and psychomotor slowing. However, individual-based analyses revealed that fluctuations in attention and executive functions were present in only a minority of patients. Significant individual fluctuations on particular attention and executive tasks were associated moderately with intradialytic hypotensive episodes, as well as with psychoactive medication, and were predicted weakly by blood leukocyte count, sodium level, dialysis vintage, and volume. LIMITATIONS: Small sample size; patient group younger and healthier than the overall HD population, limiting generalizability. CONCLUSIONS: Only a minority of patients exhibit significant individual cognitive fluctuations, predominantly showing deterioration after dialysis in attention and executive functions. Susceptibility to such fluctuations was predicted in part by both HD-dependent and -independent factors.

High dose benzodiazepines prolong reaction times in chronic users who have major depressive and/or anxiety disorders.

AIM: Short term administration of benzodiazepines (BZD) was found to prolong reaction time (RT) in experimental studies. However, studies on long term BZD use did not always adjust for important confounders and showed inconsistent results. We aimed to identify a possible relationship between long term BZD use and RT in BZD users in this large cross-sectional, observational study. METHODS: The RTs of non-users (n = 2404) were compared with low (n = 288), intermediate (n = 74), and high dose BZD users (n = 57) in the Netherlands Study of Depression and Anxiety (NESDA). RTs were obtained from the Implicit Association Test. Analyses were adjusted for sociodemographic characteristics, health indicators, severity of psychopathology and antidepressant use. RESULTS: Of the NESDA participants, 419 subjects (14.8%) used BZDs. A higher dose of BZDs was associated with prolonged RTs (P = 0.01). When comparing the different dose groups, the high dose group, but not the low and medium dose groups, had significantly longer RTs than the non-users. CONCLUSIONS: Tolerance for the RT prolonging effect of relatively high doses of BZDs does not seem to develop. As prolonged RTs can have adverse consequences in daily life, BZDs should be prescribed conservatively at the lowest possible dose.

A systematic review of the effects of experimental fasting on cognition.

Numerous investigations have been conducted on the impact of short-term fasting on cognition in healthy individuals. Some studies have suggested that fasting is associated with executive function deficits; however, findings have been inconsistent. The lack of consensus regarding the impact of short-term fasting in healthy controls has impeded investigation of the impact of starvation or malnutrition in clinical groups, such as anorexia nervosa (AN). One method of disentangling these effects is to examine acute episodes of starvation experimentally. The present review systematically investigated the impact of short-term fasting on cognition. Studies investigating attentional bias to food-related stimuli were excluded so as to focus on general cognition. Ten articles were included in the review. The combined results are equivocal: several studies report no observable differences as a result of fasting and others show specific deficits on tasks designed to test psychomotor speed, executive function, and mental rotation. This inconsistent profile of fasting in healthy individuals demonstrates the complexity of the role of short-term fasting in cognition; the variety of tasks used, composition of the sample, and type and duration of fasting across studies may also have contributed to the inconsistent profile. Additional focused studies on neuropsychological profiles of healthy individuals are warranted in order to better develop an understanding of the role of hunger in cognition.