The clock drawing test is an important contribution to the Mini Mental State Examination in screening for cognitive impairment.

BACKGROUND: The clock drawing test (CDT) and the Mini Mental State Examination (MMSE) are frequently used screening instruments for cognitive impairment, however, the precise contribution of the CDT to the MMSE is largely unknown. METHODS: We studied patients with subjective cognitive impairment (SCI, n = 481), mild cognitive impairment (MCI, n = 628) and Alzheimer's disease (AD, n = 1099). Discrimination between patients was examined with multiple logistic regression, adjusted for age, sex, and education. Four groups were constructed based on a normal/abnormal MMSE (cut-off <24/30) versus normal/abnormal CDT (cut-off ≤2/3). Visually rated medial temporal lobe atrophy (MTA) on CT was used as parameter of neurodegeneration. RESULTS: The CDT significantly contributed to the MMSE in discriminating SCI from both MCI and AD patients. Our four group analyses showed that of those patients with a normal MMSE and incorrectly classified as SCI, an abnormal CDT could significantly identify 10.0% as MCI and 13.2% as AD. Among those with an abnormal MMSE, the percentage AD patients shifted from 53.1% to 82.1% due to an abnormal CDT. Presence of an abnormal CDT was significantly related to MTA increase, regardless of the MMSE score. CONCLUSION: The CDT is an important additional screening tool to the MMSE. An abnormal CDT with a normal MMSE is an indicator for cognitive impairment. An abnormal CDT in combination with an abnormal MMSE can be considered as an indicator of disease progression.

Subjective cognition in adults with common psychiatric classifications; a systematic review.

The aim is to assess whether instruments developed to measure subjective cognitive complaints (SCCs) and in neurology and aging can reliably be used in ADHD and other common psychiatric classifications. MEDLINE, PsycINFO, CINAHL and EMBASE+EMBASE CLASSIC were searched for relevant work on SCCs in psychiatric classifications (ADHD, autism, mood disorders, schizophrenia) in two phases: 1 identify instruments, 2 relevant studies. 35 studies with varying study quality were included. SCCs are most commonly studied in ADHD and mood disorders, but are found in all psychiatric classifications. SCCs show inconsistent and low associations to objective cognition across disorders, but higher and consistent relations are found with behavioral outcomes. SCCs are not qualitatively different for ADHD compared to other psychiatric classifications, and should thus not be seen as analogous to well validated measures of objective cognition. However, SCCs do reflect suffering, behavioral difficulties and problems experienced by across those with psychiatric problems in daily life.

Endotoxemia-induced inflammation and the effect on the human brain.

INTRODUCTION: Effects of systemic inflammation on cerebral function are not clear, as both inflammation-induced encephalopathy as well as stress-hormone mediated alertness have been described. METHODS: Experimental endotoxemia (2 ng/kg Escherichia coli lipopolysaccharide [LPS]) was induced in 15 subjects, whereas 10 served as controls. Cytokines (TNF-alpha, IL-6, IL1-RA and IL-10), cortisol, brain specific proteins (BSP), electroencephalography (EEG) and cognitive function tests (CFTs) were determined. RESULTS: Following LPS infusion, circulating pro- and anti-inflammatory cytokines, and cortisol increased (P < 0.0001). BSP changes stayed within the normal range, in which neuron specific enolase (NSE) and S100-beta changed significantly. Except in one subject with a mild encephalopathic episode, without cognitive dysfunction, endotoxemia induced no clinically relevant EEG changes. Quantitative EEG analysis showed a higher state of alertness detected by changes in the central region, and peak frequency in the occipital region. Improved CFTs during endotoxemia was found to be due to a practice effect as CFTs improved to the same extent in the reference group. Cortisol significantly correlated with a higher state of alertness detected on the EEG. Increased IL-10 and the decreased NSE both correlated with improvement of working memory and with psychomotor speed capacity. No other significant correlations between cytokines, cortisol, EEG, CFT and BSP were found. CONCLUSIONS: Short-term systemic inflammation does not provoke or explain the occurrence of septic encephalopathy, but primarily results in an inflammation-mediated increase in cortisol and alertness. TRIAL REGISTRATION: NCT00513110.

Being homebound with chronic fatigue syndrome: A multidimensional comparison with outpatients.

Many patients with chronic fatigue syndrome (CFS) seem to experience periods in which they are homebound due to their symptomatology. Despite a growing body of research about CFS, little is known about patients who no longer feel able to leave their homes. The purpose of the present study was to examine whether homebound patients differ from other CFS patients on illness-specific characteristics. Besides experiencing more impairment in daily functioning than participants of an outpatient intervention study, homebound patients were characterised by extremely high levels of daily fatigue, predominant somatic attributions, and pervasively passive activity patterns. The course of symptomatology was similarly stable in both groups. Our findings suggest that homebound patients form a distinct subgroup of CFS patients who might profit from a treatment approach that is tailored to their specific needs. The exploratory nature of this first systematic investigation of homebound CFS patients is stressed, and suggestions for future research are made.

Post-stroke depressive symptoms are associated with post-stroke characteristics.

BACKGROUND: Several studies have described the frequency and risk factors of post-stroke depressive symptoms (PSDS). However, most studies did not exclude patients with depressive symptoms shortly before stroke and paid little attention to prestroke risk factors of depression, including previous depressive episodes, white matter lesions, and brain atrophy. These are potential limitations to assess the true effect of stroke on the occurrence of depressive symptoms. Our aim was to investigate the prevalence and risk factors of PSDS with adjustments for the previously mentioned prestroke factors. METHODS: 420 consecutive patients with an acute clinical symptomatic transient ischemic attack or cerebral infarction were eligible for enrolment in this study. The presence of PSDS was rated by the Hospital Anxiety and Depression Scale 6-8 weeks after stroke. The relation between (pre-) stroke factors and PSDS was assessed with multivariate regression analysis. RESULTS: The prevalence of PSDS was 13% and did not differ between stroke subtype or first-ever/ever occurrence of stroke. Higher degree of post-stroke handicap was related to PSDS (OR = 5.39; 95% CI = 2.40-12.08) and more functional independence had a protective effect on PSDS (OR = 0.88; 95% CI = 0.77-1.00). CONCLUSIONS: This is the largest study that investigated the prevalence and risk factors of PSDS by carefully excluding patients with depressive symptoms shortly before stroke. PSDS were not related to lesion side or location, but to the degree of post-stroke handicap and functional independence. Early detection of PSDS and their risk factors might help to predict long-term outcome and could promote early interventions of (behavioral) rehabilitation treatment strategies.

Apathy is not depression in Huntington's disease.

Apathy and depression are common neuropsychiatric features of Huntington's disease. The authors studied a group of 34 Huntington's disease patients. In addition to the conventional classification according to DSM-IV criteria of depression, emphasis was put on a dimensional approach using scores on several different scales. Severe depression was found in 12% and severe apathy in 52% of all study patients. The authors found that apathy and depression are not related and are clearly distinct dimensions. Apathy was related to disease characteristics such as cognitive deterioration and functional decline, whereas depression was not.

Long-term pain, fatigue, and impairment in neuralgic amyotrophy.

OBJECTIVES: Recently, it has become clear that neuralgic amyotrophy (NA; idiopathic and hereditary brachial plexus neuropathy) has a less optimistic prognosis than usually assumed. To optimize treatment and management of these patients, one needs to know the residual symptoms and impairments they suffer. Therefore, the objective of this study was to describe the prevalence of pain, psychologic symptoms, fatigue, functional status, and quality of life in patients with NA. SETTING: Neurology outpatient department of an academic teaching hospital. PARTICIPANTS: NA patients (N=89) were studied, and clinical details were recorded. Self-report data were on average collected 2 years after the onset of the last NA episode. MAIN OUTCOME MEASURES: Pain was assessed with the McGill Pain Questionnaire, fatigue with the Checklist Individual Strength, and psychologic distress with the Symptom Checklist 90. Functional status and handicap were assessed with the modified Rankin Scale and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Pain was usually localized in the right shoulder and upper arm, matching the clinical predilection site for paresis in NA. About a quarter to a third of the patients reported significant long-term pain and fatigue, and half to two thirds still experienced impairments in daily life. Over one third of the individual patients suffered from severe fatigue. The group did not fulfill the criteria of chronic fatigue or major psychologic distress. There was no correlation of pain or fatigue with the level of residual paresis on a Medical Research Council scale, but patients with a comorbid condition fared worse than patients without. CONCLUSIONS: A significant number of NA patients suffer from persistent pain and fatigue, leading to impairment. Symptoms were not correlated with psychologic distress. This makes it likely that they are caused by residual shoulder or arm dysfunction but not as part of a chronic pain or fatigue syndrome in these patients.

Sensitivity and specificity of the 3-item memory test in the assessment of post traumatic amnesia.

PRIMARY OBJECTIVE: To investigate how the type of stimulus (pictures or words) and the method of reproduction (free recall or recognition after a short or a long delay) affect the sensitivity and specificity of a 3-item memory test in the assessment of post traumatic amnesia (PTA). METHODS: Daily testing was performed in 64 consecutively admitted traumatic brain injured patients, 22 orthopedically injured patients and 26 healthy controls until criteria for resolution of PTA were reached. Subjects were randomly assigned to a test with visual or verbal stimuli. Short delay reproduction was tested after an interval of 3-5 minutes, long delay reproduction was tested after 24 hours. Sensitivity and specificity were calculated over the first 4 test days. RESULTS: The 3-word test showed higher sensitivity than the 3-picture test, while specificity of the two tests was equally high. Free recall was a more effortful task than recognition for both patients and controls. In patients, a longer delay between registration and recall resulted in a significant decrease in the number of items reproduced. CONCLUSIONS: Presence of PTA is best assessed with a memory test that incorporates the free recall of words after a long delay.

Accelerated long-term forgetting after TIA or minor stroke: A more sensitive measure for detecting subtle memory dysfunction?

Cognitive changes after minor stroke or TIA have been reported, with studies describing a 'vascular' cognitive profile with spared episodic memory. Still, many patients also report memory complaints. Studies using long-term forgetting paradigms have detected memory impairment after prolonged intervals in contrast to standard delayed testing in other patient groups. This study examined whether accelerated long-term forgetting (ALF) is present in patients with minor stroke or TIA by comparing one-week delayed recall and recognition with the performance of a healthy control group. Results revealed that the patients' performance after one week was worse than the controls, in the absence of an impairment after a short delay. Patients did, however, not report more memory worries than controls. Possibly, reduced effort, attention or mnemonic strategies may contribute to subtle consolidation problems, which go undetected in daily functioning.

Panic features strongly predict the subjective but not the objective benefit of pulmonary vein isolation.

PURPOSE: Clinically observed discrepancies between electrocardiogram findings and subjective report of symptoms related to atrial fibrillation (AF) often remain unexplained. One could hypothesize that after a technically successful ablation, preoperative panic behavior might affect the report of AF-related symptoms. However, research on comorbid panic behavior in patients with AF is limited. METHODS: In this observational prospective cohort study, we investigated psychological characteristics, in particular the prevalence of panic features, among 112 patients with AF and its possible influence on experienced outcome of subsequent ablation treatment. RESULTS: Twelve percent of the AF patients (n = 12) were pre-operatively characterized by panic features. This group experienced higher levels of distress and more limitations in daily life compared to AF patients without panic features, but was not characterized by higher levels of neuroticism. However, AF-ablation resulted in a similar reduction of experienced limitations in daily functioning and levels of distress in both groups. CONCLUSION: Patients with panic features experience more distress and more limitations in daily life from AF, but these complaints are reduced by AF ablation in a similar rate as in patients without panic features. Additional psychological therapy is suggested as a method to further reduce subjective AF disease burden in these patients.

Neural correlates of strategic memory retrieval: differentiating between spatial-associative and temporal-associative strategies.

Remembering complex, multidimensional information typically requires strategic memory retrieval, during which information is structured, for instance by spatial- or temporal associations. Although brain regions involved in strategic memory retrieval in general have been identified, differences in retrieval operations related to distinct retrieval strategies are not well-understood. Thus, our aim was to identify brain regions whose activity is differentially involved in spatial-associative and temporal-associative retrieval. First, we showed that our behavioral paradigm probing memory for a set of object-location associations promoted the use of a spatial-associative structure following an encoding condition that provided multiple associations to neighboring objects (spatial-associative condition) and the use of a temporal-associative structure following another study condition that provided predominantly temporal associations between sequentially presented items (temporal-associative condition). Next, we used an adapted version of this paradigm for functional MRI, where we contrasted brain activity related to the recall of object-location associations that were either encoded in the spatial- or the temporal-associative condition. In addition to brain regions generally involved in recall, we found that activity in higher-order visual regions, including the fusiform gyrus, the lingual gyrus, and the cuneus, was relatively enhanced when subjects used a spatial-associative structure for retrieval. In contrast, activity in the globus pallidus and the thalamus was relatively enhanced when subjects used a temporal-associative structure for retrieval. In conclusion, we provide evidence for differential involvement of these brain regions related to different types of strategic memory retrieval and the neural structures described play a role in either spatial-associative or temporal-associative memory retrieval.

Is fatigue a disease-specific or generic symptom in chronic medical conditions?

OBJECTIVE: Severe fatigue is highly prevalent in various chronic diseases. Disease-specific fatigue models have been developed, but it is possible that fatigue-related factors in these models are similar across diseases. The purpose of the current study was to determine the amount of variance in fatigue severity explained by: (a) the specific disease, (b) factors associated with fatigue across different chronic diseases (transdiagnostic factors), and (c) the interactions between these factors and specific diseases. METHOD: Data from 15 studies that included 1696 patients with common chronic diseases and disorders that cause long-term disabilities were analyzed. Linear regression analysis with the generalized least-squares technique was used to determine fatigue-related factors associated with fatigue severity, that is, demographic variables, health-related symptoms and psychosocial variables. RESULTS: Type of chronic disease explained 11% of the variance noted in fatigue severity. The explained variance increased to 55% when the transdiagnostic factors were added to the model. These factors were female sex, age, motivational and concentration problems, pain, sleep disturbances, physical functioning, reduced activity and lower self-efficacy concerning fatigue. The predicted variance increased to 61% when interaction terms were added. Analysis of the interactions revealed that the relationship between fatigue severity and relevant predictors mainly differed in strength, not in direction. CONCLUSIONS: Fatigue severity can largely be explained by transdiagnostic factors; the associations vary between chronic diseases in strength and significance. This suggests that severely fatigued patients with different chronic diseases can probably benefit from a transdiagnostic fatigue-approach which focuses on individual patient needs rather than a specific disease. (PsycINFO Database Record

Cognitive complaints after mild traumatic brain injury: things are not always what they seem.

OBJECTIVE: To compare nonreferred, emergency department (ED)-admitted mild traumatic brain injury (MTBI) patients with and without self-reported cognitive complaints on (1) demographic variables and injury characteristics; (2) neuropsychological test performance; (3) 12-day self-monitoring of perceived cognitive problems; and (4) emotional distress, physical functioning, and personality. METHODS: (Neuro)psychological assessment was carried out 6 months post-injury in 79 patients out of a cohort of 618 consecutive MTBI patients aged 18-60, who attended the ED of our level I trauma centre. Cognitive complaints were assessed with the Rivermead Postconcussional Symptoms Questionnaire (RPSQ). In addition, patients monitored concentration problems and forgetfulness during 12 consecutive days. RESULTS: Self-reported cognitive complaints were reported by 39% of the patients. These complaints were strongly related to lower educational levels, emotional distress, personality, and poorer physical functioning (especially fatigue) but not to injury characteristics. Severity of self-reported cognitive complaints was neither associated with the patients' daily observations of cognitive problems nor with outcome on a range of neuropsychological tests. CONCLUSION: Self-reported cognitive complaints were more strongly related to premorbid traits and physical and emotional state factors than to actual cognitive impairments. In line with previous work, this suggests that treatment of emotional distress and fatigue may also reduce cognitive complaints. Cognitive outcome assessment of symptomatic MTBI patients should not be restricted to checklist ratings only, but also include a (neuro)psychological screening. In addition, daily monitoring of complaints is a useful method to gather information about the frequency and pattern of cognitive problems in daily life.

Writer's cramp: restoration of striatal D2-binding after successful biofeedback-based sensorimotor training.

INTRODUCTION: Previous studies of writer's cramp have detected cerebral sensorimotor abnormalities in this disorder and, more specifically, a reduced striatal D2-binding as assessed by [(123)I]IBZM SPECT. However, empirical data were lacking about the influence of effective biofeedback-based sensorimotor training on D2 receptor binding. METHODS: To determine whether there is a restoration of D2-binding after successful sensorimotor treatment, pre- and posttreatment SPECTs were compared in five patients with writer's cramp and correlated with improvement in handwriting. RESULTS: After treatment, the clinical and electromyographic picture appeared substantially improved connected with a significant increase in D2-binding to nearly normal levels similar to normative data in age/sex-matched healthy subjects. CONCLUSION: The current study supported the view that writer's cramp results from a plastic adaptation of a rectifiable nigrostriatal dopaminergic system and that effective sensorimotor training leads to increased efficacy of striatal dopaminergic transmission.

Impact of additional extracranial injuries on outcome after mild traumatic brain injury.

Many patients with mild traumatic brain injury (MTBI) concurrently sustain extracranial injuries; however, little is known about the impact of these additional injuries on outcome. We assessed the impact of additional injuries on the severity of postconcussional symptoms (PCS) and functional outcome 6 months post-injury. A questionnaire (including the Rivermead Post-Concussion Questionnaire and SF-36) was sent to consecutive MTBI patients (hospital admission Glasgow Coma Score 13-15; age range 18-60 years) admitted to the emergency department of a level-I trauma center, and, to serve as a baseline for PCS, a control group of minor-injury patients (ankle or wrist distortion). Of the 299 MTBI respondents (response rate 52%), 89 had suffered additional injuries (mean Injury Severity Score [ISS] of 14.5 +/- 7.4). After 6 months, 44% of the patients with additional injuries were still in some form of treatment, compared to 14% of patients with isolated MTBI and 5% of the controls. Compared to patients with isolated injury, MTBI patients with additional injuries had resumed work less frequently and reported more limitations in physical functioning. Overall, they did not report higher levels of PCS, despite somewhat more severe head injury. Regardless of the presence of additional injuries, patients that were still in treatment reported significantly more severe PCS, with highest rates in patients with isolated MTBI. In conclusion, many patients with additional extracranial injuries are still in the process of recovery at 6 months after injury. However, despite more severe impact to the head and inferior functional outcomes, these patients do not report more severe PCS.

Recovery from mild traumatic brain injury: a focus on fatigue.

BACKGROUND: Fatigue is one of the most frequently reported symptoms after Mild Traumatic Brain Injury (MTBI). To date, systematic and comparative studies on fatigue after MTBI are scarce, and knowledge on causal mechanisms is lacking. OBJECTIVES: To determine the severity of fatigue six months after MTBI and its relation to outcome. Furthermore, to test whether injury indices, such as Glasgow Coma Scale scores, are related to higher levels of fatigue. METHODS: Postal questionnaires were sent to a consecutive group of patients with an MTBI and a minor-injury control group, aged 18-60, six months after injury. Fatigue severity was measured with the Checklist Individual Strength. Postconcussional symptoms and limitations in daily functioning were assessed using the Rivermead Post Concussion Questionnaire and the SF-36. RESULTS: A total of 299 out of 618 eligible (response rate 52%) MTBI patients and 287 out of 482 eligible (response rate 60%) minor-injury patients returned the questionnaire. Ninety-five MTBI patients (32%) and 35 control patients (12%) were severely fatigued. Severe fatigue was highly associated with the experience of other symptoms, limitations in physical and social functioning, and fatigue related problems like reduced activity. Of various trauma severity indices, nausea and headache experienced on the ED were significantly related to higher levels of fatigue at six months. CONCLUSIONS: In conclusion, one third of a large sample of MTBI patients experiences severe fatigue six months after injury, and this experience is associated with limitations in daily functioning. Our finding that acute symptoms and mechanism of injury rather than injury severity indices appear to be related to higher levels of fatigue warrants further investigation.

Subjective Memory Ability and Long-Term Forgetting in Patients Referred for Neuropsychological Assessment.

It has been suggested that the memory complaints of patients who are not impaired on formal memory tests may reflect accelerated forgetting. We examined this hypothesis by comparing the 1-week delayed recall and recognition test performance of outpatients who were referred for neuropsychological assessment and who had normal memory performance during standard memory assessment with that of a non-patient control group. Both groups performed equally in verbal learning and delayed recall. However, after 1 week, the patients performed worse than controls on both recall and recognition tests. Although subjective memory ability predicted short-term memory function in patients, it did not predict long-term delayed forgetting rates in either the patients or controls. Thus, long-term delayed recall and recognition intervals provided no additional value to explain poor subjective memory ability in the absence of objective memory deficits.

Neural correlates of the chronic fatigue syndrome--an fMRI study.

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS. We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups. Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error. Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

Accelerated forgetting? An evaluation on the use of long-term forgetting rates in patients with memory problems.

The main focus of this review was to evaluate whether long-term forgetting rates (delayed tests, days, to weeks, after initial learning) are more sensitive measures than standard delayed recall measures to detect memory problems in various patient groups. It has been suggested that accelerated forgetting might be characteristic for epilepsy patients, but little research has been performed in other populations. Here, we identified eleven studies in a wide range of brain injured patient groups, whose long-term forgetting patterns were compared to those of healthy controls. Signs of accelerated forgetting were found in three studies. The results of eight studies showed normal forgetting over time for the patient groups. However, most of the studies used only a recognition procedure, after optimizing initial learning. Based on these results, we recommend the use of a combined recall and recognition procedure to examine accelerated forgetting and we discuss the relevance of standard and optimized learning procedures in clinical practice.

Antecedent adrenaline attenuates the responsiveness to but not the release of counterregulatory hormones during subsequent hypoglycemia.

Hypoglycemia unawareness is thought to be the consequence of recurrent hypoglycemia, yet the underlying mechanism is still incompletely understood. The aim of the present study was to determine the role of antecedent elevated adrenaline in the pathogenesis of hypoglycemia unawareness. Sixteen healthy volunteers (eight of either sex) participated in two experiments, performed in random order and at least 3 wk apart. During the morning, three consecutive doses of 0.04, 0.06, and 0.08 microg.kg(-1).min(-1) of adrenaline or matching placebo (normal saline) were infused for the total duration of 1 h. Three hours later, a hyperinsulinemic (360 pmol.m(-2).min(-1)) two-step hypoglycemic (5.0-3.5-2.5 mmol.liter(-1)) clamp study was performed. During hypoglycemia, hypoglycemic symptoms, counterregulatory hormones, cardiovascular responses, and cognitive function were monitored. Hypoglycemia induced similar responses of autonomic and neuroglycopenic symptoms, counterregulatory hormones, and lengthening in reaction time on the choice reaction time task, irrespective of antecedent infusions. However, prior adrenaline was associated with higher exogenous glucose requirements at hypoglycemic nadir (10.1 +/- 1.3 vs. 7.3 +/- 1.3 micromol.kg(-1).min(-1), P = 0.017), an attenuated hypoglycemia-induced fall in blood pressure (mean arterial pressure, -13 +/- 2 vs. -8 +/- 2 mm Hg, P = 0.006), and preserved cognitive function as assessed by the symbol digit test during hypoglycemia, when compared with prior placebo. We conclude that elevated adrenaline attenuates the responsiveness to, but not the release of counterregulatory hormones during subsequent hypoglycemia. As such, adrenaline's role in the development of hypoglycemia unawareness is limited.