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.

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.

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

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.

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.

Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance?

OBJECTIVE: A subgroup of patients with Chronic Fatigue Syndrome (CFS) has cognitive impairments, reflected by deviant neuropsychological test performance. However, abnormal test scores can also be caused by suboptimal effort. We hypothesized that worse neuropsychological test performance and underperformance were related to each other and to a smaller reduction in fatigue, functional impairments, physical limitations and higher dropout rates following cognitive behavior therapy (CBT) for CFS. METHODS: Data were drawn from a previous trial, in which CFS patients were randomized to two conditions; 1) guided self-instruction and additional CBT (n=84) or 2) waiting period followed by regular CBT for CFS (n=85). Underperformance was assessed using the Amsterdam Short Term Memory Test (<84). To test neuropsychological test performance, the Symbol Digit Modalities Task, a simple reaction time task and a choice reaction time task were used. Interaction effects were determined between underperformance and neuropsychological test performance on therapy outcomes. RESULTS: Underperformance was associated to worse neuropsychological test performance, but there were no significant interaction effects of these two factors by therapy on fatigue severity, functional impairments and physical limitations, but there was a significant main effect of underperformance on functional impairments, physical limitations and dropout rates. CONCLUSION: Underperformance or neuropsychological test performance was not related to the change in fatigue, functional impairments, and physical limitations following CBT for CFS. However, underperforming patients did drop out more often. Therapists should pay attention to beliefs and behavioral or environmental factors that might maintain underperformance and increase the risk of dropout.

Memory worries and self-reported daily forgetfulness: a psychometric evaluation of the Dutch translation of the Multifactorial Memory Questionnaire.

The expression of memory worries and the self-reporting of daily forgetfulness easily spark discussion among sufferers and their family or friends about what is normal or abnormal forgetfulness. One way to investigate whether the reporting of forgetfulness might be excessive is to use a standardized memory questionnaire--for instance, the Multifactorial Memory Questionnaire (MMQ). The MMQ measures worries, daily forgetfulness, and memory strategy use. In this study we present a psychometric evaluation of the Dutch translation of the MMQ and provide normative data to determine the significance of individual differences in subtest scores. In addition, clinical examples are given of the use and interpretation of percentile norms and single-case statistics.

How mild traumatic brain injury may affect declarative memory performance in the post-acute stage.

Memory deficits are among the most frequently reported sequelae of mild traumatic brain injury (MTBI), especially early after injury. To date, these cognitive deficits remain poorly understood, as in most patients the brain is macroscopically intact. To identify the mechanism by which MTBI causes declarative memory impairments, we probed the functionality of the medial temporal lobe (MTL) and the prefrontal cortex (PFC), within 6 weeks after injury in 43 patients from a consecutive cohort, and matched healthy controls. In addition to neuropsychological measures of declarative memory and other cognitive domains, all subjects underwent functional magnetic resonance imaging (fMRI). Behavioral results showed poorer declarative memory performance in patients than controls, and decreasing performance with increasing duration of post-traumatic amnesia (a measure of injury severity). Task performance in the scanner was, as intended by the task and design, similar in patients and controls, and did not relate to injury severity. The task used reliably activated the MTL and PFC. Although we did not find significant differences in brain activity when comparing patients and controls, we revealed, in agreement with our neuropsychological findings, an inverse correlation between MTL activity and injury severity. In contrast, no difference in prefrontal activation was found between patients and controls, nor was there a relation with injury severity. On a behavioral level, injury severity was inversely related to declarative memory performance. In all, these findings suggest that reduced medial temporal functionality may contribute to poorer declarative memory performance in the post-acute stage of MTBI, especially in patients with longer post-traumatic amnesia.

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.

Cognitive function after pre-eclampsia: an explorative study.

BACKGROUND: Pre-eclampsia and eclampsia relate to cerebral damage. Memory and concentration problems are frequently reported after these pregnancy-related vascular complications. We tested the hypothesis that in formerly pre-eclamptic women cognitive functioning is impaired as compared with healthy parous controls. METHODS: Women with a recent history of pre-term pre-eclampsia (PPE; n = 47), term pre-eclampsia (TPE; N = 18), pre-term birth (PBI; n = 32) or an uneventful pregnancy (UPR; n = 72) completed a set of questionnaires, measuring cognitive problems, PTSD, depression, anxiety and fatigue. In addition, in PPE and UPR participants we tested neuropsychological performance. RESULTS: PBI is related to higher levels of post-traumatic distress symptoms, which in turn diminished the neuropsychological test performance of PPE women. Nonetheless, women in the PPE and TPE groups did not report more cognitive problems than women in the PBI and UPR groups, but PPE raised the need for psychosocial cared. CONCLUSIONS: Cognitive complaints are common amongst young mothers. When tested, only those with psychological co-morbidity have neuropsychological impairment.

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.

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.

Cognitive performance after mild traumatic brain injury: the impact of poor effort on test results and its relation to distress, personality and litigation.

PRIMARY OBJECTIVE: To compare consecutive Mild Traumatic Brain Injury (MTBI) patients with and without adequate effort on cognitive performance, litigation status, fatigue, distress and personality. RESEARCH DESIGN: (Neuro)psychological assessment was done 6 months post-injury in 110 patients from a cohort of 618 consecutive MTBI patients aged 18-60, who attended the emergency department of our level I trauma centre. Effort was tested with the Amsterdam Short Term Memory test. MAIN OUTCOME AND RESULTS: Thirty patients (27%) failed the effort test. Poor effort was associated with significantly poorer scores on seven out of eleven measures, covering all tested domains. Poor effort was associated with lower educational level and changes in work status, but not litigation. Furthermore, poor effort was related to high levels of distress, Type-D personality and fatigue. CONCLUSIONS: Even in a sample of non-referred MTBI patients, poor effort was common and was strongly associated with inferior test performance. These findings imply that effort testing should be part of all cognitive assessments, also outside mediolegal settings. Behavioural factors like distress and personality should be considered as potential threats to the validity of neuropsychological testing after MTBI.