Per Hellström

The Goteborg MCI study: mild cognitive impairment is a heterogeneous condition

Background: Mild cognitive impairment (MCI) has been considered a transitional state between normal aging and dementia, characterised by memory impairment but normal general cognitive functioning. Recently other cognitive deficits have been reported. This has led to a modification of MCI criteria. Objective: To examine which neuropsychological tests most clearly distinguish MCI subjects from normal controls. Methods: 112 consecutive MCI subjects and 35 controls were included in the study. The diagnosis of MCI was based on an objective history of cognitive decline and a neuropsychiatric examination, comprising instruments STEP, I-Flex, MMSE, and CDR. Participants were examined with 21 neuropsychological tests in the cognitive domains speed/attention, memory and learning, visuospatial function, language, and executive function. Results: Controls were significantly older. No differences were found in education or general intellectual capacity. Controls performed significantly better than MCI on tests within all five cognitive domains. The clearest differences were seen on language tests, followed by executive function, and learning and memory. Only two subjects (1.8%) were purely amnestic; 17% showed no impairment compared with controls, with a cut off of 1.5 SD below age mean. These subjects were better educated and performed significantly better on measures of general cognitive capacity. Conclusions: The results illustrate the heterogeneity of MCI, with a significant degree of impairment in all five cognitive domains. When examined with a comprehensive neuropsychological battery, very few subjects had an isolated memory impairment.

The European iNPH Multicentre Study on the predictive values of resistance to CSF outflow and the CSF Tap Test in patients with idiopathic normal pressure hydrocephalus

Objective The objective was to determine the sensitivity, specificity, and positive and negative predictive values of the CSF Tap Test (CSF TT) and resistance to CSF outflow (Rout) for the outcome of shunting in a sample of patients with idiopathic normal pressure hydrocephalus (iNPH). Methods 115 patients were included in this European multicentre study. Diagnosis was based on clinical symptoms and signs, and MRI changes. All patients were treated with programmable ventriculoperitoneal shunts and re-examined 12 months after surgery. Outcomes were measures with a newly developed iNPH Scale and the modified Rankin Scale (mRS). Before surgery, a CSF TT and measurement of Rout was performed, with the results blinded to all caregivers. The 12 month outcome was correlated with Rout and the result of the CSF TT. Results Rout and the results of the CSF TT showed no correlation with outcome measured by either domain, or with total iNPH score or mRS score. Only an increase in the gait task (10 m of walking at free speed) of the CSF TT correlated significantly (r=0.22, p=0.02) with improvement in iNPH score. The positive predictive value of both tests was >90% and the negative predictive value <20%. Rout >12 had an overall accuracy of 65% and the CSF TT 53%. Combining both tests did not improve their predictive power. No correlation was found between Rout and the results of the CSF TT. Conclusions Rout and the results of the CSF TT did not correlate with outcome after 12 months. Rout and CSF TT can be used for selecting patients for shunt surgery but not for excluding patients from treatment. Trial registration The study has been registered at clinicaltrials.gov, identifier NCT00874198.

Natural course of idiopathic normal pressure hydrocephalus

Objectives The natural course of idiopathic normal pressure hydrocephalus (iNPH) has not been thoroughly studied. The consequences of postponing shunt treatment are largely unknown. We aimed to describe the effects of waiting for more than 6 months before surgery and to compare the outcome with that seen in patients who waited for less than 3 months. Methods 33 patients (iNPHDelayed) underwent an initial investigation (Pre-op 1), followed by re-examination, just prior to surgery, after waiting for at least 6 months (Pre-op 2). Outcome was evaluated after 3 months of treatment. 69 patients who were surgically treated within 3 months after Pre-op 1 and who were also evaluated after 3 months of treatment constituted a comparison group (iNPHEarly). Evaluations were done with the iNPH scale and the modified Rankin Scale (mRS). iNPHDelayed patients were prospectively studied with regard to outcome, whereas the comparison group iNPHEarly was defined and analysed retrospectively. Results iNPHDelayed patients deteriorated significantly during their wait for surgery, with progression of symptom severity ranging from +7 to −47 on the iNPH scale, and from 0 to +3 on the mRS (both p<0.001). The magnitude of change after surgery was similar in the groups, but since the symptoms of iNPHDelayed patients had worsened while waiting, their final outcome was significantly poorer. Conclusions The natural course of iNPH is symptom progression over time, with worsening in gait, balance and cognitive symptoms. This deterioration is only partially reversible. To maximise the benefits of shunt treatment, surgery should be performed soon after diagnosis.

THE NEUROPSYCHOLOGY OF PATIENTS WITH CLINICALLY DIAGNOSED IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS

OBJECTIVETo compare the neuropsychological performance of patients with idiopathic normal pressure hydrocephalus (INPH) with that of healthy individuals and to examine its relation to neurological signs, vascular comorbidity, and background factors. METHODSA consecutive series of 58 patients with INPH underwent neurological, neuroradiological, and neuropsychological examinations. The neuropsychological tests, measuring vigilance, fine movements of the hands, learning, working memory, and aspects of executive functioning, were also administered to 108 healthy individuals. RESULTSPatients performed worse than healthy individuals on all included tests. Significant correlations between test results were more frequent and stronger among patients and the degree of neuropsychological impairment was related to the severity of other signs of INPH. Patients with vascular risk factors performed worse than those without. CONCLUSIONThe neuropsychological deficits in INPH are widely distributed, interrelated, associated with neurological signs, and aggravated by vascular comorbidity.

A new scale for assessment of severity and outcome in iNPH

To present a new, continuous, calibrated and norm‐based scale for the grading of severity and assessment of treatment outcome in idiopathic normal pressure hydrocephalus (iNPH).

NEUROPSYCHOLOGICAL EFFECTS OF SHUNT TREATMENT IN IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS

OBJECTIVETo prospectively evaluate the effects of shunting on the neuropsychological performance of patients with idiopathic normal pressure hydrocephalus (INPH), to compare their performance with that of healthy individuals, and to estimate the predictive utility of putatively important factors. METHODSA consecutive series of 47 patients with INPH underwent neurological, radiological, and neuropsychological examinations before and 3 months after shunt surgery. The same neuropsychological tests, measuring simple and target reaction times, dexterity, memory and learning, working memory, and aspects of executive functioning, were also administered to 159 healthy individuals. RESULTSPerformance on all neuropsychological tests, except Simple Reaction Time and Digit Span, significantly improved after surgery, with more severe functional deficits showing greatest improvement. Age, education, duration, vascular comorbidity, sex, and onset symptom all failed to predict the neuropsychological effects of treatment. Despite improvement 3 months after shunt surgery, INPH patients were still outperformed by healthy individuals. CONCLUSIONMost of the wide range of neuropsychological functions that are affected by INPH are markedly improved by shunt treatment, but not completely restored.

Impaired wakefulness is associated with reduced anterior cingulate CBF in patients with normal pressure hydrocephalus.

Objective – To evaluate if impaired wakefulness (IW) in normal pressure hydrocephalus (NPH) is associated with reduced blood flow in regions associated with the brain arousal system.

Shunt surgery in patients with hydrocephalus and white matter changes.

OBJECT Patients with idiopathic normal pressure hydrocephalus (iNPH) often present with impaired gait and cognition together with ventricular enlargement and normal intracranial pressure. Many have vascular risk factors as well as periventricular and deep white matter changes on MR imaging. Abnormal CSF dynamics, that is, high resistance to outflow or improvement after CSF drainage, indicate good effects of shunt surgery. The authors examined whether the worst-case iNPH patients with extensive vascular white matter disease and normal CSF dynamics would benefit from shunt surgery. These patients also fulfilled the criteria for Binswanger disease. Therefore, a randomized controlled double-blind study was performed. METHODS Fourteen consecutive patients fulfilling the above criteria were randomized to receive either open or closed shunts. At 3 months after surgery, the patients with initially ligated shunts had their shunts opened. Clinical evaluation consisting of 7 quantitative psychometric and 6 continuous gait tests was performed preoperatively and 3 and 6 months after surgery. RESULTS Patients randomized to receive open shunts had improved motor (30% increase) and psychometric (23% increase) scores 3 months after shunt placement. There were no significant changes between the 3- and 6-month follow-up in these same patients. Conversely, those with initially ligated shunts were unchanged during the first 3-month period, although they improved in both motor (28%) and cognitive (18%) functions following removal of the ligature. CONCLUSIONS Patients with enlarged ventricles, hydrocephalic symptoms, and extensive vascular white matter changes benefit from shunt surgery.

Facial emotion recognition in myotonic dystrophy type 1 correlates with CTG repeat expansion

Objective: To investigate the ability of patients with myotonic dystrophy type 1 to recognise basic facial emotions. We also explored the relationship between facial emotion recognition, neuropsychological data, personality, and CTG repeat expansion data in the DM-1 group. Methods: In total, 50 patients with DM-1 (28 women and 22 men) participated, with 41 healthy controls. Recognition of facial emotional expressions was assessed using photographs of basic emotions. A set of tests measured cognition and personality dimensions, and CTG repeat size was quantified in blood lymphocytes. Results: Patients with DM-1 showed impaired recognition of facial emotions compared with controls. A significant negative correlation was found between total score of emotion recognition in a forced choice task and CTG repeat size. Furthermore, specific cognitive functions (vocabulary, visuospatial construction ability, and speed) and personality dimensions (reward dependence and cooperativeness) correlated with scores on the forced choice emotion recognition task. Conclusion: These findings revealed a CTG repeat dependent facial emotion recognition deficit in the DM-1 group, which was associated with specific neuropsychological functions. Furthermore, a correlation was found between facial emotional recognition ability and personality dimensions associated with sociability. This adds a new clinically relevant dimension in the cognitive deficits associated with DM-1.

The neuropsychology of iNPH: Findings and evaluation of tests in the European multicentre study

OBJECTIVE Neuropsychological dysfunction is common in patients with idiopathic normal pressure hydrocephalus (iNPH). Shunt treatment is beneficial, some patients reaching complete or almost complete recovery, while others show only minor improvement. We aimed to assess the efficacy of a small selection of well characterized and sensitive neuropsychological tests in the context of the European multicentre study on iNPH (Eu-INPH). METHODS One hundred and forty-two iNPH patients included in Eu-iNPH were tested with the Rey Auditory Verbal Learning Test (RAVLT), the Grooved Pegboard and the Stroop test before and after three and twelve months of treatment with a ventriculoperitoneal shunt. Their performance was compared to that of 108 healthy individuals (HI). RESULTS INPH patients performed significantly worse than HI on all of the neuropsychological measures at entry. The discriminative capacities of the eight variables were similar, with areas under the curve (AUC; ROC analysis) ranging between .86 (Delayed Recall) and .95 (Grooved Pegboard). The most usable test was RAVLT (Learning and Delayed Recall), administered to ≥90% of the patients at all occasions. However, the Grooved Pegboard and the Stroop test were more sensitive to treatment effects. CONCLUSION The three neuropsychological tests used in the Eu-iNPH are expedient, highly diagnostically discriminative, and well suited to evaluate changes following shunt treatment.