cover image European Journal of Neurology

European Journal of Neurology

2018 - Volume 25
Issue 4 | April 2018
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Original Article

Background and purpose

Detection of occult atrial fibrillation (AF) is crucial for optimal secondary prevention in stroke patients. The AF detection rate was determined by implantable cardiac monitor (ICM) and compared to the prediction rate of the probability of incident AF by software based analysis of a continuously monitored electrocardiogram at follow‐up (stroke risk analysis, SRA); an optimized AF detection algorithm is proposed by combining both tools.

Methods

In a monocentric prospective study 105 out of 389 patients with cryptogenic stroke despite extensive diagnostic workup were investigated with two additional cardiac monitoring tools: (a) 20 months’ monitoring by ICM and (b) SRA during hospitalization at the stroke unit.

Results

The detection rate of occult AF was 18% by ICM ( = 19) (range 6–575 days) and 62% ( = 65) had an increased risk for AF predicted by SRA. When comparing the predictive accuracy of SRA to ICM, the sensitivity was 95%, specificity 35%, positive predictive value 27% and negative predictive value 96%. In 18 patients with AF detected by ICM, SRA also showed a medium risk for AF. Only one patient with a very low risk predicted by SRA developed AF revealed by ICM after 417 days.

Conclusions

A combination of SRA and ICM is a promising strategy to detect occult AF. SRA is reliable in predicting incident AF with a high negative predictive value. Thus, SRA may serve as a cost‐effective pre‐selection tool identifying patients at risk for AF who may benefit from further cardiac monitoring by ICM.

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Authors:
F. Reinke, M. Bettin, L. S. Ross, S. Kochhäuser, I. Kleffner, M. Ritter, J. Minnerup, D. Dechering, L. Eckardt and R. Dittrich
Article first published online:
13 Feb 2018 | DOI: 10.1111/ene.13538

Original Article

Background and purpose

The aim of this study was to address the vascular depression hypothesis in Parkinson's disease (PD) from a large cohort of Chinese population.

Methods

A cross‐sectional analysis of 1784 Chinese patients with PD was conducted. Patients were divided into absence of depression (score ≤ 20) and presence of depression (score > 20) based on assessment of the Hamilton Depression Rating Scale. Other clinical assessments included the Unified PD Rating Scale (UPDRS), the Hamilton Anxiety Rating Scale, the frontal assessment battery (FAB) and the Montreal Cognitive Assessment (MoCA).

Results

Patients with depression showed a higher proportion of women, longer disease duration, higher UPDRS part III score, higher levodopa equivalent daily dose use, higher occurrences of motor fluctuation and dyskinesia, lower FAB score and lower MoCA score than those without depression ( < 0.05). The proportions of drinking and overweight/obesity in the depression group were significantly lower than those in the non‐depression group ( < 0.05). A forward binary logistic regression model indicated that depression in PD was associated with female sex [odds ratio (OR) 1.376, = 0.025], higher UPDRS part III score (OR 1.042, < 0.001), lower FAB score (OR 0.937, = 0.015), anxiety (OR 18.156, < 0.001) and overweight/obesity (OR 0.700, = 0.019), whereas no associations were found with hypertension, diabetes, smoking, drinking, hyperlipidaemia and heart disease.

Conclusions

Our study failed to verify the vascular depression hypothesis in PD. On the contrary, it was demonstrated that overweight/obesity is negatively associated with the presence of depression in PD.

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Authors:
R. Ou, Q. Wei, Y. Hou, X. Yuan, W. Song, B. Cao, H. Liu, L. Zhang, Y. Chen and H. Shang
Article first published online:
16 Feb 2018 | DOI: 10.1111/ene.13551

Original Article

Background and purpose

Zika virus (ZIKV) infection has been associated with an increased incidence of Guillain−Barré syndrome (GBS) but the relative frequency of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and axonal GBS subtypes is controversial.

Methods

Twenty GBS patients diagnosed according to the Brighton criteria during the ZIKV outbreak in Cúcuta, Colombia, were evaluated clinically and electrophysiologically. The electrodiagnosis of GBS subtypes was made according to a recently described criteria set that demonstrated a high diagnostic accuracy on the basis of a single test. The electrophysiological features of 34 Italian AIDP patients were used as control.

Results

All patients had symptoms compatible with ZIKV infection before the onset of GBS and ZIKV infection was laboratory confirmed through a plaque reduction neutralization test (PRNT) in 100% of patients. The median time from onset of ZIKV infection symptoms to GBS was 5 days (interquartile range 1–6 days). Cranial nerve palsy was present in 85% of patients (facial palsy in 75%, bulbar nerve involvement in 60%), autonomic dysfunction in 85%, and 50% of patients required invasive mechanical ventilation. AIDP was diagnosed in 70% of patients. 40% of nerves of AIDP patients showed a prevalent distal demyelinating involvement but this pattern was not different from the Italian AIDP patients without ZIKV infection.

Conclusions

Guillain−Barré syndrome associated with ZIKV infection in Cúcuta is characterized by a high frequency of cranial nerve involvement, autonomic dysfunction and requirement of mechanical ventilation indicating an aggressive and severe course. AIDP is the most frequent electrophysiological subtype. Demyelination is prevalent distally but this pattern is not specific for ZIKV infection.

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Authors:
A. Uncini, D. C. González‐Bravo, Y. Y. Acosta‐Ampudia, E. C. Ojeda, Y. Rodríguez, D. M. Monsalve, C. Ramírez‐Santana, D. A. Vega, D. Paipilla, L. Torres, N. Molano‐González, J. E. Osorio and J.‐M. Anaya
Article first published online:
06 Feb 2018 | DOI: 10.1111/ene.13552

CME Article

Background and purpose

Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis.

Methods

Sixty‐eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid‐specific oligoclonal IgM bands (LS‐OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored.

Results

The mean time of follow‐up of our series was 46.4 months. Twenty‐five patients (36.7%) developed CDMS during follow‐up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5,  = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3,  = 0.003) and LS‐OCMBs were associated with a shorter time to CDMS (HR = 116.6,  < 0.001).

Conclusions

Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS‐OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions.

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Authors:
A. Tejeda‐Velarde, L. Costa‐Frossard, S. Sainz de la Maza, Á. Carrasco, M. Espiño, C. Picón, I. Toboso, P. E. Walo, D. Lourido, A. Muriel, J. C. Álvarez‐Cermeño and L. M. Villar
Article first published online:
06 Feb 2018 | DOI: 10.1111/ene.13553

Original Article

Background and purpose

Sensory neuronopathy is a cardinal feature of cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS). Having observed that two patients with CANVAS had small median and ulnar nerves on ultrasound, we set out to examine this finding systematically in a cohort of patients with CANVAS, and compare them with both healthy controls and a cohort of patients with axonal neuropathy. We have previously reported preliminary findings in seven of these patients with CANVAS and seven healthy controls.

Methods

We compared the ultrasound cross‐sectional area of median, ulnar, sural and tibial nerves of 14 patients with CANVAS with 14 healthy controls and 14 age‐ and gender‐matched patients with acquired primarily axonal neuropathy. We also compared the individual nerve cross‐sectional areas of patients with CANVAS and neuropathy with the reference values of our laboratory control population.

Results

The nerve cross‐sectional area of patients with CANVAS was smaller than that of both the healthy controls and the neuropathy controls, with highly significant differences at most sites ( < 0.001). Conversely, the nerve cross‐sectional areas in the upper limb were larger in neuropathy controls than healthy controls ( < 0.05). On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one patient with CANVAS.

Discussion

Small nerves in CANVAS probably reflect nerve thinning from loss of axons due to ganglion cell loss. This is distinct from the ultrasound findings in axonal neuropathy, in which nerve size was either normal or enlarged. Our findings indicate a diagnostic role for ultrasound in CANVAS sensory neuronopathy and in differentiating neuronopathy from neuropathy.

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Authors:
L. Pelosi, E. Mulroy, R. Leadbetter, D. Kilfoyle, A. M. Chancellor, S. Mossman, L. Wing, T. Y. Wu and R. H. Roxburgh
Article first published online:
26 Feb 2018 | DOI: 10.1111/ene.13563

Original Article

Background and purpose

Genetic research in multiple sclerosis (MS) mostly compares patients with MS with healthy controls, but does not differentiate between MS disease courses. We compared peripheral blood gene expression patterns between extremes of MS phenotypes, i.e. patients with mild relapsing‐remitting MS (mRRMS) and primary progressive MS (PPMS).

Methods

We analyzed global gene expression profiles of peripheral blood samples of age‐ and gender‐matched patients with mRRMS and PPMS. Detailed bioinformatic and gene set enrichment analysis, pathway and principle component analyses were used to identify differentially expressed genes and pathways.

Results

A total of 84 genes were significantly deregulated between the groups. Of those, 19 had been previously reported to be deregulated in patients with MS as compared with healthy controls, including major histocompatibility complex, interferon receptor 2 and interleukin 6 receptor. Detailed molecular pathway analysis revealed significant up‐regulation of antigen processing and presentation, leukocyte transendothelial migration, nucleotide‐binding oligomerization domain‐like receptor signaling, chemokine signaling and down‐regulation of RNA transport, spliceosome and aminoacyl‐tRNA biosynthesis pathways in PPMS compared with mRRMS.

Conclusion

Our analyses show significant differences between mRRMS and PPMS gene expression. Surprisingly, the differentially expressed genes were mostly involved in immunological and inflammatory pathways, suggesting that the difference in MS phenotypes is caused primarily by a difference in immune responses. It should be kept in mind that our analyses were in peripheral blood only, and that the observed differences in inflammatory pathways may be a substrate of the analysed tissue. Further research into gene expression differences between disease courses including analyses in central nervous system tissue is warranted.

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Authors:
M. W. Koch, Y. Ilnytskyy, A. Golubov, L. M. Metz, V. W. Yong and O. Kovalchuk
Article first published online:
13 Feb 2018 | DOI: 10.1111/ene.13565

Letter to the Editor

IgLON5 antibodies are infrequent in patients with isolated sleep apnea

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Authors:
K. Hasselbacher, A. Steffen, K.‐P. Wandinger and N. Brüggemann
Article first published online:
25 Mar 2018 | DOI: 10.1111/ene.13566

Original Article

Background and purpose

The aim was to study the effects of rasagiline on sleep quality in patients with Parkinson's disease (PD) with sleep disturbances. Sleep disorders are common in PD. Rasagiline is widely used in patients with PD, but double‐blind polysomnographic trials on its effects on sleep disturbances are missing.

Methods

This was a single‐center, double‐blind, baseline‐controlled investigator‐initiated clinical trial of rasagiline (1 mg/day) over 8 weeks in patients with PD with sleep disturbances. Blinding was achieved by running a strategic matched placebo parallel group. Co‐primary outcome measures were the changes between baseline and end of the treatment period in sleep maintenance/efficiency as assessed by polysomnography and the Parkinson's Disease Sleep Scale Version 2 (PDSS‐2) score.

Results

A total of 20 of 30 patients were randomized to rasagiline (mean ± SD age, 69.9 ± 6.9 years; 10 male; Hoehn–Yahr stage, 1.9 ± 0.8). Compared with baseline, sleep maintenance was significantly increased at the end of the treatment period (relative change normalized to baseline, +16.3 ± 27.9%; = 0.024, paired two‐sided ‐test) and a positive trend for sleep efficiency was detected (+12.1 ± 28.6%; = 0.097). Treatment with rasagiline led to significantly decreased wake time after sleep onset, number of arousals, percentage of light sleep and improved daytime sleepiness as measured by the Epworth Sleepiness Scale. We did not observe changes in the co‐primary endpoint PDSS‐2 score, and no correlations of polysomnographic sleep parameters or PDSS‐2 score with motor function (Unified Parkinson's Disease Rating Scale motor score). Rasagiline was well tolerated with no unexpected adverse events.

Conclusions

In patients with PD with sleep disturbances, rasagiline showed beneficial effects on sleep quality as measured by polysomnography. These effects were probably not related to motor improvement or translated into improved overall sleep quality perception by patients.

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Authors:
W. Schrempf, M. Fauser, M. Wienecke, S. Brown, A. Maaß, C. Ossig, K. Otto, M. D. Brandt, M. Löhle, U. Schwanebeck, X. Graehlert, H. Reichmann and A. Storch
Article first published online:
27 Feb 2018 | DOI: 10.1111/ene.13567

Original Article

Background and purpose

The purpose of this study was to determine whether switching from branded levetiracetam (Keppra) to a levetiracetam generic equivalent product (Matever) in an epilepsy cohort could provide adequate results in terms of seizure control and tolerability.

Methods

To be eligible for the study, patients had to have been taking Keppra as monotherapy or polytherapy for at least 6 months. Between March 2013 and April 2017, patients were invited to switch to Matever as part of their follow‐up. We evaluated the number of seizures per month, drug‐related adverse events and electroencephalography before the switch (T0, baseline) and 6 months after switching (T1). Furthermore, we reported the long‐term follow‐up of patients who continued to use Matever after the end of the study, considering the most recent visit for each patient (T2).

Results

A total of 55 patients refused the switch. Among the remaining 125 patients, 59 (47%) were treated using Keppra as monotherapy and 66 (53%) were on Keppra as polytherapy. All 125 patients were subjected to switching from Keppra to Matever. Comparing patients before (T0) and after (T1) switching, we found no statistically significant differences in terms of seizure frequency and occurrence of adverse effects. There were no significant differences (number of seizures/month and drug‐related adverse events) between patients treated with Matever as monotherapy and patients who refused the switch and continued to use Keppra as monotherapy for a long‐term follow‐up of 48 months. Electroencephalography findings were also unchanged.

Conclusion

In our sample, brand‐to‐generic levetiracetam switching was effective and safe in both monotherapy and polytherapy regardless of the epilepsy syndrome.

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Authors:
M. Trimboli, E. Russo, L. Mumoli, G. Tripepi, F. Fortunato, G. Mastroianni, F. Abate, G. De Sarro, A. Gambardella and A. Labate
Article first published online:
01 Feb 2018 | DOI: 10.1111/ene.13568

Letter to the Editor

Unilateral pain and shorter duration of chronic migraine are significant predictors of response to onabotulinumtoxin A

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Authors:
C. Domínguez, P. Pozo‐Rosich, Y. Leira and R. Leira
Article first published online:
25 Mar 2018 | DOI: 10.1111/ene.13570

Short Communication

Background and purpose

Multiple sclerosis (MS) is most frequent in Caucasian populations. However, studies of MS in other ethnic groups may offer unique insights into genetic and environmental influences on the disease, and data on long‐term outcomes in these patients is limited. In this work clinical features and time to disability milestones were investigated in ethnic minority (EM) patients with MS in a UK population and comparisons were made to a Caucasian cohort from the same region.

Methods

In all, 1949 MS patients (1866 Caucasian, 83 EM) were identified from a regional disease registry. Cox proportional hazards regression was used to analyse the time to Expanded Disability Status Scale (EDSS) 3.0, 4.0 and 6.0.

Results

Ethnic minority patients were younger at disease onset (28.6 years vs. 32.8 years,  = 0.001), and primary progressive MS was less common (EM 4.8%, Caucasian 11.6%,  = 0.03). After correction for clinical variables, ethnicity was associated with time to EDSS 3.0 [EM: hazard ratio (HR) 1.75,  < 0.0001] and 4.0 (HR 1.46,  = 0.03), but not 6.0 (HR 1.5,  = 0.05).

Conclusions

Ethnic minority patients reach early levels of fixed disability more rapidly than Caucasian patients, but this effect diminishes at later stages of the disease. This has implications for clinical management of these patients.

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Authors:
M. O. Alsaeed, K. E. Harding, O. H. Williams, M. D. Willis, J. Hrastelj, E. C. Tallantyre, F. G. Joseph, M. Wardle, T. P. Pickersgill and N. P. Robertson
Article first published online:
16 Feb 2018 | DOI: 10.1111/ene.13571

Review Article

Abstract

Some research suggests that 40% of people in the vegetative state are misdiagnosed. This review investigates the frequency, nature and causes of reported misdiagnosis of patients in the vegetative state, focusing on the nature of the error. It is a systematic review of all relevant literature, using references from key papers identified. The data are summarized in tables. Five clinical studies of the rate of misdiagnosis in practice were identified, encompassing 236 patients in the vegetative state of whom 80 (34%) were reclassified as having some awareness, often minimal. The studies often included patients in the recovery phase after acute injury, and were poorly reported. Five systematic reviews of signs and technologically based neurophysiological tests were identified, and they showed that most studies were small, lacked accurate or important details, and were subject to bias. Studies were not replicated. Many signs and tests did not differ between people in the vegetative state and in the minimally conscious state, and those that did were unable to diagnose an individual patient. The few single case reports suggest that failure to ensure an accurate diagnosis of the underlying neurological damage and dysfunction could, rarely, lead to significant misdiagnosis usually in patients who had brain‐stem damage with little thalamic or cortical damage. Significant misdiagnosis of awareness, with an apparently ‘vegetative’ patient having good awareness, is rare. Careful neurological assessment of the cause and routine measurement of awareness using the Coma Recovery Scale − Revised should further reduce mistakes.

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Authors:
D. T. Wade
Article first published online:
16 Feb 2018 | DOI: 10.1111/ene.13572

Original Article

Background and purpose

The aim was to investigate the diagnostic utility of signal intensity measurement of the substantia nigra pars compacta (SNc) using three‐dimensional (3D) neuromelanin‐sensitive magnetic resonance imaging (MRI), for discrimination of patients with Parkinson's disease (PD) from healthy controls.

Methods

T1‐weighted neuromelanin‐sensitive images of 16 patients with PD and 15 controls were quantitatively analyzed by placing circular 10 mm regions of interest over the central and lateral parts of the bilateral SNc and anterior to the cerebral aqueduct at three levels of the midbrain. Signal intensities and contrast ratios (CRs) were calculated, after which significant differences, correlations, sensitivity and specificity were calculated.

Results

The CRs of the central and lateral SNc were significantly lower in patients with PD. Lateral CRs were lower than the central CRs in both groups and significantly correlated with duration of illness. CRs of central and lateral parts of the SNc also correlated with the Unified Parkinson's Disease Rating Scale III OFF state scores. Receiver operating characteristic analysis revealed lateral CRs to be more sensitive and central CRs to be more specific for the discrimination of patients with PD from controls.

Conclusions

Contrast ratio analysis of the SNc using 3D neuromelanin‐sensitive MRI may serve as a quick and accurate tool to discern between patients with PD and healthy controls.

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Authors:
S. Prasad, A. Stezin, A. Lenka, L. George, J. Saini, R. Yadav and P. K. Pal
Article first published online:
08 Feb 2018 | DOI: 10.1111/ene.13573

Editorial

Abstract

Click to view the accompanying paper in this volume.

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Authors:
V. M. Rivera
Article first published online:
07 Feb 2018 | DOI: 10.1111/ene.13574

Original Article

Background and purpose

Neutrophils, a pivotal immune responder to ischaemic brain insult, have been involved in neuroplasticity and increase after stroke. Recombinant tissue plasminogen activator (r‐tPA), a promising treatment improving neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile of neutrophils after r‐tPA treatment and their effect on neurological recovery after stroke are not well studied.

Methods

Cell counts of neutrophils, lymphocytes and their ratio (NLR) were measured on admission and 24 h after r‐tPA infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age 64 years). Death or major disability at 3 months after stroke was diagnosed based on the modified Rankin Scale (mRS ≥ 3) obtained by neurologists who were blinded to any hospital records. The longitudinal associations of percentage increase in neutrophils, lymphocytes and the NLR with death or major disability were examined by logistic regression adjusting for covariates including neurological deficits at baseline.

Results

Neutrophils exhibited a steeper increase after r‐tPA infusion in patients with death or major disability than in those without ( < 0.001). A 10% increase in neutrophils after r‐tPA infusion was associated with an 83% increased risk for death or major disability within 3 months after stroke onset [odds ratio (OR) 1.99, = 0.009]. Increased neutrophils at 24 h after r‐tPA (OR 6.30, < 0.001 after log transformation) but not on admission significantly predicted increased risks for death or major disability within 3 months after stroke onset. A similar phenomenon was also observed for the NLR.

Conclusions

A dynamic increase in neutrophils after stroke significantly predicts 3‐month death or major disability in acute ischaemic stroke patients receiving r‐tPA treatment.

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Authors:
J. Shi, H. Peng, S. You, Y. Liu, J. Xu, Y. Xu, H. Liu, R. Shi, Y. Cao and C.‐F. Liu
Article first published online:
08 Feb 2018 | DOI: 10.1111/ene.13575

Editorial

Abstract

Click to view the accompanying paper in this volume.

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Authors:
M. Zedde and R. Pascarella
Article first published online:
01 Mar 2018 | DOI: 10.1111/ene.13576

Original Article

Background and purpose

Although mechanical thrombectomy (MT) appears to be superior in stroke patients with extracranial carotid disease (ECD) compared to thrombolysis alone, the impact of emergent carotid stenting during MT remains unclear. The MT outcomes were assessed in anterior stroke patients with ECD, especially when combined with carotid stenting.

Methods

A retrospective analysis of our registry was performed and an update of a systematic review and meta‐analysis of MT studies with or without stenting for anterior circulation stroke with ECD published between November 2010 and April 2017 was conducted.

Results

In our registry, 46 patients with ECD underwent MT. In the meta‐analysis including 13 primary studies plus our prospective registry data (590 patients in total), the successful reperfusion rate (modified thrombolysis in cerebral infarction score ≥2b) reached 75% [95% confidence interval (CI) 69%–81%]. The rate of symptomatic intracranial haemorrhage (sICH) was 8% (95% CI 6%–11%), 90‐day favourable outcome was achieved in 50% (95% CI 42%–59%) and mortality rate was 16% (95% CI 11%–22%). When using carotid stenting, rates of successful reperfusion, sICH, 90‐day favourable outcome and mortality were 80% (95% CI 73%–87%), 7% (95% CI 4%–12%), 53% (95% CI 43%–62%) and 14% (95% CI 9%–19%), respectively.

Conclusions

Our data report an association between acute stenting and successful reperfusion rates in stroke patients with tandem lesion treated with MT. Further studies are warranted to determine the intracranial bleeding risk after MT and stenting according to the antiplatelet therapy.

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Authors:
U. Sadeh‐Gonik, N. Tau, T. Friehmann, S. Bracard, R. Anxionnat, A.‐L. Derelle, R. Tonnelet, L. Liao, S. Richard, X. Armoiry and B. Gory
Article first published online:
01 Mar 2018 | DOI: 10.1111/ene.13577

Editorial

Abstract

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Authors:
M. Papagianni and K. Tziomalos
Article first published online:
26 Feb 2018 | DOI: 10.1111/ene.13584

Letter to the Editor

Smoking is a cause of ischaemic stroke, not a risk factor!

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Authors:
A. Braillon
Article first published online:
25 Mar 2018 | DOI: 10.1111/ene.13585

Review Article

Background and purpose

There is now a wide consensus at recognizing social and economic circumstances as main determinants of an individual's health status. Nevertheless, characteristics relating to socioeconomic status (SES) are poorly described in research reports. The aim of the present review was to verify whether the SES of participants is adequately reported in interventional studies targeting Alzheimer's disease (AD), and to explore the impact of SES proxy measures on the efficacy of the considered medications.

Methods

A systematic review of available randomized controlled trials (RCTs) on the currently marketed drugs for AD (i.e. cholinesterase inhibitors and memantine) was conducted by performing a structured search on PubMed and the Cochrane databases. The following indicators of SES were considered in the retained studies: (i) educational level, (ii) lifetime job category, (iii) income and (iv) wealth. The study quality was assessed using the Cochrane Risk of Bias Tool for Randomized Controlled Trials.

Results

A total of 48 articles were finally selected. Overall, only eight RCTs reported data concerning the four considered SES indicators. Indeed, only information pertaining to the educational level of participants was provided. Only one RCT ( = 60) performed , secondary analyses accounting for the SES of participating subjects.

Conclusions

The research and clinical relevance of SES has mistakenly been overlooked by the vast majority of RCTs on AD. A greater effort should be made to collect and report data on those SES indicators that may significantly affect the clinical manifestations and trajectories of patients with cognitive disturbances.

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Authors:
M. Canevelli, G. Bruno, C. Vico, V. Zaccaria, E. Lacorte, I. Iavicoli, N. Vanacore and M. Cesari
Article first published online:
26 Feb 2018 | DOI: 10.1111/ene.13587

Editorial

Abstract

Click to view the accompanying paper in this volume.

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Authors:
M. Al‐Khaled
Article first published online:
27 Feb 2018 | DOI: 10.1111/ene.13588

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Article first published online:
25 Mar 2018 | DOI: 10.1111/ene.13609