Early- vs late-onset subcortical vascular cognitive impairment

Posted on February 8, 2016 by Maurice Preter MD

 

Early- vs late-onset subcortical vascular cognitive impairment

http://tinyurl.com/hyhtq4n

Young Kyoung Jang, MD, Hunki Kwon, MS, Yeo Jin Kim, MD, Na Yeon Jung, MD, Jin SanLee, MD, Juyoun Lee, MD, Juhee Chin, PhD, Kiho Im, PhD, Seun Jeon, PhD, Jong Min Lee, PhD, Joon-Kyoung Seong, PhD, Jeong Hun Kim, MS, Seonwoo Kim, PhD, Yearn Seong Choe, PhD, Kyung-Han Lee, MD, PhD, Sung Tae Kim, MD, PhD, Jae Seung Kim, MD, PhD, Jae Hong Lee, MD, PhD, Duk L. Na, MD, PhD, Sang Won Seo, MD, PhD and Hee Jin Kim, MD

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Correspondence to Dr. Kim: evekhj@gmail.com

Published online before print January 13, 2016, doi: http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002357
Neurology February 9, 2016 vol. 86 no. 6 527-534

ABSTRACT

Objective: To evaluate the differences between early-onset subcortical vascular cognitive impairment (EO-SVCI) and late-onset subcortical vascular cognitive impairment (LO-SVCI) with regard to pathologic burden, structural changes, and cognitive function.

Methods: We prospectively recruited 142 patients from a single referral center. Patients were divided into EO-SVCI (n = 30, age at onset <65 years) and LO-SVCI (n = 112, age at onset ≥65 years) groups. All patients underwent neuropsychological tests, 3T brain MRI, and [11C] Pittsburgh compound B (PiB)–PET. We compared pathologic burden such as small vessel disease and amyloid burden; structural changes such as structural network, cortical thickness, and hippocampal volume; and cognitive function between EO-SVCI and LO-SVCI.

Results: EO-SVCI patients had more lacunes, while LO-SVCI patients had higher PiB standardized uptake value ratios. EO-SVCI patients exhibited more severe structural network disruptions in the frontal area, while LO-SVCI patients exhibited more severe cortical and hippocampal atrophy. Although disease severity did not differ between the 2 groups, frontal-executive dysfunction was more severe in EO-SVCI patients.

Conclusions: EO-SVCI patients showed more vascular related factors, while LO-SVCI patients exhibited more Alzheimer disease–related characteristics. The greater number of lacunes in EO-SVCI might account for the more severe frontal network disruption and frontal-executive dysfunction, while the greater amyloid burden in LO-SVCI might account for the more severe cortical and hippocampal atrophy. Our findings suggest that the age at onset is a crucial factor that determines distinct features in SVCI patients, such as pathologic burden, structural changes, and cognitive function.

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Midlife milk consumption and substantia nigra neuron density at death

Posted on February 8, 2016 by Maurice Preter MD

 

Midlife milk consumption and substantia nigra neuron density at death

http://tinyurl.com/jjwookb

Robert D. Abbott, PhD, G. Webster Ross, MD, Helen Petrovitch, MD, Kamal H. Masaki, MD, Lenore J. Launer, PhD, James S. Nelson, MD, Lon R. White, MD and Caroline M. Tanner, MD, PhD

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Correspondence to Dr. Abbott: rda3e@virginia.edu

Published online before print December 9, 2015, doi: http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002254

Neurology February 9, 2016 vol. 86 no. 6 512-519

ABSTRACT

Objective: To examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study.

Methods: Milk intake data were collected from 1965 to 1968 in 449 men aged 45–68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm2) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s.

Results: Neuron density was lowest in nonsmoking decedents who consumed high amounts of milk (>16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake >16 oz/d vs intake that was less (95% confidence interval 22.7%–55.7%, p < 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent.

Conclusions: Milk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study.

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Accuracy of clinical diagnosis of Parkinson disease

Posted on February 8, 2016 by Maurice Preter MD

Accuracy of clinical diagnosis of Parkinson disease

http://tinyurl.com/jq9aakn

A systematic review and meta-analysis

Giovanni Rizzo, MD, Massimiliano Copetti, PhD, Simona Arcuti, PhD, Davide Martino, MD, Andrea Fontana, MScand Giancarlo Logroscino, MD

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Correspondence to Dr. Logroscino: giancarlo.logroscino@uniba.it

Published online before print January 13, 2016, doi: http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002350 

Neurology February 9, 2016 vol. 86 no. 6 566-576

ABSTRACT

Objective: To evaluate the diagnostic accuracy of clinical diagnosis of Parkinson disease (PD) reported in the last 25 years by a systematic review and meta-analysis.

Methods: We searched for articles published between 1988 and August 2014. Studies were included if reporting diagnostic parameters regarding clinical diagnosis of PD or crude data. The selected studies were subclassified based on different study setting, type of test diagnosis, and gold standard. Bayesian meta-analyses of available data were performed.

Results: We selected 20 studies, including 11 using pathologic examination as gold standard. Considering only these 11 studies, the pooled diagnostic accuracy was 80.6% (95% credible interval [CrI] 75.2%–85.3%). Accuracy was 73.8% (95% CrI 67.8%–79.6%) for clinical diagnosis performed mainly by nonexperts. Accuracy of clinical diagnosis performed by movement disorders experts rose from 79.6% (95% CrI 46%–95.1%) of initial assessment to 83.9% (95% CrI 69.7%–92.6%) of refined diagnosis after follow-up. Using UK Parkinson’s Disease Society Brain Bank Research Center criteria, the pooled diagnostic accuracy was 82.7% (95% CrI 62.6%–93%).

Conclusion: The overall validity of clinical diagnosis of PD is not satisfying. The accuracy did not significantly improve in the last 25 years, particularly in the early stages of disease, where response to dopaminergic treatment is less defined and hallmarks of alternative diagnoses such as a typical parkinsonism may not have emerged. Misclassification rate should be considered to calculate the sample size both in observational studies and randomized controlled trials. Imaging and biomarkers are urgently needed to improve the accuracy of clinical diagnosis in vivo.

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Vitamin D3 for uncontrolled childhood asthma: a pilot study

Posted on February 6, 2016 by Maurice Preter MD

 

Vitamin D3 for uncontrolled childhood asthma: a pilot study

htttp://tinyurl.com/jzar3y7

Kerley CP1,2,3, Hutchinson K4, Cormican L3, Faul J3, Greally P1, Coghlan D5, Elnazir B1.
 

Author information

  • 1Paediatric Respiratory Deparment, National Children’s Hospital, Dublin 24, Ireland.
  • 2School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland.
  • 3Asthma Research Centre, Connolly Hospital, Blanchardstown, Dublin 15, Ireland.
  • 4Biomnis Ireland, Sandyford business Estate, 3 Rock Rd, Dublin, Ireland.
  • 5Deparment of Paediatric Medicine, National Children’s Hospital, Dublin 24, Ireland.
 

Abstract

BACKGROUND:

Observational and mechanistic data suggest a role for vitamin D in childhood asthma. However, subsequent interventional trials have been inconsistent. We aimed to assess the effect of 15 weeks of vitamin D3 supplementation compared to placebo in Irish asthmatic children.

METHODS:

We conducted a double-blind, randomized, placebo-controlled trial of vitamin D supplementation (2,000IU/d) in 44 urban, Caucasian children at high latitude. Assessments were completed at baseline and after 15 weeks of supplementation. Outcome measures lung function, subjective asthma control and biochemical parameters of total vitamin D, allergy, immunity, airway inflammation and systemic inflammation. Finally, parents/gaurdians completed a weekly diary during the trial.

RESULTS:

There was no significant difference in baseline 25(OH)D levels but there was a significant increase in median 25(OH)D in the vitamin D3group (57.5 to 105nmol/L) compared to the placebo group (52.5 to 57.5nmol/L) (p <0.0001). There was no significant difference between groups regarding subjective asthma control. Compared to placebo, there was as a significant decrease in school days missed due to asthma (1 vs. 5 days, p = 0.04) and alkaline phosphatase (-3.4 vs. +16; p = 0.037) in the vitamin D3 group but there were no beneficial effects regarding several other secondary endpoints. However, there were non-significant, advantageous changes in the placebo group compared to the vitamin D3 group in subjective asthma control and lung function, particularly percentage of predicted forced expiratory volume in 1 second (+2.5 vs. -4; p = 0.06).

CONCLUSION:

Vitamin D3 supplementation led to a significant increase in serum 25(OH)D and decreased school days missed (p = 0.04) but no other advantageous changes in asthma parameters compared to placebo. The potential adverse effect of vitamin D deficiency on growth and the potential negative effect of high serum 25(OH)D on pulmonary function warrant further investigation. This article is protected by copyright. All rights reserved.

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CCBYNC Open access Research Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

Posted on February 6, 2016 by Maurice Preter MD

CCBYNC Open access Research Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

http://tinyurl.com/hmgdrmx

  1. arang Sharma, PhD student1 2,
  2. Louise Schow Guski, medical student1 2,
  3. Nanna Freund, medical student1 2,
  4. Peter C Gøtzsche, professor1 2

Author affiliations

  1. Correspondence to: T Sharma Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, Department 7811, 2100 Ø Copenhagen, Denmark ts@cochrane.dk
  • Accepted 3 December 2015

Abstract

Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.

Design Systematic review and meta-analysis.

Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.

Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website.

Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms.

Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model).

Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.

Conclusions Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.

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