Can MRI screen for CSF biomarkers in neurodegenerative disease?

Imaging advances are always potentially interesting but the immediate risk might be more dementia diagnoses delivered without much regard to functional context, and without proper support and follow-up.

Can MRI screen for CSF biomarkers in neurodegenerative disease?

  1. Corey T. McMillan, PhD,
  2. Brian Avants, PhD,
  3. David J. Irwin, MD,
  4. Jon B. Toledo, MD,
  5. David A. Wolk, MD,
  6. Vivianna M. Van Deerlin, MD, PhD,
  7. Leslie M. Shaw, PhD,
  8. John Q. Trojanoswki, MD, PhD and
  9. Murray Grossman, MD, EdD

+ Author Affiliations


  1. From the Department of Neurology (C.T.M., D.J.I., D.A.W., M.G.), Center for Neurodegenerative Disease Research (D.J.I., J.B.T., V.M.V.D., L.M.S., J.Q.T.), Department of Radiology (B.A.), Penn Memory Center (D.A.W.), and Department of Pathology & Laboratory Medicine (V.M.V.D., L.M.S., J.Q.T.), University of Pennsylvania, Philadelphia.
  1. Correspondence to Dr. McMillan: mcmillac@mail.med.upenn.edu

View Complete Disclosures

Abstract

Objective: Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) may have overlapping clinical presentations despite distinct underlying neuropathologies, thus making in vivo diagnosis challenging. In this study, we evaluate the utility of MRI as a noninvasive screening procedure for the differential diagnosis of AD and FTLD.

Methods: We recruited 185 patients with a clinically diagnosed neurodegenerative disease consistent with AD or FTLD who had a lumbar puncture and a volumetric MRI. A subset of 32 patients had genetic or autopsy-confirmed AD or FTLD. We used singular value decomposition to decompose MRI volumes and linear regression and cross-validation to predict CSF total tau (tt) and β-amyloid (Aβ1-42) ratio (tt/Aβ) in patients with AD and patients with FTLD. We then evaluated accuracy of MRI-based predicted tt/Aβ using 4 converging sources including neuroanatomic visualization and categorization of a subset of patients with genetic or autopsy-confirmed AD or FTLD.

Results: Regression analyses showed that MRI-predicted tt/Aβ is highly related to actual CSF tt/Aβ. In each group, both predicted and actual CSF tt/Aβ have extensively overlapping neuroanatomic correlates: low tt/Aβ consistent with FTLD is related to ventromedial prefrontal regions while high tt/Aβ consistent with AD is related to posterior cortical regions. MRI-predicted tt/Aβ is 75% accurate at identifying underlying diagnosis in patients with known pathology and in clinically diagnosed patients with known CSF tt/Aβ levels.

Conclusion: MRI may serve as a noninvasive procedure that can screen for AD and FTLD pathology as a surrogate for CSF biomarkers.

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 126

  • Supplemental data at www.neurology.org

  • Received May 17, 2012.
  • Accepted August 14, 2012.

via Can MRI screen for CSF biomarkers in neurodegenerative disease?.

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Scientists plead for urgent action to tackle the growing dementia crisis | Society | The Observer

Scientists plead for urgent action to tackle the growing dementia crisis

As the number of sufferers from dementia nears a million, and drugs companies fail to find therapies that work, doctors fear services may soon become overwhelmed

via Scientists plead for urgent action to tackle the growing dementia crisis | Society | The Observer.

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Time to confront the global dementia crisis : The Lancet Neurology

Time to confront the global dementia crisis

The Lancet Neurology

High-income countries are not the only ones facing a dementia crisis as their populations age. According to the Alzheimer’s Disease International (ADI) Delphi consensus study, by 2040, 71% of all people with dementia will be living in developing countries. In addition to the personal devastation for these 58 million people and their families, the economic burden is likely to be immense: in this issue of The Lancet Neurology, Kalaria and colleagues estimate that the total costs of ageing-related dementia in developing countries were already more than US$70 billion per year in 2005, when prevalence was only 15 million. Despite the scale of the problem, there is relatively little research into dementia in developing nations—just 10% has focussed on countries where more than 66% of people with these disorders live. The 10/66 Dementia Research Group, which celebrates its tenth anniversary at the end of August, is working with ADI to address this imbalance, but dementia in the developing world remains dangerously neglected within communities, by researchers, and by policy makers.

Greater awareness, policy change, and development of health-care services all stem from good research. Over the past decade, through collaborations between researchers in developed and developing countries, the 10/66 group has begun to quantify the occurrence of dementia in low-income and middle-income countries. This major undertaking has included development of more sensitive methods to diagnose dementia, because previous standard assessments are inappropriate in many settings—no-one will do well on a clock-drawing test if they are not familiar with clocks or drawing. 10/66 has also assessed availability of care, and the effects of care-giving on families. Their research, and the work of ADI and its 77 national member associations, is already starting to increase awareness at the community and primary-care levels. For example, after a successful randomised trial in India, the 10/66 research group’s “helping carers to care” initiative is now being rolled out in other countries.

These achievements should not detract from the challenges that remain. Dementia is under-diagnosed in many societies owing to stigma or misclassification as normal ageing. Reliable prevalence data are available for only two countries in Africa, and even less is known about the prevalence of different dementia types. How prevalence, incidence, and survival are affected by ethnic subgroup or economic status remain largely unknown. Better understanding of dementia in developing countries is likely to provide valuable new information on risk factors, genetics, and potential new treatments. Lower age-adjusted rates of Alzheimer’s disease in Nigeria and India than in high-income countries could reflect differences in lifestyle or genetics—for example, APOE ɛ4 is not a risk factor for Alzheimer’s disease in several sub-Saharan African populations. Traditional medicines such as some Chinese herbs are also a promising source of potential new treatments. Collaborations between researchers in developing and developed countries will benefit all parties.

But research and grass-roots implementation of care strategies can take us only so far. Unfortunately, the problem of dementia in developing countries is still largely neglected by governments and international funding agencies. While high-profile initiatives such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria have increased awareness about infectious diseases, other diseases have been left behind. When non-communicable diseases have made their way on to the global health policy agenda, the focus has been on cardiovascular disease, diabetes, and cancer, with no mention of dementia. Estimates suggest that similar numbers of people had dementia worldwide in 2007 as had HIV/AIDS—about 33 million in each case. The proportions of these people who were living in developing countries were given at about 95% for HIV/AIDS and 60—70% for dementia. Figures for aid awarded to dementia initiatives in developing countries are scarce, but they are likely to be a tiny fraction of the 25% of international health-care aid currently ear-marked for HIV/AIDS. This difference is in large part attributable to advocacy: unfortunately, patients with dementia in developing countries are rarely in a position to campaign about their disorder.

In addition to their ongoing research, over the next 2 years the 10/66 Dementia Research Group aims to increase awareness of dementia in developing countries at the regional, national, and international levels. Their plans include regular policy briefings based on results from their population surveys, and annual forums for policy makers. When these initiatives begin, governments and international funding agencies must listen. Further neglect of this issue is unacceptable in the face of a global dementia epidemic with which even high-income countries are expected to struggle.

via Time to confront the global dementia crisis : The Lancet Neurology.

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1.7% of 65+ Chinese have Parkinson Disease, accounting for half of the world’s 200 million PD patients

我国每百名老人有1人患帕金森病

胡浩, 新华网


2012年4月16日

中国

今 年4月11日是第16个世界帕金森日。在14日举行的“健康小屋关爱行动”中,专家指出, 我国的帕金森患者已达200万,占全国老年人口的1%。为进一步提高帕金森病患者及其家人 的生活质量,专家建议在帕金森病患者和家庭中间推广正确的疾病管理知识和健康的生活方式, 为帕金森病患者营造一个安全舒适的家居环境。

北京协和医院神经科主任张振馨教授介绍,中国内地1.7%的65岁以上老年人深受帕金森病 的困扰。最新的流行病学调查显示,中国大陆地区的帕金森病患者已达200万,占全球帕金森 病患者总人数的一半。此外,临床数据显示,帕金森病正以每年10万新增病例的速度在我国递 增,成为继心脑血管疾病和老年痴呆症后严重威胁我国中老年人身心健康的“第三杀手”。

帕金森病是一种中老年人常见的中枢神经系统变性疾病,主要影响中老年人,多在50岁以后发 病。其运动症状表现为静止时肢体不自主地震颤、肌强直、运动迟缓以及姿势平衡障碍等,晚期 会导致患者生活不能自理。

由于行动迟缓及平衡障碍,帕金森病患者较常人更容易跌倒骨折,所以安全舒适的居家环境对帕 金森患者非常重要。

中华医学会北京神经病学分会帕金森病及运动障碍学组组长、卫生部北京医院神经内科主任陈海 波建议,为帕金森病患者营造“健康小屋”,即通过对起居室、厨房,卧室和浴室等家具设计和 摆放等生活环境中的细节改善,如采用杠杆式的门把手、选择不容易绊倒的轻便的整块地毯、将 卧床紧贴墙壁等,方便帕金森病患者的生活。

他还建议,为便于帕金森病患者起身和落座,椅子和沙发坐垫不宜过软,高度不宜过低。家具在 选择时应选择边角为圆钝弧形,以免患者跌倒受伤。

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JAMA Network | JAMA | Association Between Use of Interferon Beta and Progression of Disability in Patients With Relapsing-Remitting Multiple Sclerosis

Association Between Use of Interferon Beta and Progression of Disability in Patients With Relapsing-Remitting Multiple Sclerosis

Afsaneh Shirani, MD; Yinshan Zhao, PhD; Mohammad Ehsanul Karim, MSc; Charity Evans, PhD; Elaine Kingwell, PhD; Mia L. van der Kop, MSc; Joel Oger, MD, FRCPC; Paul Gustafson, PhD; John Petkau, PhD; Helen Tremlett, PhD

[+] Author Affiliations

JAMA. 2012;308(3):247-256. doi:10.1001/jama.2012.7625.

Context Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established.

Objective To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS.

Design, Setting, and Patients Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts.

Main Outcome Measures The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication.

Results The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta–treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results.

Conclusion Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.

via JAMA Network | JAMA | Association Between Use of Interferon Beta and Progression of Disability in Patients With Relapsing-Remitting Multiple Sclerosis.

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