بررسی مقایسه ای توان پروتئین تائو پلاسما و NFL مایع مغزی نخاعی در پیش بینی میزان کاهش متابولیسم گلوکز نواحی مختلف مغزی اندازه گیری شده توسط اسکن FDG PET در بیماران مبتلا به دمانس موجود در پایگاه داده ADNI

بررسی مقایسه ای توان پروتئین تائو پلاسما و NFL مایع مغزی نخاعی در پیش بینی میزان کاهش متابولیسم گلوکز نواحی مختلف مغزی اندازه گیری شده توسط اسکن FDG PET در بیماران مبتلا به دمانس موجود در پایگاه داده ADNI

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بیماری آلزایمر شایع ترین اختلال نورودژنراتيو است که  بار سنگینی روزافزوني را بر جوامع تحميل می کند. مطالعات اخیر درمان هاي موثري را پیشنهاد کرده اند كه در مراحل اولیه زوال عقل مانع از پيشروي نورودژنراسيون ميشوند. بنابراین، تحقیقات بیشتر در مورد تشخیص زود هنگام زوال عقل، اهميت مجدد يافته است. نوروفيلامنت زنجيره سبك )(NFL) به عنوان یکی از ماركرهاي زيستي ارزشمند در تشخيص زوال عقل شناخته شده است. با توجه به همبستگی قوی بین سطح سرمی این ماده و سطح آن در مايع مغزي نخاعي، اگر سطح اين شاخص زيستي در مايع مغزي نخاعي نشان دهنده همبستگی قابل توجهی با استانداردهای قبلی تشخیص زوال عقل باشد، اين شاخص ميتواند به عنوان شاخص زيستي دمانس مورد استفاده قرار بگيرد. توموگرافی انتشار پوزیترون فلوئورودزوكسي گلوكز (FDG PET) به عنوان استاندارد طلایی تشخیص زوال عقل مطرح شده است. با 93٪ حساسیت و 76٪ اختصاصيت، FDG PET  توان بالايي در تشخیص زوال عقل دارد.
هدف: در اين مطالعه، قدرت NFL CSF در مقايسه با پروتئين Tau سرم در پيش بيني كاهش متابوليسم گلوكز در 97 ناحيه مغز مورد بررسي قرار گرفت.
روش ها: در اين مطالعه مقطعی، داده ها از پايگاه داده ADNI تهيه شده است. جامعه آماری نهایی شامل 149 مورد با میانگین سنی 67.46 سال و میانگین نمره دمانس ١٩.٢٥ از 50 بر اساس نمره ADAS بود. ما تجزیه و تحلیل همبستگی نسبي در رابطه با همبستگی بین CSF NFL و Tau سرم را با امتياز اسكن PET براي ٩٧ ناحيه مغزي انجام دادیم. سن و جنس عوامل مخدوش كننده در نظر گرفته شدند. پس از آن، تجزیه و تحلیل رگرسیون را برای مناطقي كه همبستگي  معنادار با شاخص NFL  مايع مغزي نخاعي و يا پروتئين تائو سرم داشتند  انجام داديم.
يافته ها: غلظت پروتئين تائو سرم  همبستگی معنی داری با امتياز اسكن PET  در نواحي سينگوليت خلفی، کليدهاي ميانی و مخچه بود. CSF NFL همبستگی معنی داری با امتياز اسكن PET  در نواحي پره كونئوس دوطرفه، سينگوليت دوطرفه، سينگوليت خلفی و ناحیه تمپورال مياني داشت. در تجزیه و تحلیل رگرسیون، تمام مدل های مربوط به مناطق داراي همبستگی نسبي  با Tau و NFL معنی دار بود. با این حال، شاخص R2 در مدل تجزیه و تحلیل stepwise   براي مواردي كه  که غلظت پروتئين تائو در نقش پروکسی ابتدائاً وارد مطالعه شده بود به طرز معناداري بالاتر بود.
بحث و نتيجه گيري: مطالعه ما نشان مي دهد که NFL به طور قابل ملاحظه اي با مناطق اساسي مرتبط با مراحل اوليه زوال عقل ارتباط دارد. در مطالعه ما داده های CSF NFL تنها در سطح مبدا موجود بود. بنابراین، ما قادر به انجام تجزیه و تحليل طولی نبودیم. با این حال، با توجه به معنادار بودن تمامي مدل هاي رگرسیون ما در همين مرحله سطح ابتدايي،پیش بینی می شود که بیومارکر NFL اگر در مراحل مختلف دمانس اندازه گيري شود، با توان بالايي قادر به پیش بینی پیشروي زوال عقل خواهد.
كليد واژه ها : دمانس؛ نوروفیلامان سبک زنجیر؛ پروتئین تائو؛ اسکن PET
مشخصات دانشجو:
نام:            سید محمد میرشاه ولد        رشته تحصيلي           پزشکی         مقطع:                  عمومی              گروه آموزشي   اعصاب و روان       پست الكترونيك دانشجو: mmirshahvalad@yahoo.com
اساتيد راهنما و داور:
دکتر وجیهه آقامولایی
دکتر عباس تفاخری
 
زمان دفاع : 20/6/1397
 
اطلاعات به زبان انگليسي
Title: Comparing the power of CSF NFL and Plasma Tau in predicting glucose metabolism reduction measured by PET scan in different regions of brain in patients with dementia
Abstract:
Introduction: Alzheimer’s disease is the most common neurodegenerative disorder, forcing an ever increasing burden on the societies. Recent studies have proposed disease modifying treatments effective in the early stages of neurodegeneration. Therefore, further investigations regarding early detection of dementia has came back to significance. Neurofilament light chain (NFL), has emerged as the most promising biomarker of dementia. Considering the strong correlation between the serum level of this substance with its level in CSF, if the CSF level of this biomarker reveals a significant correlation with previous standards of dementia diagnosis, this biomarker can further be utilized as a routine dementia diagnosis test. Fluorodeoxy glucose Positron emission tomography (FDG PET), has been considered as the gold standard of dementia diagnosis. With 93% of sensitivity and 76% of specificity, FDG PET was suggested to be the gold standard of dementia diagnosis.
Objective: In this study, we have investigated the power of CSF NFL in comparison with serum Tau protein in predicting glucose metabolism reduction regarding 97 brain regions.
Methods: In this cross sectional study we have acquired data from ADNI database. Our final study population consisted of 149 cases with a mean age of 67.46 and mean dementia score of 19.25 out of 50 based on ADAS score. We have performed partial correlation analysis regarding the correlation between CSF NFL and serum Tau with PET scores of 97 brain regions. Age and sex were considered as confounding factors. Afterwards, regression analysis was conducted for those regions in significant partial correlation with serum tau and/or CSF NFL.
Results: serum tau was in significant partial correlation with PET score of  posterior cingulate, middle occipital and cerebellum. CSF NFL was in significant correlation with PET score of bilateral precuneus, bilateral middle cingulate, cingulate posterior and middle temporal regions. In regression analysis, all the models regarding the regions insignificant partial correlation with Tau and NFL were significant. However, R squared regarding the stepwise analysis when Tau performed the proxy role were higher.
Conclusion: Our study suggests that NFL is significantly correlated with critical regions involved in the early stages of dementia. In our study, CSF NFL data was only available at baseline. Therefore, we were unable to perform longitudinal analysis. However, considering the significance of our regression model at baseline, we predict that NFL biomarker if acquired at various episodes, is capable of highly predicting the progression of dementia.
 
Keywords:  Dementia; NFL; Tau; PET
 
فهرست منابع و ماخذ فارسي و لاتين:
 
  1. Mattsson N, Andreasson U, Zetterberg H, et al. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2017. doi:10.1001/jamaneurol.2016.6117.
  2. Maass A, Landau S, Horng A, et al. Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer’s disease. Neuroimage. 2017. doi:10.1016/j.neuroimage.2017.05.058.
  3. Arnemann KL, Stöber F, Narayan S, Rabinovici GD, Jagust WJ. Metabolic brain networks in aging and preclinical Alzheimer’s disease. NeuroImage Clin. 2018;17:987-999. doi:10.1016/j.nicl.2017.12.037.
  4. Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673-684. doi:10.1016/S1474-4422(16)00070-3.
  5. Ishiki A, Okamura N, Furukawa K, et al. Longitudinal Assessment of Tau Pathology in Patients with Alzheimer’s Disease Using [18F]THK-5117 Positron Emission Tomography. PLoS One. 2015. doi:10.1371/journal.pone.0140311.
  6. Kang MS, Shin M, Zimmer ER, et al. Elevated Csf Levels of Neurofilament Light Chain Is Associated With Gray Matter Neurodegeneration in Both Humans and Transgenic Rat Model of Alzheimer’S Disease. Alzheimer’s Dement. 2017;13(7):P41. doi:10.1016/j.jalz.2017.06.2320.
  7. Skillbäck T, Farahmand BY, Rosén C, et al. Cerebrospinal fluid tau and amyloid-β<inf>1-42</inf> in patients with dementia. Brain. 2015;138(9):2716-2731. doi:10.1093/brain/awv181.
  8. Delacourte A, Sergeant N, Champain D, et al. Nonoverlapping but synergetic tau and APP pathologies in sporadic Alzheimer’s disease. Neurology. 2002. doi:10.1212/WNL.59.3.398.
  9. Silverman DHS, Small GW, Chang CY, et al. Positron Emission Tomography in Evaluation of Dementia Regional Brain Metabolism and Long-term Outcome. http://jama.jamanetwork.com/.
  10. Association A. 2018 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2018;14(3):367-429. doi:10.1016/j.jalz.2018.02.001.
  11. Grill JD, Di L, Lu PH, et al. Estimating sample sizes for predementia Alzheimer’s trials based on the Alzheimer’s Disease Neuroimaging Initiative. Neurobiol Aging. 2013;34(1):62-72. doi:10.1016/j.neurobiolaging.2012.03.006.
  12. AARP Research Report (2016). Better Together: A Comparative analysis of age-friendly and dementia friendly communities. http://www.aarp.org/content/dam/aarp/livable- communities/documents-2016/Better-Together-Research-Report.pdf
  13. ACT on Alzheimer’s. Dementia Capable Community: Key Elements & Resources. http://www.actonalz.org/elements-and-resources. Accessed August 4, 2015.
  14. Alliance for Aging Research. (2012) Translating Innovation to Impact: Evidence-based Interventions to Support People with Alzheimer’s Disease and their Caregivers at Home and in the Community.
  15. s Association. 2016 Alzheimer’s Disease Facts and Figures.
  16. ’s Association. Diagnosis of Alzheimer’s Disease and Dementia. http://www.alz.org/alzheimers_disease_diagnosis.asp. Accessed June 8, 2015.
  17. ’s Association. Early Detection, accessed from website: http://www.alz.org/publichealth/early-detection.asp. Accessed June 8, 2015.
  18. ’s Association. Health Care Professionals and Alzheimer’s, http://www.alz.org/health-care-professionals/medical-management-patient-care.asp. Accessed June 8, 2015.
  19. ’s Association. Prevention and Risk of Alzheimer’s & Dementia. http://www.alz.org/research/science/alzheimers_prevention_and_risk.asp. Accessed July 16, 2015.
  20. ’s Association and Centers for Disease Control and Prevention. (2013) The CDC Healthy Brain Initiative: Public Health Road Map for State and National Partnerships, 2013-2018.
  21. ’s Disease International. World Alzheimer Report 2015: 'The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends.
  22. ’s Disease International (ND). Dementia friendly communities key principles. https://www.alz.co.uk/adi/pdf/dfc-principles.pdf
  23. ’s Society (UK) Building dementia-friendly communities: A priority for everyone. (2013). https://www.alzheimers.org.uk/site/scripts/download_info.php?fileID=1916
  24. American Elder Care Research Organization. (2015) Home Care Financial Assistance and Payment Options.
  25. Baumgart, M., Snyder, H.M., Carrillo, M.C., Fazio, S., Kim, H., Johns, H. (2015) “Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective.” Alzheimer’s & Dementia 11: 718-726.
  26. Centers for Disease Control and Prevention. The Concept of Prevention. http://www.cdc.gov/arthritis/temp/pilots-201208/pilot1/online/arthritis-challenge/03- Prevention/concept.htm. Accessed August 14, 2015.
  27. Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System (BRFSS) 2015 Cognitive Decline Module. http://www.cdc.gov/aging/healthybrain/brfss- faq.htm. Accessed June 10, 2015.
  28. Centers for Disease Control and Prevention. Older Adults Falls: Get the Facts. http://www.cdc.gov/HomeandRecreationalSafety/Falls/adultfalls.html. Accessed July 27, 2015.
  29. Centers for Disease Control and Prevention, Division of Nutrition, Physical Activity, and Obesity. Physical Activity is Essential to Healthy Aging. http://www.cdc.gov/physicalactivity/basics/older_adults/. Accessed September 1, 2015.
  30. Centers for Disease Control and Prevention, Division of Healthy Aging. What is a Healthy Brain? New Research Explores Perceptions of Cognitive Health Among Diverse Older Adults.
  31. Dementia Friendly America press release. Dementia Friendly America Initiative Launches in Communities Across the U.S., from Maryland to California, July 13, 2015.
  32. Institute of Medicine. (2015) Cognitive Aging: Progress in Understanding and Opportunities for Action.
  33. National Institute on Aging. About Alzheimer’s Disease: Mild Cognitive Impairment. https://www.nia.nih.gov/alzheimers/topics/mild-cognitive-impairment. Accessed June 10, 2015.
  34. Paraprofessional Healthcare Institute (PHI). (2013). Fact Sheet: America’s Direct-Care Workforce.
  35. The Gerontological Society of America (2015). Special Issue: 2015 WHCoA. Dementia Friendly, Dementia Capable, and Dementia Positive: Concepts to Prepare for the Future. http://gerontologist.oxfordjournals.org/content/early/2015/03/18/geront.gnv013.full.p df
  36. Tilly, J., Wiener, J., & Gould, E. (2014). Dementia-capable states and communities: the Basics. http://www.aoa.acl.gov/AoA_Programs/HPW/Alz_Grants/docs/BH-Brief- Dementia-Capable-Basics.pdf
  37. Tilly, J, Weiner, J, Gould, E, and O’Keefe, J. (2011). Making the Long-Term Services and Supports System Work for People with Dementia and Their Caregivers.
  38. U.S. Administration for Community Living/Administration on Aging. (2014) Dementia-
  39. Wall Street Journal (2015). “More Cities Aim to be Dementia Friendly”
  40. World Health Organization. (2012) Dementia: A Public Health Priority. World Health Organization. (2016) Report by the Secretariat. EB139/3
  41. The Council on Linkages Between Academia and Public Health Practice. (2014) Core Competencies for Public Health Professionals.
  42. National Commission for Health Education Credentialing, Inc. (2010) Areas of Responsibilities, Competencies, and Sub-competencies for the Health Education Specialists 2010.
  43. ’s and Dementia Alliance of Wisconsin. Dementia Friendly Community. http://www.alzwisc.org/Dementia%20Friendly.html.

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