Database Open Access
Cerebromicrovascular Disease in Elderly with Diabetes
Published: Oct. 9, 2020. Version: 1.0.0 <View latest version>
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Novak, V., & Quispe, R. (2020). Cerebromicrovascular Disease in Elderly with Diabetes (version 1.0.0). PhysioNet. https://doi.org/10.13026/t92y-x219.
Novak V, Zhao P, Manor B, Sejdic E, Alsop D, Abduljalil A, Roberson PK, Munshi M, Novak P. (2011). Adhesion molecules, altered vasoreactivity, and brain atrophy in type 2 diabetes. Diabetes Care. 34(11):2438-41. doi: 10.2337/dc11-0969. Epub 2011 Sep 16.
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Goldberger, A., Amaral, L., Glass, L., Hausdorff, J., Ivanov, P. C., Mark, R., ... & Stanley, H. E. (2000). PhysioBank, PhysioToolkit, and PhysioNet: Components of a new research resource for complex physiologic signals. Circulation [Online]. 101 (23), pp. e215–e220.
This dataset was collected as part of a prospective observational study to evaluate the effects of type 2 diabetes mellitus (DM) on cerebral vasoregulation, perfusion and functional outcomes, measured by blood flow responses to hypocapnia and hypercapnia, Valsalva maneuver, head-up tilt, and sit-to-stand test. The dataset comprises of observations from 69 diabetic and control participants (aged 55 to 75 years) with continuous measurements of cerebral blood flow using transcranial Doppler and MRI (magnetic resonance imaging), heart rate, blood pressure, and respiratory parameters, balance, walking, laboratory and retinopathy measures at baseline, and 41 subjects who completed the two-years of follow-up. Regional gray, white matter and cerebrospinal fluid volumes were quantified using a segmentation method applied on T1- and T2- weighted images and perfusion maps, using a continuous arterial spin labeling (CASL) images at 3 Tesla MRI. White matter integrity was determined from fluid attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) MRI. Dynamics of cerebral vasoregulation to CO2 challenge and orthostatic stress were measured using Transcranial Doppler ultrasound (TCD).
Diabetes mellitus (DM) alters the permeability of the blood-brain barrier, thus affecting regional metabolism and microcirculatory regulation. We conducted a single-center study with the aim of prospectively determining the neurovascular and neuroanatomical implications of type 2 diabetes mellitus and its consequences for cognition and balance in the elderly. Our goal was to determine the mechanisms by which diabetes alters cerebral microcirculation and contributes to brain tissue damage and cognitive decline in the elderly.
The study was approved by Institutional Review Board of Beth Israel Deaconess Medical Center (BIDMC #2008P000286). Full details of the experimental protocol are provided in the Research Design and Method section of the
GE-79_Protocol.pdf document (p13-20).
A total of 120 participants were recruited for the study based on inclusion and exclusion criteria. The group comprised of 60 people with diabetes, along with 60 people as a control group.
Screening (First Visit)
Subjects were asked to sign informed consent form. Medical history and activity questionnaires were completed. Pre-tests, including ECG, TCD window, MMSE (Mini Mental State Exam), and laboratory tests were performed.
Blood pressure (BP) Medications Taper: To establish a baseline, blood pressure was monitored for 3 days while the subject was taking their usual dose of antihypertensive medications. Antihypertensive medications were held on Day 2 of the study.
Visit 2 (Baseline)
Day 1: Subjects were admitted to CRC (Clinical Research Center). Physical and neurological examinations and neuropathy assessments were performed. Ophthalmological and cognitive examinations were done. Vital signs, anthropometrics and adiposity measures using skin fold thickness, and waist-to-hip-ratio were obtained. 24 hour ECG (electrocardiogram) recordings were performed during Day 1 (sleep) and Day 2 (daily activities, TCD and walking test).
Day 2: Blood was collected for fasting glucose, A1c (hemoglobin A1c), C-peptide, lipids, hematocrit, WBC (white blood cells count) , and inflammatory markers. A renal panel was obtained using blood and urine samples. TCD and MRI studies were then done.
Follow-up visits (6, 12, 18 months)
Subjects visited biannually for a follow-up visits that included measurements of fasting glucose, A1C, renal panels, vital signs, anthropometric and body fat measures, and updates on medical history and medications.
Visit 8 (Two-year follow-up)
Identical to Visit 2 (Baseline).
GE-79_Protocol.pdf in the main directory contains the description of the experimental protocol.
1. The following .csv files are located in
GE-79_Files_and Channels.csvfile enlists the signals and calibration that are in each open-format data files from Data folder. (ECG and conberted Labview data files are presented separately in the Data directory.)
GE-79_Files_per_subject.csvfile enlists open-format data files from Data folder available for each subject. (ECG and converted Labview data files are presented separately in the
GE-79_Summary_Table-Demographics-MRI-Part1.csvThis file contains the data summary table’s first part which includes demographics, MRI data for every subject in Visit 2 and Visit 8.
GE-79_Summary_Table-MRI-Part2.csvThis file contains the data summary table’s second part which includes MRI data for every subject in Visit 2 and Visit 8.
GE-79_Summary_Table-MRI-Part3.csvThis file contains the data summary table’s third part which includes MRI data for every subject in Visit 2 and Visit 8.
GE-79_Summary_Table-MRI-Part4.csvThis file contains the data summary table’s fourth part which includes MRI data for every subject in Visit 2 and Visit 8.
GE-79_Summary_Table-MRI-Part5-History.csvThis file contains the data summary table’s fifth part which includes MRI data and medical and medication history for every subject in Visit 2 and Visit 8.
GE-79_Summary_Table-Labs-BP-Ophthalmogic-Walk.csvThis file contains the data summary table’s sixth part which includes labs, 24-hour blood pressure monitoring, ophthalmogical testing, and walking test for every subject in Visit 2 and Visit 8.
GE-79_Summary_Table-Cognitive-Testing.csvThis file contains the data summary table's seventh part which includes all the of the data collected for cognitive testing.
GE-79_Data_Dictionary.csvThis file enlists all the variables of the study (variable description and units) and provides actual values from two participants as examples.
2. The following open-format data files are located in the
Data directory. See
GE-79_Files_and Channels.csv for details:
- ECG - 24 hour ECG monitoring using the ME6000 device, sampled at 1000 Hz during sleep, daily activities and walking test for 12 min during day 1.
- Labview – DB files (s####DB-v2.dat and s####DB-v8.dat) from Visit 2 and Visit 8. Cardiovascular, respiratory and TCD ultrasonography recordings (blood flow velocity in ACA and MCA) during Valsalva maneuver, 5 min supine baseline, 3 min hyperventilation, 3 min CO2 rebreathing, 5 min supine rest, head-up tilt 10 min.
In addition, the
Papers folder contains many articles published from this database.
Formats in which the files are provided:
- ECG files converted from original format to WFDB format.
- Labview files were converted to WFDB format.
The work was supported by the National Institutes of Health (NIH-NIA1R01-AG0287601A2, NIH-NIDDK 5R21 DK084463), American Diabetes Association (Clinical 1-03-CR-23 and 1-06-CR-25 to Dr. Vera Novak). The work was also in part supported NIH-NIDDK 1R01DK103902-01A1 to Dr. Novak. The project described was supported by Harvard Clinical and Translational Science Center (Grant Number UL1 RR025758) and National Center for Research Resources (M01-RR-01032).
Conflicts of Interest
Authors report no conflict of interest.
- Manschot,S.M. et al. Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. Diabetes 55, 1106-1113 (2006).
- Aiello,L.M., Cavallerano,J.D., Cavallerano,A.A., & Bursell,S.E. The Joslin Vision Network (JVN) Innovative Telemedicine Care for Diabetes. Ophthalmol. Clin. North. Am. 13, 213-224 (2000).
- Bursell,S.E. et al. Stereo nonmydriatic digital-video color retinal imaging compared with Early Treatment Diabetic Retinopathy Study seven standard field 35-mm stereo color photos for determining level of diabetic retinopathy. Ophthalmology 108, 572-585 (2001).
- Cavallerano,A.A. et al. Use of Joslin Vision Network digital-video nonmydriatic retinal imaging to assess diabetic retinopathy in a clinical program. Retina 23, 215-223 (2003).
- Cavallerano,A.A. et al. A telemedicine program for diabetic retinopathy in a Veterans Affairs Medical Center--the Joslin Vision Network Eye Health Care Model. Am. J. Ophtalmol 139, 597-604 (2005).
- Fong,D.S., Warram,J.H., Aiello,L.M., Rand,L.I., & Krolewski,A.S. Cardiovascular autonomic neuropathy and proliferative diabetic retinopathy. Am. J. Ophtalmol 120, 317-321 (1995).
- Wilson,C., Horton,M., Cavallerano,J.D., & Aiello,L.M. Addition of primary care-based retinal imaging technology to an existing eye care professional referral program increased the rate of surveillance and treatment of diabetic retinopathy. Diabetes Care 28, 318-322 (2005).
- Bastyr,E.J.3., Price,K.L., Bril,V., & the MMBQ Study group Development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy. Clin. Ther. 27, 1278-1294 (2005).
- Bril,V. & Perkins,B.A. Validation of the Toronto Clinical Scoring System for diabetic polyneuropathy. Diabetes Care 25, 2048-2052 (2002).
- Kamimura,M.A. et al. Comparison of skinfold thicknesses and bioelectrical impedance analysis with dual-energy X-ray absorptiometry for the assessment of body fat in patients on long-term haemodialysis therapy. Nephrol. Dial. Transplant. 18, 101-105 (2003).
- Cohen,J. Statistical power analysis for the behavioral sciences.(Lawrence Erlbaum Associates, New Jersey, 1988).
- Launer,L.J. Diabetes and brain aging: epidemiologic evidence. Curr. Diab. Rep. 5, 59-63 (2006).
- Horani,M.H. & Mooradian,A.D. Effect of diabetes on the blood brain barrier. Curr. Pharm. Des. 9, 833-840 (2003).
- Korf,E.S., White,L.R., Scheltens,P., & Launer,L.J. Brain aging in very old men with type 2 diabetes: the Honolulu-Asia Aging Study. Diabetes Care 29, 2268-2274 (2006).
- Schmidt,R. et al. Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study. Diabetes 53, 687-692 (2004).
- Xu,W.L., Qiu,C.X., Wahlin,A., Winblad,B., & Fratiglioni,L. Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology 63, 1181-1186 (2004).
- Task Force on Community Preventive Services Strategies for reducing morbidity and mortality from diabetes through health-care system interventions and diabetes self-management education in community settings. A report on recommendations of the task force on community preventive services. National Center for Chronic Disease Prevention and Health Promotion, MMWRI 50, (2001).
- Makimattila,S. et al. Brain metabolic alterations in patients with type 1 diabetes-hyperglycemia-induced injury. J Cereb Blood Flow Metab 24, 1393-1399 (2004).
- Brownlee,M. The pathobiology of diabetic complications. Diabetes 54, 1615-1625 (2006).
- Keymeulen,B. et al. Regional cerebral hypoperfusion in long-term type 1 (insulin-dependent) diabetic patients: relation to hypoglycaemic event. Nucl. Med. Commun. 16, 10-6 (1995).
- Kannel,W.B., Kannel,C., Paffenbarger,R.S.J., & Cupples,L.A. Heart rate and cardiovascular mortality: The Framingham study. Am. Heart J. 113, 1494 (1987).
- Gunning-Dixon,F.M. & Raz,N. The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology 14, 224-232 (2000).
- Vazquez,L.A. et al. Decreased plasma endothelin-1 levels in asymptomatic type I diabetic patients with regional cerebral hypoperfusion assessed by Spect. J. Diabetes Complications 13, 325-331 (1999).
- Jimenez-Bonilla,J.F. et al. Assessment of cerebral blood flow in diabetic patients with no clinical history of neurological disease. Nucl Med Commun 17, 790-794 (1996).
- Kadoi,Y., Saito,S., Goto,F., & Fujita,N. The effect of diabetes on the interrelationship between jugular venous oxygen saturation responsiveness to phenylephrine infusion and cerebrovascular carbon dioxide reactivity. Anesth Analg 99, 325-331 (2004).
- Kadoi,Y. et al. Diabetic patients have an impaired cerebral vasodilatory response to hypercapnia under propofol anesthesia. Stroke 34, 2399-2403 (2003).
- Wakisaka,M. et al. Reduced regional cerebral blood flow in aged noninsulin-dependent diabetic patients with no history of cerebrovascular disease: evaluation by N-isopropyl-123I-p-iodoamphetamine with single-photon emission computed tomography. J. Diabetes Complications 4, 170-174 (1990).
- MacLeod,K.M. et al. The effects of acute hypoglycemia on relative cerebral blood flow distribution in patients with type I (insulin-dependent) diabetes and impaired hypoglycemia awareness. Metabolism 45, 974-980 (1996).
- Cranston,I. et al. Regional differences in cerebral blood flow and glucose utilization in diabetic man: the effect of insulin. J Cereb Blood Flow Metab 18, 130-140 (1998).
- Vermeer,S.E. et al. Silent brain infarcts and white matter lesions increase stroke risk in the general population: The Rotterdam scan study. Stroke 34, 1126-1129 (2003).
- Schmidt,R. et al. White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease. Neurology 63, 139-144 (2004).
- Musen,G. et al. Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry. Diabetes 55, 326-333 (2006).
- Ikram,M.K. et al. Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study. Brain182-188 (2006).
- Vermeer,S.E., Prins,N.D., den Heijer,T., Koudstaal,P.J., & Breteler,M.M. Silent brain infarcts and the risk of dementia and cognitive decline. N. Engl. J. Med. 27, 1215-1222 (2003).
- deGroot,J.C. et al. Cerebral white matter lesions and subjective cognitive dysfunction: the Rotterdam Scan Study. Neurology 56, 1539-1541 (2001).
- Meyer,J.S., Rogers,R.L., Judd,B.W., Mortel,K.F., & Sims,P. Cognition and cerebral blood flow fluctuate together in multi-infarct dementia. Stroke 19, 163-169 (2003).
- DeCarli,C. & et al. The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology 45, 2077-2084 (1995).
- Looi,J.C. & Sachdev,P.S. Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 53, 670-678 (1999).
- Laughton,C.A. et al. Aging, muscle activity, and balance control: physiologic changes associated with balance impairment. Gait Posture 18, 101-108 (2003).
- Norris,J.A., Marsh,P.M., Smith,I.J., Kohut,R.I., & Miller,M.E. Ability of static and statistical mechanics posturographic measures to distinguish between age and fall risk. Journal of Biomechanics 38, 1263-1272 (2005).
- Nardone,A., Grasso,M., & Schieppati,M. Balance control in peripheral neuropathy: are patients equally unstable under static and dynamic conditions? Gait Posture 23, 364-373 (2006).
- Tell,G.S., Lefkowitz,D.S., Diehr,P., & Elster,A.D. Relationship between balance and abnormalities in cerebral magnetic resonance imaging in older adults. Arch. Neurol. 55, 73-9 (1998).
- Whitman,G.T. & Tang,T. A prospective study of cerebral white matter abnormalities in older people with gait dysfunction. Neurology 57, 990-994 (2001).
- Baloh,R.W., Ying,S.H., & Jacobson,K.M. A longitudinal study of gait and balance dysfunction in normal older people. Arch. Neurol. 60, 835-839 (2003).
- Mehagnoul-Schipper,D.J., Colier,W.N., & Jansen,R.W. Reproducibility of orthostatic changes in cerebral oxygenation in healthy subjects aged 70 years and older. Clin. Physiol. 21, 77-84 (2001).
- Novak,V., Novak,P., Spies,J.M., & Low,P.A. Autoregulation of cerebral blood flow in orthostatic hypotension. Stroke 29, 104-111 (1998).
- Novak,V. et al. Cerebral blood flow velocity and periventricular white matter hyperintensities in type 2 diabetes. Diabetes Care 29, 1529-1534 (2006).
- Last,D. et al. Global and regional effects of type 2 diabetes mellitus on brain tissue volumes and cerebral vasoreactivity . Diabetes Care 30, 1193-1199 (2007).
- Knopman,D.S., Mosley,T.H., Catellier,D.J., & Sharrett,A.R. Cardiovascular risk factors and cerebral atrophy in a middle-aged cohort. Neurology 65, 876-881 (2005).
- Schmidt,M.I. et al. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study. Lancet 15, 1649-1652 (1999).
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