Cerebral Hemodynamics in Mild Cognitive Impairment: A Systematic Review.

BACKGROUND The incidence of dementia is projected to rise over the coming decades, but with no sensitive diagnostic tests available. Vascular pathology precedes the deposition of amyloid and is an attractive early target. OBJECTIVE The aim of this review was to investigate the use of cerebral hemodynamics and oxygenation as a novel biomarker for mild cognitive impairment (MCI), focusing on transcranial Doppler ultrasonography (TCD) and near-infrared spectroscopy (NIRS). METHODS 2,698 articles were identified from Medline, Embase, PsychINFO, and Web of Science databases. 306 articles were screened and quality assessed independently by two reviewers; 26 met the inclusion criteria. Meta-analyses were performed for each marker with two or more studies and limited heterogeneity. RESULTS Eleven studies were TCD, 8 NIRS, 5 magnetic resonance imaging, and 2 positron/single photon emission tomography. Meta-analyses showed reduced tissue oxygenation index, cerebral blood flow and velocity, with higher pulsatility index, phase and cerebrovascular resistance in MCI compared to controls. The majority of studies found reduced CO2 reactivity in MCI, with mixed findings in neuroactivation studies. CONCLUSION Despite small sample sizes and heterogeneity, meta-analyses demonstrate clear abnormalities in cerebral hemodynamic and oxygenation parameters, even at an early stage of cognitive decline. Further work is required to investigate the use of cerebral hemodynamic and oxygenation parameters as a sensitive biomarker for dementia.

[1]  P. Al-Rawi,et al.  Tissue Oxygen Index: Thresholds for Cerebral Ischemia Using Near-Infrared Spectroscopy , 2006, Stroke.

[2]  R. Panerai Transcranial Doppler for evaluation of cerebral autoregulation , 2009, Clinical Autonomic Research.

[3]  Panteleimon Giannakopoulos Arterial spin labeling may contribute to the prediction of cognitive deterioration in healthy elderly individuals , 2016 .

[4]  Christina E. Wierenga,et al.  The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer’s Disease , 2016, Cellular and molecular neurobiology.

[5]  J. Zhou,et al.  Decreased cerebral blood flow velocity in apolipoprotein E epsilon4 allele carriers with mild cognitive impairment. , 2007, European journal of neurology.

[6]  David H K Shum,et al.  Reduced Frontal Activations at High Working Memory Load in Mild Cognitive Impairment: Near-Infrared Spectroscopy , 2016, Dementia and Geriatric Cognitive Disorders.

[7]  V. Šerić,et al.  Breath holding index in detection of early cognitive decline , 2010, Journal of the Neurological Sciences.

[8]  Ronney B Panerai,et al.  Cerebral and systemic hemodynamic changes during cognitive and motor activation paradigms. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[9]  Rong Zhang,et al.  Dynamic cerebral autoregulation and tissue oxygenation in amnestic mild cognitive impairment. , 2014, Journal of Alzheimer's disease : JAD.

[10]  B. Zlokovic Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders , 2011, Nature Reviews Neuroscience.

[11]  B. Borroni,et al.  Volume cerebral blood flow reduction in pre-clinical stage of Alzheimer disease: , 2005, Journal of Neurology.

[12]  Khaled Restom,et al.  Assessment of Alzheimer's disease risk with functional magnetic resonance imaging: an arterial spin labeling study. , 2012, Journal of Alzheimer's disease : JAD.

[13]  Jeffrey N. Browndyke,et al.  Phenotypic regional functional imaging patterns during memory encoding in mild cognitive impairment and Alzheimer's disease , 2013, Alzheimer's & Dementia.

[14]  E. Gommer Dynamic cerebral autoregulation : from methodology towards clinical application , 2013 .

[15]  J. Claassen,et al.  Cerebral Autoregulation: An Overview of Current Concepts and Methodology with Special Focus on the Elderly , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  B. Zlokovic,et al.  Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. , 2016, Biochimica et biophysica acta.

[17]  Jakub Hort,et al.  Utility of transcranial ultrasound in predicting Alzheimer's disease risk. , 2014, Journal of Alzheimer's disease : JAD.

[18]  J. Cummings,et al.  The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment , 2005, Journal of the American Geriatrics Society.

[19]  Y. Yuan,et al.  Fluorodeoxyglucose–Positron-Emission Tomography, Single-Photon Emission Tomography, and Structural MR Imaging for Prediction of Rapid Conversion to Alzheimer Disease in Patients with Mild Cognitive Impairment: A Meta-Analysis , 2008, American Journal of Neuroradiology.

[20]  J. Gladman,et al.  The evidence for treating hypertension in older people with dementia: a systematic review , 2014, Journal of Human Hypertension.

[21]  Takao Suzuki,et al.  Reduced prefrontal oxygenation in mild cognitive impairment during memory retrieval , 2016, International journal of geriatric psychiatry.

[22]  H. Arai,et al.  A quantitative near-infrared spectroscopy study: A decrease in cerebral hemoglobin oxygenation in Alzheimer’s disease and mild cognitive impairment , 2006, Brain and Cognition.

[23]  Xin Li,et al.  Reduced Frontal Activation during a Working Memory Task in Mild Cognitive Impairment: a Non‐Invasive Near‐Infrared Spectroscopy Study , 2013, CNS neuroscience & therapeutics.

[24]  M. Albert,et al.  Medial temporal lobe function and structure in mild cognitive impairment , 2004, Annals of neurology.

[25]  M. Prince,et al.  The Global Impact of Dementia 2013-2050 , 2013 .

[26]  M. Ikram,et al.  Cardiovascular risk factors and future risk of Alzheimer’s disease , 2014, BMC Medicine.

[27]  V. Magnotta,et al.  Global Cerebral Blood Flow in Relation to Cognitive Performance and Reserve in Subjects with Mild Memory Deficits , 2006, Molecular Imaging and Biology.

[28]  Claudio Babiloni,et al.  Hypercapnia affects the functional coupling of resting state electroencephalographic rhythms and cerebral haemodynamics in healthy elderly subjects and in patients with amnestic mild cognitive impairment , 2014, Clinical Neurophysiology.

[29]  Shi-Jiang Li,et al.  Perfusion fMRI detects deficits in regional CBF during memory-encoding tasks in MCI subjects , 2007, Neurology.

[30]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, International Coaching Psychology Review.

[31]  J. Petrella,et al.  Prognostic Value of Posteromedial Cortex Deactivation in Mild Cognitive Impairment , 2007, PloS one.

[32]  Jan Warnking,et al.  Impaired cerebral vasoreactivity to CO2 in Alzheimer's disease using BOLD fMRI , 2011, NeuroImage.

[33]  R. Petersen Mild cognitive impairment as a diagnostic entity , 2004, Journal of internal medicine.

[34]  S. Viola,et al.  Tissue oxygen saturation and pulsatility index as markers for amnestic mild cognitive impairment: NIRS and TCD study , 2013, Clinical Neurophysiology.

[35]  K. Blennow CSF biomarkers for mild cognitive impairment , 2004, Journal of internal medicine.

[36]  M. Silvestrini,et al.  Metabolic syndrome and cerebrovascular impairment in Alzheimer's disease , 2015, International journal of geriatric psychiatry.

[37]  H. Makizako,et al.  Brain activation during dual-task walking and executive function among older adults with mild cognitive impairment: a fNIRS study , 2013, Aging Clinical and Experimental Research.

[38]  Linda Heskamp,et al.  Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment , 2016, Brain Imaging and Behavior.

[39]  Christina E. Wierenga,et al.  Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease. , 2014, Journal of Alzheimer's disease : JAD.

[40]  B. Yoon,et al.  Cognitive correlates of cerebral vasoreactivity on transcranial Doppler in older adults. , 2015, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[41]  Sterling C. Johnson,et al.  4D flow MRI for intracranial hemodynamics assessment in Alzheimer’s disease , 2016, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  D. Blazer,et al.  The new DSM-5 diagnosis of mild neurocognitive disorder and its relation to research in mild cognitive impairment , 2015, Aging & mental health.

[43]  Norbert Schuff,et al.  ASL Perfusion MRI Predicts Cognitive Decline and Conversion From MCI to Dementia , 2010, Alzheimer disease and associated disorders.

[44]  L. Lipsitz,et al.  Antihypertensive Therapy and Cerebral Hemodynamics in Executive Mild Cognitive Impairment: Results of a Pilot Randomized Clinical Trial , 2013, Journal of the American Geriatrics Society.

[45]  R. Westendorp,et al.  Cerebrovascular hemodynamics in Alzheimer's disease and vascular dementia: A meta-analysis of transcranial Doppler studies , 2012, Ageing Research Reviews.

[46]  Eri Shijaku,et al.  Dynamic cerebral autoregulation in subjects with Alzheimer's disease, mild cognitive impairment, and controls: evidence for increased peripheral vascular resistance with possible predictive value. , 2012, Journal of Alzheimer's disease : JAD.

[47]  J. Pickard,et al.  Transcranial Doppler Pulsatility Index: What it is and What it Isn’t , 2012, Neurocritical Care.

[48]  K. Hajian‐Tilaki,et al.  Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation. , 2013, Caspian journal of internal medicine.

[49]  M. O. Olde Rikkert,et al.  Incorrect Performance of the Breath Hold Method in the Old Underestimates Cerebrovascular Reactivity and Goes Unnoticed Without Concomitant Blood Pressure and End‐Tidal CO2 Registration , 2011, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[50]  Sven Haller,et al.  Altered cerebrovascular reactivity velocity in mild cognitive impairment and Alzheimer's disease , 2015, Neurobiology of Aging.

[51]  Xi-Nian Zuo,et al.  Toward systems neuroscience in mild cognitive impairment and Alzheimer's disease: A meta‐analysis of 75 fMRI studies , 2015, Human brain mapping.

[52]  Joaquim Radua,et al.  Meta-analysis of functional network alterations in Alzheimer's disease: Toward a network biomarker , 2013, Neuroscience & Biobehavioral Reviews.

[53]  S. Leh,et al.  Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers , 2016, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[54]  R. Yu,et al.  Altered Frontal Lateralization Underlies the Category Fluency Deficits in Older Adults with Mild Cognitive Impairment: A Near-Infrared Spectroscopy Study , 2016, Front. Aging Neurosci..

[55]  R. Sperling,et al.  Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[56]  Po-Han Chou,et al.  The role of near-infrared spectroscopy in Alzheimer's disease , 2013 .

[57]  Tao Wang,et al.  Pattern of cerebral hyperperfusion in Alzheimer’s disease and amnestic mild cognitive impairment using voxel-based analysis of 3D arterial spin-labeling imaging: initial experience , 2014, Clinical interventions in aging.

[58]  Rachel L. Mistur,et al.  Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[59]  J. Gati,et al.  Cerebral blood flow velocity underestimates cerebral blood flow during modest hypercapnia and hypocapnia. , 2014, Journal of applied physiology.

[60]  D. Salmon,et al.  Cortical and subcortical cerebrovascular resistance index in mild cognitive impairment and Alzheimer's disease. , 2013, Journal of Alzheimer's disease : JAD.

[61]  James Duffin,et al.  Factors affecting the determination of cerebrovascular reactivity , 2014, Brain and behavior.

[62]  R. Stewart,et al.  Cardiovascular risk factors and cognitive decline in adults aged 50 and over: a population-based cohort study. , 2013, Age and ageing.

[63]  Benjamin D. Levine,et al.  Global brain hypoperfusion and oxygenation in amnestic mild cognitive impairment , 2014, Alzheimer's & Dementia.

[64]  James T Becker,et al.  Mild cognitive impairment and alzheimer disease: patterns of altered cerebral blood flow at MR imaging. , 2009, Radiology.

[65]  D J Mikulis,et al.  Measuring cerebrovascular reactivity: what stimulus to use? , 2013, The Journal of physiology.

[66]  Theodore A. Henderson The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging , 2012, CNS Spectrums.

[67]  Manuel Desco,et al.  Cerebral Blood Flow is an Earlier Indicator of Perfusion Abnormalities than Cerebral Blood Volume in Alzheimer's Disease , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[68]  N. Schuff,et al.  Patterns of Cerebral Hypoperfusion in Amnestic and Dysexecutive MCI , 2009, Alzheimer disease and associated disorders.

[69]  R. Panerai,et al.  A systematic review of cerebral hemodynamic responses to neural activation following stroke , 2013, Journal of Neurology.

[70]  Carmen E. Westerberg,et al.  Distinct medial temporal contributions to different forms of recognition in amnestic mild cognitive impairment and Alzheimer's disease , 2013, Neuropsychologia.

[71]  J. C. de la Torre Cerebral hemodynamics and vascular risk factors: setting the stage for Alzheimer's disease. , 2012, Journal of Alzheimer's disease : JAD.

[72]  Sven Haller,et al.  Arterial spin labeling may contribute to the prediction of cognitive deterioration in healthy elderly individuals. , 2015, Radiology.

[73]  S. Galluzzi,et al.  Autonomic dysfunction in mild cognitive impairment: a transcranial Doppler study , 2011, Acta neurologica Scandinavica.

[74]  D. Pomeroy,et al.  Cerebrovascular Function in Aging and Dementia: A Systematic Review of Transcranial Doppler Studies , 2012, Dementia and Geriatric Cognitive Disorders Extra.

[75]  M. Bondi,et al.  Use of Functional Magnetic Resonance Imaging in the Early Identification of Alzheimer's Disease , 2007, Neuropsychology Review.

[76]  R. Panerai,et al.  Cerebral blood flow velocity during mental activation: interpretation with different models of the passive pressure-velocity relationship. , 2005, Journal of applied physiology.

[77]  Aisha S S Meel-van den Abeelen,et al.  Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network , 2016, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[78]  Marek Belohlavek,et al.  Transcranial Doppler ultrasound blood flow velocity and pulsatility index as systemic indicators for Alzheimer’s disease , 2011, Alzheimer's & Dementia.

[79]  J. Simpson,et al.  DSM-5 and neurocognitive disorders. , 2014, The journal of the American Academy of Psychiatry and the Law.

[80]  H. Barthel,et al.  Changes in local cerebral blood flow by neuroactivation and vasoactivation in patients with impaired cognitive function , 1996, European Journal of Nuclear Medicine.

[81]  R. Subramaniam,et al.  Brain PET in the Diagnosis of Alzheimer’s Disease , 2014, Clinical nuclear medicine.