<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03030365</url>
  </required_header>
  <id_info>
    <org_study_id>AssutaMC</org_study_id>
    <nct_id>NCT03030365</nct_id>
  </id_info>
  <brief_title>Orientation in AD Patients: PET-MR Study</brief_title>
  <official_title>The Orientation System, the Default-network and Brain Metabolism in Patients With Early Stage Alzheimer's Disease: a Multimodal Functional Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assuta Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hadassah Medical Organization</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assuta Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Despite the high prevalence of Alzheimer's disease (AD), its underlying mechanisms remain&#xD;
      poorly understood. An emerging body of evidence supports disorientation as an early marker&#xD;
      for AD-related neurodegeneration. In this study we intend to collect, coregister and analyze&#xD;
      Positron Emission Tomography (PET) and , functional and structural magnetic resonance imaging&#xD;
      (MRI, fMRI) data from AD-spectrum patients to establish orientation as core disturbance in&#xD;
      AD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As population aging is progressively contributing to the global burden of dementia,&#xD;
      Alzheimer's disease (AD) is gaining recognition as a health-and social-care priority.&#xD;
      Evidence converging from recently published works as well as our own preliminary results,&#xD;
      propose that orientation is a sensitive marker for preclinical AD-related neurodegeneration.&#xD;
&#xD;
      Our behavioral results show a simple orientation test to surpass currently used&#xD;
      neuropsychological tests in classification of patients along the AD spectrum. A subsequential&#xD;
      fMRI study revealed the orientation task to preferentially recruit brain regions identified&#xD;
      as susceptible to early AD-related cortical atrophy, including the posterior cingulate&#xD;
      cortex, parietooccipital sulcus and hippocampus bilaterally, as well as to significantly&#xD;
      overlap with the default mode network (DMN) - a set of interconnected brain regions which&#xD;
      were independently recognized as highly perturbed in AD.&#xD;
&#xD;
      In an attempt to further support the role of orientation in AD we propose to use&#xD;
      co-registration of several modalities of neuroimaging in patients with AD, mild cognitive&#xD;
      impairment (MCI) and healthy controls (HC): resting-state fMRI, task-fMRI, structural MRI and&#xD;
      co-registered PET.&#xD;
&#xD;
        1. Resting-state functional magnetic resonance (fMRI) imaging detecting temporally&#xD;
           synchronous, spatially distributed, spontaneous low frequency blood-oxygen&#xD;
           level-dependent signal fluctuations in task-free settings, that are further clustered&#xD;
           into maps of functional large-scale neural networks. A major network revealed in rest is&#xD;
           the default DMN. DMN includes the posterior cingulate (PCC), inferior parietal (IPL),&#xD;
           lateral (LTC) and medial temporal (MTL), and medial prefrontal cortical regions (MPFC),&#xD;
           and is known to be involved in self-referential processes including introspection,&#xD;
           memory retrieval, daydreaming and orientation.&#xD;
&#xD;
        2. Task fMRI - using this module we recently demonstrated that fMRI activation generated by&#xD;
           orientation task in the person, space and time domains activated the PCC, IPL, and MPFC&#xD;
           and MTL hubs of the DMN. This task is now to be applied in patients with AD.&#xD;
&#xD;
        3. Structural MRI - a decrease in hippocampus volume is an early imaging finding followed&#xD;
           by cortical atrophy as AD progresses.&#xD;
&#xD;
        4. PET - FDG-PET (glucose metabolism) is known to show temporo-parietal hypometabolism in&#xD;
           AD.&#xD;
&#xD;
      Considered these findings alongside ongoing research at the dynamics of anatomical and&#xD;
      functional AD associated brain dysfunction, we propose a thorough, and to the best of our&#xD;
      knowledge, a never before attempted study aimed at linking markers for AD pathology (cortical&#xD;
      atrophy, decrease of functional connectivity, cerebral glucose metabolism) to the disruption&#xD;
      of specific cognitive faculties, particularly orientation in the space, time and person&#xD;
      domains.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 15, 2017</start_date>
  <completion_date type="Anticipated">February 15, 2020</completion_date>
  <primary_completion_date type="Anticipated">February 15, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Orientation performance</measure>
    <time_frame>1 day</time_frame>
    <description>Evaluation of Performance in orientation task using success rate and response time. Response time and success rate would be combined into an efficacy score: success rate-response time quotient, measured in units of second^-1. A primary effort in this work is to establish a model that links all primary Outcome Measures, in an attempt to examine how pathological markers predict cognitive performance and weather there relations are modulated by fMRI activity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cortical atrophy</measure>
    <time_frame>1 Day</time_frame>
    <description>Cortical atrophy will be evaluated by applying voxel-based morphometry analysis on T1-weighted images. This outcome would be evaluated as number of voxels significantly different from from a distribution of corresponding voxels gathered from a healthy control cohort. significantly different voxels would be considered atrophic.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Functional connectivity analysis</measure>
    <time_frame>1 Day</time_frame>
    <description>Functional connectivity measurements within and between functional networks. This outcome would be evaluated by using correlation values computed between single voxels/region of interest, such that correlation values reflect integrity of functional networks.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mental-orientation evoked fMRI activity</measure>
    <time_frame>1 Day</time_frame>
    <description>Contrasting mental-orientation evoked activity between controls , MCIs and AD. This outcome would be evaluated by applying a contrast between fMRI patterns of activity evoked by the mental-orientation task in clinical groups (AD and MCI) to their control counterparts, to reveal the number and location of voxels showing reduced or increased activity in mental-orientation processing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>[18]F-fluorodeoxyglucose (FDG) uptake</measure>
    <time_frame>1 Day</time_frame>
    <description>[18]F-fluorodeoxyglucose glucose analog uptake is measured using positron emission tomography, and is regarded as a marker for neural activity. This outcome would be evaluated by normalizing FDG absorption values and examining voxels statistically different in their metabolic activity relative to highly validated norms.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Alzheimer Disease</condition>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Age matched controls for the various clinical groups will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi (millicurie) of 18F (fluorodeoxyglucose) -FDG prior to PET MRI, using &quot;Biograph mMR&quot; PET-MR (3T).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amnestic Mild cognitive impaired</arm_group_label>
    <description>Patients diagnosed with mild cognitive impairment, exhibiting impairment mostly in memory that is significant but does not interfere with everyday activities.&#xD;
Subjects will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI, using &quot;Biograph mMR&quot; PET-MR (3T).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alzheimer's disease patients</arm_group_label>
    <description>Patients exhibiting significant loss of intellectual ability that interferes with everyday functioning that meet Alzheimer's pattern of decline, and following exclusion of alternative neurodegenerative, cerebrovascular, and metabolic etiologies.&#xD;
Subjects will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI, using &quot;Biograph mMR&quot; PET-MR (3T).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Siemens &quot;Biograph mMR&quot; PET-MR (3T)</intervention_name>
    <description>Standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI.</description>
    <arm_group_label>Alzheimer's disease patients</arm_group_label>
    <arm_group_label>Amnestic Mild cognitive impaired</arm_group_label>
    <arm_group_label>Healthy Controls</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study Population includes patients diagnosed as amnestic mild cognitively impaired,&#xD;
        patients suffering from Alzheimer's disease, and age-matched healthy controls.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. subjects aged 50-79 years.&#xD;
&#xD;
          2. patients suffering from memory disorder.&#xD;
&#xD;
          3. Test score mini-mental state examinations higher than 20.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contraindication to MR imaging&#xD;
&#xD;
          2. pregnant women.&#xD;
&#xD;
          3. patients with contraindications for injection of gadolinium.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Groshar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Head of nuclear medicine unit in Assuta Medical Centers</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David Groshar, MD</last_name>
    <phone>+972-37645497</phone>
    <email>davidg@assuta.co.il</email>
  </overall_contact>
  <results_reference>
    <citation>Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.</citation>
    <PMID>21514249</PMID>
  </results_reference>
  <results_reference>
    <citation>Arzy S, Collette S, Ionta S, Fornari E, Blanke O. Subjective mental time: the functional architecture of projecting the self to past and future. Eur J Neurosci. 2009 Nov;30(10):2009-17. doi: 10.1111/j.1460-9568.2009.06974.x. Epub 2009 Nov 11.</citation>
    <PMID>19912333</PMID>
  </results_reference>
  <results_reference>
    <citation>Berrios GE. Disorientation states and psychiatry. Compr Psychiatry. 1982 Sep-Oct;23(5):479-91. doi: 10.1016/0010-440x(82)90161-4. No abstract available.</citation>
    <PMID>7140264</PMID>
  </results_reference>
  <results_reference>
    <citation>Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, Sheline YI, Klunk WE, Mathis CA, Morris JC, Mintun MA. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005 Aug 24;25(34):7709-17. doi: 10.1523/JNEUROSCI.2177-05.2005.</citation>
    <PMID>16120771</PMID>
  </results_reference>
  <results_reference>
    <citation>deIpolyi AR, Rankin KP, Mucke L, Miller BL, Gorno-Tempini ML. Spatial cognition and the human navigation network in AD and MCI. Neurology. 2007 Sep 4;69(10):986-97. doi: 10.1212/01.wnl.0000271376.19515.c6.</citation>
    <PMID>17785667</PMID>
  </results_reference>
  <results_reference>
    <citation>Jheng SS, Pai MC. Cognitive map in patients with mild Alzheimer's disease: a computer-generated arena study. Behav Brain Res. 2009 Jun 8;200(1):42-7. doi: 10.1016/j.bbr.2008.12.029. Epub 2008 Dec 31.</citation>
    <PMID>19162077</PMID>
  </results_reference>
  <results_reference>
    <citation>Kunz L, Schroder TN, Lee H, Montag C, Lachmann B, Sariyska R, Reuter M, Stirnberg R, Stocker T, Messing-Floeter PC, Fell J, Doeller CF, Axmacher N. Reduced grid-cell-like representations in adults at genetic risk for Alzheimer's disease. Science. 2015 Oct 23;350(6259):430-3. doi: 10.1126/science.aac8128.</citation>
    <PMID>26494756</PMID>
  </results_reference>
  <results_reference>
    <citation>McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.</citation>
    <PMID>21514250</PMID>
  </results_reference>
  <results_reference>
    <citation>Monacelli AM, Cushman LA, Kavcic V, Duffy CJ. Spatial disorientation in Alzheimer's disease: the remembrance of things passed. Neurology. 2003 Dec 9;61(11):1491-7. doi: 10.1212/wnl.61.11.1491.</citation>
    <PMID>14663030</PMID>
  </results_reference>
  <results_reference>
    <citation>Peer M, Salomon R, Goldberg I, Blanke O, Arzy S. Brain system for mental orientation in space, time, and person. Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11072-7. doi: 10.1073/pnas.1504242112. Epub 2015 Aug 17.</citation>
    <PMID>26283353</PMID>
  </results_reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 8, 2017</study_first_submitted>
  <study_first_submitted_qc>January 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>January 21, 2017</last_update_submitted>
  <last_update_submitted_qc>January 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assuta Medical Center</investigator_affiliation>
    <investigator_full_name>david groshar</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Orientation, Disorientation.</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Only in the case where publication of coded data is required\encouraged by the Journal for publication</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03030365
org study id: AssutaMC
nct id: NCT03030365
lead sponsor: 
collaborator: 
has dmc: No
Despite the high prevalence of Alzheimer's disease (AD), its underlying mechanisms remain
      poorly understood. An emerging body of evidence supports disorientation as an early marker
      for AD-related neurodegeneration. In this study we intend to collect, coregister and analyze
      Positron Emission Tomography (PET) and , functional and structural magnetic resonance imaging
      (MRI, fMRI) data from AD-spectrum patients to establish orientation as core disturbance in
      AD.
As population aging is progressively contributing to the global burden of dementia,
      Alzheimer's disease (AD) is gaining recognition as a health-and social-care priority.
      Evidence converging from recently published works as well as our own preliminary results,
      propose that orientation is a sensitive marker for preclinical AD-related neurodegeneration.

      Our behavioral results show a simple orientation test to surpass currently used
      neuropsychological tests in classification of patients along the AD spectrum. A subsequential
      fMRI study revealed the orientation task to preferentially recruit brain regions identified
      as susceptible to early AD-related cortical atrophy, including the posterior cingulate
      cortex, parietooccipital sulcus and hippocampus bilaterally, as well as to significantly
      overlap with the default mode network (DMN) - a set of interconnected brain regions which
      were independently recognized as highly perturbed in AD.

      In an attempt to further support the role of orientation in AD we propose to use
      co-registration of several modalities of neuroimaging in patients with AD, mild cognitive
      impairment (MCI) and healthy controls (HC): resting-state fMRI, task-fMRI, structural MRI and
      co-registered PET.

        1. Resting-state functional magnetic resonance (fMRI) imaging detecting temporally
           synchronous, spatially distributed, spontaneous low frequency blood-oxygen
           level-dependent signal fluctuations in task-free settings, that are further clustered
           into maps of functional large-scale neural networks. A major network revealed in rest is
           the default DMN. DMN includes the posterior cingulate (PCC), inferior parietal (IPL),
           lateral (LTC) and medial temporal (MTL), and medial prefrontal cortical regions (MPFC),
           and is known to be involved in self-referential processes including introspection,
           memory retrieval, daydreaming and orientation.

        2. Task fMRI - using this module we recently demonstrated that fMRI activation generated by
           orientation task in the person, space and time domains activated the PCC, IPL, and MPFC
           and MTL hubs of the DMN. This task is now to be applied in patients with AD.

        3. Structural MRI - a decrease in hippocampus volume is an early imaging finding followed
           by cortical atrophy as AD progresses.

        4. PET - FDG-PET (glucose metabolism) is known to show temporo-parietal hypometabolism in
           AD.

      Considered these findings alongside ongoing research at the dynamics of anatomical and
      functional AD associated brain dysfunction, we propose a thorough, and to the best of our
      knowledge, a never before attempted study aimed at linking markers for AD pathology (cortical
      atrophy, decrease of functional connectivity, cerebral glucose metabolism) to the disruption
      of specific cognitive faculties, particularly orientation in the space, time and person
      domains.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Orientation performance
time frame: 1 day
description: Evaluation of Performance in orientation task using success rate and response time. Response time and success rate would be combined into an efficacy score: success rate-response time quotient, measured in units of second^-1. A primary effort in this work is to establish a model that links all primary Outcome Measures, in an attempt to examine how pathological markers predict cognitive performance and weather there relations are modulated by fMRI activity.
measure: Cortical atrophy
time frame: 1 Day
description: Cortical atrophy will be evaluated by applying voxel-based morphometry analysis on T1-weighted images. This outcome would be evaluated as number of voxels significantly different from from a distribution of corresponding voxels gathered from a healthy control cohort. significantly different voxels would be considered atrophic.
measure: Functional connectivity analysis
time frame: 1 Day
description: Functional connectivity measurements within and between functional networks. This outcome would be evaluated by using correlation values computed between single voxels/region of interest, such that correlation values reflect integrity of functional networks.
measure: Mental-orientation evoked fMRI activity
time frame: 1 Day
description: Contrasting mental-orientation evoked activity between controls , MCIs and AD. This outcome would be evaluated by applying a contrast between fMRI patterns of activity evoked by the mental-orientation task in clinical groups (AD and MCI) to their control counterparts, to reveal the number and location of voxels showing reduced or increased activity in mental-orientation processing.
measure: [18]F-fluorodeoxyglucose (FDG) uptake
time frame: 1 Day
description: [18]F-fluorodeoxyglucose glucose analog uptake is measured using positron emission tomography, and is regarded as a marker for neural activity. This outcome would be evaluated by normalizing FDG absorption values and examining voxels statistically different in their metabolic activity relative to highly validated norms.
arm group label: Healthy Controls
description: Age matched controls for the various clinical groups will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi (millicurie) of 18F (fluorodeoxyglucose) -FDG prior to PET MRI, using "Biograph mMR" PET-MR (3T).
arm group label: Amnestic Mild cognitive impaired
description: Patients diagnosed with mild cognitive impairment, exhibiting impairment mostly in memory that is significant but does not interfere with everyday activities.
Subjects will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI, using "Biograph mMR" PET-MR (3T).
arm group label: Alzheimer's disease patients
description: Patients exhibiting significant loss of intellectual ability that interferes with everyday functioning that meet Alzheimer's pattern of decline, and following exclusion of alternative neurodegenerative, cerebrovascular, and metabolic etiologies.
Subjects will undergo standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI, using "Biograph mMR" PET-MR (3T).
intervention type: Device
intervention name: Siemens "Biograph mMR" PET-MR (3T)
description: Standardly used Magnetic resonance imaging (MRI) protocols, including resting state fMRI, task fMRI, T1 weighted imaging. In addition Patients will receive an intravenous injection of 2-5mCi of 18F-FDG prior to PET MRI.
arm group label: Alzheimer's disease patients
arm group label: Amnestic Mild cognitive impaired
arm group label: Healthy Controls
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: 79 Years
healthy volunteers: No
last name: David Groshar, MD
role: Principal Investigator
affiliation: Head of nuclear medicine unit in Assuta Medical Centers
last name: David Groshar, MD
phone: +972-37645497
email: davidg@assuta.co.il
citation: Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
PMID: 21514249
citation: Arzy S, Collette S, Ionta S, Fornari E, Blanke O. Subjective mental time: the functional architecture of projecting the self to past and future. Eur J Neurosci. 2009 Nov;30(10):2009-17. doi: 10.1111/j.1460-9568.2009.06974.x. Epub 2009 Nov 11.
PMID: 19912333
citation: Berrios GE. Disorientation states and psychiatry. Compr Psychiatry. 1982 Sep-Oct;23(5):479-91. doi: 10.1016/0010-440x(82)90161-4. No abstract available.
PMID: 7140264
citation: Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, Sheline YI, Klunk WE, Mathis CA, Morris JC, Mintun MA. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005 Aug 24;25(34):7709-17. doi: 10.1523/JNEUROSCI.2177-05.2005.
PMID: 16120771
citation: deIpolyi AR, Rankin KP, Mucke L, Miller BL, Gorno-Tempini ML. Spatial cognition and the human navigation network in AD and MCI. Neurology. 2007 Sep 4;69(10):986-97. doi: 10.1212/01.wnl.0000271376.19515.c6.
PMID: 17785667
citation: Jheng SS, Pai MC. Cognitive map in patients with mild Alzheimer's disease: a computer-generated arena study. Behav Brain Res. 2009 Jun 8;200(1):42-7. doi: 10.1016/j.bbr.2008.12.029. Epub 2008 Dec 31.
PMID: 19162077
citation: Kunz L, Schroder TN, Lee H, Montag C, Lachmann B, Sariyska R, Reuter M, Stirnberg R, Stocker T, Messing-Floeter PC, Fell J, Doeller CF, Axmacher N. Reduced grid-cell-like representations in adults at genetic risk for Alzheimer's disease. Science. 2015 Oct 23;350(6259):430-3. doi: 10.1126/science.aac8128.
PMID: 26494756
citation: McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.
PMID: 21514250
citation: Monacelli AM, Cushman LA, Kavcic V, Duffy CJ. Spatial disorientation in Alzheimer's disease: the remembrance of things passed. Neurology. 2003 Dec 9;61(11):1491-7. doi: 10.1212/wnl.61.11.1491.
PMID: 14663030
citation: Peer M, Salomon R, Goldberg I, Blanke O, Arzy S. Brain system for mental orientation in space, time, and person. Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):11072-7. doi: 10.1073/pnas.1504242112. Epub 2015 Aug 17.
PMID: 26283353
responsible party type: Principal Investigator
investigator affiliation: Assuta Medical Center
investigator full name: david groshar
investigator title: Professor
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
sharing ipd: Undecided
ipd description: Only in the case where publication of coded data is required\encouraged by the Journal for publication