Orientation in AD Patients: PET-MR Study

NCT ID: NCT03030365

Last Updated: 2017-01-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-02-15

Study Completion Date

2020-02-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Alzheimer Disease Mild Cognitive Impairment

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Healthy Controls

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).

Siemens "Biograph mMR" PET-MR (3T)

Intervention Type DEVICE

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.

Amnestic Mild cognitive impaired

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).

Siemens "Biograph mMR" PET-MR (3T)

Intervention Type DEVICE

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.

Alzheimer's disease patients

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).

Siemens "Biograph mMR" PET-MR (3T)

Intervention Type DEVICE

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.

Interventions

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Siemens "Biograph mMR" PET-MR (3T)

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. subjects aged 50-79 years.
2. patients suffering from memory disorder.
3. Test score mini-mental state examinations higher than 20.

Exclusion Criteria

1. Contraindication to MR imaging
2. pregnant women.
3. patients with contraindications for injection of gadolinium.
Minimum Eligible Age

50 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hadassah Medical Organization

OTHER

Sponsor Role collaborator

Assuta Medical Center

OTHER

Sponsor Role lead

Responsible Party

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david groshar

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David Groshar, MD

Role: PRINCIPAL_INVESTIGATOR

Head of nuclear medicine unit in Assuta Medical Centers

Central Contacts

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David Groshar, MD

Role: CONTACT

+972-37645497

References

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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.

Reference Type RESULT
PMID: 21514249 (View on PubMed)

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.

Reference Type RESULT
PMID: 19912333 (View on PubMed)

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.

Reference Type RESULT
PMID: 7140264 (View on PubMed)

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.

Reference Type RESULT
PMID: 16120771 (View on PubMed)

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.

Reference Type RESULT
PMID: 17785667 (View on PubMed)

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.

Reference Type RESULT
PMID: 19162077 (View on PubMed)

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.

Reference Type RESULT
PMID: 26494756 (View on PubMed)

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.

Reference Type RESULT
PMID: 21514250 (View on PubMed)

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.

Reference Type RESULT
PMID: 14663030 (View on PubMed)

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.

Reference Type RESULT
PMID: 26283353 (View on PubMed)

Other Identifiers

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AssutaMC

Identifier Type: -

Identifier Source: org_study_id

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