Conditions

Alzheimer's Disease

Keywords

Mild Cognitive ImpairmentBrain Imaging BiomarkersMagnetic resonance imaging biomarkerPositron Emission Tomography

Outcome Measures

Primary Outcomes (5)

Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI) - Brain Boundary Shift Integral (BBSI) and Ventricular Boundary Shift Integral (VBSI)
BBSI and VBSI were calculated based on the voxel-wise difference between co-registered baseline and follow-up scans. Least squares (LS) mean value was controlled for baseline value and visit.
Baseline, 6 Mos; Baseline, 12 Mos
Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI) - Hippocampus Volume Average Percent (%) Change (Chg)
Automated hippocampal volumetry was performed using the Learning Embeddings for Atlas Propagation (LEAP) algorithm. LS mean value was controlled for baseline value and visit.
Baseline, 6 Mos; Baseline, 12 Mos
Change From Baseline in Resting State Functional Magnetic Resonance Imaging (rsfMRI)
Distributed functional connectivity in selected brain networks was calculated from the rsfMRI scans. Values were derived from low-frequency (0.01-0.1 hertz \[Hz\]) temporal correlations between different regions over the approximately 6-minute rsfMRI time series scan. Distributed measures of functional connectivity were calculated as the mean Pearson correlation between the average low-frequency time courses in predefined sets of regions of interest (ROI) within the default mode network (DMN), salience network (SN) and sensorimotor networks (SMN). LS mean value was controlled for baseline value and visit.
Baseline, 6 Mos; Baseline, 12 Mos
Change From Baseline in Diffusion Tensor Imaging (DTI) Using Fractional Anisotropy (FA)
DTI scans used FA to measure water diffusion directionality in selected white matter (WM) tracts. ROI: Corpus collosum (CC), internal capsule (IC), posterior cingulum bundle (PCB), temporal white matter (TWM), uncinate fasciculus (UF), superior longitudinal fasciculus (SLF). LS mean value was controlled for baseline value and visit.
Baseline, 6 Mos; Baseline, 12 Mos
Change From Baseline in Diffusion Tensor Imaging (DTI) Using Mean Diffusivity (MD)
DTI scans used MD to measure the overall magnitude of water diffusion in selected WM tracts, without specific regard to directionality. ROI: CC, IC, PCB, TWM, UF, SLF. LS mean value was controlled for baseline value and visit.
Baseline, 6 Mos; Baseline, 12 Mos

Secondary Outcomes (6)

Baseline Brain Amyloid Load Using Positron Emission Tomography (PET) and Florbetapir
Baseline
Number of Participants With Vasogenic Edema on MRI Scan at a Field Strength of 3 Tesla (3T)
Baseline
Number of Participants With Microhemorrhage on MRI Scan at a Field Strength of 3T
Baseline, 6 Mos; Baseline, 12 Mos
Change From Baseline in the Mini Mental State Examination (MMSE) Total Score
Baseline, 6 Mos; Baseline, 12 Mos
Change From Baseline in the Alzheimer's Disease Assessment Scale Extended Cognitive Subscale (ADAS-Cog14) Total Score
Baseline, 6 Mos; Baseline, 12 Mos
+1 more secondary outcomes

Study Arms (1)

Imaging Biomarkers

EXPERIMENTAL

Other: PET scan using florbetapirOther: MRI Scan

Interventions

PET scan using florbetapirOTHER

A single intravenous microdose of 260 MBq (7 mCi) 18F-AV-45 (florbetapir F 18) will be administered.

Also known as: AV-45

Imaging Biomarkers

MRI ScanOTHER

Three different measurements will be taken: volumetric MRI (vMRI), diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI). In addition, radiological MRI scans will be taken to monitor vasogenic edema and microhemorrhages.

Imaging Biomarkers

Eligibility Criteria

Age55 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Present with prodromal Alzheimer's Disease (AD) or mild AD based on the disease diagnostic criteria
Are men or post-menopausal women, at least 55 years of age. Post-menopausal women are defined as women who have had a hysterectomy and/or bilateral oophorectomy; or who have been amenorrheic for at least 2 years
Have a caretaker/study informant who provides a separate written informed consent to participate. If a caretaker/study informant cannot continue, one replacement is allowed
Gradual and progressive change in memory function reported by participants or informants over more than 6 months
Objective evidence of significantly impaired episodic memory characteristic of hippocampal dysfunction on testing: Free and Cued Selective Reminding Test (FCSRT): less than or equal to (≤) 16 for free recall or ≤ 40 for total recall. Protocol amendment: FCSRT ≤ 24 for free recall or ≤ 44 for total recall
Clinical Dementia Rating (CDR) equals 0.5 or 1, Memory box score greater than or equal to 0.5
Mini Mental Scale Examination (MMSE) 20-30. Protocol amendment: MMSE 23-30, inclusive
Positive florbetapir F 18 scan
Participants must meet all of the Disease Diagnostic Criteria to be considered for enrollment

You may not qualify if:

Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders
Frontotemporal dementia, Lewy body disease, vascular dementia, Huntington's Disease or concomitant Parkinson's disease, progressive supranuclear palsy (PSNP) or other movement disorder
Has B12 \<200 pg/L or folate \<7.5 nmol/L indicating vitamin deficiency
Has a history within the past 5 years of a serious infectious disease affecting the brain, including meningitis, or encephalitis
Significant history of alcoholism or substance abuse (at the judgment of the investigator)
Severe or recurrent head injury that is clinically relevant to the disease under study, (that is, with permanent neurological/cognitive sequelae)
Onset of dementia following heart surgery or cardiac arrest
Diagnosis or history of cerebrovascular disease (for example, stroke, transient ischemic attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's current cognitive or functional status, impair ability to fully participate in the trial or that may impact status
Has had a Positron Emission Tomography (PET) within 6 months of the scheduled imaging follow-up
Greater than 4 cerebral microhemorrhages (CMH) on T2\* -weighted gradient-recalled echo sequences (regardless of their anatomical or diagnostic characterization as "possible" or "definite"), a single area of superficial siderosis, or prior evidence of macrohemorrhage
Any indications of severe deep white matter lesions or vasogenic edema that present as hyperintense regions on the Fluid Attenuated Inversion Recovery (FLAIR) sequence, or other clinically relevant findings observed on the Magnetic Resonance Imaging (MRI) scans
History within the past 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen (PSA) post resection
History of clinically significant cardiovascular or renal events
Diastolic blood pressure of 95 or more and systolic blood pressure of 160 or more in sitting position after at least 5 minutes of rest
Any history of seizure
+16 more criteria

Contact the study team to confirm eligibility.