Multimodal Ocular Imaging in Neurodegeneration

University of Michigan16 enrolled

Overview

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two of the most common types of age-related neurodegenerative disorders. Identifying at-risk patients and gauging disease progression in a non-invasive manner would be invaluable. Early and correct diagnosis is crucial for coordinating supportive care, patient expectations, caregiver arrangements and family planning. In addition, as treatments become available, beginning therapy early in the disease before symptoms become severe will be important. Multimodal ocular imaging (MOI) includes an ophthalmic (eye) exam and eye photographs to evaluate different layers of the retina, which is the light sensing layer of the eye. Newer technologies make it possible to visualize the disease process occurring in AD and FTD by using MOI to look at the retina, since the retina is fundamentally an outward extension of the brain itself. This study will attempt to correlate signs of disease in the retina, as determined by MOI, with plaque buildup in the brain as seen by imaging. This will demonstrate the sensitivity and specificity of MOI for diagnosing AD and FTD in a noninvasive manner.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Alzheimer Disease Alzheimer Dementia Frontotemporal Dementia

Interventions

Positron Emission Tomography (PET)DEVICE

Each participant in this study will undergo a single Positron emission tomography (PET) scan of the brain. PET is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the brain as an aid to the diagnosis of disease using the combination of a radioactive tracer, camera, and a computer.

Comprehensive Ophthalmic ExaminationDIAGNOSTIC_TEST

Each participant in this study will receive one comprehensive eye examination which will be performed by a licensed ophthalmologist at the University of Michigan. This examination will include the assessment of the participant's visual acuity, a slit lamp examination which will look at the anterior and posterior tissues of the eye including the retina using various lights and lenses, and intraocular pressures.

Eligibility

Sex: ALLMin age: 45 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects with dementia must have known diagnosis of Alzheimer's dementia (AD) or frontotemporal dementia (FTD) * Subjects with dementia must have Moderate/severe dementia as preferentially defined by a documented MoCA score of less than 17, or by MMSE score of less than 17, within the last 12 months * Individuals with no evidence of AD or FTD as age-matched controls. Exclusion Criteria: * Preexisting retinal or optic nerve disorder including macular degeneration, diabetic retinopathy, retinal dystrophy, and glaucoma * Anterior segment abnormalities of the eye limiting ocular imaging (e.g. corneal disorders, dense cataract). * Use of medications with known effects on the retina or optic nerve (e.g. hydroxychloroquine, ethambutol). * Pregnant or lactating women. * Prisoners. * Subjects with advanced dementia who cannot be independently and reliably positioned at the ocular imaging device for reliable imaging. * Subjects with contraindications to magnetic resonance (MR) imaging, including pacemakers or claustrophobia. * Evidence of large vessel stroke or mass lesion identified on MR imaging. * Subjects limited by participation in research procedures involving ionizing radiation. * Subjects who are already participating in another clinical study or clinical trial * Participants with a clinically significant or unstable medical or surgical condition that, in the opinion of any of the investigators, might preclude safe completion of the study or might affect the results of the study. These include conditions causing significant central nervous system or autonomic dysfunction, such as congestive heart failure, recent (\<6 months) myocardial infarction, thrombocytopenia (\<50 x 10(9)/L), immunosuppressed state, severe uncontrolled hypertension, severe cardiopulmonary disease, severe anemia (hemoglobin \<8g/dl), severe liver or kidney disease (creatinine \>2.3 mg/dl) uncontrolled diabetes mellitus (HgbA1c \>10g%), alcoholism, malignant neoplasms, amyloidosis, uncontrolled hypothyroidism, unstable peripheral neuropathies, concurrent infections, orthopedic problems that compromise mobility and activities of daily living, severe cerebrovascular accidents (causing symptoms such as hemiplegia, aphasia and non-dominant parietal lobe syndrome), history of exposure to neurotoxins or neuroactive drugs, or parkinsonism due to drugs (including neuroleptics, alpha-methyldopa, reserpine, metoclopramide).

Outcomes

Primary Outcomes

Presence of Retinal Thinning

Imaging of the eye will be used to measure differences in retinal thickness between subjects with Alzheimer's Dementia, Frontotemporal Dementia, and healthy age-matched controls.

Time frame: 45 minutes

Secondary Outcomes

Presence of Amyloid Plaque

Fundus autofluorescence (FAF) will be used to detect the presence of lipofuscin

Time frame: 45 Minutes

Presence of Brain Pathology

MRI of the brain will be performed in order to determine if pathology observed on neuroimaging correlates quantitatively and/or qualitatively with retinal thickness.

Time frame: 60 Minutes

Presence of Brain Metabolism

PET scanning of the brain will be performed in order to determine if brain metabolism observed on neuroimaging correlates quantitatively and/or qualitatively with retinal thickness.

Time frame: 180 Minutes

Presence of Macular Vascular Anomalies

Imaging of the eye will be used to measure differences in vascular density between subjects with Alzheimer's Dementia, Frontotemporal Dementia, and healthy age-matched controls.