Mild Alzheimer's Disease, Mild Cognitive Impairment
Conditions
Brief summary
Our central hypothesis is that the early metabolic lesions of MCI can be reliably detected in individual subjects by objective analysis of \[18\]F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) brain images, earlier and more accurately than by subjective clinician rating.
Detailed description
Our goal with this proposal is a prospective, longitudinal study that will examine subjects over a three-year span to establish the presence of MCI, evaluate progression of disease, and determine the validity of this method in detecting early MCI. Specifically, we predict that by using our Cognitive Decline Index (CDI) method of objective examination of FDG PET brain images from patients diagnosed with MCI or mild AD, we can accurately discriminate very early abnormalities in cerebral metabolism, and that this research method can be validated and translated into a clinically useful tool for the early detection of MCI. Our long-range goals are the development of methods and tools that enable the detection of pathology in individual patients at risk for cognitive impairment.
Interventions
OTHERPET scan & fMRI
Subjects will be screened and if applicable for the study will be scheduled for an MRI. At the third visit they will complete the PET scan. They will return at 6, 12, 24, and 36 months and complete another PET scan at the last visit.
Sponsors
Louisiana State University Health Sciences Center Shreveport
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
MCI Inclusion Criteria (patients): MCI criteria met: 1. Memory complaint, preferably corroborated by an informant. 2. Objective memory impairment (based on cognitive test scores). 3. Normal general cognitive function. 4. Intact ADL. 5. Not demented. * At least 10 years of education, or GED, or equivalent. * Patients with ApoE4 positive homozygous or heterozygous status and/or first-degree relative with probable AD are preferred, but patients who meet all other criteria including well-defined MCI criteria will be accepted. * Age: 55-85 * Have normal or clinically unimportant physical exam, beyond those consistent with a diagnosis of MCI. * Able to give informed consent, or assent and informed consent from a legal representative. * Centrally acting medications will be closely tracked, patients on any such medications will be PET-scanned only after a 24-hour washout, with meds restarted immediately after the scan. * Because depression and depressive pseudodementia are often prodromal to cognitive decline, these diagnoses will not be exclusive. * MRI findings must be normal or unremarkable for the age of the patient. Examples of abnormal (exclusory) findings are occult lacunar infarct, arteriovenous malformation) Examples of non-exclusory findings include mild atrophy, mild to moderate periventricular white matter changes. Other MRI findings will be evaluated in consultation with coinvestigator neuroradiologists and clinical judgment will be used to determine if the subject can continue in the study. MCI
Exclusion criteria
(patients): * Other neuropsychiatric diagnoses (e.g., stroke, head trauma, any psychotic disorder, Parkinson's) other than MCI. * Major medical illness (e.g., diabetes, severe or uncontrolled hypertension), especially potential secondary causes of cognitive decline (e.g., hypothyroidism). * Disease, combination of disease, or presentation that, in the clinician's judgment, could introduce intolerable variance into the PET brain scan image (example: coronary artery disease, hypercholesterolemia, on 5 medications, HTN 2 yrs controlled with meds, random glucose of 125, but no Dx of DM, Hx of ?TIA). * Current substance or alcohol dependence or history of same, and no alcohol or substance abuse within the last eight weeks. Mild Alzheimer's Disease (AD) Inclusion criteria (patients): 1. You must have a Mini Mental State Examination score of greater than 20. 2. You must have one or more of these signs and symptoms of mild AD: Cognitive impairment manifested as memory problems, problems with language, difficulty carrying out motor activities, difficulty naming things, and/or problems planning or organizing, all of which impair function and are worsening over time. * You must have at least 10 years of education, or a GED, or its equivalent. * We will be drawing blood to determine your ApoE genotype. ApoE4 is a risk factor for Alzheimer's disease. We will share these results with you, if you desire to know the results. ApoE4 is only a risk factor. That means it is possible to get Alzheimer's without being ApoE4 positive, and it is possible to be ApoE4 positive and not get Alzheimer's. If you are positive for the ApoE4 genetic marker, you can be included. If you do NOT have the ApoE4 genetic marker, then you must have all other criteria. * Age: 55-85. * Normal or clinically unimportant physical exam, beyond those consistent with a diagnosis of mild AD. * Able to give informed consent, or assent and informed consent from a legal representative. You will be assessed for capacity and assent/consent obtained as appropriate based on the Consensus Recommendations for Research Consent for Cognitively Impaired Adults (2004, Alzheimer's Disease Association Disorder, 18 (3):171-175). * If you take medications that have an effect on the brain, they will be closely monitored. You will be PET-scanned only after a 24-hour washout of this medication(s), but this medication(s) will be restarted immediately after the scan. Mild Alzheimer's Disease (AD)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine if the Cognitive Decline Index will discriminate subtle lesions earlier than the standard analysis of the Nuclear Medicine physician. | within the next 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Determine if sensitivity, specificity, receiver-operator characteristics, and predictive value of our method are appropriate for translation into a clinically useful tool. | within the next three years |
Countries
United States
Outcome results
None listed