A brain PET scan is recognized as "reasonable and necessary" for some patients with "a recently established diagnosis of dementia" (Centers for Medicare and Medicaid Services, Decision Memo CAG-00088R, 2004), but evidence is less clear for patients having less severe cognitive problems. A substantial portion of such patients will develop Alzheimer's disease and other forms of dementia, which affect millions of people in the U.S., costing us over $100 billion annually. This project employs a prospective randomized protocol to determine whether PET scanning can help distinguish those patients with early Alzheimer's changes in their brains from those having other causes of cognitive impairment more accurately than is done with current clinical practices alone, and lead to earlier, more effective therapies which extend patients' abilities to think and function independently.

People experiencing mild cognitive changes represent an epidemiologically major segment of the geriatric patient population. In the present proposal, we aim to measure how knowledge of cerebral metabolic information 1) influences working diagnoses and management of patients being evaluated for symptoms of early cognitive decline, and 2) impacts upon long-term clinical outcomes, particularly of subjects having metabolic patterns consistent with presence of Alzheimer's disease (AD)-like changes in their brains. A total of 710 patients suffering from documentable decline of cognitive function in the absence of overt dementia will be studied at nine U.S. institutions with extensive experience and infrastructure in place for the evaluation of Alzheimer's disease and related disorders, and for neuroimaging. In this prospective, investigation, subjects will undergo baseline neuropsychologic testing and neuroimaging with MRI and FDGPET. PET scan reports will be sealed and randomized with respect to whether they are released to patients' managing physicians at the time of interpretation, or two years after the time that scanning is performed.

Working diagnoses of managing physicians will be recorded, as will the treatment decisions made by the managing physicians and their patients. Cognitive abilities, functional status, utilization of healthcare resources, and other clinical and social contact parameters will be assessed every six months. Our major hypotheses are that among patients whose PET results are immediately conveyed to their referring physicians, diagnoses and management plans will be positively affected, leading to more effective utilization of healthcare resources and to maintenance of cognitive and functional abilities at a higher level. This project will also provide a rich source of data that can be used to address questions outside of its major focus (e.g., prognostic accuracy of volumetric MRI data used instead of, or in conjunction with, FDG-PET data; incremental predictive value of applying statistically parameterizing and/or quantifying software tools to imaging data).

Inclusion Criteria:

• Cognitive deficit and/or personality change is present, as observable by physician and/or close contact(s) of the patient; or in the absence of this, the patient provides a clear history of decline which the patient's physician deems to be reliable.
• If history or neurologic exam reveals findings suspicious for stroke, tumor, bleed, ictal activity, or hydrocephalus, then CT/MRI and appropriate neurological or neurosurgical consultation must have been obtained.
• Standard history, physical, and laboratory screen have been performed to identify possible presence of depression, substance abuse, malnourishment, medication effects and interactions, cardiopulmonary compromise, electrolyte/calcium imbalance, anemia, hypoxemia, infection, thyroid dysfunction, renal dysfunction, hepatic dysfunction, or glucose dysregulation.
• Any positive findings revealed in 2) or 3) above have been appropriately treated, wherever possible, but cognitive/behavioral deficit persists post-therapy.

Exclusion Criteria:

• Subjects under age 65 will not be recruited, in order to enhance the clinical relevance of the project by focusing on the age groups in whom serious concerns about early signs and symptoms of senile onset dementia are most typically emerging.
• Overt dementia, as discussed above.
• Cognitive dysfunction has impaired subject's ability to perform activities of daily living.
• Present or past history of thyroid disease (due to effects of both the disease and thyroid hormone replacement therapy on brain metabolism that we and others have begun to identify, but which remain incompletely characterized.)
• Claustrophobia or metal in body or other condition that would preclude PET or MRI from being acquired, or visual, auditory or motor deficits that would preclude accurate neuropsychological testing.
• Cholinesterase inhibition therapy already initiated.