Metabolic Cerebral Imaging in Incipient Dementia (MCI-ID)

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.