Impact of Grape Consumption on Brain Metabolism and Cognitive Function

People experiencing mild cognitive changes represent an epidemiologically major segment of
the geriatric patient population. Numerous studies have been carried out to study the
benefits of grapes associated with dementia and Alzheimer's disease (AD). In the present
proposal, the investigators aim to determine 1) whether cognitive and regional cerebral
metabolic changes associated with grape powder use can be identified, 2) if the presence and
magnitude of therapeutic responses to grape in patients having mild cognitive decline can be
predicted by particular patterns of regional brain metabolism, and 3) for any changes
identified, the magnitude of those changes that correlate with the magnitude of the changes
noted in the neuropsychologic parameters will be examined, which might be useful as an
objective biomarker for therapeutic effect. A total of 12 patients suffering from documented
decline of cognitive function (in the absence of overt dementia) will be studied. In this
placebo-controlled, double-blinded study, the 12 recruited subjects who have met the
screening criteria will be randomized to receive 72 g of grape powder per day or placebo.
The subjects will undergo a baseline brain PET study with the radiotracer [F - 18]
fluorodeoxyglucose (FDG). In addition, neuropsychological assessments will be performed at
baseline and six months after initiation of therapy. Follow-up PET scans will also be
obtained at six months to assess the changes in metabolism occurring with each therapy
regimen.

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.

- Already diagnosed with Alzheimer's disease or other cause of dementia

- 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.

- Currently receiving medication used specifically to treat Alzheimer's disease or
other dementia-related disorder