Impact of Grape Consumption on Brain Metabolism and Cognitive Function
Impact of Grape Consumption on Brain Metabolism and Cognitive Function
Constituents of grapes have been studied for their antioxidant, anti-inflammatory, and
 anticarcinogenic properties. In the past decade, there has been emerging evidence regarding a
 potential role for grapes in slowing cognitive decline and other effects of aging.
 Furthermore, evidence has been obtained in vivo that supplementation of aged rats with grape
 seed extract improves cognitive performance. Despite the promising accumulating data
 supporting the use of grapes as a safe and effective strategy for delaying the incidence of
 dementia, it remains unclear how grape intake would be useful with respect to factors such as
 dose schedule or stage of dementing illness. In general, well-controlled experimental data
 obtained in human subjects is in need of much further development. The investigators aim to
 measure effects of grape intake on cerebral metabolism and cognitive function, and to
 determine whether initial patterns, and magnitude of change, of cerebral metabolism assessed
 by positron emission tomography (PET) can serve respectively as a predictor of, and biomarker
 for, the magnitude of cognitive changes resulting from intake of grapes.
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