Alzheimer's disease (AD) has no cure or nullifying pharmacological interventions. Nutritional supplementation represents a systemic approach that in some studies has provided benefit and has augmented pharmacological approaches. However, additional studies report no benefit of supplementation. We review herein how studies of nutrition on dementia, including those combining nutrition and dementia, are inherently compromised. We also review studies with mice, which demonstrate that nutritional supplementation can alleviate multiple genetic risk factors for AD. An individual diagnosed with AD has by definition undergone considerable cognitive decline; anticipating restoration/maintenance of cognitive performance following nutritional supplementation alone may be misdirected. Nutrition declines in aging, and even more so in AD. While optimization of nutrition should ideally be initiated well before any cognitive decline, we present evidence that the systemic benefit alone of nutritional supplementation at the very minimum warrants initiation along with pharmacological intervention.