Caloric Intake and Alzheimer’s Disease

Alzheimer’s disease (AD) is a rapidly growing public health concern with potentially devastating effects. Presently, there are no known cures or effective preventive strategies. While genetic factors are relevant in early-onset cases, they appear to play less of a role in late-onset sporadic AD cases, the most common form of AD. Due to the fact that the disease typically strikes very late in life, delaying symptoms could be as good as a cure for many people. For example, it is now widely accepted that if the onset of the disease could be delayed by even 5 years, the incidence could be cut in half. Both clinical and epidemiological evidence suggests that modification of lifestyle factors such as nutrition may prove crucial to AD management given the mounting experimental evidence suggesting that brain cells are remarkably responsive to ‘what somebody is doing’. Among other nongenetic factors influencing AD, recent studies strongly support the evidence that caloric intake may play a role in the relative risk for AD clinical dementia. Indeed, the effect of diet in AD has been an area of research that has produced promising results, at least experimentally. Most importantly, as mechanistic pathways are defined and their biochemical functions scrutinized, the evidence supporting a direct link between nutrition and AD neuropathology continues to grow. Our work, as well as that of others, has recently resulted in the development of experimental dietary regimens that might promote, attenuate or even reverse features of AD. Most remarkably, while we found that high caloric intake based on saturated fat promotes AD type Β-amyloidosis, conversely we found that dietary restriction based on reduced carbohydrate intake is able to prevent it. This evidence is very exciting and is, in part, consistent with current epidemiological studies suggesting that obesity and diabetes are associated with a >4-fold increased risk of developing AD. The clarification of the mechanisms through which dietary restriction may beneficially influence AD neuropathology and the eventual discovery of future ‘mimetics’ capable of anti-Β-amyloidogenic activity will help in the development of ‘lifestyle therapeutic strategies’ in AD and possibly other neurodegenerative disorders.