Recommendations for Development of New Standardized Forms of Cocoa Breeds and Cocoa Extract Processing for the Prevention of Alzheimer’s Disease: Role of Cocoa in Promotion of Cognitive Resilience and Healthy Brain Aging

Abstract

It is currently thought that the lackluster performance of translational paradigms in the prevention of age-related cognitive deteriorative disorders, such as Alzheimer's disease (AD), may be due to the inadequacy of the prevailing approach of targeting only a single mechanism. Age-related cognitive deterioration and certain neurodegenerative disorders, including AD, are characterized by complex relationships between interrelated biological phenotypes. Thus, alternative strategies that simultaneously target multiple underlying mechanisms may represent a more effective approach to prevention, which is a strategic priority of the National Alzheimer's Project Act and the National Institute on Aging. In this review article, we discuss recent strategies designed to clarify the mechanisms by which certain brain-bioavailable, bioactive polyphenols, in particular, flavan-3-ols also known as flavanols, which are highly represented in cocoa extracts, may beneficially influence cognitive deterioration, such as in AD, while promoting healthy brain aging. However, we note that key issues to improve consistency and reproducibility in the development of cocoa extracts as a potential future therapeutic agent requires a better understanding of the cocoa extract sources, their processing, and more standardized testing including brain bioavailability of bioactive metabolites and brain target engagement studies. The ultimate goal of this review is to provide recommendations for future developments of cocoa extracts as a therapeutic agent in AD.

Chocolate, “Food of the Gods”: History, Science, and Human Health

“…The polyphenol-dependent antioxidant potential could contribute to amelioration of some neurodegenerative disorders [11,93,94]. This inference is based on the fact that age-related cognitive impairment and disorders, such as Alzheimer's and Parkinson's diseases, are related to the accumulation of reactive oxygen species in the brain [11,94,95].…”

Flavonoid‐Derived Human Phenyl‐γ‐Valerolactone Metabolites Selectively Detoxify Amyloid‐β Oligomers and Prevent Memory Impairment in a Mouse Model of Alzheimer's Disease

“…These include pro‐neuritogenic, anti‐inflammatory, and antioxidant activities . The existence of a positive correlation between intake of flavan‐3‐ol rich foods (especially cocoa) and cognitive performance has also been documented . Notably, an enhancement of dentate gyrus function and cognition, attributed to an improved brain microcirculation, has been reported in healthy 50–69 year‐old subjects who consumed a high cocoa flavan‐3‐ol containing diet …”

“…This largely unsatisfactory outlook has spurred great interest in various natural compounds, especially polyphenols, that in various experimental settings have proven capable of modifying different neuropathological features of AD and to promote Aβ peptide detoxification by either interfering with AβO formation and/or by inducing the conversion of pre‐existing AβOs into nontoxic higher‐order aggregates . Special attention, in this context, has been given to flavan‐3‐ols, polycyclic flavonoids that are particularly abundant in cocoa, tea, berries, red wine, and other plant‐derived foods and beverages . Much less investigated, instead, have been the human metabolites of flavan‐3‐ols, only a few of which have been shown to mitigate Aβ (including AβO) toxicity …”

Dark Chocolate: Opportunity for an Alliance between Medical Science and the Food Industry?

“…The possible effects of DC on neurological functions may also originate from the antioxidant properties of cocoa polyphenols. Age-related cognitive deterioration and certain neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, are closely related to the accumalation of reactive oxygen species (ROS) in the brain ( 45 , 46 ). Therefore, the preventive effect of cocoa polyphenols on various molecular events initiated by ROS (inhibition of mitochondrial complex I, activation of caspase-3, and apoptosis) reported in different experiments might be explained by the anti-radical properties of bioactive components in cocoa ( 44 , 46 ).…”