The Role of Resveratrol in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review

The neuropathological hallmarks of Alzheimer disease (AD) include "positive" lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between "normal" aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI.

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. In this review, current understanding of the epidemiology, genetics, pathology and pathogenesis of Alzheimer's disease is outlined, before its clinical presentation and current treatment strategies are discussed. Finally, the review discusses how our enhanced understanding of Alzheimer pathogenesis, including the recognition of a protracted preclinical phase, is informing new therapeutic strategies with the aim of moving from treatment to prevention.