The Progression of Alzheimer's Disease: A Comprehensive Review

Abstract

AThe most common form of dementia worldwide is AD (Alzheimer's disease). Currently, over 55 million people worldwide are living with dementia, and this is projected to more than triple by 2050. It is a slowly progressive neurodegenerative disease, defined by the build-up of amyloid-beta (A) plaques, neurofibrillary tau tangles, inflammation, loss of synapses, and neurons. The disease occurs along a continuum, starting from the preclinical stages of the disease, leading to mild cognitive impairment and eventually the full disease of dementia, with pathological changes occurring decades before the onset of clinical symptoms. We look at genetic risks for AD (e.g., APOE4) as well as cardiovascular and modifiable lifestyle risks. We look at the current treatment strategies that are FDA approved: cholinesterase inhibitors, memantine, and the newly approved anti-amyloid monoclonal antibodies, lecanemab and donanemab, as well as emerging new treatments, non-pharmacological treatments, and preventions. To identify new therapeutic targets to prevent, delay, or modify the disease course and to formulate management strategies, we must appreciate the complex, multifactorial nature of AD.