Alzheimer's disease: a review on the current trends of the effective diagnosis and therapeutics

Abstract

The most prevalent cause of dementia is Alzheimer's disease. Cognitive decline and accelerating memory loss characterize it. Alzheimer's disease advances sequentially, starting with preclinical stages, followed by mild cognitive and/or behavioral impairment, and ultimately leading to Alzheimer's disease dementia. In recent years, healthcare providers have been advised to make an earlier diagnosis of Alzheimer's, prior to individuals developing Alzheimer's disease dementia. Regrettably, the identification of early-stage Alzheimer's disease in clinical settings can be arduous due to the tendency of patients and healthcare providers to disregard symptoms as typical signs of aging. Therefore, accurate and prompt diagnosis of Alzheimer's disease is essential in order to facilitate the development of disease-modifying and secondary preventive therapies prior to the onset of symptoms. There has been a notable shift in the goal of the diagnosis process, transitioning from merely confirming the presence of symptomatic AD to recognizing the illness in its early, asymptomatic phases. Understanding the evolution of disease-modifying therapies and putting effective diagnostic and therapeutic management into practice requires an understanding of this concept. The outcomes of this study will enhance in-depth knowledge of the current status of Alzheimer's disease's diagnosis and treatment, justifying the necessity for the quest for potential novel biomarkers that can contribute to determining the stage of the disease, particularly in its earliest stages. Interestingly, latest clinical trial status on pharmacological agents, the nonpharmacological treatments such as behavior modification, exercise, and cognitive training as well as alternative approach on phytochemicals as neuroprotective agents have been covered in detailed.

Keywords: AD; Alzheimer’s disease; clinical trial; dementia; diagnosis; treatment.

FIGURE 1

Alzheimer’s pathogenesis based on two classical hallmarks on amyloid beta and neurofibrillary tangles.

FIGURE 2

The AD continuum can be categorized into various stages, ranging from preclinical AD to severe AD dementia. The terminology used to describe each stage can vary based on the specific clinical and scientific classifications. This diagram presents an overview of the naming standards employed in the AD community, along with the symptoms associated with each stage of the continuum. Aβ, amyloid beta; AD, Alzheimer’s disease; FDA, Food and Drug Administration; IWG, International Working Group; MCI, mild cognitive impairment; NIA-AA, National Institute on Aging—Alzheimer’s Association. Adaptation and modification from Porsteinsson et al. (2021).

FIGURE 3

Illustration of neurodegenerative deterioration in the brain and associated indicators. As portrayed, brain damage could be caused by the deposition of amyloid beta protein in the brain, resulting in amyloid plaques, as well as the creation of neurofibrillary tangles among neurons. These alterations cause the loss of neurons in the cortex, the brain’s outer layer. The results imply that brain traumas sustained in the NfL may raise the incidence of AD.

FIGURE 4

(A) Visualization of current drugs (donepezil, galantamine, rivastigmine) (B) mechanism of action of memantine for Alzheimer’s disease (AD). Adaptation from Breijyeh and Karaman (2020).

FIGURE 5

Summary of pharmacological approaches for AD involving amyloid-related DMTs strategies, tau-related DMT strategies and other DMTs mechanisms.