Molecular pathways and biomarkers associated with age-related cognitive decline

Age-related cognitive decline is the gradual decrease in memory, reduced attention, difficulty with multitasking, reduced ability to recall information, and decreased processing speed with age. These changes are considered normal, and the rate and extent of cognitive decline can be significantly impacted by genetics and environmental factors, such as lifestyle behavior, diet, and physical activity. Mild cognitive impairment (MCI) is an intermediate phase between normal aging and Alzheimer’s disease (AD). MCI is a risk factor for Alzheimer’s disease, but not all individuals with MCI develop AD. There exists a significant challenge in diagnosing MCI and early Alzheimer’s disease as they involve very subtle differences in cognitive ability. Thus, several studies are focused on identifying biomarkers that could be utilized for early diagnosis. The decline in cognition with age is influenced by several molecular processes that include protein aggregation, synaptic and mitochondrial dysfunction, epigenetic changes, and oxidative damage. The interplay between these mechanisms can be tracked using genetic, neurophysiological, neuroimaging, biochemical, and neuroinflammatory biomarkers. Despite the existence of several molecular biomarkers, detecting cognitive decline before the clinical symptoms appear remains challenging. There is an unmet need for reliable and non-invasive biomarkers that can precisely monitor the impact of lifestyle on normal aging, which would be able to identify individuals at risk of cognitive decline. In this review, we have summarized the different classes of biomarkers that have been associated with age-related cognitive decline and highlighted the need for integrating different approaches for accurate diagnosis of early cognitive decline.