Overlooked cases of mild cognitive impairment: Implications to early Alzheimer's disease

Abstract

Mild cognitive impairment (MCI) marks the initial phase of memory decline or other cognitive functions like language or spatial perception, while individuals typically retain the capacity to carry out everyday tasks independently. Our comprehensive article investigates the intricate landscape of cognitive disorders, focusing on MCI and Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD). The study aims to understand the signs of MCI, early Alzheimer's disease, and healthy brain aging while assessing factors influencing disease progression, pathology development and susceptibility. A systematic literature review of over 100 articles was conducted, emphasizing MCI, AD and ADRD within the elderly populations. The synthesis of results reveals significant findings regarding ethnicity, gender, lifestyle, comorbidities, and diagnostic tools. Ethnicity was found to influence MCI prevalence, with disparities observed across diverse populations. Gender differences were evident in cognitive performance and decline, highlighting the need for personalized management strategies. Lifestyle factors and comorbidities were identified as crucial influencers of cognitive health. Regarding diagnostic tools, the Montreal Cognitive Assessment (MoCA) emerged as superior to the Mini-Mental State Examination (MMSE) in early MCI detection. Overall, our article provides insights into the multifaceted nature of cognitive disorders, emphasizing the importance of tailored interventions and comprehensive assessment strategies for effective cognitive health management.

Keywords: Cognitive disorders; Early detection; Healthy brain aging; Intervention strategies; Mild Cognitive Impairment (MCI).

Figure 1:. Symptoms of Alzheimer’s Disease (AD).

(Drafted by BioRender). This infographic provides a visual representation of the symptoms commonly associated with Alzheimer’s Disease (AD). These visuals help to convey the multifaceted nature of the symptoms experienced by individuals with AD. Additionally, the infographic emphasizes the progression of symptoms from the early stages of the disease to its more advanced forms. The infographic also highlights the relationship between Mild Cognitive Impairment (MCI) and AD. MCI serves as a precursor to AD, representing a milder form of cognitive decline characterized by subtle changes in memory and thinking abilities. Individuals with MCI may exhibit early signs of some AD symptoms, such as mild forgetfulness or difficulty with cognitive tasks. Over time, MCI can progress to AD, with individuals experiencing a gradual worsening of symptoms.

Figure 2:. Pathological Changes in Synapse Associated with Alzheimer’s Disease (AD).

(Drafted by BioRender). This infographic provides an illustrative depiction of the pathological alterations occurring within a synapse in Alzheimer’s Disease (AD). Central to the depiction are numerous β-amyloid oligomers located within the synapse. These oligomers play a pivotal role in AD pathology, as they activate microglia, the immune cells of the brain, leading to neuroinflammation. This inflammatory response exacerbates neuronal damage and contributes to the degenerative process characteristic of AD. The infographic also illustrates the presence of tau proteins, which are abnormally aggregated within both the pre-synaptic and post-synaptic neurons. These tau protein accumulations disrupt normal neuronal function and contribute to synaptic dysfunction. Furthermore, the infographic highlights the dysregulation of calcium ions within the pre-synaptic neuron. Calcium ions enter the neuron through channels, leading to an accumulation within the endoplasmic reticulum and subsequent calcium overload. This disruption in calcium homeostasis further compromises synaptic integrity and neuronal viability. Moreover, the depiction includes the bursting of mitochondria within the pre-synaptic neuron, indicative of mitochondrial dysfunction—a hallmark feature of AD pathology. Mitochondrial dysfunction results in impaired energy production and oxidative stress, contributing to synaptic degeneration and neuronal death. Importantly, these pathological changes depicted in the infographic are not exclusive to advanced stages of AD but also manifest in Mild Cognitive Impairment (MCI). As MCI progresses, these pathological alterations intensify, leading to the development of full-blown AD.

Figure 3:. Pathology of MCI and Alzheimer’s Disease in Relation to a Healthy Brain.

(Drafted by BioRender). This infographic offers a concise representation of the neurological changes associated with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) compared to a healthy brain. Positioned between the healthy and AD states, the MCI stage highlights the critical juncture where cognitive decline may either progress to AD or potentially regress to a healthier brain state, contingent upon an array of factors. Lifestyle choices, genetic predispositions, and comorbidities play pivotal roles in determining the trajectory of cognitive health. While individuals with MCI may advance to AD due to the depicted pathological changes, proactive management of modifiable risk factors, genetic influences, and comorbid conditions can facilitate regression toward a healthier brain state. This dynamic portrayal underscores the importance of multifaceted interventions aimed at preserving cognitive function and mitigating the progression of AD.

Figure 4:. Lifestyle Factors in Brain Health.

(Drafted by BioRender). This infographic visually presents the approach of factors on brain health that may progress or delay the onset of Alzheimer’s Disease (AD) depending on one’s lifestyle factors. Lifestyle modifications are emphasized as pivotal strategies for promoting brain health. These lifestyle choices have been extensively discussed in this article as effective measures for reducing the risk of cognitive decline and AD onset. Importantly, these choices hold promise not only for individuals experiencing Mild Cognitive Impairment (MCI) but in healthy individuals to not worsen brain health- MCI and healthy individuals may benefit from lifestyle modifications to delay the progression to AD. By targeting lifestyle factors, this approach offers insights from different avenues of life for mitigating the risk of AD onset and preserving cognitive function across the continuum of cognitive decline from MCI to AD.