Tuning into the Stages and Symptoms of Alzheimer’s Disease

Writers: Vijaya Varadarajan, Prahalad Srinivasan and Brianna Viets

Preclinical Stage: 

The brain starts to neurologically change even though there are no detectable symptoms. AD neuropathology begins to build up, however, cognitive performance has yet to decline. The accumulation of the notorious amyloid plaques and tau tangles creep in the brain for 15 to 20 years before symptoms start to show. This is the preclinical stage. This stage is the most optimal in early detection, because biomarkers and therapeutics work best at early stages. Individuals that are genetically predisposed, via hereditary factors or exposed to the APOE genotype, should be aware of the preclinical stage. Seeing their doctors regularly and participating in early detection tests. On a similar page of early detection, it is important for people who know the affected individual well enough to identify differences between what he/she could have done in the past and is now incapable of doing. Affected individuals can themselves report worsening of their cognitive capabilities, which is known as Subjective Cognitive Impairment (SCI). [1]

Preclinical Stage: 

• Episodic Memory Loss: this is due to hippocampal damage and executive defects. 

• Reduced Word and list learning curves compared to normal aging

• Lower-than-expected free delayed recall: delayed recall is a verbal learning test that is used to measure amnesic mild cognitive impairment (aMCI) and early AD. 

• The earliest changes in behavior are: 

• Apathy 

• Dysphoria 

• Impaired insight

Figure 1 depicts the overall change in cognitive function over years between normal aging and aging with AD.

Prodromal Stage:

After patients experience the Preclinical stage, AD progressively gets worse, this is the Prodromal stage. During this stage, the symptoms of the patient are easily noticeable, but not yet severe. Oftentimes, patients at this stage are able to notice cognitive decline but since it is not severe, they choose not to report this to their doctor. This could be a dangerous mistake to make, as it could be the onset of severe dementia. In this stage, it is crucial for those close to the patient to notice key signs of mental decline and encourage the patient to report it to a doctor. During the prodromal stage, significant chemical changes occur within the brain, such as accumulation of the hemoprotein neuroglobin (Ngb), a protein that is responsible for shielding the brain from Alzheimer’s. However, when these defenses wear out, Alzheimer’s can quickly progress to the most severe stage, dementia. [1]

Symptoms in Prodromal Stage:

• Short-term memory deficits

• Difficulties with performing common tasks (driving, working, ect.)

• Neuropsychiatric disturbances

• Could result in: mood changes, apathy, irritability

Dementia Stage:

After a patient experiences the stages of brain dysfunction and prodromal AD, the dementia AD stage becomes apparent. They may begin to exhibit signs of progressive short-term memory loss, which is then followed by long-term memory loss. Short-term memory loss examples could include a patient accidentally misplacing their personal belongings, despite having familiar areas where they would typically put them. Moreover, they may begin to repeat questions they had previously asked, and their vocabulary may become limited as they start to forget certain words. A patient might have difficulty recalling the meaning of a word and lose the ability to correctly describe something. Their cognitive and executive functions will be significantly impacted as well; there will be a decline in their capability to think more concretely, use good judgment, think ahead, multitask, and recognize faces or places. Once a patient begins to reach the later stage of dementia AD, they will not be able to perform basic skills that include driving, cooking, cleaning, bathing, or even dressing. Additionally, some patients will exhibit certain negative attitudes—irritability, delusions, anger, restlessness, and anxiety—that often lead to their entrance to a neuropsychiatric institution for aid. Once they have been diagnosed with the progressive neurodegenerative disease at this late stage, caregiving support is usually recommended to assist with financial, social, and health related aspects. [1]

Figure 2 discusses the various key characteristics of the AD stages