Alzheimer Disease

Excerpt

Dementia is a general term used to describe a significant decline in cognitive ability that interferes with a person's activities of daily living. Alzheimer disease (AD) is the most prevalent type of dementia, accounting for at least two-thirds of cases in individuals aged 65 and older. AD is a neurodegenerative condition with insidious onset and progressive impairment of behavioral and cognitive functions. These functions include memory, comprehension, language, attention, reasoning, and judgment. While AD does not directly cause death, it substantially raises vulnerability to other complications, which can eventually lead to a person's death.

According to Centers for Disease Control and Prevention (CDC) data, AD is ranked as the seventh leading cause of death in the United States in 2022, while COVID-19 ranked fourth. Before the COVID-19 pandemic, AD was the sixth leading cause of death following stroke.. AD typically manifests after age 65, referred to as late-onset AD (LOAD). However, early-onset AD (EOAD), occurring before 65, is less common and seen in about 5% of AD patients. EOAD often exhibits atypical symptoms, and its diagnosis is usually delayed, leading to a more aggressive disease course.

Significant progress has been made in developing biomarkers for specific and early diagnosis of AD over the past decade. These biomarkers include neuroimaging markers obtained through amyloid and tau PET scans, cerebrospinal fluid (CSF), and plasma markers, such as amyloid, tau, and phospho-tau levels.

There is no cure for AD, although there are treatments available that may alleviate and manage some of its symptoms. In recent years, there have been significant advancements in the development of medications that aim to moderate the progression of the disease, particularly with the discovery of new disease biomarkers.

The symptoms of AD can vary depending on the stage of the disease. AD is classified into different stages based on the level of cognitive impairment and disability experienced by individuals. These stages include the preclinical or presymptomatic stage, mild cognitive impairment, and dementia stage. The dementia stage is further divided into mild, moderate, and severe stages (see Graph. AD Stages from Preclinical to Severe Disease). This staging system is distinct from the diagnostic criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) for AD.

Episodic short-term memory loss is the initial and most common presenting symptom of typical AD. Individuals may have difficulty retaining new information while still recalling long-term memories. Individuals may experience problem-solving, judgment, executive functioning, and organizational skills impairments following short-term memory loss.

They may struggle with tasks that require multitasking and abstract thinking. In the early stages of the disease, executive functioning impairments can range from subtle to significant. Instrumental activities of daily living such as driving, financial management, cooking, and detailed activity planning are affected relatively early in their dementia.

These early signs of cognitive decline are followed by language disorder and impaired visuospatial skills. Neuropsychiatric symptoms like apathy, social withdrawal, disinhibition, agitation, psychosis, and wandering are also common in the moderate to late stages. Difficulty performing learned motor tasks (dyspraxia), olfactory dysfunction, sleep disturbances, and extrapyramidal motor signs like dystonia, akathisia, and Parkinsonian symptoms occur late in the disease. Primitive reflexes, incontinence, and total dependence on caregivers follow this.