Alzheimer's Disease | Is This Common Form of Dementia Preventable?

Alzheimer's disease is fundamentally characterized by two key abnormalities in the brain: amyloid plaques and neurofibrillary tangles. Amyloid plaques are dense, sticky clumps of a protein fragment called beta-amyloid that accumulate in the spaces between nerve cells (neurons). In a healthy brain, these fragments are broken down and eliminated. In Alzheimer's, they aggregate, disrupting communication between neurons and triggering an inflammatory response that can further damage brain cells. The second hallmark, neurofibrillary tangles, forms inside the neurons themselves. They are twisted fibers of another protein called tau. The tau protein's normal function is to stabilize microtubules, which are essential for transporting nutrients and other molecules within the cell. In Alzheimer's, tau proteins become abnormal, detaching from microtubules and clumping together. This collapse of the internal transport system leads to impaired synaptic communication and, ultimately, cell death. The accumulation of these plaques and tangles is not random; it typically begins in brain regions crucial for memory, such as the hippocampus and entorhinal cortex, and then spreads to other areas as the disease progresses, explaining the gradual decline in cognitive functions.

The progression of Alzheimer's disease is a gradual continuum of cognitive and functional decline. In the earliest stage, often referred to as preclinical Alzheimer's, the pathological changes are occurring in the brain, but individuals show no obvious symptoms. As the disease advances to the mild cognitive impairment (MCI) stage, individuals experience memory lapses, such as forgetting recent conversations or appointments, that are noticeable but do not significantly interfere with daily life. When the condition progresses to Alzheimer's dementia, the cognitive decline becomes more pronounced. Short-term memory is severely affected, and individuals may struggle with problem-solving, planning, and language (e.g., finding the right words). As the disease moves from the mild to moderate stages, confusion worsens, and individuals may get lost in familiar places or have difficulty performing routine tasks. Personality and behavioral changes, such as irritability or withdrawal, are also common. In the severe, final stage, individuals lose the ability to communicate, respond to their environment, and perform basic self-care. They become completely dependent on others for their care as brain tissue shrinks significantly.

The primary distinction between early-onset and late-onset Alzheimer's is the age of diagnosis. Late-onset Alzheimer's is the most common form, accounting for over 95% of cases, and it typically develops after the age of 65. Its etiology is complex, involving a combination of genetic susceptibility—most notably the APOE ε4 gene variant—environmental factors, and lifestyle choices. In contrast, early-onset Alzheimer's is rare and is diagnosed in individuals younger than 65. While some cases have the same risk factors as the late-onset form, a significant portion is linked to specific genetic mutations in one of three genes: amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2). These mutations are inherited in an autosomal dominant pattern, meaning that inheriting just one copy of the mutated gene from a parent is sufficient to cause the disease.

While both forms of Alzheimer's share the same underlying pathology of plaques and tangles, there can be differences in the initial presentation of symptoms and the rate of progression. Late-onset Alzheimer's most classically begins with deficits in short-term memory and episodic memory. Early-onset Alzheimer's, particularly the genetically driven form, can sometimes present with atypical symptoms. For example, some individuals may first experience difficulties with language (logopenic aphasia), visuospatial processing (posterior cortical atrophy), or executive functions like planning and decision-making, with memory problems emerging later. The progression in early-onset cases can also be more aggressive and rapid compared to the late-onset form, leading to a faster decline in cognitive and functional abilities.

Beyond the well-established genetic risks, several modifiable and non-modifiable factors influence the likelihood of developing late-onset Alzheimer's. The single greatest non-modifiable risk factor is advancing age. However, numerous lifestyle and cardiovascular factors play a crucial role. Conditions that affect the heart and blood vessels, such as high blood pressure, high cholesterol, type 2 diabetes, and obesity, are strongly linked to an increased risk of Alzheimer's. This highlights the critical connection between cardiovascular health and brain health; a healthy blood supply is essential for optimal brain function. Other modifiable risk factors include a sedentary lifestyle, a diet low in fruits and vegetables, smoking, and excessive alcohol consumption. Conversely, maintaining a physically active lifestyle, engaging in continuous learning and socially stimulating activities, and adopting a balanced diet like the Mediterranean diet have been shown to be protective and may help delay or reduce the risk of cognitive decline.