Alzheimer's Disease – Another Pandemic on the Horizon?

Unstoppable Increase in Prevalence

Dementia is a clinical syndrome characterized by a decline in intellect and other cognitive functions, which results in a disruption of daily activities and self-care. It adversely affects not only patients but society as a whole. Globally, dementia affects approximately 47 million people, and by 2050, this number is likely to at least double.

Etiopathogenesis and Initial Symptoms

The most common type of dementia is Alzheimer's dementia. During its course, there is an increased formation of amyloid plaques (composed of beta-amyloid) and neurofibrillary tangles (tau protein) and a progressive loss of cortical cells in the brain, hippocampus, and subcortical areas.

The onset of difficulties is usually insidious and subtle, often first noticed by the patient's surroundings. It primarily involves problems with learning and remembering information, word distortion, mood swings, and personality changes. In the next phase (moderate dementia), problems deepen, the patient forgets the names of family members, loses self-sufficiency, and requires assistance with washing, toileting, or eating. They lose the ability to perceive time and space, wandering around the apartment or nearby areas. Illusions or hallucinations may appear. In the terminal phase, there is a total breakdown of personality and complete dependence on others, along with pseudobulbar impairment.

Clinical Picture and Diagnosis

The diagnosis of Alzheimer's disease relies mainly on clinical manifestations. In the first phase, after raising suspicion, a neurological and neuropsychological examination should follow, along with detailed history taking from both the patient and their close ones. A crucial criterion is the presence of dementia defined as a newly arising long-term impairment in cognition in at least two cognitive domains leading to impaired self-sufficiency. A typical history involves a gradual onset and worsening.

Supportive criteria include biomarker evaluation – decreased amyloid β42 in cerebrospinal fluid, positive positron emission tomography (PET) with amyloid β binding ligands, increased tau and phospho tau in cerebrospinal fluid, hypometabolism in the temporal and parietal cortex on FDG-PET, and temporal and parietal atrophy detected by brain imaging using magnetic resonance imaging (MRI).

Comprehensive Therapy Approach

The treatment of Alzheimer's dementia should be comprehensive. Accompanying symptoms or comorbidities such as depression, anxiety states, sleep disorders, and behavioral problems, as well as patient activation, should not be neglected. Regarding the therapy of cognitive disorders, so-called nootropics (cholinesterase inhibitors and memantine) are used. This is not causal treatment but a method to slow the progression of symptoms, ensuring the preservation of self-sufficiency and prolonging the ability to stay in one's own environment.

Mild to Moderate Stage

In the treatment of mild to moderate stages of Alzheimer's dementia, cholinesterase inhibitors are indicated.

One of these is donepezil, a reversible non-competitive inhibitor of acetylcholinesterase with a high degree of selectivity for the central form of the enzyme and low affinity for peripheral forms. Due to this action, the breakdown of acetylcholine is reduced, leading to an increase in cholinergic transmission in the synaptic cleft. The advantage of donepezil is its long half-life, which allows for once-daily dosing.

Another cholinesterase inhibitor is rivastigmine. It facilitates cholinergic transmission by slowing the breakdown of acetylcholine released by functionally intact cholinergic neurons.

The third drug in this group is galantamine. Besides inhibiting brain acetylcholinesterases, it also demonstrates significant neuroprotective and anti-inflammatory effects.

Moderate to Severe Stage

For moderate to severe forms of Alzheimer's dementia, both cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists are indicated. An example is memantine, a non-competitive NMDA receptor antagonist that modulates glutamatergic transmission in the central nervous system. It adjusts the effects of pathologically elevated excitatory levels of glutamate, which can lead to neuronal dysfunction.

Don't Forget Prevention

Although the effectiveness of nootropics has been demonstrated by numerous extensive studies, primary prevention remains a fundamental aspect capable of influencing the adverse trend. Therefore, patients should be encouraged to engage in sufficient mental and physical activity, follow a quality diet, and maintain a healthy sleep regimen.

(dos)

Sources:
1. Arvanitakis Z., Shah R.C., Bennett D.A. Diagnosis and management of dementia: review. JAMA 2019; 322 (16): 1589-1599, doi: 10.1001/jama.2019.4782.
2. Atri A. The Alzheimer's disease clinical spectrum: diagnosis and management. Med Clin North Am 2019; 103 (2): 263–293, doi: 10.1016/j.mcna.2018.10.009.