Many families have acquaintances who use pills to aid sleep. For some individuals, these drugs are useful during periods of anxiety, while for others, they have become part of a continuous usage routine. Medications such as clonazepam, alprazolam, diazepam, zolpidem, and similar ones are among the most prescribed globally; in Brazil, clonazepam (Rivotril®) has been one of the most consumed for years. Simultaneously, news frequently emerges alleging that such substances could increase the probability of developing Alzheimer's disease.
However, a recent review analyzing thirteen large observational studies, in which the author participated, demonstrates that science does not yet have a definitive answer to this question. Researchers confirm, however, that prolonged use of these medications is linked to several side effects affecting cognition and health, regardless of any link to dementia. Understanding this distinction is crucial for correctly interpreting current scientific findings.
In the last two decades, various studies have observed that people who use benzodiazepines or sleeping medications tend to show a higher incidence of Alzheimer's disease years later. At first glance, this suggests that the medication increases the risk. However, in the medical field, a simple association does not necessarily imply that one factor causes the other.
One can imagine a case where, long before an Alzheimer's diagnosis, an individual begins to suffer from insomnia, increased anxiety, and depressive symptoms. This person may seek medical help due to these symptoms and be prescribed a benzodiazepine or a sleeping pill. In this scenario, the medication would not be the trigger for the disease, but rather an indication that the neurodegenerative process was already underway, a phenomenon known as reverse causality.
Differentiating association (when two events occur together frequently) from causality (when one effectively causes the other) constitutes one of the biggest challenges in analyzing observational studies, making the establishment of cause-and-effect relationships in medicine considerably more complex than it appears. It was precisely this problem that drove the research conducted, which consisted of a systematic review with meta-analysis, gathering the main published works on benzodiazepines and medications classified as Z-drugs (such as zolpidem) and the risk of Alzheimer's.
Z-drugs promote sleep more specifically than benzodiazepines, but their extended use is also associated with risks such as dependence, withdrawal syndrome, falls, and fractures. Data from over 720,000 participants from important observational studies were examined, in which researchers monitor people over time without determining who receives or does not receive treatment. By consolidating all the studies, a correlation was identified between the consumption of these drugs and an increased chance of developing Alzheimer's. However, the perception changed when analyzing the data in greater detail, noting that the results showed great variation between different studies.
This means that, with the evidence available currently, it is still not possible to state that there is a cause-and-effect relationship, meaning it cannot be concluded that the medications cause Alzheimer's. However, there is a vital aspect that should not be confused: the fact that science does not yet know if these medications cause the disease does not imply that they are safe for long-term use. Decades of research demonstrate that continuous use of benzodiazepines can deteriorate memory, attention span, information processing speed, and other cognitive functions, particularly in the elderly.
Additionally, these medications increase the risk of dependence, tolerance, daytime drowsiness, falls, fractures, and accidents. These are effects that underpin the recommendations present in various national and international guidelines, advising against prolonged use whenever feasible. Unlike the relationship with Alzheimer's, these risks are well established. Thus, the main scientific dispute does not lie in knowing whether benzodiazepines cause cognitive impairment—because that is known—but rather whether they directly participate in the onset of Alzheimer's disease or merely signal individuals whose neurodegenerative process had already begun before prescription.
Perhaps the most relevant question is why so many people resort to benzodiazepines. Today, it is known that problems with insomnia or poor quality sleep transcend mere quality of life issues. During sleep, especially in the deepest phases, the brain performs vital tasks for its maintenance, including the elimination of proteins and metabolites accumulated throughout the day. Furthermore, chronic sleep disorders are linked to inflammation, metabolic changes, poorer blood pressure control, and increased cardiovascular risk—factors that can contribute to cognitive decline with age. Insomnia itself can be an independent risk factor for cognitive changes in many cases, or represent one of the first signs of undiagnosed neurodegenerative diseases.
So, should the recommendation be to stop using sleeping medications? Benzodiazepines and sleeping aids remain valuable tools in medicine. In specific circumstances—such as intense anxiety attacks, acute insomnia, certain neurological pathologies, and defined psychiatric conditions—they can provide significant benefits and substantially improve quality of life. The core of the problem is rarely the prescription itself, but rather when a treatment initially planned for a few days or weeks is maintained for months or years without periodic reassessment.
Current guidelines remain valid: these medications should be used at the lowest effective dose, for the shortest possible time, whenever feasible, and should be combined with treatment for the cause of insomnia or anxiety and under the supervision of a healthcare professional. The greatest contribution of this research, besides clarifying the absence of definitive conclusions linking the use of benzodiazepines to an increased risk of Alzheimer's, is illustrating how intricate science is compared to what headlines suggest. Identifying an association is only the first step; proving that it constitutes a cause-and-effect relationship is a much greater challenge. Until this answer is consolidated, benzodiazepines should not be seen as harmless medications when used for long periods.
The review reinforces that these findings must be interpreted with caution, given that the available studies are observational, highly heterogeneous, and susceptible to confounding factors and reverse causality. While new investigations seek to define whether these medications directly participate in the development of Alzheimer's disease, the prudent guidance is to focus on sleep quality. Consulting specialist doctors, appropriately diagnosing and treating sleep disturbances, and periodically reassessing the need for these drugs remains one of the most important strategies for preserving brain health during aging.
