Chemotherapy for Alzheimer’s disease

People who receive chemotherapy to treat cancer are less likely to develop Alzheimer’s disease in later years.

Chronic diseases (cardiovascular diseases, cancers, dementia and diabetes, in particular) are most of the time considered as independent pathologies, which have no links between them.

However, this is not the case: for example, it is well established that diabetes considerably increases the risk of cardiovascular disease, cancer and dementia, that cancer can increase the risk of myocardial infarction and, conversely, that Cardiovascular disease increases the chances of developing cancer.

These interactions therefore suggest that the development of these chronic diseases does not occur in isolation, but rather involves certain common biochemical and physiological mechanisms. This is why it is possible to reduce the risk of developing all of these diseases by adopting the five golden rules of prevention, namely:

1. NO SMOKING
2. Maintain normal body weight
3. Eat well (vegetables, whole grains, fish, little red meat)
4. Do regular physical activity (40 min./day walking or cycling, for example)
5. Drink alcohol in moderation (maximum of 1 drink/day for women, 2 drinks/day for men)

Cancer and Alzheimer’s disease

One of the most surprising links between different chronic diseases is that which seems to exist between cancer and dementias such as Alzheimer’s disease.

At first glance, however, the two diseases are very different: cancer is caused by faulty genes that lead to uncontrolled cell growth, while Alzheimer’s disease is characterized by the accumulation of amyloid plaques and neurofibrillary tangles that lead to neurodegeneration leading to an alteration of behavior, personality and all cognitive functions (reasoning, analysis, language).

However, several population studies have consistently observed a lower risk of Alzheimer’s disease among people with various types of cancers, including lung, kidney, colorectal and lymphoma, even when taking into account the potential reduction in life expectancy in patients⁽¹⁾.

It has been suggested that chemotherapy used for the treatment of these cancers could have protective effects on dementia, possibly by targeting certain phenomena common to both types of diseases (abnormal cell division cycle, deficient recycling of cellular components by autophagy, stress high oxidative).

Anti-Alzheimer chemotherapy

To better characterize this phenomenon, a group of Korean researchers examined the incidence of Alzheimer’s disease in 116,506 cancer patients aged 65 and older who received different types of anticancer drugs between 2008 and 2018.⁽²⁾.

Two main types of chemotherapy have been evaluated, namely antimetabolites (which interfere with the production of DNA and therefore with cell division and the growth of tumors) and targeted therapies, which act by specifically blocking one or more proteins essential for progression of cancer (Herceptin, used for the treatment of breast cancers overexpressing the EGF receptor, for example).

The analysis shows that treating patients with antimetabolites is associated with a slight reduction (9%) in Alzheimer’s disease, but that this protection is much more pronounced in those who received targeted therapies, including Alzheimer’s inhibitors. EGF receptor (40% reduction) and multikinase inhibitors (51% reduction).

In all cases, chemotherapy drugs have no effect on the incidence of dementia caused by vascular pathologies (e.g. stroke), which suggests that these molecules have a site of action at the level neurons as such.

These results are interesting because there is still no truly effective treatment for Alzheimer’s disease. An antibody that prevents the deposition of beta-amyloid responsible for the disease (lecanemab) was recently approved by the American FDA, but its impact seems rather modest and significant side effects (cerebral hemorrhage) have been observed (not to mention its very high cost). high, almost $30,000 per year).

The potential use of certain anticancer drugs or their derivatives to prevent the development of Alzheimer’s disease could therefore represent an important breakthrough for the treatment of this devastating disease.

⁽¹⁾ Zhang DD et coll. Risk of dementia in cancer survivors: A meta-analysis of population-based cohort studies. J. Alzheimer’s Dis. 2022; 89: 367–380.
⁽²⁾ Lee EH et coll. Dementia incidence varied by anticancer drugs and molecular targeted therapy in a population-based cohort study. Sci. Rep. 2024; 14: 17485.