Could Your Genes Increase Dementia Risk from Common Medications, like Benadryl?

Millions of people take anticholinergic drugs to treat conditions like depression, overactive bladder, allergies, and Parkinson's disease. However, these commonly prescribed medications come with an insidious risk - they may increase your chances of developing dementia. Even more concerningly, new research shows certain gene variants can significantly amplify this risk.

What Are Anticholinergic Drugs?

Anticholinergics work by blocking the neurotransmitter acetylcholine in the brain and body. This can help treat various disorders related to overactive muscles and glands. However, acetylcholine also plays a key role in memory, concentration, and other cognitive processes.

Common anticholinergic drugs include:

• Antidepressants like amitriptyline (Elavil) and paroxetine (Paxil)
• Antihistamines like diphenhydramine (Benadryl)
• Antipsychotics like olanzapine (Zyprexa) and quetiapine (Seroquel)
• Overactive bladder drugs like oxybutynin (Ditropan) and tolterodine (Detrol)
• Parkinson's medications like benztropine (Cogentin)

The Dementia Link

Over a dozen large studies have found long-term use of anticholinergic drugs is associated with higher dementia risk, including Alzheimer's disease. The more you take and the longer you take them, the greater the potential brain impacts.

A 2015 study found dementia risk increased by 50% in people taking anticholinergic drugs for 3+ years, compared to non-users. A 2019 study estimated 10% of dementia cases are potentially attributable to anticholinergic medications.

The potential mechanisms behind this association are not fully understood, but it is believed that the blockade of acetylcholine by these drugs can disrupt cognitive processes and lead to neuronal damage over time.

Some key points about the link between anticholinergic drugs and dementia risk:

1. Dose-response relationship: Higher cumulative exposure to anticholinergic drugs, either through higher doses or longer duration of use, is associated with a greater risk of developing dementia.
2. Elderly population: The risk appears to be more significant in older adults, as they are more susceptible to the cognitive effects of anticholinergic drugs and may have underlying age-related brain changes.
3. Cognitive decline: Studies have shown that anticholinergic drugs can impair cognitive functions such as memory, attention, and executive function, which are also affected in dementia.
4. Potential reversibility: Some research suggests that the cognitive impairment associated with anticholinergic drug use may be partially reversible if the drugs are discontinued.

It is important to note that the evidence is based on observational studies, and more research is needed to establish a direct causal relationship. However, given the potential risks, healthcare professionals generally recommend using anticholinergic drugs with caution, especially in older adults, and minimizing their use when possible. Regularly reviewing medication regimens and considering alternative treatments with lower anticholinergic burden is advisable, particularly for individuals at higher risk of developing dementia.

Your Genes Could Amplify the Risk

New research reveals certain gene variants may drastically increase the dementia risk from anticholinergic exposure. The strongest association is with the APOE gene, which produces apolipoprotein E implicated in Alzheimer's disease.

About 25% of people carry the high-risk APOE4 variant. Those with this genetic risk factor who also take anticholinergic drugs long-term have more than double the dementia risk versus non-carriers taking the same medications.

Other potentially relevant genes include:

1. BCHE: Codes for an enzyme that breaks down acetylcholine. Variants may amplify cognitive effects of anticholinergics.
2. CHAT: Involved in acetylcholine production. Variants may increase vulnerability.
3. CHRM genes: Code for the muscarinic acetylcholine receptors targeted by these drugs.

Reducing Your Risk

If you currently take an anticholinergic medication, don't stop cold turkey as withdrawal can be dangerous. However, discuss alternatives with your doctor, especially if you have concerning genetic variants.

Other tips to reduce dementia risk:

1. Use the lowest effective dose for the shortest duration
2. Monitor for early cognitive changes
3. Adopt brain-healthy lifestyle habits like exercise and mental stimulation
4. Consider supplements like curcumin with anti-inflammatory and neuroprotective effects
5. Ask your pharmacist about your anticholinergic burden from all medications

For those at increased genetic risk, minimizing anticholinergic exposure may be prudent whenever feasible. While more research is still needed, being proactive about this risk could help preserve your brain health for the future.