Dementia risk in common over the counter drugs

Common medications far from harmless for those at risk of dementia: study.

Female pharmacist discusses medication with senior customer

Freely available drugs used for allergies and colds may be associated with an increased risk of cognitive decline, including those at risk of Alzheimer’s disease.

A study published in the journal Neurology focuses on anticholinergic drugs, many of which can be bought over the counter at the chemist.

The researchers reported that cognitively normal study participants taking at least one anticholinergic drug were 47 per cent more likely to develop mild cognitive impairment (MCI), often a precursor to various types of dementia including Alzheimer’s.

“This study suggests that reducing anticholinergic drug use before cognitive problems appear may be important for preventing future negative effects on memory and thinking skills,” said study author Associate Professor Lisa Delano-Wood, from the University of California San Diego in the US.

Anticholinergics are often used to inhibit the involuntary movements of muscles or balance the production of chemicals in the body. They are used to treat conditions as varied as depression, epilepsy, urinary incontinence and hypertension, but some cold and flu medications also contain anticholinergic properties.

Dementia Australia says anticholinergic drugs may be used by up to 60 per cent of older Australians at some time and an estimated 33 per cent of Australians over the age of 65 take enough medications with anticholinergic effects to potentially increase their risk of harm.

None of the study’s 688 participants, with an average age of 74, displayed cognitive or memory problems at the start of the study. One-third were taking anticholinergic medications, with an average of 4.7 anticholinergic drugs per person. Participants undertook annual cognitive tests for up to 10 years.

The scientists also examined whether participants had biomarkers for Alzheimer’s in their cerebrospinal fluid. They found that participants with Alzheimer’s biomarkers who took anticholinergic drugs were four times more likely to develop MCI than those without biomarkers and not taking the drugs.

People with a genetic risk for Alzheimer’s who took anticholinergic drugs were 2.5 times more likely to develop MCI than those without genetic risk factors who were not taking the drugs.

“We believe this interaction between anticholinergic drugs and Alzheimer's risk biomarkers acts in a ‘double hit’ manner,” said Alexandra Weigand, the study's lead author.

“In the first hit, Alzheimer's biomarkers indicate that pathology has started to accumulate and degenerate in a small region called the basal forebrain that produces the chemical acetylcholine, which promotes thinking and memory.

“In the second hit, anticholinergic drugs further deplete the brain's store of acetylcholine. This combined effect most significantly impacts a person's thinking and memory.”

Study authors noted that older adults often took anticholinergic medications at levels much higher than the lowest effective dose recommended for older adults, with 57 per cent taken at twice the recommended dosage and 18 per cent at four times the recommended dosage.

“This points to a potential area for improvement, since reducing anticholinergic drug dosages may possibly delay cognitive decline,” said Ms Weigand.

“It's important for older adults who take anticholinergic medications to regularly consult with their doctors and discuss medication use and dosages.

“Clinical ‘deprescribing’ studies are currently underway at certain research sites across the nation in an effort to investigate whether reducing or stopping use of these drugs does, in fact, lead to reductions in progressive cognitive impairment,” Assoc. Prof. Delano-Wood said.

The study confirms the findings of a 2015 study undertaken by the Group Health Research Institute and the University of Washington, Seattle. The Cumulative Use of Strong Anticholinergic Medications and Incident Dementia study concluded: “Higher cumulative anticholinergic medication use is associated with an increased risk for dementia. Efforts to increase awareness among health professionals and older adults about this potential medication-related risk are important to minimise anticholinergic use over time.”

That study began in 1994, with follow-ups every two years and involved 3434 participants aged 65 and older who had no dementia when the study began.

It found that higher cumulative use of anticholinergic medications was associated with “an increased risk of all-cause dementia and Alzheimer’s disease”.

“It is worth noting that the increased risk for dementia was consistent across anticholinergic subclasses, with increased risk found for people with high use of anticholinergic medications other than antidepressants, such as first generation antihistamines and bladder antimuscarinics.

“We found that among the heaviest users, people who had past heavy use had a similar dementia risk as those with recent or continued heavy use. This suggests that the risk for dementia with anticholinergic use may persist despite discontinuation.

“In a small autopsy study of patients with Parkinson’s disease, participants that were receiving anticholinergic drugs for two years or longer had increased levels of AD neuropathology compared with those using for shorter durations.

“Prescribers should be aware of this potential association when considering anticholinergic medications for their older patients and should consider alternatives when possible. For conditions where therapeutic alternatives may not be available, prescribers should use the lowest effective dose and discontinue therapy if ineffective. These findings also have public health implications for education of older adults about potential safety risks since some anticholinergic medications are available as over the counter (OTC) products.

“Given the devastating consequences of dementia, informing older adults about this potential modifiable risk would allow them to choose alternative products and collaborate with their health professionals to minimise overall anticholinergic use.”

The June 2019 study Anticholinergic Drug Exposure and the Risk of Dementiaanalysed associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.

It was unequivocal about the danger of such medications.

“Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.

“In this nested case-control study of 58,769 patients with a diagnosis of dementia and 225,574 matched controls, there were statistically significant associations of dementia risk with exposure to anticholinergic antidepressants, anti-Parkinson’s drugs, antipsychotic drugs, bladder antimuscarinics and antiepileptic drugs after adjusting for confounding variables.

“The associations observed for specific types of anticholinergic medication suggest that these drugs should be prescribed with caution in middle-aged and older adults.”

Are you concerned about medications you take? Has your doctor discussed the dangers of any medications he or she may have prescribed?

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    COMMENTS

    To make a comment, please register or login
    clancambo
    9th Sep 2020
    10:51am
    What drugs are we talking about here?
    This is straight out of a scientific journal and NOT informative at all!
    TighterWriter
    9th Sep 2020
    10:54am
    Exactly! See my comment...
    Laura52
    9th Sep 2020
    11:01am
    Hi Clancambo

    I am a pharmacist, well made redundant so now retired to care for my vulnerable elderly parents, ( won't risk passing covid onto them) ...I can answer this one for you. The over counter drugs only available in Australia that do this are Polaramine and Demazin, which contain sedating antihistamines and also nausetil, which is used for nausea associated with migraine. Pharmacists can only recommend these medications. I agree this is straight out of a scientific journal.
    TighterWriter
    9th Sep 2020
    10:53am
    It would be far more helpful to have identified some of these ‘over the counter’ drugs. I imagine that some people might not necessarily have the resources to research common preparations, as to whether they contain anticholinergic properties. An article that more clearly targeted people in this group, with appropriate warnings and advice to consult their doctors would have been a good idea.
    Laura52
    9th Sep 2020
    11:03am
    Hi TightWriter, see my post. I mentioned the over the counter medication available in Australia. The over counter medications mentioned in the article from the USA can be quite different in ingredients. I agree with you totally!
    TighterWriter
    9th Sep 2020
    11:06am
    Thank you, Laura52
    I had found a list which included those you mentioned. Possibly the others in the list were differently formulated in the US. This is why we need comments from people like you rather than cut-and-paste ‘articles’ which might alarm some people.
    Laura52
    9th Sep 2020
    11:11am
    Your welcome TighterWriter. The medications I mentioned are the common ones used in Australia. I wouldn't give a sedating histamine to an elderly person, as the new generation non sedating antihistamines are safer. I am very conservative when it comes to over the counter medications. I don't even recommend Nausetil for migraines/headaches because of the side effect profile. I refer the patient to the doctor. That was when I worked as a pharmacist...don't want to go back to it for many reasons. Queensland wants pharmacies to do COVID-19 testing....trialing it. Yes, you heard it from the horses mouth, so to speak.
    tobymyers
    9th Sep 2020
    11:18am
    I was just about to say what a useless article that does not list the drugs ..as useful as tits on a bull
    Laura52
    10th Sep 2020
    7:59am
    Indeed Tobymyers and it is actually not an Australian article!
    Bkk Chris
    9th Sep 2020
    10:59am
    a useless posting as we need the common names for the drugs mentioned, not just the scientific name for the group of drugs, Come on you guys can do better.
    Laura52
    9th Sep 2020
    11:07am
    Hi Bkk Chris...see my post, the medication that is available in Australia over the counter are Demazin, sedating histamine which contains chlorpheniramine maleate, Polaramine, another sedating histamine which contains Dexchlorpheniramine and Nausetil for nausea associated with migraines, contains prochloperazine.
    Maggie
    9th Sep 2020
    11:17am
    Laura's response has been enlightening.
    Thank you for informing us about the over the counter products.
    There's an advert for Demazin which is literally screeched at us by an apparently crazy mother and wife,on channel 10.
    Please Laura could you give us the names of the prescription drugs we need to worry about?
    tobymyers
    9th Sep 2020
    11:20am
    thank you for listing the drugs it seems this article was written by a cub reporter or was a cut and paste job
    Laura52
    10th Sep 2020
    7:52am
    Hi Maggie, Michael kindly listed the medication below, but bear in mind, not all of these medications are available in Australia.
    Canman
    9th Sep 2020
    2:05pm
    If these are over the counter drugs, have please give them a name
    johna53
    9th Sep 2020
    2:52pm
    As already stated many times - the heading to this includes "available over the counter" so bloody state their names. This type of lead in is just as bad as a Murdock Special. The editor should do the job they're paid to do.
    Laura52
    10th Sep 2020
    7:58am
    On point Johna53!
    Michael
    9th Sep 2020
    3:52pm
    Hello Everyone,
    A Comprehensive List of Anticholinergic Drugs
    Here's a comprehensive list of Anticholinergic Drugs (AC) (allergy and sleep-aid medications). This list is courtesy of The People's Pharmacy and were included in Dr. Shelly Gray's study at the University of Washington:

    RELATED: New Study Links Allergy Medicine And Alzheimer’s Disease
    Amitriptyline (Elavil)
    Atropine
    Benztropine (Cogentin)
    Chlorpheniramine (Actifed, Allergy & Congestion Relief, Chlor-Trimeton, Codeprex, Efidac-24 Chlorpheniramine, etc.)
    Chlorpromazine (Thorazine)
    Clomipramine (Anafranil)
    Clozapine (Clozaril)
    Cyclobenzaprine (Amrix, Fexmid, Flexeril)
    Cyproheptadine (Periactin)
    Desipramine (Norpramin)
    Dexchlorpheniramine
    Dicyclomine (Bentyl)
    Diphenhydramine (Advil PM, Aleve PM, Bayer PM, Benadryl, Excedrin PM, Nytol, Simply Sleep, Sominex, Tylenol PM, Unisom, etc.)
    Doxepin (Adapin, Silenor, Sinequan)
    Fesoterodine (Toviaz)
    Hydroxyzine (Atarax, Vistaril)
    Hyoscyamine (Anaspaz, Levbid, Levsin, Levsinex, NuLev)
    Imipramine (Tofranil)
    Meclizine (Antivert, Bonine)
    Nortriptyline (Pamelor)
    Olanzapine (Zyprexa)
    Orphenadrine (Norflex)
    Oxybutynin (Ditropan, Oxytrol)
    Paroxetine (Brisdelle, Paxil)
    Perphenazine (Trilafon)
    Prochlorperazine (Compazine)
    Promethazine (Phenergan)
    Protriptyline (Vivactil)
    Pseudoephedrine HCl/Triprolidine HCl (Aprodine)
    Scopolamine (Transderm Scop)
    Thioridazine (Mellaril)
    Tolterodine (Detrol)
    Trifluoperazine (Stelazine)
    Trimipramine (Surmontil)
    Other Anticholinergic Drugs (with lesser AC effect)
    Here are some other anticholinergic drugs to watch out for but they have fewer effects on the brain.

    Alprazolam (Xanax)
    Amantadine (Symmetrel)
    Baclofen
    Carisoprodol (Soma)
    Cetirizine (Zyrtec)
    Cimetidine (Tagamet)
    Clorazepate (Tranxene)
    Codeine
    Colchicine
    Digoxin (Lanoxicaps, Lanoxin)
    Diphenoxylate (Lomotil)
    Fluphenazine (Prolixin)
    Furosemide (Lasix)
    Hydrochlorothiazide (Esidrix, Dyazide, HydroDIURIL, Maxzide & literally scores of other medications for high blood pressure)
    Loperamide (Imodium)
    Loratadine (Alavert, Claritin)
    Maprotiline
    Nifedipine (Adalat, Procardia)
    Ranitidine (Zantac)
    Thiothixene (Navane)
    Tizanidine (Zanaflex)
    Why are Anticholinergic drugs used?
    Drugs with anticholinergic properties have been used in medicine for decades to treat conditions such as:

    Diarrhea
    Asthma
    Overactive bladder and urinary incontinence
    Chronic obstructive pulmonary disease (COPD)
    Surgery and anesthesia for muscle relaxation
    Insomnia
    Motion sickness
    Toxicity of certain poisonings
    Parkinson’s disease symptoms
    Psychiatric disorders
    Gastrointestinal disorders
    Some symptoms of Parkinson’s disease
    Anesthesia during surgery
    What are the signs of a possible overdose?
    Dizziness
    Severe drowsiness
    Fever
    Severe hallucinations
    Confusion
    Trouble breathing
    Clumsiness and slurred speech
    Fast heartbeat
    Flushing and warmth of the skin
    Tell your doctor if you have any of these conditions. Also, tell your doctor if you have a history of allergies to anticholinergics.

    Besides the elderly, who else shouldn’t use anticholinergics?
    People with a diagnosis of:

    Myasthenia gravis
    Hyperthyroidism
    Glaucoma
    Enlarged prostate
    Hypertension (high blood pressure)
    Urinary tract blockage
    Increased heart rate (tachycardia)
    Heart failure
    Severe dry mouth
    Hiatal hernia
    Severe constipation
    Liver disease
    Down syndrome
    Laura52
    10th Sep 2020
    7:57am
    Thanks Michael for the comprehensive list. I applaud you. Many of these drugs are obviously not available in Australia and some of the drugs that are listed that are available in Australia have different brand names, generic etc in Australia. So please everyone here, look at the actual name of the drug as they are available in different brands. This makes it so confusing for, even for me and I am a pharmacist, well used to be...long story. There are many hospital admissions due to people using the same medications under different brands. Always check with the pharmacist as to not double dose. I have come across this so many times in my working life.


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