Alzheimer's: certain combinations of prescription drugs may slow progression of the disease, says mice study
Millions of older adults take five or more prescription drugs every day to manage chronic illnesses. While polypharmacy is often necessary, this practice has also been linked to many negative health outcomes in older adults – including memory problems, increased risk of falls and greater frailty.
The most common prescription drugs involved in polypharmacy are those used to treat conditions such as high blood pressure, high cholesterol and depression. Importantly, these same conditions are also known risk factors for Alzheimer's disease.
This raises an important question: could polypharmacy have any influence on the progression of Alzheimer's disease?
Our recent research in mice suggests that certain prescription drugs combinations might actually have a positive effect on memory and signs of Alzheimer's disease. However, these effects appeared to differ depending on whether the mouse was male or female.
To better understand how polypharmacy may affect Alzheimer's disease, we designed an experiment using mice that were genetically altered to develop Alzheimer's-like brain changes. These mice had amyloid plaques – clumps of protein in the brain that, with time, are linked with memory loss and considered a hallmark of Alzheimer's disease .
We tested two different combinations of five commonly prescribed drugs, including: analgesics (painkillers), antithrombotics (to prevent blood clots), lipid-modifying agents (such as statins, which lower cholestrol), beta-blockers (which help controlling arrythmias and hypertension) and Ace inhibitors (used to treat cardiovascular conditions), as well as antidepressants.
Both groups of mice were given paracetamol, aspirin, an antidepressant, a statin and a blood pressure drug. The only differences between the two groups were the specific types of statin and cardiovascular drugs used. The first group were given simvastatin and metoprolol, while the second group was given atorvastatin and enalapril.
We gave these prescription drug combinations to both male and female mice. We then tested their memory, examined their brains for signs of disease and analysed blood samples for disease-related markers.
Our findings showed that polypharmacy has both positive and negative effects on Alzheimer's disease progression. The effects largely depended on which specific drug combinations were used as well as the sex of the mice.
The first drug combination had beneficial effects in male mice. These mice showed better memory, reduced signs of Alzheimer's pathology in the brain (such as the number and size of amyloid plaques) and fewer signs of the disease in their blood. This suggested that polypharmacy delayed the progression of Alzheimer's disease.
In females, however, the same combination had very little to no effect on signs and symptoms of the disease.
But for the mice in the second combination group, the results were different. The benefits previously seen in males disappeared. In female mice, their memory worsened.
We also looked at what happened when some of the drugs were taken on their own. In some cases, they had beneficial effects for the female mice – improving memory and signs of Alzheimer's disease in the brain. For instance, the statin simvastatin improved memory and reduced signs of brain inflammation in female mice when the drug was taken on its own.
Polypharmacy and brain health
These results show how complex the effects of polypharmacy can be, especially in the context of a brain disease such as Alzheimer's. They also suggest that men and women may respond differently to certain drug combinations.
This is not surprising. Biological sex is known to influence how drugs are absorbed and metabolised and their effect on the body. When it comes to polypharmacy, these differences can become more pronounced, having an even stronger effect on drug safety and efficacy.
This could partly help explain why the same drug combinations had very different effects in the male and female mice in our study. Other possible explanations for why certain drug combinations only improved signs and symptoms of the disease in male mice include sex differences in hormone levels and differences in immune responses that may influence how drugs work in the brain. Understanding these mechanisms will be key to tailoring safer and more effective treatments for the disease.
Our study confirms that current, universal prescribing approaches for older adults may not be ideal.
It's also worth noting that older women are more likely to be polypharmacy users compared to men. This highlights the importance of understanding the effects of polypharmacy that are specific to men and women, and developing more personalised prescribing approaches.
Future translational studies (from mice to humans) looking at how drug combinations affect Alzheimer's in males and females are also warranted to help reduce risks and improve healthcare in the ageing population.
Residents play Scrabble on a house's terrace in Village Landais, a residential care village for people suffering from various stages of dementia that encourages a sense of autonomy and accomplishment, in Dax, France. Photographer: Nathan Laine/Bloomberg via Getty Images
The global population is continuing to age, which means that an even greater number of people are going to be at risk of developing Alzheimer's disease. This is why it's so important we understand all of the causes of the disease and how it can be prevented. DM
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
eNCA
3 days ago
- eNCA
US may revise hormone replacement therapy warnings
WASHINGTON - US Food and Drug Administration Commissioner Marty Makary signalled that he is open to revising strict warning labels on Hormone Replacement Therapy, following testimony from experts who said the treatment's risks have long been exaggerated. HRT is taken to replace estrogen, the body stops producing after menopause -- when periods end permanently -- and helps relieve symptoms such as hot flashes, vaginal discomfort, and pain during sex. But its use has plummeted in recent years amid concerns, including a possible link to invasive breast cancer. Food and Drug Administration (FDA) chief Marty Makary, who convened Thursday's meeting of outside experts, told AFP: "We have to revisit these topics." He argued that the framework that led to so-called "black box warnings" -- the strongest warning the FDA can require for prescription drugs -- "came from a different era." "Not only is there no clinical trial showing an increase in breast cancer mortality, but there are also other tremendous long-term health benefits," Makary added. The 12 experts convened by the agency said HRT's benefits go beyond easing menopausal symptoms. They cited evidence for reduced fracture risk, improved cardiovascular and cognitive health, and fewer urinary tract infections. "Estrogen is the only well-established intervention to reduce the frequency of osteoporotic fracture in postmenopausal women, to the tune of 30 to 50 percent," said Vonda Wright, an orthopaedic surgeon at the University of Central Florida. Roberta Diaz Brinton, director of the Center for Innovation in Brain Science, said her research suggests the reason two-thirds of people globally with Alzheimer's are women is not because they live slightly longer than men, but because the disease begins during the menopausal transition. "Depending upon when hormone therapy is introduced... there's a significant reduction in risk of developing Alzheimer's disease," she said. The University of Arizona researcher linked menopause to a drop in the brain's ability to metabolise glucose and a rise in protein plaque deposits. Panellists blamed the collapse in HRT use on the Women's Health Initiative (WHI), a landmark clinical trial halted in 2002 after flagging a possible increased breast cancer risk -- findings they say were misinterpreted. "Prescriptions for hormone replacement therapy plummeted in the United States, women flushed their pills down the toilet," Makary said in his opening remarks, mentioning his own mother's experience of multiple bone fractures in old age. Critics of the WHI argue it included participants well past menopause -- when risks are higher and benefits lower -- and used outdated formulations no longer common today. - Label changes - Still, the issue remains divisive within the medical community. HRT can be administered through various means and is given either as estrogen alone or with progesterone. The FDA's own warning label for it cites risks including endometrial cancer, breast cancer, and life-threatening blood clots. Adriane Fugh-Berman, who directs a project that promotes rational prescribing at Georgetown University, attended as an observer and criticized the lack of dissenting voices. "This was a very one-sided panel of people who are all proponents of hormone therapy and who seem to have a very poor understanding of the evidence," she told AFP. "While hormones can be a useful treatment for severe menopausal symptoms, they should not be used for chronic disease prevention," she added, noting that no randomised clinical trial -- the gold standard of evidence -- has found HRT beneficial for cognition or dementia prevention. She also said that after the WHI findings were released, hormone use fell globally -- and breast cancer rates dropped across registries tracking them. Several of the panellists had ties to companies offering menopause treatments or are affiliated with the advocacy group "Let's Talk Menopause," which receives pharmaceutical funding and campaigns to revise FDA warning labels.
eNCA
3 days ago
- eNCA
US health experts reassess hormone replacement therapy risks
US health authorities on Thursday began a reassessment of the risks surrounding Hormone Replacement Therapy (HRT), a treatment used by menopausal women around the world but long clouded by fear over its side effects. HRT is taken to replace estrogen the body stops producing after menopause -- when periods end permanently -- and helps relieve symptoms such as hot flashes, vaginal discomfort, and pain during sex. But its use has plummeted in recent years amid concerns including a potential link to invasive breast cancer. Food and Drug Administration (FDA) chief Marty Makary, who convened Thursday's meeting of outside experts, has long advocated for HRT, saying its risks have been overstated. "For decades, hormone replacement therapy for women -- that is estrogen or estrogen plus progesterone -- has helped women alleviate the symptoms of menopause, including hot flashes, dryness, mood swings, weight gain and poor sleep quality, to name a few," he said in a video ahead of the meeting. He added that when initiated within a decade of the onset of the transitional period before menopause, HRT may even reduce cognitive decline, the risk of Alzheimer's, and prevent osteoporosis and cardiovascular disease. Makary blamed the drop in HRT use on a landmark clinical trial, the Women's Health Initiative, which was halted in the early 2000s after it flagged increased risks of breast cancer and stroke. But he said subsequent studies had not replicated the findings on breast cancer. "The many benefits of hormone therapy were ignored as it was seen as a carcinogen. Prescriptions for hormone replacement therapy plummeted in the United States, women flushed their pills down the toilet," he said Thursday. "Fifty million plus women have not been offered the incredible potential health benefits of hormone replacement therapy because of medical dogma," he added, including his own mother, who suffered multiple bone fractures in her older life. Critics of the trial argue it was flawed because the participants were too far from menopause, when risks are elevated and benefits limited, and that the formulations used are now outdated. - Label changes - Still, the issue remains divisive within the medical community. The FDA's own warning label for HRT -- which can be administered through various means including orally, through skin patches, or vaginally -- cites risks including endometrial cancer, breast cancer, and life-threatening blood clots. This week, the American Family Physician journal published an editorial that found limited benefits and significant harms associated with HRT. "Menopause is a positive life experience for many women and should not be medicalized," the authors concluded. The nature of the FDA expert meeting is also unusual. Unlike standard practice before the Trump administration, no agenda was publicly posted. Several of the named panelists have ties to companies offering menopause treatments or who belong to the advocacy group "Let's Talk Menopause," which receives funding from pharmaceutical companies and campaigns to revise the FDA warning label.
Daily Maverick
06-07-2025
- Daily Maverick
Tech a beat — if you're feeling overwhelmed, you have yourself – and apps
A Roz Chast cartoon, first published in The New Yorker in 2024, circulated on social media recently. It is of a man walking jauntily down a city street, hands in his pockets, whistling a happy tune with nary a care in the world. The caption reads: 'The guy who didn't know his cholesterol, BMI, his net worth, his IQ, his credit score, his astrological sign or his ancestry.' To this we could add: who didn't wear a wristwatch which recorded his heart rate, paid his bills, monitored his sleep and eating patterns, checked how far he has walked and how infrequently, and judged how often he has jerked off. It is perfectly clear that knowing your cholesterol count can prevent major illnesses further down the line, including heart disease, stroke and Alzheimer's. This is a good thing; this is progress. However, beware too much intrusive data gathering. Imagine a world where your medical insurance turns down what appears to be a valid claim. You can argue, but the data from your wrist or your cellphone could be their artificial intelligence receipts. Those emails you failed to respond to, those 'membership' health initiative apps you just didn't download and those gym membership offers ignored will all be there to justify the rejection. 'Our reasons for declining medical assistance are that we note several days of the week the client spent 24-hours watching Netflix series in a pronate position. The client/patient's heart rate was that of a bear in hibernation. This is a self-inflicted health issue.' Before apps, acknowledging you were overweight, now known as a body mass index, required you to look in the mirror. And then the fridge. And then make a plan. Or not, and happily settle into yourself. So, although blissful ignorance about one's health might be lethal, so too is an obsession with every morsel that passes from lips to toilet bowl. Data surveillance prisons If there is an epidemic of dissociation and loneliness in the world today, it might be because billions spend their 'free time' only on and by themselves – eyes growing myopic, stuck to screens while eating, sitting on buses and trains and even walking, crossing roads, cycling or ambling on city pavements. This leads to an intense inward journey that feeds straight into the data bank, contributing, in the end, to the quantum computer, soon to make its appearance like a big tech messiah. (Google it.) But in order to have any sort of relatively successful 'output' in life, you need 'input'. If millions are growing up or old scrolling through TikTok or Instagram, then we can safely say there is a lot of electronic debris floating around in human consciousness right now. Hence the attraction to 'fake news' and 'permanent outrage'. When life, reality and the world keeps coming as a surprise, this can destabilise the fragile mind. Although social media provides much comic relief as ordinary people find a platform to mock and troll the powerful and rich, the greatest driver on social media is fear, and it is mostly a fear of growing old and dying. This is why Botoxed, bleached-toothed, steroid-pumped, airhead, breast-enhanced 'influencers' thrive on the internet. The idea is to surgically alter yourself to look like an 80-year-old newborn so that death might pass you by. Taxes used to be included in the saying 'the only thing you can be sure of in life is death and taxes', but this no longer applies to the world's billionaires. However, they have forgotten that they too will all perish and die regardless of Venice nuptials. Hopefully Elon Musk will be on Mars by then, performing his act of libertarian nihilism for humankind. On and off the spectrum It is unsurprising that there has been an epidemic of diagnoses of people 'on the autism spectrum'. Sometimes it feels like the internet is owned by people claiming all manner of 'neurodivergent' conditions. Today, should you feel overwhelmed, it is not the fault of the barrage of emails and WhatsApps or invitations to meetings and group meditations, these unwanted intrusions that pop up, prompted by AI's 'health and wellness' programmes. Should you feel swamped, then you must have attention deficit disorder or you self-diagnose as an 'empath' or 'introvert'. Autistic self-diagnosis is a thing now, diminishing the challenges people with real autism face. It makes sense that when our tiny brains are bombarded with so much stimulus in our work and private lives we would be rendered neurotic, anxious wrecks prone to following conspiracy theories. All around the world (where there is no war) there are initiatives to connect without screens. The silent reading gatherings in South Africa – which are like book clubs without the wine or assigned reading – are one such example. It is a hunger for real life, outside the electronic noise. Tune out and drop off. Leave the internet some days. Go on, read a book, watch a bird. DM This story first appeared in our weekly Daily Maverick 168 newspaper, which is available countrywide for R35.
