A Swedish registry of 7,308 patients links newer blood thinners to slower cognitive decline in people who also have Alzheimer’s disease.

A heart that quivers instead of beating cleanly lets blood pool long enough to clot, so doctors put people with that rhythm on blood thinners.

Plenty of those patients also have Alzheimer’s disease, and no one had tracked what that pill does to their memory once the diagnosis is in. A new Swedish study finds that it might slow down cognitive decline.

People on the newer blood thinners slipped on a standard memory test more slowly than people on warfarin, the older drug. They also slipped more slowly than people on no blood thinner at all. On a 30-point scale, the difference ran to about a fifth of a point a year.

Nanbo Zhu, Maria Eriksdotter and three colleagues at the Karolinska Institutet in Stockholm studied Swedish patients who had both conditions. No one was assigned a drug for the research. The team read what doctors had already prescribed, so the work points to a link and not a cause.

“Our findings strengthen the indication to treat people with atrial fibrillation and Alzheimer’s disease with NOAC, and our data suggest that NOACs are a preferable option to warfarin in this population,” Eriksdotter told Earth.com. NOAC is shorthand for this newer class of blood thinners.

A-fib and Alzheimer’s often overlap

Atrial fibrillation is a heartbeat that has lost its timing. The upper chambers shiver rather than squeeze, blood lingers where it should be moving, and a clot forming there can travel to the brain and cause a stroke.

It turns up in nearly one in five people at the moment they’re diagnosed with dementia, and that overlap is challenging for doctors. Blood thinners cut the clot risk, but they also raise the risk of a dangerous bleed. A person who forgets doses is harder to medicate safely.

Warfarin is the harder of the two to manage, and the authors say that matters more when the patient’s memory is failing.

Researchers have suspected for years that these drugs might protect thinking as well as circulation, and they’ve seen hints of it in people without dementia. What happens after an Alzheimer’s diagnosis was unknown.

Blood thinners defined the groups

Sweden keeps a national dementia registry called SveDem, fed by every memory clinic and most primary care units. From it the team pulled every patient registered with Alzheimer’s between 2007 and 2020 who already had a fluttering heartbeat.

That pull returned 7,595 people, and 7,308 were left after the team dropped anyone with no memory score on file. The average age was 82.6, and just over half of them were women.

The researchers sorted them by what was in the medicine cabinet on the day of diagnosis. That came out at 3,341 people who were not on blood thinners, 2,277 who took warfarin, and 1,690 who were on one of the newer drugs.

Memory came from a short questionnaire that clinics run at each visit, scored out of 30. Doctors call it the Mini-Mental State Examination.

The three groups weren’t alike to begin with: the untreated were older and scored a little lower. The team weighted the data to even that out before comparing anyone.

Newer blood thinners tracked with slower decline

Everyone declined. Alzheimer’s takes memory, whatever medication a person is using. No drug in this study stopped that.

Where they differed was speed. Against the untreated group, those on the newer blood thinners lost 0.23 points a year less. Against warfarin patients, they lost 0.21 points a year less.

Warfarin showed no measurable difference against the untreated group. That comparison is a soft one, though. Over half of the untreated were on aspirin or a similar drug, and measured against aspirin users alone, both warfarin and the newer pills came with slower decline.

Follow the three lines out five years and the whole gap is about one point. All three started around 21.5. Five years on, the untreated group scored 14.3, warfarin patients 14.5, and patients on the newer drugs 15.3.

Asked by Earth.com what a fifth of a point a year adds up to, Eriksdotter didn’t oversell it.

“The difference is modest for an individual patient from one year to the next, but over a longer period also small positive cognitive benefits are of importance,” she said. “The gap also increases over time.”

Strokes and deaths were also lower

The team tracked more than test scores. Over three years, 2,588 people died, 833 had a stroke or a clot lodge somewhere else, 683 had a serious bleed, and 824 broke a bone.

Against no blood thinner, the newer drugs came with about six fewer deaths per 100 people over three years and about five fewer of those clot events per 100. Warfarin came with roughly four fewer deaths per 100 too, but about three more serious bleeds.

That’s the trade the older drug asks for. Head to head, the newer pills came with three fewer clot events and about three fewer serious bleeds per 100 people.

None of that is news for the general population, where the newer drugs have largely replaced warfarin. It’s new for this group, which clinical research has mostly skipped.

Blood flow may explain the difference

Why a clotting drug would touch memory is still open. The paper lays out four possibilities.

The plainest is that the drugs stop small strokes a patient never feels, and those chip away at thinking over years. A second is better circulation to starved brain tissue.

“There are reasons to believe that the treatment could have a positive effect on cognition, for example by improving blood flow and reducing small-scale damage in the brain,” said Eriksdotter, who is also a senior consultant in geriatrics at Karolinska University Hospital.

The third and fourth are stranger. Clotting and inflammation are wired into each other, so calming one calms the other.

Fibrin, the protein mesh that holds a clot together, also sticks to the amyloid protein that builds up in an Alzheimer’s brain. Locked together, the two are harder for the body to clear.

There’s a duller explanation too. Warfarin patients here strayed from their prescriptions far more often than the patients on the newer drugs did, and a drug taken wrongly works less well.

A trial would settle the question

Researchers have twice compared a newer blood thinner against warfarin and found no memory difference over two years.

Each of those trials enrolled no more than 200 people, though, and none of the volunteers had dementia. A third stopped early for futility; its volunteers were 30 to 60 with a low stroke risk.

The Swedish team named gaps of its own. It couldn’t tell which of the newer drugs did what, because no single one had enough patients behind it. It also assumed everyone stayed on their starting drug, and plenty did not.

“Ideally, long-term randomized trials in atrial fibrillation populations with cognitive impairment or established dementia would provide more relevant evidence on cognitive outcomes,” Eriksdotter said when Earth.com asked what it would take to test this properly.

Trials like that are hard to run, she said, especially in people already diagnosed. The realistic next step, in her view, is to repeat the work in other registries with similar patients, and few of them track thinking over years the way Sweden’s does.

For now the case for the prescription rests where it always did, on the stroke it prevents. Whether it also protects thinking is what the next registry will have to answer.

The full study was published in the journal European Heart Journal.

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