Strong Link Found Between Dementia, Common Anticholinergic Drugs Benadryl, Advil PM, Tylenol PM, or Motrin PM

Strong Link Found Between Dementia, Common Anticholinergic Drugs Benadryl, Advil PM, Tylenol PM, or Motrin PM

Thu, 04/30/2015 – 9:41am

Cynthia Fox, Science Editor

The link was found in a wide range of anticholinergics, from tricyclic antidepressants like doxepin (Sinequan), to first-generation antihistamines like chlorpheniramine (Chlor-Trimeton), Benadryl, and antimuscarinics for bladder control like oxybutynin (Ditropan).There is a strong and possibly irreversible link between Alzheimer’s disease and many commonly used medications for insomnia, allergies, and depression, according to a large recent JAMA Internal Medicine study.

Three months of taking either daily Benadryl, Advil PM, Tylenol PM, or Motrin PM pills, for example, is associated with an increased risk of Alzheimer’s of 19 percent. More than three years of the latter increases that risk association by a “significant” 54 percent, Malaz Boustani, M.D., M.P.H., told Drug Discovery & Development.

Boustani, director of the Aging Brain Care Program at Eskenazi Health in Indianapolis, Indiana, was not involved in the study. But he has done smaller scale work making similar findings. This was the largest study ever, and utilized the most rigorous standards ever, he said. “Methodologically, this is the best you can get; it doesn’t get better than this. This has established a significant link between anticholinergic drugs and Alzheimer’s.” Very few other phenomena have been found to possess such a strong potential link. “It’s rare,” he said.

The new study

Many groups have suggested such links. But for the current study, the team of senior author Eric Larson, M.D., M.P.H., of the University of Washington (UW), engaged in longer follow up (over seven years), and utilized a tighter assessment of use. The study followed some 3,500 Group Health participants, average age 73, with the Adult Changes in Thought (ACT) study, which is a Group Health/UW project funded by the National Institute on Aging.

The group showed for the first time a dose response; that is, that Alzheimer’s risk can grow with higher use. For instance, it found that people taking a minimum of 25 mg of an anticholinergic called diphenhydramine (or one Advil PM, Tylenol PM, Motrin PM, or Benadryl pill) a day for three to 12 months increased their Alzheimer’s risk by 19 percent; one to three years, 23 percent; three to seven years, 54 percent.

Furthermore, this was the first study to find that dementias associated with anticholinergics may not be reversible even years after drug use stops. Wrote Boustani and the Indiana University Center for Aging Research’s Noll Campbell, Pharm.D., in a JAMA editorial: “The risk for dementia was consistent when comparing participants with recent and past heavy use of such medications with nonusers, suggesting that the adverse cognitive effects are permanent. Other studies have consistently shown similar results.”


Lead author Shelly Gray, who is director of the geriatric pharmacy program at the UW School of Pharmacy, found the link in a wide range of anticholinergics, from tricyclic antidepressants like doxepin (Sinequan), to first-generation antihistamines like chlorpheniramine (Chlor-Trimeton), Benadryl, and antimuscarinics for bladder control like oxybutynin (Ditropan). The team came to the conclusion, for example, that people taking at least 10 mg/day of doxepin, 4 mg/day of chlorpheniramine, or 5 mg/day of oxybutynin for more than three years are at greater risk for developing dementia.

Gray herself was surprised by the findings. “There was one prior study that examined this study question, but we thought we might not find these medications were related to dementia because we had a better study design, and were able to better adjust for some health conditions that might be confounders through use of statistical methods,” she told Drug Discovery & Development. “We know that anticholinergics are related to impaired cognition acutely when people take these medicines. They feel a little groggy, less attentive, etc. But these are reversible changes. This study suggests these medicines are also related to dementia, or irreversible cognitive changes.”

Substitutes are available for some of the problems addressed by anticholinergics. Those suffering from depression can take a selective serotonin re-uptake inhibitor (SSRI) like citalopram (Celexa) or fluoxitene (Prozac). Those with allergies can take a second-generation antihistamine like loratadine (Claritin) for allergies. Behavioral changes can help urinary incontinence.

Boustani, who is also a professor of medicine at Indiana University, told Drug Discovery & Development that, when it comes to insomnia medications, “basically any cold medications that make you sleepy might contain anticholinergics, so stay away from drugs that make you sleepy.” NyQuil is an exception, he said. It makes people sleepy, but does not contain an anti-cholinergic. Still, “if your solution for a sleep problem is a pill, a quick fix, do you want that?” Any drug taken for a long time could come with problems. “I tell people, if they have to take any such drug for more than 30 days, they should think about alternatives. Maybe you should just take it easy. Maybe you should adopt Grandma’s Remedy of hot milk, hot tea, and rest. Physical fitness is always good. Mindfulness, reflection, physical fitness, tea.”

The cause

The cause of this potential link is unknown. Anticholinergics can block the neurotransmitter acetylcholine. “But there are many hypotheses” as to why anticholinergics can lead to Alzheimer’s, Boustani told Drug Discovery & Development. “The current medication for Alzheimer’s, Aricept, does the opposite of what Benadryl does, for example. We think that same pathway is involved. So anticholinergics may reduce the function of acetyl receptors, and may end up killing the brain cells.”

Nothing can be fully nailed down because it would be unethical to do a gold standard clinical trial. Clinical trials can be done to prove benefit. But to prove a deficit would mean doctors would have to assign patients to take say, Advil PM, every night for three years to assess damage.

The recent trial also did not factor in two other classes of common drugs tapped by the American Geriatrics Society as associated with cognitive problems: benzodiazapines (recently found to hamper rodent neurogenesis) and histamine receptor antagonists.

But even given these limitations, this trial, with its seven years of data, was “very, very good,” Boustani said.  Via computerized dispensing, doses and uses were well established. Potential confounding variables—like people taking anticholinergics for depression or insomnia precisely because they were in the grips of an undiagnosed dementia already—were weeded out.

Boustani’s crew is working on a mobile application to help people figure out what drugs to avoid. In the meantime, he directs clinicians and patients to a chart by the Aging Brain Care website that lists drugs containing anticholinergics.

Gray’s group is in the process of “examining whether these medications are related to changes in the brain of a subsample of this study cohort that has been autopsied after death,” she told Drug Discovery & Development. “We will be examining whether those who used anticholinergics had higher plaques, tangles and other markers of cerebrovascular disease than those who did not use these medications.”

dementia, Alzheimer’s caused by Advil, Motrin, Tylenol, Benadryl

jeezuz h…

“Three months of taking either daily Benadryl, Advil PM, Tylenol PM, or Motrin PM pills, for example, is associated with an increased risk of Alzheimer’s of 19 percent. More than three years of the latter increases that risk association by a “significant” 54 percent, Malaz Boustani, M.D., M.P.H., told Drug Discovery & Development.”

Drought Map for April 28th 2015

Amish Buggy Ride

The Teeth Mother Naked at Last… Robert Bly… for Poetry Month

Robert Bly

The Teeth Mother Naked at Last



Massive engines lift beautifully from the deck.

Wings appear over the trees, wings with eight

hundred rivets.

Engines burning a thousand gallons of gasoline a minute

sweep over the huts with dirt floors.

The chickens feel the new fear deep in the pits of

their beaks.

Buddha with Padma Sambhava.

Meanwhile, out on the China Sea,

immense gray bodies are floating,

born in Roanoke,

the ocean on both sides expanding, “buoyed on the

dense marine.”

Helicopters flutter overhead. The death-

bee is coming. Super Sabres

like knots of neurotic energy sweep

around and return.

This is Hamilton’s triumph.

This is the advantage of a centralized bank.

B-52s come from Guam. All the teachers

die in flames. The hopes of Tolstoy fall asleep in the

ant heap.

Do not ask for mercy.

Now the time comes to look into the past-tunnels,

the hours given and taken in school,

the scuffles in coatrooms, 

foam leaps from his nostrils,

now we come to the scum you take from the mouths of

the dead,

now we sit beside the dying, and hold their hands, there

is hardly time for good-bye,

the staff sergeant from North Carolina is dying—you

hold his hand,

he knows the mansions of the dead are empty, he has an

empty place

inside him, created one night when his parents came

home drunk,

he uses half his skin to cover it,

as you try to protect a balloon from sharp objects. . . .

Artillery shells explode. Napalm canisters roll end

over end.

800 steel pellets fly through the vegetable walls.

The six-hour infant puts his fists instinctively

to his eyes to keep out the light.

But the room explodes,

the children explode.

Blood leaps on the vegetable walls.

Yes, I know, blood leaps on the walls—

Don’t cry at that—

Do you cry at the wind pouring out of Canada?

Do you cry at the reeds shaken at the edge of

the sloughs?

The Marine battalion enters.

This happens when the seasons change,

This happens when the leaves begin to drop from the

trees too early

“Kill them: I don’t want to see anything moving.”

This happens when the ice begins to show its teeth in

the ponds

This happens when the heavy layers of lake water press

down on the fish’s head, and send him deeper, where

his tail swirls slowly, and his brain passes him

pictures of heavy reeds, of vegetation fallen

on vegetation. . . .

Hamilton saw all this in detail:

“Every banana tree slashed, every cooking utensil smashed,

              every mattress cut.

Now the Marine knives sweep around like sharp-edged

jets; how beautifully they slash open the rice bags,

the mattresses. . . .

ducks are killed with $150 shotguns.

Old women watch the soldiers as they move.



Excellent Roman knives slip along the ribs.

A stronger man starts to jerk up the strips of flesh.

“Let’s hear it again, you believe in the Father, the Son, and the

              Holy Ghost?”

A long scream unrolls.


“From the political point of view, democratic institutions are

              being built in Viet Nam, wouldn’t you agree?”

A green parrot shudders under the fingernails.

Blood jumps in the pocket.

The scream lashes like a tail.

“Let us not be deterred from our task by the voices

              of dissent. . . .”

The whines of the jets

pierce like a long needle,

As soon as the President finishes his press conference,

black wings carryoff the words,

bits of flesh still clinging to them.

              *   *   *

The ministers lie, the professors lie, the television lies,

the priests lie. . . .

These lies mean that the country wants to die.

Lie after lie starts out into the prairie grass,

like enormous caravans of Conestoga wagons. . . .

And a long desire for death flows out, guiding the

enormous caravans from beneath,

stringing together the vague and foolish words.

It is a desire to eat death,

to gobble it down,

to rush on it like a cobra with mouth open

It’s a desire to take death inside,

to feel it burning inside, pushing out velvety hairs,

like a clothes brush in the intestines—

This is the thrill that leads the President on to lie

              *   *   *

Now the Chief Executive enters; the press

conference begins:

First the President lies about the date the Appalachian

Mountains rose.

Then he lies about the population of Chicago, then he lies

about the weight of the adult eagle, then about the

acreage of the Everglades

He lies about the number of fish taken every year in the

Arctic, he has private information about which city is

the capital of Wyoming, he lies about the birthplace of

Attila the Hun.

He lies about the composition of the amniotic fluid, and

he insists that Luther was never a German, and that

only the Protestants sold indulgences,

That Pope Leo X wanted to reform the church, but the

“liberal elements” prevented him,

that the Peasants’ War was fomented by Italians

from the North.

And the Attorney General lies about the time the

sun sets.

              *  *   *

These lies are only the longing we all feel to die.

It is the longing for someone to come and take you by the

hand to where they all are sleeping:

where the Egyptian pharaohs are asleep, and your

own mother,

and all those disappeared children, who used to go

around with you in the rings at grade school. . . .

Do not be angry at the President—he is longing to take

in his hand

the locks of death hair—

to meet his own children dead, or unborn. . . .

He is drifting sideways toward the dusty places


This is what it’s like for a rich country to make war

this is what it’s like to bomb huts (afterwards described

as “structures”)

this is what it’s like to kill marginal farmers (afterwards

described as Communists”)  

this is what it’s like to watch the altimeter needle

going mad


Baron 25, this is 81. Are there any friendlies in the area? 81

from 25, negative on the friendlies. I’d like you to take out as

many structures as possible located in those trees within 200

meters east and west of my smoke mark.

diving, the green earth swinging, cheeks hanging back,

red pins blossoming ahead of us, 20-millimeter can-

non fire, leveling off, rice fields shooting by like tele-

phone poles, smoke rising, hut roofs loom up huge as

landing fields, slugs going in, half the huts on fire,

small figures running, palm trees burning, shooting

past, up again; . . . blue sky . . . cloud mountains

This is what it’s like to have a gross national product.

It’s because the aluminum window shade business is

doing so well in the United States that we roll fire

over entire villages

It’s because a hospital room in the average American city

now costs $90 a day that we bomb hospitals in

the North

It’s because the milk trains coming into New Jersey hit

the right switches every day that the best Vietnamese

men are cut in two by American bullets that follow

each other like freight cars

This is what it’s like to send firebombs down from air-

conditioned cock-pits.

This is what it’s like to be told to fire into a reed hut with

an automatic weapon.

It’s because we have new packaging for smoked oysters

that bomb holes appear in the rice paddies

It is because we have so few women sobbing in

back rooms,

because we have so few children’s heads torn apart by

high-velocity bullets,

because we have so few tears falling on our own hands

that the Super Sabre turns and screams down toward

the earth.

It’s because taxpayers move to the suburbs that we

transfer populations.

The Marines use cigarette lighters to light the thatched

roofs of huts because so many Americans own their

own homes.


I see a car rolling toward a rock wall.

The treads in the face begin to crack.

We all feel like tires being run down roads under

heavy cars.

The teen-ager imagines herself floating through the

Seven Spheres.

Oven doors are found


Soot collects over the doorframe, has children,

takes courses,

goes mad, and dies.

There is a black silo inside our bodies, revolving fast.

Bits of black paint are flaking off,

where the motorcycles roar, around and around,

rising higher on the silo walls,

the bodies bent toward the horizon,

driven by angry women dressed in black.

              *   *   *

I know that books are tired of us.

I know they are chaining the Bible to chairs.

Books don’t want to remain in the same room with

us anymore.

New Testaments are escaping . . . dressed as women . . .

they go off after dark.

And Plato! Plato . . . Plato wants to go backwards. . . .

He wants to hurry back up the river of time, so be can

end as some blob of sea flesh rotting on an

Australian beach.


Why are they dying? I have written this so many times.

They are dying because the President has opened a

Bible again.

They are dying because gold deposits have been found

among the Shoshoni Indians.

They are dying because money follows intellect!

And intellect is like a fan opening in the wind—

The Marines think that unless they die the rivers will

not move.

They are dying so that the mountain shadows will

continue to fall east in the afternoon,

so that the beetle can move along the ground near the

fallen twigs.


But if one of those children came near that we have set

on fire,

came toward you like a gray barn, walking,

you would howl like a wind tunnel in a hurricane,

you would tear at your shirt with blue hands,

you would drive over your own child’s wagon trying to

back up,

the pupils of your eyes would go wild—

If a child came by burning, you would dance on a lawn,

trying to leap into the air, digging into your cheeks,

you would ram your head against the wall of

your bedroom

like a bull penned too long in his moody pen—

If one of those children came toward me with both hands

in the air, fire rising along both elbows,

I would suddenly go back to my animal brain,

I would drop on all fours, screaming,

my vocal chords would turn blue, so would yours,

it would be two days before I could play with my own

children again.


I want to sleep awhile in the rays of the sun slanting over

the snow.

Don’t wake me.

Don’t tell me how much grief there is in the leaf with its

natural oils.

Don’t tell me how many children have been born with

stumpy hands all those years we lived in St.

Augustine’s shadow.

Tell me about the dust that falls from the yellow daffodil

shaken in the restless winds.

Tell me about the particles of Babylonian thought that

still pass through the earthworm every day.

Don’t tell me about “the frightening laborers who do not

read books.”

Now the whole nation starts to whirl,

the end of the Republic breaks off,

Europe comes to take revenge,

the mad beast covered with European hair rushes

through the mesa bushes in Mendocino County,

pigs rush toward the cliff,

the waters underneath part: in one ocean luminous

globes float up (in them hairy and ecstatic men—)

in the other, the teeth mother, naked at last.

Let us drive cars


the light beams

to the stars . . .

And return to earth crouched inside the drop of sweat

that falls

from the chin of the Protestant tied in the fire.

[From Sleepers Joining Hands by Robert Bly. Copyright © 1973 by Robert Bly. Reprinted by arrangement with HarperCollins Publishers, Inc.]



The twittering of the Munchkins

Posted on April 19, 2015 by Michael J Smith

And now for something completely different.

I’ve spent the last forty — not quite, but almost — years of my life paying the rent by writing computer code. It hasn’t been a bad living, and I can’t complain. It’s also been more fun than not: nothing deep about it, really, but intellectually interesting enough to make the days pass quickly.

I always tell people that it’s like solving crossword puzzles for a living, which is not exactly right but isn’t too far off, at least as regards the hour-by-hour texture of the work. It’s very finical. A letter out of place spoils the whole thing.

The element that isn’t captured by that description is that there’s a certain very modest scope for creativity. A crossword puzzle, after all, has only one right answer, but any programming problem has many, and coders, like Talmudists, dearly love to wrangle about why solution A is better than solution B. There’s such a thing as elegant code, and such a thing as ugly, clunky code, and we all aspire to write the former.

This too is fun. People who don’t appear macho at all suddenly become very assertive. And people who you would think have no taste at all — judging by the way they dress, and the books they read — suddenly come out as aesthetes, and make good their claim to the title.

Alas, that’s all gone now. At least in the corporate world where I still have to make a living. I bet it’s still alive in the open-source world — in fact, I know it is. But in the sweatshops where most of us coders earn our bread, the glory has departed. It’s mere drudgery now: Taylorized and overmanaged. One of the chief villains is something called ‘Agile methodology’, nicely satirized in the TV series ‘Silicon Valley’ as ‘scrum’. ‘Agile’ is a horrible neocult, and it has become the bane of my existence.

If you read the Agile manifesto or the Wikipedia entry it doesn’t sound too unreasonable, though the smarminess of the prose ought to ring alarm bells in any reasonably alert and cautious person’s mind.

But what it has led to in practice is an extraordinary bureaucratization of programming, accompanied by an extraordinary proliferation of cult-speak. For example, there really are ‘scrums’. In fact there’s one every day, usually in the morning. Scrums are presided over by ‘scrum masters’. I am not making this up.

I believe it is now possible to get some kind of credential as a scrum master. Scrum masters are usually people who don’t write code, and don’t know how to write code, but presumably understand scrums.

One is expected to stand during scrums, and they really do consist of moving post-it notes around on a whiteboard. This is very important. The post-it notes must also be color-coded, which is a sore trial to color-blind me. I always use a note of the wrong color, and must be called sharply to order, usually by a scrum master who is younger than some of my own children.

These things are referred to as ‘scrum ceremonies’. Again, I assure you: I am not making this up.

There are other picturesquely-named personages too, besides the scrum master: stakeholders and advocates and what not. But as the old proverb has it, shit rolls downhill, and all the shit ends up on the heads of the coders. Coders are supposed to be able to push back, but in practice they can’t, and so they get stuck with whimsical arbitrary deadlines for code whose behavior has never been clearly specified. Then somebody changes his mind about the expected behavior halfway through the development process. It’s a case of bricks without straw, Pharaoh!

It’s a testimony to the decency of human nature, and perhaps to a certain vestigial sense of Munchkin solidarity, that the coders seldom turn on each other and try to shift the blame when the preposterous deadlines are missed. (Though there are exceptions, may they burn in Hell.) The usual excuse, often true enough, is that some emergency supervened because the last delivery of crummy code failed in production, and a fire had to be fought.

One could go on and on — really, somebody ought to write a book about it — but perhaps this gives you some idea.

All this has of course made the programming workplace a much more anxious, unpleasant setting. The sense of solidarity, though it’s not entirely gone, is much impaired. We all used to make merciless fun of the boss, among ourselves. No more. Every so often an easily-disavowed emoji will turn up in some chat application. That’s about the extent of it.

Much of this work is done by contractors rather than regular employees. I’m one of that mercenary army myself, these days. Contractors don’t ordinarily stick around very long — and for that matter regular employees don’t either. There is, of course, no such thing as job security for either category of prole.

One of the sad consequences of this transience and casuality, combined with the nutty deadlines and the absence of specification, is that one really ceases to care about writing good code. It will probably never go into production anyway, and if it does, you’ll be long gone by the time it blows up and exposes the bank to a billion-dollar lawsuit or public disgrace. Or both. And if it does, they will richly deserve it.

Not that I would ever deliberately leave a time bomb in some odious employer’s code base. Oh no. As Richard Nixon once memorably said, That would be wrong. Retro me, Sathanas!

But I write shit code these days. I used to care about error handling. I used to make no assumptions at all about the validity and canonicality of the data feed I was working with. I used to spend a lot of effort making sure that my code worked with improbable but possible edge cases. I used to care about optimization and thread and socket pooling and re-use and short execution paths and compact footprints. I used to care whether threads really bought you anything, or just made the code easier to write.

Admittedly, I was never very good at including comments. I have gotten better at that, because after all, they’re much easier to write than code.

I haven’t quite descended to the Skid Row of coding yet, which is what I call ‘cut-and-paste code.’ You take a block of four or five lines, and in your editor you replicate it a dozen times, from top of screen to bottom, with one or two variable names changed in each copied block. This is a sin against God and man. What you ought to do is factor out the repeated common logic into a function or macro or something, and call it repeatedly with different parameters.

But you see the cut-and-paste approach a lot these days, created by people who certainly know better. A couple of years back I had a boss at a big American bank — one that you love to hate; trust me — who insisted that I ought to take the cut-and-paste approach. Why? Because it was easier for him to read the code that way.

It hasn’t gotten quite that bad for me yet; the cut-and-paste gig didn’t last, and the bad boss is now a more or less distant memory. (God, how I hated him at the time, though.) But my product is crap these days, even without that particular descent to the Ninth Circle.

And it seems that really, this is what my employers want. Or rather, as Madeline Albright once said, it’s a price they’re willing to pay for turning an eccentric, artisanic occupation into assembly-line work.

Whither Baltimore…

“… my greater source of personal concern, outrage and sympathy beyond this particular case is focused neither upon one night’s property damage nor upon the acts, but is focused rather upon the past four-decade period during which an American political elite have shipped middle class and working class jobs away from Baltimore and cities and towns around the U.S. to third-world dictatorships like China and others, plunged tens of millions of good, hard-working Americans into economic devastation, and then followed that action around the nation by diminishing every American’s civil rights protections in order to control an unfairly impoverished population living under an ever-declining standard of living and suffering at the butt end of an ever-more militarized and aggressive surveillance state.

“The innocent working families of all backgrounds whose lives and dreams have been cut short by excessive violence, surveillance, and other abuses of the Bill of Rights by government pay the true price, and ultimate price, and one that far exceeds the importances of any kids’ game played tonight, or ever, at Camden Yards. We need to keep in mind people are suffering and dying around the U.S., and while we are thankful no one was injured at Camden Yards, there is a far bigger picture for poor Americans in Baltimore and everywhere who don’t have jobs and are losing economic civil and legal rights, and this makes inconvenience at a ballgame irrelevant in light of the needless suffering government is inflicting upon ordinary Americans.”

Orioles COO John Angelos