For about a year now, I've been trying to figure out what to make of data coming in about the association between Benzodiazepine (BZD) use and dementia.
To start from the very beginning, I recognize that BZDs are potentially addictive, can cause gait and memory impairment, and precipitate withdrawal seizures with continued use, and don't mix well with other drugs like EtOH and Opioids, for instance. They're not ideal drugs.
But for a certain subpopulation, they're helpful. Anxious people who are on other meds that don't quite hold them, and who don't escalate their doses, for instance. Patients who are scared of flying, and who need a Xanax to get them there, and another to get them back. And sure, everyone knows BZDs have, at best, a short duration of helping with insomnia, and still, some patients do well with them long-term.
I'm definitely more liberal with BZDs than I was taught to be as a resident, where they were viewed as the evil purview of manipulative drug seekers. I consider that perspective a bit extreme. On the other hand, I try to encourage other methods for coping with anxiety, and taper patients off them, when I can.
Lately, though, I've been worrying about the connection between BZDs and dementia. In a 2012, French study by Billioti de Gage, et al, 1063 men and women, (mean age 78.2) who were dementia free were followed for up to 15 years. Those who used BZDs prior to the onset of the study were excluded, so only those who used BZDs three or more years into the study were included. They found that new use of BZDs was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60, 95% confidence interval 1.08 to 2.38). They also found that:
"Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users. The results were similar in past users (odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but reached significance only for past users."
This was the part I found particularly perplexing. I didn't understand this separate, complementary study, or what to make of "ever use" vs. "never use". For instance, what are the implications for someone who gets a versed fentanyl drip for a colonoscopy? Does that constitute "ever use"?
Other studies cited by this one demonstrate increased risk of dementia in chronic use, former use, and ever use (please see study for citations). The "ever use" particularly bothered me, because why should I encourage patients to stop taking BZDs if their risk is already well-established.
Another study, (same author, 2014) looked at people already diagnosed with Alzheimers, and considered a dose response relationship to BZDs. They found an association with "ever use", but not with cumulative dose. Also, the strength of association was greater for long half-lifed BZDs than for short half-lived. There were a whole bunch of confusing points and confounders.
Finally, there's this study:
Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study, by Gray, et al, published in the BMJ last month. It's a prospective, population-based study done in Seattle, "To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline."
They had 3434 participants age > 65, dementia-free at study entry. They screened for dementia every 2 years over the course of 10, with the CASI (Cognitive Abilities Screening Instrument), and got data about BZD use via computerized pharmacy records.
They concluded:
The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.
There's so much inconsistency here that I don't know what to think. At least all three of the articles are open access.
I'm off to the Far East for several weeks, see you when I get back.
Showing posts with label cognitive decline. Show all posts
Showing posts with label cognitive decline. Show all posts
Tuesday, March 1, 2016
Sunday, May 24, 2015
Tools to Prevent Cognitive Decline?
I like to play Hitori. For those not familiar, it's another one of those Sudoku-type games that are great for convincing yourself you're doing something useful, i.e. keeping your reasoning skills sharp, when you're probably just wasting time. Those games-minesweeper, ken-ken, pixel games (I'm partial to Pic-a-Pix), are all wonderful for dealing with mild anxiety. They require just enough concentration to be distracting, but not enough to really be a strain, or make you feel like it's an effort to play.
But today, I was playing Hitori, and the site came up with one of its weird ads. This particular site may be a little sketchy, which is why I didn't link to it, because when I first started playing, I got ads for what seemed like mail-order brides from Eastern Europe. I'm not sure what text Big Brother Google was reading in my emails that made it believe those ads would appeal to me, but that's what I got. Those ads went away pretty quickly.
Then I started to get ads for devices to treat depression. At least that's not so surprising, given my professional searches and email exchanges. One of these days, I'll read up on the research on that device, the Fisher Wallace Stimulator, which you use for 20 minutes once or twice a day.
Then the ads moved on to brain games like Lumosity. Again, not surprising, since Hitori is another brain game. I've tried out Lumosity, for free, and I found some of the memory games challenging. I didn't use it long enough to see if my memory improved.
Today, I got an ad for cremation planning. I did celebrate a birthday earlier this month, but not one that puts my age at death's door. So I guess people are using games like Hitori to ward off dementia and their expected mental decline due to aging.
Lumosity claims to take standard neuropsych testing out of the lab, and turn it into games. It adds new games, and then tailors a program "for you". There's a whole section on their research, some of which is performed in Lumos Labs. The site has 13 summaries of peer reviewed papers, including topics like cognitive training in cancer survivors, training for girls with Turner's syndrome, Lumosity in the classroom, Lumosity for emotion regulation, etc.
There's one study called, Investigating the effects of Lumosity cognitive training for healthy adults:
Twenty-three volunteer participants were randomly assigned to one of two groups: a training intervention group or a waitlist control group. Intervention group participants completed Lumosity training 20 minutes a day for 5 weeks. At the end of the training period, participants in this group saw improved performance on a divided visual attention assessment in which the user must identify a central target and report the location of a peripheral target, and on a forward and reverse working memory assessment in which the user must click in the same or opposite order that they were highlighted. Control participants, on the other hand, who did not undergo Lumosity training, did not show changes in performance on these assessments.
The original article, published in Mensa Research Journal, is here.
Another study, not performed at Lumos, examined use of Lumosity in adults with MCI. The summary is this:
Dr. Maurice Finn, a clinical psychologist and researcher at the University of New South Wales in Sydney, Australia found that training with Lumosity improved visual attention performance on the Cambridge Automated Neuropsychological Test Battery (CANTAB) in patients with Mild Cognitive Impairment (MCI).
The original article, in Brain Impairment, concludes:
Results indicated that participants were able to improve their performance across a range of tasks with training. There was some evidence of generalisation of training to a measure of visual sustained attention. There were no significant effects of training on self-reported everyday memory functioning or mood. The results are discussed along with suggestions for future research.
There's a poster about age-related effects on learning. And another poster about Lumosity's Brain Performance Test (BPT).
There's also a link to ongoing research topics.
Basically, there's a lot of self-serving noise, which doesn't mean Lumosity isn't helpful, but it doesn't mean it is, either. It seems to me that these studies measure improvement on their own tasks, or games, as they call them. It's not clear what these improvements imply for the rest of life.
On the flip side, there's this piece in Science, indicating that:
Aging baby boomers and seniors would be better off going for a hike than sitting down in front of one of the many video games designed to aid the brain, a group of nearly 70 researchers asserted this week in a critique of some of the claims made by the brain-training industry.
Furthermore:
For those who choose to play brain games regardless, recent research suggests that playing some video games developed solely for fun may be as effective, or more, than those developed for cognitive self-improvement. Scientists at Florida State University randomly assigned 77 undergraduates to play either Lumosity or the popular video game Portal 2, in which players take on the roles of robots to solve interactive puzzles to face off against a “lethally inventive, power-mad A.I. named GLaDOS.” After 8 hours of play, Portal 2 players scored higher than Lumosity players on three standard cognitive tests of problem-solving and spatial skill, and Lumosity players “showed no gains on any measure,” the team reported online this summer inComputers & Education.
A 2010 Systematic Review of the Literature, published in the Annals of Medicine, found:
...high-quality evidence for only 1 factor's effect on cognitive decline. Cognitive training on processing speed or reasoning showed a decreased risk for cognitive decline in the specific targeted cognitive abilities over a 2-year follow-up, and the evidence was rated as high-quality primarily on the basis of 1 RCT . Observational studies of self-reported engagement in cognitively stimulating activities suggest an association with less cognitive decline, but this exposure is probably different from the cognitive training used in the RCT.
A chapter from the Handbook on the Neuropsychology of Aging and Dementia
Clinical Handbooks in Neuropsychology 2013, pp 167-192, indicates:
Specific dietary changes rich in vegetables, fruits, and fish and low in carbohydrates and saturated fat are advisable, with particular emphasis in patients at risk of developing Alzheimer’s disease (AD) or vascular dementia. Patients should remain active physically and mentally. Physical exercise is among the best of all potential interventions against AD.
One study with an n of 488 initially cognitively intact subjects found that doing crossword puzzles delayed the onset of accelerated memory decline by 2.54 years, in those subjects who ultimately developed dementia. It's not clear from the abstract if doing crossword puzzles kept subjects from developing dementia, at all-I assume that's not what they were studying, or able to study.
The most frequent preventive factor I could find was physical activity. But it's clear that there's something unclear here. So maybe I should stop playing Hitori and swim more. Or maybe I should stop researching whether I should stop playing Hitori.
But today, I was playing Hitori, and the site came up with one of its weird ads. This particular site may be a little sketchy, which is why I didn't link to it, because when I first started playing, I got ads for what seemed like mail-order brides from Eastern Europe. I'm not sure what text Big Brother Google was reading in my emails that made it believe those ads would appeal to me, but that's what I got. Those ads went away pretty quickly.
Then I started to get ads for devices to treat depression. At least that's not so surprising, given my professional searches and email exchanges. One of these days, I'll read up on the research on that device, the Fisher Wallace Stimulator, which you use for 20 minutes once or twice a day.
Then the ads moved on to brain games like Lumosity. Again, not surprising, since Hitori is another brain game. I've tried out Lumosity, for free, and I found some of the memory games challenging. I didn't use it long enough to see if my memory improved.
Today, I got an ad for cremation planning. I did celebrate a birthday earlier this month, but not one that puts my age at death's door. So I guess people are using games like Hitori to ward off dementia and their expected mental decline due to aging.
Lumosity claims to take standard neuropsych testing out of the lab, and turn it into games. It adds new games, and then tailors a program "for you". There's a whole section on their research, some of which is performed in Lumos Labs. The site has 13 summaries of peer reviewed papers, including topics like cognitive training in cancer survivors, training for girls with Turner's syndrome, Lumosity in the classroom, Lumosity for emotion regulation, etc.
There's one study called, Investigating the effects of Lumosity cognitive training for healthy adults:
Twenty-three volunteer participants were randomly assigned to one of two groups: a training intervention group or a waitlist control group. Intervention group participants completed Lumosity training 20 minutes a day for 5 weeks. At the end of the training period, participants in this group saw improved performance on a divided visual attention assessment in which the user must identify a central target and report the location of a peripheral target, and on a forward and reverse working memory assessment in which the user must click in the same or opposite order that they were highlighted. Control participants, on the other hand, who did not undergo Lumosity training, did not show changes in performance on these assessments.
The original article, published in Mensa Research Journal, is here.
Another study, not performed at Lumos, examined use of Lumosity in adults with MCI. The summary is this:
Dr. Maurice Finn, a clinical psychologist and researcher at the University of New South Wales in Sydney, Australia found that training with Lumosity improved visual attention performance on the Cambridge Automated Neuropsychological Test Battery (CANTAB) in patients with Mild Cognitive Impairment (MCI).
The original article, in Brain Impairment, concludes:
Results indicated that participants were able to improve their performance across a range of tasks with training. There was some evidence of generalisation of training to a measure of visual sustained attention. There were no significant effects of training on self-reported everyday memory functioning or mood. The results are discussed along with suggestions for future research.
There's a poster about age-related effects on learning. And another poster about Lumosity's Brain Performance Test (BPT).
There's also a link to ongoing research topics.
Basically, there's a lot of self-serving noise, which doesn't mean Lumosity isn't helpful, but it doesn't mean it is, either. It seems to me that these studies measure improvement on their own tasks, or games, as they call them. It's not clear what these improvements imply for the rest of life.
On the flip side, there's this piece in Science, indicating that:
Aging baby boomers and seniors would be better off going for a hike than sitting down in front of one of the many video games designed to aid the brain, a group of nearly 70 researchers asserted this week in a critique of some of the claims made by the brain-training industry.
Furthermore:
For those who choose to play brain games regardless, recent research suggests that playing some video games developed solely for fun may be as effective, or more, than those developed for cognitive self-improvement. Scientists at Florida State University randomly assigned 77 undergraduates to play either Lumosity or the popular video game Portal 2, in which players take on the roles of robots to solve interactive puzzles to face off against a “lethally inventive, power-mad A.I. named GLaDOS.” After 8 hours of play, Portal 2 players scored higher than Lumosity players on three standard cognitive tests of problem-solving and spatial skill, and Lumosity players “showed no gains on any measure,” the team reported online this summer inComputers & Education.
A 2010 Systematic Review of the Literature, published in the Annals of Medicine, found:
...high-quality evidence for only 1 factor's effect on cognitive decline. Cognitive training on processing speed or reasoning showed a decreased risk for cognitive decline in the specific targeted cognitive abilities over a 2-year follow-up, and the evidence was rated as high-quality primarily on the basis of 1 RCT . Observational studies of self-reported engagement in cognitively stimulating activities suggest an association with less cognitive decline, but this exposure is probably different from the cognitive training used in the RCT.
A chapter from the Handbook on the Neuropsychology of Aging and Dementia
Clinical Handbooks in Neuropsychology 2013, pp 167-192, indicates:
Specific dietary changes rich in vegetables, fruits, and fish and low in carbohydrates and saturated fat are advisable, with particular emphasis in patients at risk of developing Alzheimer’s disease (AD) or vascular dementia. Patients should remain active physically and mentally. Physical exercise is among the best of all potential interventions against AD.
One study with an n of 488 initially cognitively intact subjects found that doing crossword puzzles delayed the onset of accelerated memory decline by 2.54 years, in those subjects who ultimately developed dementia. It's not clear from the abstract if doing crossword puzzles kept subjects from developing dementia, at all-I assume that's not what they were studying, or able to study.
The most frequent preventive factor I could find was physical activity. But it's clear that there's something unclear here. So maybe I should stop playing Hitori and swim more. Or maybe I should stop researching whether I should stop playing Hitori.
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