This expert says most people with MCI won’t progress to dementia anytime soon, and here’s why not

Being diagnosed with mild cognitive impairment can come as a shock.

Invariably, the first thing people want to know is, does this mean I’m going to get dementia?

Ask a physician less versed in MCI, and you may be told the answer is yes.

Ask Dr. Mary Ganguli, and the answer is probably not.

And she’s got the evidence to prove it.

Ganguli and her colleagues at the University of Pittsburgh have just published a study showing that across a broad general population of adults with mild cognitive impairment, relatively few of them went on to develop dementia over a period of five years.

“Most people with MCI do not progress to dementia in the near term, but rather remain stable with MCI or revert to normal cognition,” the study says.

In fact, according to the study, of nearly 900 adults with mild cognitive impairment:

Those findings fly in the face of a widely held perception that MCI is a precursor to dementia and that if you are diagnosed with it, you are destined to progress to Alzheimer’s disease.

Dr. Ganguli is a geriatric psychiatrist at Pitt. In addition to teaching residents, fellows and graduate student there, she also does research and provides outpatient services at the University of Pittsburgh Medical Center.

She was the lead author of this study, and in a wide-ranging interview, here’s what she had to say on the topic of MCI and dementia:

“We want people to understand that not all mild cognitive impairment is MCI due to Alzheimer’s, and I think it’s come to mean that,” she told me. “In general parlance, people have come to think MCI is the stage before dementia and it isn’t.”

So where does this misperception come from? Well, in part, it depends on who you look at.

Neurologists at dementia centers typically treat MCI patients who are at the greatest risk of Alzheimer’s. So they tend to see that as the expected outcome.

But that’s a very narrow, skewed population. Most people with MCI don’t fall in that category and shouldn’t be automatically perceived as cases of dementia in waiting, Ganguli says.

“In the broader heterogeneous population, that’s not the case,” she says. “Don’t assume all mild cognitive impairment is going to progress to dementia.”

That’s just one of many observations that I gleaned during my interview with Ganguli. Here are my 10 key takeaways from our discussion, told mostly in Ganguli’s own words.

Takeaway #1: Some people with MCI are more likely to progress to dementia, and they seem to have three things in common.

Among the small percentage of people who progressed to dementia, they tended to be older, have more prominent memory loss and have the APOE4 gene, which is associated with a greater risk of Alzheimer’s.

Ganguli says these three factors represent a “typical Alzheimer’s disease profile” that’s been shown in previous studies as well.

Takeaway #2: Just as certain factors make one more likely to progress to dementia, other factors seem to make people less prone to progress.

Actually, this is one of the more significant contributions of this study. Scant research has been done to identify things that might leave someone at lower risk to progress.

“One reason we wanted to get this paper out is that people like me are the ones who are seeing the majority of these patients, and they shouldn’t believe everyone who is mildly cognitively impaired is on the threshold of developing dementia, because some are not,” Ganguli says.

“Many (studies) around the world have shown that at the population level, the majority don’t progress to dementia. But we were able to take it one step beyond that and say, over five years, these people don’t progress to dementia and here’s what else was wrong with them that might have been responsible for their cognitive impairment.”

Takeaway #3: The people who reverted to normal were  less likely to score poorly on memory tests. Their problems were more focused in other cognitive domains.

The people who fell into this category were worried about memory loss, and expressed concerns about their memory, but cognitive testing showed that their memory fell into a range that’s considered normal for their age.

Based on cognitive testing, their actual deficits were in such areas as language or decision-making.

“So the people with MCI who get better might be the ones who have a lot of memory concerns to begin with, even though their memory is not impaired and other things may be impaired, and then whatever is causing those deficits might get better and then they don’t have MCI anymore,” Ganguli says.

Takeaway #4: A common factor for not progressing to Alzheimer’s is having a medical condition such as diabetes or low blood pressure.

Ganguli says these conditions are associated with cognitive problems, but they are treatable. So if they are detected and treated, perhaps that is a reason the person doesn’t progress — even if they otherwise might seem a likely candidate to develop dementia.

“Things like diabetes and depression, we consider them to be modifiable,” Ganguli says. “So improving them might improve the outcome or reduce the chances of developing a bad outcome.”

She goes on to say:

“Even in my clinical practice, I might see a person for the first time and think, this one might have some cognitive impairment, and she also has some diabetes, but the impairment looks really bad and I’m afraid this one is going to go downhill.

“But then I’ll see her three months or six months or a year later and she is not going downhill. And again a year after that, and she’s still not going downhill. And then she gets better. What happened? Well, somebody put her on an insulin pump and now her sugar is well-controlled or perhaps she had a little bit of heart failure and someone put in a pacemaker and suddenly she gets better.”

Takeaway #5: Another factor  associated with not progressing to dementia is being on three or more medications.

“If you have a little diabetes or a little hypertension, you might be taking a bit of medication for that,” Ganguli says. “But here, we can specifically say that people who are taking multiple medications could be taking them for something like diabetes, so getting that treatment might have allowed them to get better, especially if it was something acute.”

Takeaway #6: Taking certain medications or combinations of medications may affect cognition in other ways, although that was not the target of this study.

“There is another factor that we didn’t go into in this paper, and that will be the subject of future research,” Ganguli says. “Are they taking medications that are making them cognitively impaired? They could be.

“ Benadryl is not a prescription medication, it’s an over the counter allergy pill which people also take for sleep, and anything with PM, whether it’s Advil PM or Alka Seltzer PM, contains Benadryl, which makes people sleepy but also does impair their cognition a little bit, and if they stop taking that, they might get better.

“There are many prescriptions that also might have this effect.  Somebody recently asked me about that, and I said, ‘Are you looking at all the particular medications these people are taking that might be the cause of the cognitive impairment?’ “Obviously if you stop that medication, people should improve, so that’s something we’ll be looking at.”

Takeaway #7: Family history can play a role in your risk of progressing or not progressing. But genetics is less of a factor that you might expect. Family history also includes all sorts of lifestyle factors, and those can potentially  play an even bigger role than your genetic makeup.

“You get your genes from your parents,” Ganguli says. “That is one part of family history. The ones we know that are deterministic genes — and it’s a gene mutation — if you have that gene, you will get Alzheimer’s, but that is less than 5 percent of all cases. And it is the ones that are very early onset Alzheimer’s.

“So if you have a parent or grandparent who developed Alzheimer’s in their 70s or 80s, we share genes with our parents, but we also share environment with our parents, and diet and family lifestyle with our parents, so everything that’s familial may not be genetic.”

Takeaway #8: Exercise is recommended for anyone with MCI, as a way to potentially reduce the risk of progressing to dementia.

“We really don’t understand why, but exercise seems to have a pretty big effect size,” Ganguli says. “We are working on a paper about exercise. There’s a lot of excitement about it. I don’t think can we tell people why exercise is helpful, but we can tell them that it is helpful.”

Takeaway #9: Staying socially engaged and cognitively challenged could be beneficial, too, but the evidence around that is less definitive.

“We do have information suggesting that cognitively engaging activity and social engagement are associated with a lower likelihood of progressing,” Ganguli says.

“The trouble is, you can never completely say which is the chicken and which is the egg, because people who give up playing bridge or whatever, they may be giving up because it’s getting too hard because they have an underlying disease. It’s not like they gave up, so they went unstimulated and therefore they developed dementia. It might be the other way around.

“So even though we are showing people who are cognitively normal or had MCI might be more likely to remain that way if they do certain things, it might be the ones who are able to do those things are the ones who are not progressing. In dealing with older adults, we encourage them to do those things but we don’t punish them for not doing them because maybe they are withdrawing because they are experiencing difficulties.”

Takeaway #10: There are broad risks that apply across large populations of people, but what you care about is your own individual risk.  That’s unique to you, and you deserve medical treatment that is specific to you and your situation.

“We are talking about relative risk and not absolute risk at the group level,” Ganguli says. “You can’t say an individual who has diabetes is not going to progress to dementia. That’s obviously wrong.  You can have diabetes and Alzheimer’s. And having diabetes might even increase the risk of having some of the pathology of Alzheimer’s or of the cardiovascular pathology, which again can increase the risk of getting dementia.

“But one would like clinicians who see someone who says, ‘I’m having trouble remembering,’  and not say, ‘That’s it, this is Alzheimer’s, I’m just going to give you Aricept or something and I’m not going to worry about your other conditions.’  We don’t want them to do that.

“We want clinicians to realize that not everyone who appears mildly impaired has an underlying progressive dementia-causing disease, although even if they do, you still need to pay attention to diabetes and blood pressure. Low blood pressure usually suggests something like either they’re taking too much blood-pressure medicine or maybe they are in heart failure, and by the way, the brain isn’t going to get enough oxygen if there isn’t enough pressure to pump it up to the brain.

“In a broad sense, it’s asking clinicians to please pay attention to all these other conditions and not say, ‘Oh, it’s Alzheimer’s and there’s no treatment for it.” Patients need to understand that. Health care providers need to understand that, and play close attention to the modifiable risk factors that people might have and not focus on the things we can’t do anything about.”