Dementia’s Behavioral Changes: A Psychiatrist Explains

Behavioral symptoms of dementia, like agitation, paranoia, depression, and anxiety, can be challenging for caregivers and people living with the disease to navigate. In addition, when some people are experiencing early signs of cognitive decline, sometimes they can be misdiagnosed with depression or anxiety, and it takes years to receive an accurate diagnosis. 

So, what do we know about dementia and the reasons for these behavioral and psychiatric symptoms? 

Tufts University’s Dr. Brent P. Forester joined Being Patient founder Deborah Kan in a conversation about how dementia can impact behavior and the importance of seeking a diagnosis. He’ll also discuss the connection between depression and dementia. 

Forester is the Dr. Frances S. Arkin Professor and Chair of Psychiatry at Tufts University School of Medicine, the Psychiatrist in Chief and Chairman for the Department of Psychiatry at Tufts Medical Center, and the Director of Behavioral Health for Tufts Medicine. 

He’s an expert in geriatric psychiatry, specializing in the treatment of older adults with depression, bipolar disorder, and behavioral complications of Alzheimer’s disease and related dementias. His research focuses on treatments to manage disabling behavioral complications of dementia, such as agitation and aggression. Forester also works to implement and evaluate collaborative care models for comprehensive dementia care within primary care medical settings.

Read or watch the conversation below. 

Being Patient: What are some of the behavioral early signs of dementia?

Dr. Brent P. Forester: It’s the anxiety, the agitation, the depression, the paranoia, [and] the aggression, sometimes, that are not only universal over the course of the illness of dementia, but they truly are the factors that drive the burden of this illness for both individuals with dementia and especially their loved ones who care for them. 

If you look at why people with dementia wind up in long-term care, in the hospital, or the emergency room— it’s not because of the inability to remember someone’s name; it’s because of these behavioral symptoms. This is often the final straw that breaks the camel’s back. So, they’re critical to recognize. The good news is they’re highly treatable but need to be assessed, and we need to figure out the cause. 

“If you look at why people with dementia wind up in long-term care, in the hospital, or the emergency room— it’s not because of the inability to remember someone’s name; it’s because of these behavioral symptoms.”

In the early stages of a memory disorder like Alzheimer’s disease, which is one form of dementia, it’s very common that there are people who are aging. They’re becoming more forgetful, and they feel depressed, or they feel a lack of motivation. Sometimes, we call that apathy, or they feel worried and anxious, and they just can’t put their finger on it. 

Memory loss is certainly an early sign of Alzheimer’s, but frankly, these mood and anxiety symptoms are an early sign potentially of dementia. It may be that it’s the underlying disease process coming out, and it’s manifesting with these psychiatric symptoms. 

What’s important to figure out, when I’m assessing somebody who’s coming to me with, say, depression or anxiety, and they’re in their 70s or 80s— is this the first time in your life this has happened? Or do you have some lifelong recurring history of depression since your 20s and 30s, and now you happen to be in your 70s, and it’s another episode? 

That’s a big difference because if someone has never had these symptoms earlier in life, and now they’re having them, it’s more likely to be a medical or a neurological cause. It’s not always dementia as the cause, but that’s definitely one of the causes. 

Sorting it out is sometimes tricky, and families try to figure it out, but that’s not your job as a family member. You need to bring your loved one to a professional who can assess what’s a medical problem, what’s a psychiatric issue, and what’s dementia with a psychiatric issue. Once you figure out the cause, you can come up with the right treatment.

Being Patient: Across different types of dementia, paranoia is a common behavioral symptom. What do we know about those early signs? How is it that these symptoms cross dementias?

Forester: When it comes to understanding the changes in the brain causing symptoms like paranoia, that’s an area which, honestly, is incredibly understudied. There’s a fair amount of research going on right now. The NIA, the National Institute of Aging, is trying to support research to uncover the biology of these symptoms like delusions, paranoia, anxiety, depression, and so forth. 

“You need to bring your loved one to a professional who can assess what’s a medical problem, what’s a psychiatric issue, and what’s dementia with a psychiatric issue.”

Paranoia often doesn’t happen in the very, very early stages, but what might happen is that the person had the disease in the brain for five [or] seven years, and no one knew it. So, it looks to the family like it’s the early stages, but honestly, the horse has been out of the barn for a while. [Some examples are] where somebody mistakes a loved one for someone else or can’t find an object around the house and comes up with a story that someone stole from them. 

We call that a delusion. A delusion is a fixed false belief by definition. [It] says nothing about why. It says nothing about the cause of that delusion. What often happens in Alzheimer’s disease because the classic cognitive symptom is the inability to store new information, [is] that person cannot remember from moment to moment what just happened. If they can’t find something, it’s the brain’s natural tendency to come up with a story about why. 

Now, I can’t explain to you why it goes down the paranoid root of an explanation, as opposed to, “I must have just misplaced it,” but that paranoia is rooted in specific brain regions, and the hippocampus is the part of the brain where we store new information. 

The parietal lobe is sometimes the part of the brain that allows [that.] It’s like spatial awareness, things like that, and insight. The lack of insight that we often see in people with dementia, the awareness that they have a problem is often a parietal lobe impairment that sometimes feeds into the paranoid beliefs that people have in terms of, “Why does that even happen?” Parietal reduction in function early on is [what] we see biologically with Alzheimer’s disease, so it’s not surprising. 

“The lack of insight that we often see in people with dementia, the awareness that they have a problem is often a parietal lobe impairment that sometimes feeds into the paranoid beliefs that people have” 

Being Patient: Where is the parietal lobe, and what is it responsible for?

Forester: The frontal cortex is behind your forehead, and the parietal lobe is right next to it, like over your ear lobe. It’s responsible for some things that are hard to measure, like awareness, insight, and appreciation of illness. People [who] have had strokes, and their parietal lobe will often develop a syndrome of neglect, where they’re unable to recognize [parts] of their body. 

The thing that we often see in parietal deficits, as well as a lack of insight into an illness or into a deficit. A deficit could be a neurological hand function thing, or it could be a memory thing. In any case, the most important issue about these symptoms is that we figure out why. 

If it’s an acute onset of a paranoid delusion in someone who never had the problem, it’s not schizophrenia all of a sudden in a 70-year-old, right? That’s not the problem, and it may or may not be Alzheimer’s, Frontotemporal dementia, or anything else. It could be an infection, especially if it’s an acute onset. 

We need to make sure that families are bringing their loved ones to medical attention to find out the cause. I cannot stress that highly enough because if we don’t get the cause right, and you bring your mom, say to a psychiatrist who doesn’t think about what the cause is, and I give your mom a drug to treat a symptom that’s caused by something else, it’s not helpful, and it potentially could be harmful. 

Being Patient: How do you know when depression is associated with dementia?

Forester: A colleague of mine literally asked me this question last night about a patient of hers that she’s been treating for depression. Now, this person of hers [is] age 70, had depression, on an antidepressant, and now has a brother with dementia. The patient with depression is worried that they now also have dementia. This is a highly trained, skilled, decades-long clinician who’s not a geriatric psychiatrist. She says to me, “I don’t think it’s dementia.” I said, “Well, how do you know that? What workup have you done?” 

What I would try to find out is, first of all, the history. Sometimes it’s helpful. I would say always, it’s helpful to hear from families what they’re noticing because [there could be a] lack of awareness. Even though the person may say, “I’ve never had it before,” what does the adult daughter or spouse think? Even the grandson or daughter— so getting collateral— that information from family is number one, their perspective. 

“I would say always, it’s helpful to hear from families what they’re noticing because [there could be a] lack of awareness.” 

[The] second thing is, let’s get an objective measure of depression. I can ask you the questions that meet the criteria, but I could also give you a rating scale to get a severity score. Then, very importantly, no matter what, I’m going to do a cognitive assessment, and I’m going to see on a basic test, like a Montreal cognitive exam, test eight domains of cognition in about 15 minutes, and see if there are any deficits. 

If the depression severity is high enough, it will affect cognitive performance. If the depression severity is normal [or] there is no depression now, then what you’re seeing from a cognitive assessment probably truly reflects cognitive performance. Anyway, that’s the beginning, the history of the person and their loved one, and a further assessment of mood and cognition— then we go from there.

Being Patient: Can we see depression in the brain? What do we know about what’s happening inside the brain when somebody is diagnosed with depression?

Forester: It also depends on the age of onset of it. Somebody in their 30s with depression is different [from] an 80-year-old with depression in terms of biological cause and so forth. Let’s talk about [a] 70-year-old patient who had no history. 

First of all, if anyone were to tell you that we understand the cause of depression, they would be lying to you. We don’t know. We know associated findings in the brain that are correlated with the symptoms of depression. 

Remember, depression is a syndrome of symptoms. It’s not a disease that we can identify like Alzheimer’s, [which] is defined by plaques and tangles in the brain that we can see and measure. Depression, not so much. With depression, we know there are neurochemical changes in the brain, and we know that in part because people respond to certain medications that alter those neurochemical chemicals in the brain. 

“Remember, depression is a syndrome of symptoms. It’s not a disease that we can identify like Alzheimer’s, [which] is defined by plaques and tangles in the brain that we can see and measure.”

We also know that depression is an illness that involves brain circuits. So in somebody who’s in their 70s, who’s now getting depression for the first time in their life, in my mind, I want to know if they have risk factors for small strokes, like high blood pressure, diabetes, or high cholesterol. 

In many cases, you’ll see somebody who presents with depression for the first time in their 70s, and it turns out they [have] high blood pressure. Then it turns out that you get an MRI of their brain, and they have these small, little white spots scattered throughout their brain. 

There’s a theory called vascular depression, which is a hypothesis of late-onset depression that’s associated with not memory loss but executive dysfunction, like an inability to plan, to organize, or to make decisions. In that case, you’re disrupting, with those mini-strokes, the connections between the frontal lobe and the lower brain structures called the subcortical brain, and in that situation, people have depression. It’s very frustrating for the person. 

It’s also very frustrating for the family members because they’ve never seen this in their loved one. That depression is not a sadness, melancholia, and hopeless depression. It’s an apathetic depression. It’s [an] “I don’t feel like doing anything” depression. It’s a “can’t initiate or initiate activity” depression. That is a very difficult to treat depression, but it speaks to this vascular brain change that often occurs. 

Being Patient: Would that be in the case of vascular dementia rather than Alzheimer’s, or is it across the board?

Forester: If you follow someone like I just described, with vascular brain changes and the apathetic a-motivated depression and executive dysfunction, if you follow those people for five years, 50 percent will have dementia, and again, it may be vascular dementia at that point. 

Commonly, and this is an important point for you all to understand, if someone presents with memory loss and cognitive changes and is diagnosed with dementia in their 60s, it’s usually a singular brain disease. But the older you get, especially into your 80s, it’s way more common to [have] multiple brain diseases and the most common co-occurring brain diseases are Alzheimer’s-type dementia and vascular dementia. 

We could debate forever, like, “How do you define vascular dementia? Is it like one big stroke, or are these mini-strokes or some combo?” But, that combination is so much more common in later life.

Being Patient: What do you know about out-of-body feelings and dementia, where you feel like you’re floating outside your body? This can be a symptom for people who have CTE.

Forester: It’s so hard for me to comment on anyone’s experience with such little information, but when I hear somebody talk about an out-of-body experience, my mind goes to symptoms that we often see in lot [of] people with [a] psychiatric illness called dissociation. It’s a phenomenon where we don’t feel connected to our bodies. 

“If someone presents with memory loss and cognitive changes and is diagnosed with dementia in their 60s, it’s usually a singular brain disease. But the older you get, especially into your 80s, it’s way more common to [have] multiple brain diseases.” 

We feel like we’re outside of ourselves, or we’re looking at ourselves from up above or from outside of ourselves. It’s a real disconnection. We see [the] dissociation phenomenon in people who’ve had some traumatic injuries or have been exposed to trauma. 

It could be related to that; no matter what, it’s likely related to the part of the brain that’s been traumatized. Whatever the injury was or wherever it occurred, you could consider it to be an anxiety-like phenomenon, and I’m curious what treatments [clinicians use] to try to treat it, but really, I often think of it as dissociation. It’s often associated with the exposure to trauma.

Being Patient: What about early onset Alzheimer’s concerning depression? What about people in their 50s?

Forester: That’s a really good question. I would be guessing if we knew that there was a difference in the symptoms of early-onset Alzheimer’s disease if early is defined by 52 versus 70. In other words, I don’t think age matters as much as what’s going on in your brain. 

If it’s happening to a 52 or if it’s happening to you at 70, the process of Alzheimer’s disease is usually pretty predictable in terms of where in the brain it starts. What’s not always predictable is that, and I say this often, if you’ve seen one person with Alzheimer’s, you’ve seen one person with Alzheimer’s because everyone has a little bit of a different pathway. 

I would think of it the same way: the number one thing we do is figure out why. If you’ve never had it until now [at] 52,  anxiety, depression— what’s going on biologically in your brain? Are there other medical factors? 

By the way, I didn’t mention this before, but it’s really important. I’m a psychiatrist, but I spend most of my time figuring out the medical causes of psychiatric symptoms because if I miss them, I’m missing a treatable opportunity. 

I worry that people go too long with symptoms [and] they don’t figure out why. Just ask the question, “Why?” If your 12-year-old develops depression, you would want to know why. So, when your 70-year-old mom or your spouse develops depression, you want to know why.

Being Patient: How much do we know about the relationship between glucose metabolism and behavioral symptoms?

Forester: Let’s just say, are there any characteristic findings on brain imaging, whether it’s metabolism changes, structural networks that you would see with what’s called functional MRI findings in like a structural picture of the brain, are there any characteristic findings that would be associated with certain psychiatric symptoms, depression, paranoia, etc? These are not clinical tools. 

“If your 12-year-old develops depression, you would want to know why. So, when your 70-year-old mom or your spouse develops depression, you want to know why.”

I don’t go around getting glucose metabolism studies on people with depression who are older if we know they don’t have dementia. I’m still going to treat their symptoms because I don’t understand as a clinician, either. No one does. The relationship between these glucose metabolism symptoms and depression, and I say this because the world of psychiatry, unfortunately, is a world where we don’t have biomarkers that predict underlying causes or response to treatment. 

Some of the research I’ve been involved in with certain kinds of imaging studies, and a lot of my colleagues have with PET scans and MRI scans and things like that, so those are great questions. There’s a lot of research on this, and there’s a lot of effort to try to understand the biological causes of these psychiatric symptoms in dementia. 

Being Patient: For depression and anxiety in someone with dementia, do psychiatric medications work? Does that change with different types of dementia?

Forester: If we use psychiatric medications to treat paranoia, depression, and anxiety, does it work in dementia? The answer is yes. However, let’s take depression. The biological cause of depression in a 75-year-old who’s never had depression is very different [from] the biological cause of depression in a 30-year-old who has never had depression. 

Not only is your brain 45 years older, but if you have dementia now, you have plaques and tangles in your brain. You may have many strokes in your brain. You’ve had inflammation in your brain. You’ve had degeneration of brain tissue. Why would we expect the medicines to work the same? 

There’s a lot of research that’s going on now and needs to continue to find out— do we treat someone who’s 75 with dementia and depression differently than a 35-year-old? The answer is yes, and it depends on the symptoms in some ways.

I don’t know how much you want to get into this, but some of our medications, like Prozac, Zoloft, Paxil, the SSRI medications, work well for depression and late life, but when you have depression plus dementia, they don’t work as well in that same age person who’s older when there’s dementia, because of these other biological factors. 

“If anything about dementia is treatable,
it’s these behavioral and
psychological symptoms.”

If the person’s on Zoloft at a good dose and a little bit better, but not fully better, then I look to see, well, what are still the symptoms that remain? Is it anxiety and worry? Is it sleep? Is it feeling blah or lacking in motivation? 

Based on that, I will choose a medication to go along with the SSRI to try to improve symptoms. The most important point here is if you feel this way or a loved one that feels this way, there are treatments that can be used to help you feel better and function better. If anything about dementia is treatable, it’s these behavioral and psychological symptoms. 

Being Patient: What types of drug treatments are in the pipeline for treating behavioral and psychological symptoms of dementia? What is available now?

Forester: My personal opinion is that drug development for behavioral symptoms of dementia is so far behind where it needs to be, and there are a lot of reasons for it, in part because the world of dementia care has been dominated by the amyloid hypothesis. The good news is [that] if these drugs work like the anti-amyloid therapies, one would presume they might also secondarily help some of these symptoms, and the data on that is forthcoming. 

The first ever [FDA-approved] drug to treat agitation and dementia was about a year and a half ago. It’s an anti-psychotic medication called brexpiprazole. There are many other atypical antipsychotics, we call them, that have been studied for decades and show that they work and that they’re relatively safe. 

There are side effects. They’re worrisome side effects, but they’ve not gotten FDA approval for a whole variety of reasons. There is some drug development in this area, but it’s not consistent, and it’s been the repurposing of existing medications.

Being Patient: Rexulti is one of those repurposed psychiatric drugs that is now being tested for treating Alzheimer’s disease symptoms. Would you prescribe that to a patient?

Forester: Rexulti is the brand name for brexpiprazole. That is indeed the only FDA-approved treatment for agitation for Alzheimer’s. There may be others next year. There is drug development, but that medication shows that it reduces agitation in people with dementia of the Alzheimer’s type. 

There’s a dose-response kind of thing we can follow, but what we don’t have is head-to-head studies. I don’t know if that’s better or worse than drug B, olanzapine, risperidone, or seroquel. However, for patients who have delusions, they’re agitated, and they’re at risk of harming themselves or others, and they’re distraught, and their families are distraught— 100 percent, I would prescribe that medication,

Then, I would warn the families that there are side effects. It could cause sedation or unsteadiness on their feet or dizziness when they stand up, or it could cause an elevation in blood sugar or diabetes, or it may increase the risk of stroke or even mortality, which is very, very low. But those are the things that have to happen. 

We have to have these risk-benefit discussions. You mentioned your mom. If her delusions [are] to the point where they’re scaring her, keeping her up at night, making her feel anxious and worried and distraught, if the agitation is being driven by paranoia, I would recommend an anti-psychotic. 

Being Patient: Do drugs like Rexulti work on other dementias like Lewy body?

Forester: Lewy Body dementia is one where we have to be careful with any anti-psychotics because it’s Parkinsonian-like dementia, as you probably know. Any of these anti-psychotics could make those Parkinsonian symptoms worse, not just the tremor, but the balance and the risk of falling and maybe even confusion. Not that we wouldn’t use it, but we try other things first. 

Being Patient: What have you learned about cannabinoids in your research?

Forester: First, cannabinoids are so understudied. For all the things that people go to dispensaries and everything for, do we know? The study that I did is a study of a synthetic THC compound called dronabinol, or Marinol, [which] has been on the market since 1985 for two other non-dementia indications, and so it’s available and any doctor could prescribe it. 

We studied it in people with Alzheimer’s disease with agitation compared to placebo over three weeks and found that five milligrams twice a day was both effective and safe. Our paper is about to be submitted for publication, but it’s one study. 

There’ll be some caveats about our patient population, their age, and their other medical factors, et cetera, but this is a known compound. We know how it works. We know it’s biology, which is a promising avenue. 

Being Patient: How does it work and why are you not surprised you’re seeing good efficacy?

Forester: There are a couple of cannabinoid receptors in the brain, one of which mediates its calming effect and one of which mediates its other biological effects, like reducing inflammation and possibly even amyloid accumulation. 

It’s through one of the cannabinoid receptors that it mediates its calming effect. It also has euphoria effects, and it has effects on potentially creating psychosis at the wrong dose in the wrong person at the wrong time. But this one, we kind of know the dose. We’ve been studying it. 

We know the side effects [and] minimal drug interactions, but when you go to a dispensary, you don’t know what you’re getting. You don’t know what’s in here. You don’t know the dose. You certainly don’t know the other compounds beyond the cannabinoid.

Being Patient: How long would it take for something like that to be used to treat dementia? If it’s not able to be prescribed, what would you recommend?

Forester: I get asked this all the time. I don’t know what to tell my patients and their families when they say to me, “What should I ask for at the dispensary?” Because I don’t know what to tell them. I really don’t. 

“We know the side effects [and] minimal
drug interactions, but when you go
to a dispensary, you don’t know
what you’re getting.”

I’m talking about a synthetic product. When it’s a plant-based product, there are all sorts of other compounds in there, too, that may have other psychoactive effects that are unpredictable [versus] synthetic THC and the formulation we studied. 

We’re not the only people to study a formulation of synthetic THC. There’s an abalone trial from Canada that was also positive. I think we’re at the point where these FDA-approved cannabinoid therapies that are synthetic, again manufactured THC, have efficacy in agitation. 

I’ve been doing this now for 20 years, so I would certainly do this if I had a patient with agitation in the setting of Alzheimer’s that was not related to psychosis. There was no other major medical cause of this, like an infection, and if an antidepressant, like sertraline or citalopram, didn’t work, I would try this. It’s well tolerated. The problem is availability and access because it’s generically available, but there’s a manufacturing issue.

“When it’s a plant-based product, there
are all sorts of other compounds in
there, too, that may have other psychoactive
effects that are unpredictable [versus]
synthetic THC and the formulation
we studied.”

Being Patient: When you’re going to a doctor at that very early stage, and you’re describing behavioral symptoms, what should be included, and what should be some of the questions that you ask your doctor to kind of get a better diagnosis early on? What should that conversation look like from your perspective?

Forester: You’re going to go in equipped with more knowledge than some of the primary care doctors you see after a conversation like we just had. Depending on the doctor you see, you may need to find a specialist if this doctor is not pointing you in the right direction. The things you may want to highlight are that these symptoms are new to you, and how long they have occurred, and ask the question about the cause. 

“The things you may want to highlight
are that these symptoms are new
to you, and how long they have
occurred, and ask the
question about the cause.”

“Is this an anxiety or depression problem like I might have in my 30s, or might there be something else going on? Because I keep forgetting where I put things, and I can’t remember what I just did yesterday.” A lot of times, especially primary care clinicians, will essentially say, “Well, you’re 75, and you’re a little forgetful, and you’re anxious. So, it must be the anxiety causing that problem.” 

As we start to utilize in clinical practice, biomarkers, like blood-based biomarkers, to tell us the brain pathology of Alzheimer’s, like plaques and tangles in the brain, that we will learn now from just getting a blood test. That’s both a blessing and a curse. 

It’s a blessing because we’re going to have some sense if there’s any connection between the brain biology and the symptoms that you’re describing, depression [and] anxiety. In other words, the first sign of Alzheimer’s could be anxiety or depression, and now we’ll have a quicker way of knowing it biologically. 

The curse is that if we get lazy, I’m talking about clinicians. [If] we over-interpret, or under-interpret blood tests without a full assessment of the patient and their family to understand what’s been going on in the history, we’re likely to make the wrong diagnosis and provide the wrong treatment. 

Even though they may want to start getting a blood test to look for what’s going on in your brain, fine, but make sure the interpretation of that test is done in the context in which you are experiencing these symptoms. 

Being Patient: Is psychotherapy without medication for people with dementia recommended? Would a therapy session help depression for someone with a type of dementia?

Forester: Colleagues of mine at Cornell have developed a specific psychotherapy intervention for people with depression and early stage dementia and MCI, mild cognitive impairment. I would actually say, yes, psychodynamic psychotherapy and reliving of the past and traumas earlier in life to inform now. 

It’s always interesting and educational, et cetera, but specific, targeted, evidence-based psychotherapies to improve anxiety, depression, and people with cognitive impairment — they’re out there. They’re very newly being studied, but they are there. They work very well. They work well with medication. They work well alone. 

Those are the kinds of interventions that work. They’re generally of a cognitive behavioral nature. Any psychotherapy that requires someone to learn new information can be challenging if you have that inability to learn new information. These psychotherapies are much more targeted to improve activity, behavior, engagement with the world around you, and so forth, and they work.

Katy Koop is a writer and theater artist based in Raleigh, NC.