Symptoms of Alzheimer Disease

Alireza Atri, MD, PhD: Brad, you are in a frontotemporal disorders unit, so you see a lot of people who come to you who are referred, oftentimes. What are some of the major things, building on what Marc was saying, that prompt an evaluation to your unit?

Bradford C. Dickerson, MD: In frontotemporal dementia [FTD], we often see lack of insight on the part of the patient, and the spouse, or other care partner, describing changes in personality. And when I think about changes in personality, I try to distinguish between what we often see in many dementias, which is apathy—a person is diminished in their engagement with activities they used to enjoy—as opposed to altered social and interpersonal or affective behavior that’s not a mood disorder, per se—not anxiety, or depression, or related in that sense—but more that the person is no longer connected to loved ones in ways that they used to be. We often refer to that as loss of empathy, which can sometimes be thought of as a psychiatric condition.

Sometimes people raise questions about a mood disorder, but the person is not sad, not anxious. They just don’t seem to care about things that they used to care about in their relationship, whether it’s with their spouse or with their family. That’s a relatively specific symptom for FTD, in some cases. And then there’s disinhibition. People are behaving inappropriately, and are doing things that often are described as lacking a filter, whether it’s making comments or making impulsive decisions to do things that might be risky and out of character. Sometimes that’s viewed as possibly either bipolar disorder or may be part of a substance abuse condition.

And then the other one is hyperorality, which is the increased consumption of food, or sometimes cigarettes, or sometimes alcohol, or other kinds of liquids. And again, that can be thought of, in some cases, as an eating disorder or a substance abuse disorder, because those tend to be more common than some of the forms of FTD that we see when that’s part of the initial presentation. So these are symptoms that are not usually the types of things we think of as part of the constellation of symptoms that you see in early Alzheimer disease, in terms of some of those behavioral symptoms that Marc was talking about.

Alireza Atri, MD, PhD: OK, which actually kind of brings me up to a question to you, Lynn. Do all patients with Alzheimer disease [AD] generally present the same way, with memory impairment and symptoms, or can AD present in different clinical manifestations?

Lynn Shaughnessy, PsyD, ABPP/CN: AD can certainly present in a variety of different ways. While the hallmark that one typically associates with Alzheimer disease is memory loss and that kind of rapid forgetting, there are more atypical variants that may present with a primary language impairment, or a visuospatial impairment, or a behavioral executive impairment. Those actually are not as atypical as you may think, and occur more frequently than we had thought in the past. But with the language variant or the primary progressive aphasias, they oftentimes are due to another pathology. But a certain variant, the logopenic variant, has been shown to predominantly be due to Alzheimer disease pathology. Similarly, one who presents with visuospatial impairment initially, who has been diagnosed with a posterior cortical atrophy syndrome. Oftentimes, that is also due to Alzheimer disease pathology.

Alireza Atri, MD, PhD: And so, what sort of symptoms, for example, visuospatial impairment, what are the symptoms that the patient or the family may describe?

Lynn Shaughnessy, PsyD, ABPP/CN: Oftentimes, people come in… You hear a variety of different things for which once you do the testing you kind of get to the bottom of it and realize what’s actually going on. Recently, I had someone come in. The patient had a lot of difficulty recycling, and just couldn’t figure out where things went. They couldn’t put things in the right bin, and it was just so upsetting for the caregiver. In reality, this patient had trouble kind of seeing the bigger picture, and seeing the forest through the trees, so to speak, so they really could not figure out which bin was which because of those kind of visuospatial problems. People may be bumping into things, or misreaching for things. You reach for your water bottle and you completely miss it, things like that.

Alireza Atri, MD, PhD: And the language variants. Word finding tends to be an issue. Are there other types of symptoms that people may complain about?

Lynn Shaughnessy, PsyD, ABPP/CN: Yes. Word finding tends to be the primary concern. That is also something that you often hear in your more typical Alzheimer disease presentation, although the memory impairment and the word finding kind of start at the same time. Whereas, in the PPA [primary progressive aphasia] syndromes, the word finding will start before that.

Alireza Atri, MD, PhD: OK. You mentioned frontotemporal disorders. What are some typical things that you see in FTD, other than the behavior that involves language?

Bradford C. Dickerson, MD: Yes. I think like Lynn was just talking about, PPA is a good example. Primary progressive aphasia is a good example of a clinical syndrome, a cognitive syndrome that can arise as a result of either Alzheimer disease pathology, or frontotemporal lobar degeneration pathology, or sometimes other less common pathologies. And so, the clinical subtyping of these patients’ syndromes under 1 of the 3 major subtypes that we can talk about often helps us predict whether it’s likely due to AD or FTD. And there may be some treatment-related implications for that. Certainly, care planning issues.

For example, in the frontotemporal spectrum, if a person develops primary progressive aphasia, it may be a form where they don’t understand the meanings of words, or sometimes even concepts. That’s referred to as the semantic variant. That’s commonly associated, later on, with behavior symptoms that can become a big problem for the family to deal with, in ways that are similar to typical behavioral-variant frontotemporal dementia. Alternatively, patients may have more problems with the grammatical structure of sentences that they’re trying to say, or even the way they’re articulating the words from the perspective of motor speech. And that’s often thought of as what’s called the nonfluent variant of primary progressive aphasia, often due to a different form of frontotemporal degeneration, and often associated with other motor problems as the condition progresses that may be also very impactful on the patient and family.

Transcript edited for clarity.