Structural Brain Changes: How Imaging Affects Management of Late-Life Psychiatric Conditions
The Carlat Geriatric Psychiatry Report, Volume 1, Number 5&6, July 2022
https://www.thecarlatreport.com/newsletter-issue/cgprv1n56/
Issue Links: Learning Objectives | PDF of Issue
Topics: Alzheimers | Atrophy | CT | DaT Scan | fMRi | Frontotemporal dementia | Imaging | LATE | MRI | Parkinson’s | PET Scan | White matter hyperintensities
Olusola Alade Ajilore, MD, PhD
Associate professor, Department of Psychiatry, University of Illinois College of Medicine, Chicago, IL.
Dr. Ajilore, expert for this educational activity, is an employee of KeyWise AI and an advisor for Embodied Labs, Blueprint, and Sage Therapeutics. All of the relevant financial relationships listed for this individual have been mitigated.
CGPR: When do you decide to order imaging for your older adult patients?
Dr. Ajilore: I order imaging when I think there is a nonpsychiatric cause for the patient’s symptoms. This could be normal pressure hydrocephalus, vascular disease including lacunar infarcts or stroke, trauma, or (in rare cases) a brain tumor. In patients with dementia, one imaging study (preferably magnetic resonance imaging [MRI]) is warranted to rule out any other cause of cognitive decline. Although imaging can help clarify the diagnosis, it may not affect management. In some ways we can get more information from extensive neuropsychological testing, which probes cognitive abilities, memory, attention, executive function, etc.
CGPR: What is the advantage to imaging? Does it change outcomes?
Dr. Ajilore: I think it informs prognosis. For example, if imaging shows plaques consistent with multiple sclerosis, or a tumor, that would inform treatment and its associated outcomes.
CGPR: In patients with dementia, what should we be looking for on imaging?
Dr. Ajilore: We are looking for patterns of brain atrophy. If the atrophy is predominantly in the prefrontal cortex, this would be more characteristic of frontotemporal dementia (FTD). If it’s later on in a disease, like advanced Alzheimer’s disease (AD) or the more recently recognized limbic-predominant age-related TDP-43 encephalopathy (LATE), imaging can capture atrophy in parts of the brain like the medial temporal lobe. (Editor’s note: LATE is a recently defined novel dementia characterized by hyperphosphorylated TDP-43. It damages many of the areas also affected by AD, resulting in similar symptoms. LATE is estimated to cause 15%–20% of all dementias.)
CGPR: How do you decide when to order computed tomography (CT) versus MRI?
Dr. Ajilore: CT is useful when you want information quickly. Often you see CT used in emergency room settings right after somebody comes in with a traumatic brain injury (TBI). You want to get a CT scan to see if there’s a bleed or something acute. If you want more spatial resolution and detail, an MRI is always preferred.
CGPR: Radiologists often comment on white matter hyperintensities (WMH). What exactly are these?
Dr. Ajilore: These are bright spots that show up on T2-weighted MRI images of the brain, where water appears bright. They are often in various parts of the white matter; they can appear around the ventricles (periventricular WMH) or deeper in the white matter closer to subcortical regions. You can think of white matter as representing the highways connecting different brain regions. WMH is a marker of impairment in the integrity of the white matter. It can be the result of hypertension, smoking—basically all kinds of cerebrovascular risk factors. Getting older is also associated with having more WMH. There’s a strong association between having WMH and the development of some late-life conditions, such as major depression and vascular dementia.
CGPR: If you see WMH on imaging, how does this information help? Would you say a patient with WMH is at higher risk for depression? Of course, you’re going to control vascular risk factors regardless.
Dr. Ajilore: I think it’s something that you want to monitor. In a large European study that imaged older folks and then followed them for a couple of years, those with higher levels of WMH were more likely to develop depression (Teodorczuk A et al, Br J Psychiatry 2007;191:212–217). If I had a patient with no psychiatric symptoms but a high level of WMH, I would be careful about monitoring for symptoms—not just for depression, but also for cognitive symptoms.
CGPR: Are there cases in which you don’t recommend imaging because it might harm the patient more than it would help?
Dr. Ajilore: Imaging is probably pretty harmless; in fact, sometimes you might incidentally discover findings that allow you to intervene early. Whenever I order a test, I take the time to discuss the results and all of the implications to minimize the patient’s anxiety. Harms can occur when patients obtain imaging without proper clinical context. Without a clinician to interpret radiological findings, it is easier to make false assumptions about anomalies on imaging. However, I would say the biggest barrier to routine imaging is the cost.
CGPR: We discussed indications for structural imaging. When do you order functional MRI (fMRI)?
Dr. Ajilore: Although fMRI is widely used in psychiatric research, we don’t have enough valid and reliable tools for functional neuroimaging for psychiatric conditions. We use fMRIs for neuro-navigation to find the optimal site of stimulation for repetitive transcranial magnetic stimulation (rTMS).
CGPR: What are your thoughts about using positron emission tomography (PET) scans and dopamine transporter (DaT) scans to differentiate among dementias?
Dr. Ajilore: A DaT scan visualizes striatal dopamine transporters and can be very useful in patients who have concerns about Parkinsonian symptoms. PET scans have ligands for amyloid and tau that are very useful in determining whether a patient is at increased risk for converting from mild cognitive impairment to AD. PET imaging with C-Pittsburgh Compound B was found to predict the conversion with 93.5% pooled sensitivity and 56.2% specificity (Zhang S et al, Int J Clin Pract 2012;66(2):185–198). In recent years we’ve seen the development of plasma markers for amyloid and tau. I think these might be more widely used because they only require a blood draw.
CGPR: Can you walk us through a case where you would order a functional study to help with the diagnosis?
Dr. Ajilore: I had a patient with Parkinsonian symptoms. She didn’t quite meet criteria for Parkinson’s disease, but she had Parkinsonism, and so she got a DaT scan to rule out frank Parkinson’s. Her imaging showed that she didn’t have the reduction in dopamine that we’d expect to see in Parkinson’s disease, which helped to rule out the diagnosis.
CGPR: Have you ordered a fluorodeoxyglucose PET (FDG-PET) scan to differentiate between AD and FTD?
Dr. Ajilore: When I was at UCLA, we regularly ordered PET scans for patients in our geriatric evaluation clinic for that purpose. You see a distinct pattern of activity and hypometabolism for FTD versus AD (Foster NL et al, Brain 2007;130(Pt 10):2616–2635). We did use it there, although FTD can be diagnosed clinically as well. (Editor’s note: Medicare covers FDG-PET scans for the differential diagnosis of patients who meet diagnostic criteria for both FTD and AD.)
CGPR: In a complicated case with diagnostic uncertainty, do you recommend ordering neuroimaging, or do you prefer watchful waiting to monitor for the progression of symptoms?
Dr. Ajilore: At UCLA, we used neuroimaging early in the evaluation process for our older patients with severe cognitive or behavioral disturbances. We would order imaging if there was diagnostic uncertainty that imaging might help resolve. However, many times imaging may not help you resolve this uncertainty.
CGPR: Can you give an example of how imaging affected management of one of your patients?
Dr. Ajilore: I recently treated a patient in his mid-50s who had severe impulsivity and aggression that would appear randomly, seemingly unprovoked. We learned from his history that he was, unfortunately, a victim of TBI. Imaging showed that he had a lesion in his ventrolateral prefrontal cortex—the area which governs judgment, response inhibition, and impulsivity. By revealing the location of the lesion, imaging helped us understand that the lesion could lead to his psychiatric presentation. We also realized that there’s a limit to what we could do medication-wise and tempered our expectations in terms of prognosis. Recognizing that he had an injury that would make him prone to behavioral problems helped us also consider behavioral interventions and contextual changes to reduce his aggressive and impulsive behavior.
CGPR: Would you order imaging to distinguish between types of dementia?
Dr. Ajilore: If I’m considering vascular dementia or AD, I would not order imaging—this may only be sorted out through pathology. Often you see mixed pictures in the imaging that won’t help you distinguish one versus the other. You can have a patient with AD that has evidence of cerebrovascular disease that’s more consistent with vascular dementia, or you can have a patient that has a lot of cerebrovascular disease, but only on autopsy will you be able to note a significant amyloid and tau burden consistent with AD. But I may order imaging if I’m uncertain whether a patient has FTD or AD, as there are distinct patterns I could see on imaging.
CGPR: What results would necessitate repeat imaging?
Dr. Ajilore: If you find a lesion or condition where there might be expected change, like a tumor, you want to follow longitudinally and repeat imaging. You might even monitor WMH to see if they’re increasing dramatically over time. If there is a drastic change in a patient’s condition, repeat imaging may be warranted, as a significant change in the degree of atrophy or new lesions may provide a reason for the clinical change. However, tracking atrophy over time doesn’t necessarily change management.
CGPR: What do you do when family members request repeat imaging when you know it won’t change management? I’m thinking specifically about monitoring atrophy.
Dr. Ajilore: I would try to provide context because atrophy isn’t the whole picture. Imaging provides context for what we might be seeing clinically. In fact, sometimes patients and families feel a sense of relief if we can identify a reason why they’re experiencing memory loss, depression, or some other cognitive or affective symptom. Rather than making people feel anxious, imaging may provide relief and explanation. I would explain what we found on imaging within that context. If there are no unexpected changes in the patient’s condition, and the degree of cognitive decline is customary for their neurocognitive disorder, I tell family members that there’s nothing to be gained from another neuroimaging scan.
CGPR: The US has very high healthcare expenditures. We are very quick to order laboratory studies and imaging. How do you feel we’re doing in terms of making better choices based on imaging?
Dr. Ajilore: I have only practiced in academic medical centers, and we’ve always been as evidence-based as possible when making our clinical decisions. As I work in a public state-funded institution, we have to be judicious about how we use our limited resources. I see commercial settings where people can pay out of pocket for tests that may not have any clinical utility. Clinics issue unsubstantiated claims and make a lot of money doing imaging procedures that have high cost and little clinical utility.
CGPR: Thank you for your time, Dr. Ajilore.