Study suggests new way to diagnose combined Alzheimer’s and FTLD

People with Alzheimer's disease often have other neurodegenerative conditions as well, including a less-understood disorder called frontotemporal lobar degeneration (FTLD). While a precise diagnosis of FTLD has only been possible during an autopsy, new research shows how clinicians may be able to diagnose people living with both Alzheimer's and FTLD by evaluating neuropsychiatric symptoms.

In a study published in Neurology, researchers found that compared to patients who have either of the two types of dementia alone, having both Alzheimer's disease and FTLD is associated with greater likelihood of having known neuropsychiatric symptoms of both diseases.

The findings could have important implications for patients and their caregivers, the researchers noted, because patients with both disorders may experience a more complex disease course, rapid decline or unique responses to disease-modifying treatments.

"We saw that there were different neuropsychiatric symptoms if people had both pathologies, which could inform diagnosis and treatment plans," said lead study author Daliah Ross, a postdoctoral fellow in the clinical neuropsychology program at Brown University's Warren Alpert Medical School. "The development of neuropsychiatric symptoms can be really impactful on patients and their families in terms of quality of life and resources needed. It would be helpful for patients and families to have a better sense of what to expect so they can prepare."

Ross has long been interested in improving the understanding of neurodegenerative disorders and the ability to match clinical signs with accurate diagnoses. While studying the scientific literature on neuropathology and phenotyping, she was struck by the fact that most people with neurodegenerative disorders have Alzheimer's plus another type of disorder.

"We tend to study cognitive disorders in isolation, but people don't usually have just Alzheimer's by itself," Ross said.

The accompanying disorder can be FTLD, Ross said, which involves symptoms like disinhibition and personality change that are not typically expected of Alzheimer's patients. However, scientists have conducted little research on the combination of Alzheimer's and FTLD. In other neurodegenerative conditions, Ross said, multiple pathologies alter the presentation of neuropsychiatric symptoms, complicating clinical care.

To better understand what it looks like when a patient has both disorders, the researchers examined data from 29 Alzheimer Disease Research Centers funded by the National Institutes of Health, focusing on 919 patients who had been diagnosed in an autopsy with intermediate to high Alzheimer's disease and/or FTLD neuropathology. 

They found that compared to the FTLD-only group, patients in the Alzheimer's plus FTLD group were more likely to have had anxiety, delusions and irritability among their symptoms before death. Conversely, compared to the Alzheimer's-only group, patients in the Alzheimer's plus FTLD group were more likely to have had symptoms of personality change and disinhibition.

The findings are significant because they may allow clinicians to provide more education and resources for FTLD patients and their care partners, said study author Dr. Edward Huey, associate director of Brown's Center for Alzheimer's Disease Research and director of the Memory and Aging Program at Butler Hospital.

"This study shows a strong association between the amount of FTLD neuropathology and the symptoms of FTLD including personality changes, apathy and inappropriate behaviors, all of which are more common in FTLD than in Alzheimer's disease," Huey said. "While there are treatments for Alzheimer's disease, there aren't currently any known disease modifying treatments for FTLD, and we desperately need them. In the meantime, this research may inform a diagnosis of FTLD, which can help patients and caregivers know more about what to expect as the disease progresses."

There's growing excitement about new treatments emerging for Alzheimer's, Ross said, but more research is necessary to learn how those treatments affect people with multiple disorders, like Alzheimer's and FTLD.

"The literature on looking at mixed dementia and multiple co-pathologies is really important," Ross said. "I hope that our team's work helps move that along, and I'm looking forward to doing more research in that area."

The study was funded in part by the National Institute on Aging (U19 AG024904, U01 AG079850).