Experts are calling for the removal of cognitive criteria as core diagnostic features for behavioral variant frontotemporal dementia (bvFTD), one of the most common forms of younger-onset types of the disease.

Based on an analysis of more than 100 patients with bvFTD, the current cognitive requirements for diagnosis are “at best unhelpful toward diagnosis and at worst delays diagnosis and access to relevant treatment,” said investigators, with first author Olivier Piguet, PhD, professor of clinical neuropsychology, Brain and Mind Center, University of Sydney, Camperdown, Australia.

“Our findings show that the cognitive criterion — particularly the requirement for preserved memory and visuospatial skills — exclude many patients who clearly have this form of dementia,” Piguet said in a statement.

The study was published online on August 17 in Alzheimer’s & Dementia.

Loss of Empathy, Apathy More Common

FTD is a leading cause of early-onset dementia and bvFTD accounts for up to 70% of FTD cases.

Unlike Alzheimer’s disease, which primarily affects memory, bvFTD targets the brain’s frontal lobes, which govern personality and social behavior. It typically begins with subtle changes in behavior, such as apathy, disinhibition, and loss of empathy and can progress to more severe cognitive and functional decline.

The current classification and diagnosis of bvFTD rely on the 2011 consensus criteria, highlighting six core features: five behavioral — disinhibition, apathy, loss of empathy, compulsive behaviors, and hyperorality — and one cognitive, a dysexecutive profile with intact memory and visuospatial skills.

“This study stemmed from our clinical experience over the past 20 years and our previous publications. We, and others, reported many years ago, on a subset of patients with bvFTD who clearly experienced memory deficits similar to those observed in patients with Alzheimer’s disease,” Piguet, director, FRONTIER Frontotemporal Dementia Research Group and president, International Society for Frontotemporal Dementias, told Medscape Medical News.

“In addition, the difficulty with the exclusion component of the cognitive criterion (‘relatively preserved memory’) is that in clinical practice, many patients with bvFTD presenting with episodic memory disturbance are likely to receive incorrect support and advice, for example, potentially receiving cholinesterase inhibitors which will have no benefit to these patients,” he explained.

To investigate the utility of the criteria further and particularly the cognitive criteria, Piguet and colleagues studied 110 consecutive patients with a stable diagnosis of “probable” bvFTD between 2010 and 2023.

They found that the most common core criteria present at baseline were apathy or inertia (89%) followed by loss of sympathy or empathy (83%). Disinhibition, hyperorality, and dietary changes were also common (81%).

The least frequent diagnostic criterion was the cognitive one (presence of executive deficits with relative sparing of episodic memory and visuospatial skills), which was found in only 16 patients (14.5%).

When they broadened the definition to include executive dysfunction irrespective of memory and visuospatial performance, the number of patients with bvFTD increased to 80 (73%).

“This research shows that the behavioral symptoms — such as empathy loss and apathy — are far more consistent and reliable indicators for bvFTD than current cognitive benchmarks,” Piguet said.

The researchers have proposed removing the requirement for relative sparing of episodic memory (Criterion F2) and relative sparing of visuospatial skills (F3) and adding disturbances in social functioning as a core diagnostic feature.

For now, Piguet suggested that clinicians, particularly those in general care settings, adopt a “more flexible approach when applying these criteria to determine the presence or otherwise of bvFTD.”

“This is particularly important for individuals presenting with only mild behavioral changes and where a careful examination of the cognitive profile will make an important contribution to the differential diagnosis (ie, not to exclude bvFTD as a possible diagnosis in the presence of episodic or visuospatial deficits),” said Piguet.

One limitation of the study is that patients came from a single specialized dementia research clinic, which may not necessarily be representative of the broad bvFTD population, and which may influence the prevalence of some of the profiles reported.

Interesting Study, Important Caveats

Reached for comment, Nathan Herrmann, MD, a geriatric psychiatrist at Sunnybrook Health Sciences Centre and professor at the University of Toronto, Canada, said this “interesting study” raises an important issue — the validity of current bvFTD diagnostic criteria and specifically the role of the cognitive profile as part of these criteria.

“In spite of the large numbers of patients for a bvFTD study, only 25% of the patients had autopsy confirmation of the etiopathology, and of these, only 70% actually had FTLD [frontotemporal lobar degeneration] pathology,” Herrmann pointed out.

“While this would be fine for most types of investigations, for a study focused on the validity of diagnostic criteria, I would argue that this is not good enough,” Herrmann told Medscape Medical News.

Regarding the authors’ main criticism — that the diagnostic criteria inclusion of executive deficits with relative sparing of memory and visuospatial functions is unduly restrictive, Herrmann noted that “neither these authors nor the 2011 diagnostic criteria provide an operational definition for what is ‘relative sparing’ — making it very difficult to determine how these criteria may or may not influence diagnosis.”

From a clinical perspective, Herrmann said he agrees with the authors that changing the F Criteria to include only executive impairment (without mention of the relative sparing of memory and visuospatial function) “will be helpful and remove ambiguity.”

This work was supported in part by funding to ForeFront, a collaborative research group dedicated to the study of FTD and motor neuron disease, from the National Health and Medical Research Council of Australia and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Program. Piguet and Herrmann had no relevant conflicts of interest.