CONFERENCE COVERAGE

Study: Agitation-Associated Neuropsychiatric Symptoms Vary by Sex Across FTLD Syndromes

Anthony Calabro, MA

Key Highlights

  • Agitation is associated with a broader range of neuropsychiatric symptoms in men than in women with frontotemporal lobar degeneration (FTLD).
  • Men with progressive supranuclear palsy showed especially high rates of anxiety, depression, apathy, disinhibition, and motor symptoms when agitation was present.
  • Women with semantic variant primary progressive aphasia were more likely to exhibit disinhibition alongside agitation.

In a large multi-cohort study of individuals with frontotemporal lobar degeneration (FTLD)-related syndromes presented at the Alzheimer’s Association International Conference in Toronto, Ontario, CA, researchers found that men were significantly more likely than women to experience a wider spectrum of neuropsychiatric symptoms when agitation was present, particularly among those with progressive supranuclear palsy (PSP).

Agitation is a clinically significant and distressing manifestation of behavioral and psychological symptoms of dementia. Although agitation also contributes substantially to caregiver burden and worsens disease outcomes, it remains poorly characterized across FTLD syndromes. Given the heterogeneity of FTLD and its subtypes—including behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), corticobasal syndrome (CBS), and PSP—understanding how sex influences the presentation of agitation is essential. The current study addresses this gap by examining the relationship between agitation and neuropsychiatric comorbidities across a large, diverse patient population.

The investigators analyzed pooled data from 1654 participants (916 men and 738 women) with FTLD-related syndromes, with mean ages of approximately 66 years. Data were drawn from the National Alzheimer’s Coordinating Center and the ARTFL-LEFFTDS Longitudinal FTLD study. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. Prevalence ratios and odds ratios were used to quantify associations between agitation and other neuropsychiatric symptoms, and principal component analysis was performed to identify symptom clusters by sex.

The results demonstrated sex differences. In the presence of agitation, men with bvFTD, CBS, and PSP were significantly more likely to experience anxiety (P < .001, P < .01, P < .0001, respectively). Depression was more prevalent in men with bvFTD (P < .0001) and PSP (P < .01), while apathy was more strongly linked to agitation in men with non-fluent variant PPA (nfvPPA; P < .01) and PSP (P < .01). Disinhibition was significantly higher in agitated men with nfvPPA (P < .0001) and PSP (P < .001). Motor symptoms were also more strongly associated with agitation in men with bvFTD and CBS (both P < .01). In contrast, women with svPPA exhibited greater disinhibition when agitation was present (P < .001).

 “These findings underscore the need for further investigation into the underlying mechanisms driving these sex differences, particularly focusing on the neurobiological impact of agitation, the recognition of symptoms in the presence of greater behavioral disturbances, and potential variations from informant reports,” the authors concluded.

Reference:
Sakran CN, Vargas-González JC, Dimal NP, et al; ALLFTD Consortium Investigators. Sex differences in neuropsychiatric symptoms associated with agitation in frontotemporal lobar degeneration. Presented at: Alzheimer’s Association International Conference (AAIC) 2025; July 27–31, 2025; Toronto, Ontario, CA. Abstract 103036.