2026 ECNP Congress

PS03-3140

When mania is not mania: diagnostic challenges between bipolar disorder and frontotemporal dementia

Isabella Caicedo Saavedra — M. Bravo Sánchez, L. Fernández Girón, I. Oliveira Amat, S. Troyas Martínez, M.T. Peironcely Arenas, C. Zita Diaz Pisano · Hospital General Universitario Gregorio Marañón, Psiquiatría, Madrid, Spain

2026 ECNP Congress

Introduction

Neuropsychiatric symptoms in Frontotemporal dementia (FTD) significantly overlap with bipolar disorder, including excessive spending, disinhibition, impulsivity and apathy. Psychotic symptoms may also occur, although infrequently [1], further complicating diagnostic interpretation in clinical practice. Late-life bipolar disorder may present with progressive cognitive and behavioural features, complicating differentiation from FTD and phenocopy frontotemporal dementia syndrome (phFTD) [2]. In patients with long-standing affective disorders, baseline personality traits, treatment effects and age-related neurodegenerative changes may be difficult to disentangle in routine assessment. In this case, we aim to highlight the diagnostic challenge of differentiating a bipolar relapse, phFTD and the early phase of a neurodegenerative process. It remains unclear whether phFTD belongs to the FTD spectrum or represents a distinct clinical entity [3]. We examine the difficulties and obstacles involved in distinguishing these entities using different biomarkers, including neuroimaging, cognitive screening and clinical progression over time. This diagnostic uncertainty has important therapeutic and prognostic implications for clinical decision-making.

Objectives

To present the diagnostic challenges involved in distinguishing bipolar relapse from a neurodegenerative process in a patient with an important pharmacological burden, using clinical, cognitive and neuroimaging biomarkers, alongside relevant literature.

Methods

We present the case of a patient with a 40-year history of bipolar disorder type II, with a cyclothymic pattern, nine psychiatric hospitalizations for major depression, including a suicide attempt, and recurrent hypomanic episodes. The patient developed behavioural changes and new symptoms over the present year, representing a deviation from his previous clinical baseline. Current treatment included dual antipsychotic therapy with quetiapine and clozapine, long-term lithium, sertraline and high-dose benzodiazepines. A comprehensive evaluation included clinical assessment, the Mini-Mental State Examination (MMSE), brain MRI, FDG-PET and DaTscan.

Results

A 65-year-old man, who had not experienced an asymptomatic period during the previous ten years, presented with evolving symptoms over one year, including motor rigidity, frontal release signs, severe apathy, abulia, executive dysfunction and underestimation of financial risk. FDG-PET revealed symmetric hypometabolism in the medial and dorsolateral prefrontal cortices and lateral temporal cortices, with mild parietal and occipital involvement. Notably, marked putaminal hypermetabolism with caudate hypometabolism was observed. This pattern is consistent with chronic antipsychotic exposure, as neuroleptics have been shown to increase basal ganglia glucose metabolism, particularly in the putamen [4], potentially through dopamine D2 receptor up-regulation. Brain MRI showed frontotemporal atrophy. DaTscan was normal despite these findings. The MMSE score was 30/30, suggesting preserved global cognition and possibly high cognitive reserve, with no clear cognitive progression during follow-up.

Conclusions

This case highlights the possible overlap between some forms of dementia, such as FTD, and progressive features of long-standing psychiatric illness. The discordance between neuroimaging abnormalities, preserved cognition and heavy psychotropic exposure raises questions about medication-induced changes, phFTD, FTD or the presentation of long-standing psychiatric illness. Further studies incorporating biomarkers and the effects of long-term medication are needed to guide the assessment and management of these patients in clinical practice.

References

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  2. . Dols A, Krudop W, Möller C, Shulman K, Sajatovic M, Pijnenburg YA. Late life bipolar disorder evolving into frontotemporal dementia mimic. NeuropsychiatrDis Treat. 2016 Sep 7;12:2207-12. doi: 10.2147/NDT.S99229. PMID: 27660450;PMCID: PMC5019473.
  3. . Valente ES, Caramelli P, Gambogi LB, Mariano LI, Guimarães HC, TeixeiraAL, de Souza LC. Phenocopy syndrome of behavioral variant frontotemporal dementia: a systematic review. Alzheimers Res Ther. 2019 Apr 1;11(1):30. doi:10.1186/s13195-019-0483-2. PMID: 30935398; PMCID: PMC6444822.
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