Neurocognitive patterns across genetic levels in behavioral variant frontotemporal dementia: a multiple single cases study

Hernando Santamaría-García, Natalia Ogonowsky, Sandra Baez, Nicole Palacio, Pablo Reyes, Michael Schulte, Andrea López, Diana Matallana, Agustín Ibanez

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: Behavioral variant frontotemporal dementia (bvFTD) has been related to different genetic factors. Identifying multimodal phenotypic heterogeneity triggered by various genetic influences is critical for improving diagnosis, prognosis, and treatments. However, the specific impact of different genetic levels (mutations vs. risk variants vs. sporadic presentations) on clinical and neurocognitive phenotypes is not entirely understood, specially in patites from underrepresented regions such as Colombia. Methods: Here, in a multiple single cases study, we provide systematic comparisons regarding cognitive, neuropsychiatric, brain atrophy, and gene expression-atrophy overlap in a novel cohort of FTD patients (n = 42) from Colombia with different genetic levels, including patients with known genetic influences (G-FTD) such as those with genetic mutations (GR1) in particular genes (MAPT, TARDBP, and TREM2); patients with risk variants (GR2) in genes associated with FTD (tau Haplotypes H1 and H2 and APOE variants including ε2, ε3, ε4); and sporadic FTD patients (S-FTD (GR3)). Results: We found that patients from GR1 and GR2 exhibited earlier disease onset, pervasive cognitive impairments (cognitive screening, executive functioning, ToM), and increased brain atrophy (prefrontal areas, cingulated cortices, basal ganglia, and inferior temporal gyrus) than S-FTD patients (GR3). No differences in disease duration were observed across groups. Additionally, significant neuropsychiatric symptoms were observed in the GR1. The GR1 also presented more clinical and neurocognitive compromise than GR2 patients; these groups, however, did not display differences in disease onset or duration. APOE and tau patients showed more neuropsychiatric symptoms and primary atrophy in parietal and temporal cortices than GR1 patients. The gene-atrophy overlap analysis revealed atrophy in regions with specific genetic overexpression in all G-FTD patients. A differential family presentation did not explain the results. Conclusions: Our results support the existence of genetic levels affecting the clinical, neurocognitive, and, to a lesser extent, neuropsychiatric presentation of bvFTD in the present underrepresented sample. These results support tailored assessments characterization based on the parallels of genetic levels and neurocognitive profiles in bvFTD.

Original languageEnglish
Article number454
JournalBMC Neurology
Issue number1
StatePublished - Dec 2022
Externally publishedYes


  • APOE variants
  • Clinic and neurocognitive profiles
  • Cognition
  • Frontotemporal dementia
  • Gene-atrophy association
  • Gene-atrophy overlap
  • Genetics
  • MAPT
  • Magnetic Resonance Imaging
  • Mutations
  • Structural neuroimaging
  • TREM2
  • Tau haplotypes
  • bvFTD


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