Table 1.
Candidate biomarkers identified in studies of pre-symptomatic frontotemporal dementia.
| Biomarker | Example references |
|---|---|
| Fluid biomarkers | |
| Plasma | |
| Progranulin* | Galimberti et al. (2018), Benussi et al. (2019) |
| microRNA | Kmetzsch et al. (2021) |
| Cerebrospinal fluid | |
| Dipeptide repeat proteins** | Lehmer et al. (2017) |
| poly(GP)** | Meeter et al. (2018) |
| Neuroimaging biomarkers | |
| White matter | |
| Decreased FA/increased diffusivity (DTI) | Dopper et al. (2013), Lee et al. (2017), Papma et al. (2017), Bertrand et al. (2018), Jiskoot et al. (2018), Olm et al. (2018), Borroni et al. (2008), Pievani et al. (2014) |
| Increased volume of hyperintensities (T2 FLAIR) | Benussi et al. (2019) |
| Grey matter | |
| Reduced cortical/subcortical volume (T1 Segmentation) | Bertrand et al. (2018), Olm et al. (2018), Rohrer et al. (2015), Popuri et al. (2018), Walhout et al. (2015) |
| Reduced grey matter intensity (T1 VBM) | Benussi et al. (2019), Lee et al. (2017), Papma et al. (2017), Olm et al. (2018), Panman et al. (2019), Spina et al. (2008), Morbelli et al. (2016), Cash et al. (2018) |
| Increased CSF (T1 VBM) | Spina et al. (2008) |
| Cortical thinning (T1 Surface reconstruction) | Pievani et al. (2014), Popuri et al. (2018), Panman et al. (2019), Moreno et al. (2013) |
| Metabolism | |
| Hypometabolism (FDG-PET) | Morbelli et al. (2016), Caroppo et al. (2015) |
| Metabolites (MRS) | Chen et al. (2019) |
| Perfusion | |
| Decreased rCBF (ASL) | Dopper et al. (2013), Dopper et al. (2016) |
| BOLD Signal | |
| Reduced connectivity (rs-fcMRI) | Dopper et al. (2013), Lee et al. (2017), Whitwell et al. (2011), Premi et al. (2014), Premi et al. (2014), Premi et al. (2016), Alexander et al. (2018) |
| Increased connectivity (rs-fcMRI) | Premi et al. (2014), Borroni et al. (2012) |
| Reduced activation (task fMRI – matrix reasoning) | Alexander et al. (2018) |
| Multimodal imaging | |
| Structure-function composite/model/classifier | Lee et al. (2017), Premi et al. (2016), Feis et al. (2019) |
| Neurophysiological biomarkers | |
| Altered intracortical connectivity (TMS) | Benussi et al. (2019) |
| Mood/behaviour biomarkers | |
| CBI-R | Benussi et al. (2019), Rohrer et al. (2015), Tavares et al. (2020) |
| Cognitive biomarkers† | |
| Global cognition | |
| MMSE, MoCA | Benussi et al. (2019), Rohrer et al. (2015), Spina et al. (2008), Barker et al. (2021), Cheran et al. (2019) |
| Language | |
| BNT, SAT, Category fluency, Semantic word-picture matching | Rohrer et al. (2015), Spina et al. (2008), Morbelli et al. (2016), Cheran et al. (2019), Jiskoot et al. (2018) |
| Attention/processing speed | |
| Digit forwards, Digit symbol, LDST, TMT-A, Stroop (word/colour reading) | Benussi et al. (2019), Papma et al. (2017), Rohrer et al. (2015), Spina et al. (2008), Morbelli et al. (2016), Barker et al. (2021), Cheran et al. (2019), Jiskoot et al. (2018) |
| Executive function | |
| COWA/Letter fluency, Design fluency, Digits backwards, FAB, Similarities, Stroop Inhibition, TMT-B, WCST (categories, perseveration) | Papma et al. (2017), Rohrer et al. (2015), Spina et al. (2008), Morbelli et al. (2016), Barker et al. (2021), Cheran et al. (2019), Jiskoot et al. (2018) |
| Memory | |
| Verbal memory (e.g. CVLT delayed, cued, recognition intrusions; Logical memory delayed; RAVLT immediate/delayed/recognition, Selective Reminding Test), Visual memory (e.g. Complex Figure delayed, VAT, Visual Reproduction recall) | Lee et al. (2017), Bertrand et al. (2018), Rohrer et al. (2015), Spina et al. (2008), Morbelli et al. (2016), Barker et al. (2021), Cheran et al. (2019), Jiskoot et al. (2018) |
| Visuospatial | |
| Block design, Complex figure copy, Visual reproduction | Rohrer et al. (2015), Spina et al. (2008), Morbelli et al. (2016) |
| Social Cognition | |
| Happé Cartoons (ToM, non-ToM), Emotion recognition (Ekman faces), Social Norms Questionnaire, IRI-PT, RSMS | Cheran et al. (2019), Jiskoot et al. (2018), Russell et al. (2020) |
| Neuro-ophthalmic biomarkers | |
| Retinal layer thinning | Ward et al. (2014) |
*GRN mutation carriers only; ** C9ORF72 mutation carriers only; †Reduced cognitive performance.
ASL: arterial spin labelling; BOLD: Blood oxygen level dependent; COWA: Controlled Oral Word Association; CBI-R: Cambridge Behavioural Inventory Revised; CSF: Cerebrospinal Fluid; DTI: diffusion tensor imaging; FA: Fractional anisotropy; FAB: Frontal Assessment Battery; FDG-PET: fMRI; functional magnetic resonance imaging; IRI-PT: Interpersonal Reactivity Index – Perspective Taking; LDST: Letter Digit Substitution Test; MMSE: Mini Mental State Examination; MoCA: Montreal Cognitive Assessment; MRI: magnetic resonance imaging; MRS: magnetic resonance spectroscopy; RAVLT: Rey Auditory Verbal Learning Test; rCBF: Regional cerebral blood flow; rs-fcMRI: resting state functional connectivity MRI; RSMS: Revised Self-Monitoring Scale; TMS: transcranial magnetic stimulation; TMT: Trail Making Test; ToM: Theory of Mind; VAT: Visual Association Test; VBM: Voxel based morphometry; WCST: Wisconsin Card Sort Test.