Table 4.
Patients with bipolar disorder (BD) and subsequent or concomitant frontotemporal dementia (FTD).
| References | Sex | Psychiatric Antecedents | Age at BD | Age at FTD | FTD | Symptoms | Neuroimaging | MMSE | Neuropsychological Tests |
CSF
Analysis |
Genetic Tests |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Young Adulthood BD (< 40 years) Followed by FTD | |||||||||||
| Borges et al. (2019) [78] |
F | BD 1 | 16 | 78 | bvFTD | Progressive impulsivity, verbal, and physical aggression, short-term memory loss, perseverative behaviors, perambulation, persecutory delusions, disorientation, hyporexia, occupational impairment | MRI: brain atrophy with frontotemporal predominance and ischemic microangiopathy SPECT: moderate/severe bilateral frontotemporal hypoperfusion/activation |
17 | Impaired executive functions, language, memory, and attention | - | - |
| Cerami et al. (2011) [80] |
M | BSD (retrospective diagnosis) | - | 57 | bvFTD | Apathy, lack of motivation, retirement from social/community life, followed by impulsivity, aggressiveness, insomnia, motor hyperactivity, concentration difficulties | MRI: severe cortico-subcortical atrophy, predominantly affecting right frontal and temporoparietal areas | 28 | Dysexecutive profile | - | GRN mutation |
| Papazacharias et al. (2017) [75] | F | BD 1 | 20 | 56 | PPA | Early language impairment, poor coordination, aphasia, dysgraphia, disinhibition, weight gain due to the craving for sweet foods, decrease in personal hygiene, stereotyped motor behavior, disturbances in recognizing familiar faces | MRI: white matter gliosis in bilateral subcortical frontal areas, diffuse cortical atrophy in bilateral frontal and temporal areas SPECT: hypoperfusion in bilateral frontal and temporal areas |
23 | Dysexecutive profile | Normal | Normal |
| Papazacharias et al. (2017) [75] | M | BD 2 | 28 | 53 | FTD with parkinsonism | Neurological signs (dysarthria, ataxia) | MRI: cortical atrophy in frontal and temporal areas SPECT: hypoperfusion in bilateral frontal and temporal areas |
22 | Dysexecutive profile | Mild increase of tau proteins | Polymorphism associated to FTD on exon 12 of chromosome 17 (3’UTR+78C/T) |
| Pavlovic et al. (2011) [77] |
F | BD 1 | 33 | 68 | bvFTD | The manic episode followed by low mood, anhedonia, lethargy, then aggressiveness, cognitive impairment, and decline in social/personal conduct, hyperorality, craving for sweets, stereotyped behavior, utilization behavior aspontaneity, intermittent mutism | CT: mild widening of frontal sulci and enlarged frontal horns of lateral ventricles. MRI: technically limited but confirmed similar findings. SPECT: reduced blood flow in both frontal and temporal lobes, more marked on the left side |
17 to 24 | - | - | - |
| Poletti et al. (2013) [76] | M | BD (hypersexual in manic phases) | Young adulthood | 71 | bvFTD | Poor hygiene and personal care, disinhibition, prodigality | Not reported | 30 | Impaired executive functions (decision- making only) | - | - |
| Velakoulis et al. (2009) [79] | M | BD | 34 | 39 | FTD | - | - | - | - | - | - |
| Late-onset BD (> 40 Years) Followed by FTD | |||||||||||
| Cerami et al. (2011) [80] |
M | BD 2 | 42 | 60 | PPA | Dysarthria, reduced fluency, anomias, phonological errors, dropping of function words, and verbal perseverations | MRI: cerebral atrophy, predominantly affecting left frontotemporal and perisylvian areas | - | - | - | GRN mutation |
| Floris et al. (2014) [84] | M | BD 1 | 42 | 64 | bvFTD | Repeated euphoric manic and hypomanic episodes followed by one episode of sexual disinhibition, delusional fixed ideas, and repetitive behaviors (64 years) | MRI: bilateral frontotemporal atrophy, prominent in frontal areas SPECT: reduction of uptake in the left frontotemporal and right frontoparietal regions |
- | Marked deficits in attention, executive function and working memory, anomia, and verbal fluency dysfunction | - | C9ORF72 gene (>70 repeats) |
| Martins et al. (2018) [82] |
F | BD 1 | 75 | 85 | bvFTD | The manic episode with persecutory delusions and auditory hallucinations, followed by mood swings | MRI: diffuse cortical atrophy with frontal predominance; hippocampi were only slightly reduced SPECT: hypoperfusion of the frontal lobes |
16 | Visuospatial disabilities, dysexecutive profile | Normal | - |
| Monji et al. (2014) [81] | M | BD 1 | 46-47 | 52 | bvFTD | Depressive symptoms (42 years), followed by hypomanic symptoms including hypersexual talk, public masturbation at 46, and apathy at 47 | SPECT: predominant frontal hypoperfusion MRI: predominant frontal brain atrophy |
- | Frontal lobe hypofunction (WCST) | - | - |
| Rubino et al. (2017) [83] |
M | BD 1 | 55 | 70 | bvFTD | Less extroversion, indifference, hyperphagia, followed by apathy, retirement from social and leisure activities | CT: asymmetrical brain ventricles and mild frontotemporal atrophy 18-FDG PET: marked hypometabolism in bilateral frontotemporal areas |
22 | Selective attention, verbal memory, and executive functions deficits | Normal | A c.1639 C>T variant in the exon 12 of the GRN gene |
| The First Manic Episode at FTD Onset | |||||||||||
| Bretag-Norris (2019) [89] | F | Depression | - | 72 | bvFTD | The manic episode preceded by personality and behavioral change (incarcerations oversea for driving and drug offenses, property damage, and loss of money 18 months before) | MRI: moderate-severe frontotemporal parenchymal brain volume loss SPECT: marked bilateral frontotemporal hypoperfusion |
- | Dysexecutive profile | - | - |
| Dionisie et al. (2020) [91] |
F | None | - | 48 | bvFTD | Childish behavior, various and repeated verbal and physical conflicts with different people, dromomania, excessive spending, disinhibition | CT: significant global cerebral atrophy MRI: significant bilateral frontotemporal atrophy (the temporal lobes were more severely affected than the frontal lobes) |
19 | - | - | - |
| Galvez-Andres et al. (2007) [93] |
F | None | - | 59-62 | bvFTD | Progressive personality change, neglect of personal hygiene, hoarding, suspiciousness, wandering, followed by a manic episode, then anhedonia, apathy, anxiety, insomnia, somatic complaints | MRI: normal. 18-FDG PET: normal |
24 | Dysexecutive profile | - | - |
| Ibáñez (2012) [90] | M | BD 1 | 44 | 45 | bvFTD | Manic episode with psychotic features | MRI: progressive atrophy in temporoparietal regions 18-FDG PET-CT: diffuse hypometabolism, with strikingly decreased metabolic activity symmetrically in bilateral frontal and anterior temporal lobes |
- | - | - | - |
| Kerstein et al. (2013) [87] |
M | Subsyndromal hypomania (retrospective diagnosis) | - | 65 | bvFTD | Apathy, anhedonia, and lack of energy followed after 3 years by a manic episode with disinhibited sexual behavior, lability | Unremarkable | 20 | Weakness in visuospatial abilities and impairments in mental processing speed, working memory, executive functions | - | - |
| Payman et al. (2019) [92] |
M | None | - | 67 | bvFTD | Mania with psychotic features preceded by professional misconduct (misappropriating money, falsifying documents, lying to investigators) 18 months before, and followed by apathy, verbal and manual stereotypies | MRI: diffuse cerebral tissue loss predominantly in the frontotemporal lobes 18-FDG PET: hypometabolism in the anterolateral frontal lobes and anterior cingulate gyrus |
22 | Prominent and severe executive dysfunction and impaired new learning | - | C9ORF72 mutation |
| Prevezanos et al. (2017) [85] | M | None | - | 76 | bvFTD | Loosening of associations and ample profanity, night-wandering, followed by diminished volition, and increased reliance on caregivers for planning activities of daily living | CT: significant atrophy involving the frontal and temporal lobes | 30 | Visuospatial disabilities, dysexecutive profile | - | - |
| Saridin et al. (2019) [88] |
M | None | - | 69 | FTD-ALS | Manic episode (meddling and fight picking with spouse and authorities; disinhibition, incoherent thought); one year later apathy and reduced empathy, impaired speech, progressive gait instability, and hand weakness | MRI: age-related atrophy and white matter intensities (no changes after two years) | - | Dysexecutive profile | A specific profile with a slightly decreased amyloid-beta concentration, normal levels of t-tau and p-tau |
C9ORF72 repeat expansion > 30 |
| Shah (2013) [94] | M | None | 54 | 55 | bvFTD | Irritability, behavioural changes (excessive time on the phone, extra measures for grooming, stereotyped interests, incongruous planning, decreased sleep and increased demand for specific food items, hypersexuality, alcohol intake, and smoking) | MRI: diffuse cerebral atrophy, principally in the frontal and temporal area and greater on the right side | 21 | Significant impairment in remote and recent memory, poor perceptual-motor function (BVMGT), and significant executive dysfunction (WCST) | - | - |
| Vorspan et al. (2012) [86] |
F | Two MDEs | - | 54 | bvFTD | Mania with echolalia, echopraxia, amnesia, hyperorality, followed by apathy, mutism, motor retardation, anosognosia, then euthymia (two additional episodes) | CT: cortical atrophy SPECT: anterior temporal and frontal lobe hypoperfusion. MRI: frontal atrophy |
- | Dysexecutive profile with impaired working memory and attention, mild impulsivity, reduced mental flexibility | Normal | - |
| Iatrogenic Mania in FTD | |||||||||||
| Thorlacius-Ussing et al. (2020) [111] |
M | None | - | 54-58 | bvFTD with parkinsonism | Irritability, lack of empathy, and social withdrawal, followed by mild akinetic-rigid parkinsonism with right-sided bradykinesia and rigidity. Worsening of manic symptoms after levodopa | 18-FDG PET: widespread reduced metabolic activity in frontal and parieto-temporal areas with a left-sided predominance DAT-SPECT: significant tracer binding asymmetry with decreased binding especially on the left side (early loss of functional nigrostriatal dopaminergic neuron terminals) |
- | Impaired executive functions and emotional recognition | Normal | Heterozygous for hexanucleotide repeat expansion (G4C2) within C9orf72 |
Abbreviations: 18-FDG PET = 18-Fluoro-2-deoxy-d-glucose positron emission tomography, BD = Bipolar disorder, BD 1 = Bipolar disorder type 1, BD 2 = Bipolar disorder type 2, BSD = Bipolar spectrum disorder, BVMGT = Bender visual-motor gestalt test, DAT-SPECT: Dopamine transporter - single photon emission computed tomography, F = female, FAB: Frontal assessment battery, MDEs = Major depressive episodes, MMSE = Mini-mental state examination, MRI = Magnetic resonance imaging, CSF = Cerebrospinal fluid, CT = Computed tomography, M = male, NPI: Neuropsychiatric inventory, SPECT = Single photon emission computed tomography, WCST = Wisconsin card-sorting test.