[Automated speech analysis can distinguish frontotemporal dementia from depression: a pilot study]. / Geautomatiseerde spraakanalyse bij onderscheiden van frontotemporale dementie en depressie.

BACKGROUND: Differentiating the behavioural variant of frontotemporal dementia from a depression is challenging. Recent development of automated speech analyses might add to diagnostic. AIM: To investigate the value of automated speech analyses in differentiating bvFTD from a depressive disorder. METHOD: A semistructured interview was recorded in 15 patients with bvFTD, 15 patients with a depressive disorder and 15 healthy controls, which was transcribed and analysed. Acoustic and semantic values were extracted and classified using machine learning. RESULTS: Acoustic values showed an 80% accuracy for differentiating bvFTD from depressive disorder and semantic values showed an 70.8% accuracy. CONCLUSION: Acoustic as well as semantic values show significant differences between bvFTD and depressive disorder. In automated speech analyses researches should consider privacy matters as well as possible confounders like age, sex and ethnicity. This study should be repeated in a larger population.

Plasma proteome profiling identifies changes associated to AD but not to FTD.

BACKGROUND: Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. METHODS: Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. RESULTS: Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. CONCLUSIONS: We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts.

Theory of Mind and social functioning among neuropsychiatric disorders: A transdiagnostic study.

Social dysfunction is commonly present in neuropsychiatric disorders of schizophrenia (SZ) and Alzheimer's disease (AD). Theory of Mind (ToM) deficits have been linked to social dysfunction in disease-specific studies. Nevertheless, it remains unclear how ToM is related to social functioning across these disorders, and which factors contribute to this relationship. We investigated transdiagnostic associations between ToM and social functioning among SZ/AD patients and healthy controls, and explored to what extent these associations relate to information processing speed or facial emotion recognition capacity. A total of 163 participants were included (SZ: n=56, AD: n=50 and age-matched controls: n=57). Social functioning was assessed with the Social Functioning Scale (SFS) and the De Jong-Gierveld Loneliness Scale (LON). ToM was measured with the Hinting Task. Information processing speed was measured by the Digit Symbol Substitution Test (DSST) and facial emotion recognition capacity by the facial emotion recognition task (FERT). Case-control deficits in Hinting Task performance were larger in AD (rrb = -0.57) compared to SZ (rrb = -0.35). Poorer Hinting Task performance was transdiagnostically associated with the SFS (ßHinting-Task = 1.20, p<0.01) and LON (ßHinting-Task = -0.27, p<0.05). DSST, but not FERT, reduced the association between the SFS and Hinting Task performance, however the association remained significant (ßHinting-Task = 0.95, p<0.05). DSST and FERT performances did not change the association between LON and Hinting Task performance. Taken together, ToM deficits are transdiagnostically associated with social dysfunction and this is partly related to reduced information processing speed.

[Genetics of frontotemporal dementia]. / Genetica van frontotemporale dementie.

BACKGROUND: Frontotemporal dementia (FTD) is a neurodegenerative disorder leading to dementia. Because of predominant behavioural and emotional features it often presents to the psychiatrist. AIM: Provide an overview of the genetic background of FTD with recommendations for the clinician. METHOD: Review of the international literature. RESULTS: FTD is autosomal dominant hereditary in 10-25% of cases. The clinical presentation of genetic FTD is heterogeneous. In particular, the C9ORF72 mutation can manifest as a psychiatric disorder and its disease course can be slow. This mutation is also associated with ALS. CONCLUSION: In case of a late-onset psychiatric disorder it is recommended to perform a detailed family history, including dementia, ALS and psychiatric disorders. In case of an undetermined neuropsychiatric disorder one should consider genetic testing at least including the C9ORF72 hexanucleotide repeat length, even when the family history is
negative.

The behavioral variant of Alzheimer's disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex.

BACKGROUND: The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer's disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD. METHODS: VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss. RESULTS: The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5. DISCUSSION: VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.

Exploring Abstract Semantic Associations in the Frontotemporal Dementia Spectrum in a Dutch Population.

OBJECTIVE: To investigate the differential ability of the "Test Relaties Abstracte Concepten" (TRACE), a Dutch test for abstract semantic knowledge, in frontotemporal dementia (FTD). METHODS: The TRACE was administered in patients with behavioral variant FTD (bvFTD; n = 16), nonfluent variant (nfvPPA; n = 10), logopenic variant (lvPPA; n = 10), and semantic variant primary progressive aphasia (svPPA; n = 9), and controls (n = 59). We examined group differences, performed correlational analyses with other neuropsychological tests and investigated discriminative ability. We compared the TRACE with a semantic association test for concrete stimuli (SAT). RESULTS: All patient groups, except nfvPPA, performed worse on the TRACE than controls (p < .01). svPPA patients performed worse than the other patient groups (p < .05). The TRACE discriminated well between patient groups, except nfvPPA, versus controls (all p < .01) and between svPPA versus other patient groups with high sensitivity (75-100%) and specificity (86%-92%). In bvFTD and nfvPPA the TRACE correlated with language tests (ρ > 0.6), whereas in svPPA the concrete task correlated (ρ ≥ 0.75) with language tests. Patients with bvFTD, nfvPPA and lvPPA performed lower on the TRACE than the SAT (p < .05), whereas patients with svPPA were equally impaired on both tasks (p = .2). DISCUSSION: We demonstrated impaired abstract semantic knowledge in patients with bvFTD, lvPPA, and svPPA, but not nfvPPA, with svPPA patients performing worse than the other subtypes. The TRACE was a good classifier between each patient group versus controls and between svPPA versus other patient groups. This highlights the value of incorporating semantic tests with abstract stimuli into standard neuropsychological assessment for early differential diagnosis of FTD subtypes.

[Frontotemporal dementia diagnoses within the psychiatric practice: pitfalls and practical tools]. / Diagnostiek van frontotemporale dementie in de psychiatrische praktijk: handvatten en valkuilen.

BACKGROUND: The behavioural variant of frontotemporal dementia (bvFTD) strongly resembles primary psychiatric disorders. Furthermore, a bvFTD mimic may occur, without neurodegenerative aetiology. AIM: To offer psychiatrist clinical tools for making or ruling out a bvFTD diagnosis. METHOD: To present the results of the first prospective cohort study on bvFTD patients and primary psychiatric patients. Results are discussed within the context of the international literature. RESULTS: Frontotemporal atrophy on imaging confirms a suspected bvFTD diagnosis. Merely fulfilling the bvFTD clinical criteria, with or without frontotemporal hypometabolism on functional imaging, may also result from primary psychiatric disorders or the bvFTD-phenocopy syndrome. A high level of stereotypy, hyperorality, a low level of depressive symptoms, impaired social cognition or absent insight increases the probability of bvFTD. Biomarker or genetic tests and follow-up are recommended. CONCLUSIONS A bvFTD diagnosis should be made multidisciplinary. Without the confirmation of atrophy or genetics, great reserve in making the diagnosis is in place and careful analyses for psychiatric aetiologies is advised.

Late-onset presentation and phenotypic heterogeneity of the rare R377W PSEN1 mutation.

BACKGROUND AND PURPOSE: Mutations in the PSEN1 gene are the most common cause of autosomal-dominant Alzheimer's disease and have been associated with the earliest disease onset. We describe an unusual presentation of the rare R377W PSEN1 mutation with a late age of onset, and we provide for the first time in vivo pathological evidence for this mutation. METHODS: A 71-year-old female patient with progressive cognitive decline in the past 3 years and positive family history for dementia underwent neurological evaluation, neuropsychological testing, lumbar puncture, conventional brain imaging, amyloid-positron emission tomography (PET) and extensive genetic screening with a next-generation sequencing technique. RESULTS: The diagnostic workup revealed mixed behavioural and amnestic disease features on neuropsychological tests, magnetic resonance imaging, and 18-fluorodeoxyglucose (FDG)-PET. Amyloid-PET detected amyloid deposition in the frontal areas, in the parietal lobes and the precunei. The genetic screening revealed the presence of the rare R377W mutation in the PSEN1 gene. CONCLUSIONS: Extensive genetic screening is also advisable for late-onset presentations of Alzheimer's disease, especially in the presence of a positive family history or atypical clinical features.

Correction to: Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia.

The original version of this article unfortunately contained a mistake.

Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia.

INTRODUCTION: Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations. METHODS: We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27). RESULTS: Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference - 2.1; 95%CI - 4.1 to - 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference - 2.5; 95%CI - 4.7 to - 0.3) and C9orf72 (mean difference - 2.4; 95%CI - 4.5 to - 0.3). Only MAPT patients were impaired on delayed recall (mean difference - 1.4; 95%CI - 2.1 to - 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains. DISCUSSION: This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD.

Von Economo neurons are part of a larger neuronal population that are selectively vulnerable in C9orf72 frontotemporal dementia.

AIMS: The behavioural variant of frontotemporal dementia with a C9orf72 expansion (C9-bvFTD) is characterised by early changes in social-emotional cognition that are linked to the loss of von Economo neurons (VENs). Together with a subset of neighbouring pyramidal neurons, VENs express the GABA receptor subunit theta (GABRQ). It is not known if the selective vulnerability of VENs in C9-bvFTD also includes this GABRQ-expressing population. METHODS: We quantified VENs and GABRQ immunopositive neurons in the anterior cingulate cortex (ACC) in C9-bvFTD (n = 16), controls (n = 12) and Alzheimer's disease (AD) (n = 7). Second, we assessed VENs and GABRQ-expressing populations in relation to the clinicopathological profiles. RESULTS: We found the number of VENs and GABRQ-expressing neurons and their ratio over the total layer 5 neuronal population was lower in C9-bvFTD compared to control and AD. C9-bvFTD donors with underlying TDP43 type A pathology in the ACC showed the highest loss of GABRQ-expressing neurons. C9-bvFTD donors that did not present with motor neuron disease (MND) symptoms in the first half of their disease course showed a prominent loss of GABRQ-expressing neurons compared to controls. C9-bvFTD donors with no symptoms of psychosis showed a higher loss compared to controls. Across all donors, the number of VENs correlated strongly with the number of GABRQ-expressing neurons. CONCLUSION: We show that VENs, together with GABRQ-expressing neurons, are selectively vulnerable in C9-bvFTD but are both spared in AD. This suggests they are related and that this GABRQ-expressing population of VENs and pyramidal neurons, is a key modulator of social-emotional functioning.

[DNA diagnostics in dementia]. / DNA-diagnostiek bij dementie.

- Thanks to next-generation sequencing several genes can be examined in one go. Since this method has been introduced, the possibilities for DNA diagnostics in patients with dementia have increased tremendously in recent years.- DNA diagnostics is indicated for patients with an Alzheimer's disease diagnosis before they are 60 years old, for all patients with frontotemporal dementia and for patients with a positive family history.- For 15% of the patients who visited the Alzheimer centre of the VUmc, in Amsterdam, the Netherlands DNA diagnostics indicated a clear monogenic cause.- Although a hereditary cause of dementia is often a hard message for patients and their families, this knowledge often provides them with more clarity with respect to the diagnosis and the course of the disease. In addition, family members may choose to carry out presymptomatic DNA testing.- The therapeutical consequences of DNA diagnostics are currently minimal; several studies are being carried out internationally in this area.

[Chronic traumatic encephalopathy: an old acquaintance in athletes]. / Chronische traumatische encefalopathie.

- Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head injuries like those seen in sports such as boxing, American football and soccer.- The clinical features of CTE are a range of cognitive, psychiatric and motor symptoms, and histopathology involves deposits of hyperphosphorylated tau protein and the presence of TAR DNA-binding protein (TDP-43) with relatively little beta-amyloid.- CTE is difficult to differentiate clinically from Alzheimer's disease, frontotemporal dementia and psychiatric disorders because of the major symptom overlap between these conditions.- The most important risk factors for developing CTE are the cumulative effect of repetitive head injuries, with or without clinical symptoms, and the duration of exposure to the repetitive injuries (the sporting career).- There is no treatment for CTE at present and the strategy must be primarily geared to prevention.- In view of the large number of people, including those in the Netherlands, who take part in sports in which head injuries may occur, research into CTE is of major societal importance.

Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment.

Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.

Gray matter network differences between behavioral variant frontotemporal dementia and Alzheimer's disease.

We set out to study whether single-subject gray matter (GM) networks show disturbances that are specific for Alzheimer's disease (AD; n = 90) or behavioral variant frontotemporal dementia (bvFTD; n = 59), and whether such disturbances would be related to cognitive deficits measured with mini-mental state examination and a neuropsychological battery, using subjective cognitive decline subjects as reference. AD and bvFTD patients had a lower degree, connectivity density, clustering, path length, betweenness centrality, and small world values compared with subjective cognitive decline. AD patients had a lower connectivity density than bvFTD patients (F = 5.79, p = 0.02; mean ± standard deviation bvFTD 16.10 ± 1.19%; mean ± standard deviation AD 15.64 ± 1.02%). Lasso logistic regression showed that connectivity differences between bvFTD and AD were specific to 23 anatomical areas, in terms of local GM volume, degree, and clustering. Lower clustering values and lower degree values were specifically associated with worse mini-mental state examination scores and lower performance on the neuropsychological tests. GM showed disease-specific alterations, when comparing bvFTD with AD patients, and these alterations were associated with cognitive deficits.

Psychiatric diagnoses underlying the phenocopy syndrome of behavioural variant frontotemporal dementia.

INTRODUCTION: The frontotemporal dementia (FTD) consortium criteria (2011) emphasise the importance of distinguishing possible and probable behavioural variant FTD (bvFTD). A significant number of possible patients with bvFTD do not show functional decline and remain with normal neuroimaging over time, thus exhibiting the bvFTD phenocopy syndrome. A neurodegenerative nature is unlikely but an alternative explanation is missing. Our aim was to detect psychiatric conditions underlying the bvFTD phenocopy syndrome after extensive evaluation. METHODS: We included patients with the bvFTD phenocopy syndrome whereby patients with probable bvFTD served as a control group. Patients had to have undergone both neurological and psychiatric evaluation. Their charts were reviewed retrospectively. Using both qualitative and quantitative methods, psychiatric and psychological conditions associated with the clinical syndrome were determined in both groups and their relative frequencies were compared. RESULTS: Of 181 suspected bvFTD cases, 33 patients with bvFTD phenocopy syndrome and 19 with probable bvFTD were included. Recent life events, relationship problems and cluster C personality traits were the most prevalent psychiatric/psychological conditions. The frequency of these conditions was higher in the group of patients with the bvFTD phenocopy syndrome (n=28) compared to the probable bvFTD group (n=9) (χ(2) p<0.05). CONCLUSIONS: This is the first study thoroughly exploring psychiatric causes of the bvFTD phenocopy syndrome, revealing that in most cases multiple factors played a contributory role. Our study gives arguments for neurological and psychiatric collaboration when diagnosing bvFTD. Prompt diagnosis of treatable psychiatric conditions is to be gained.

Trajectories of cognitive decline in different types of dementia.

BACKGROUND: To investigate trajectories of cognitive decline in patients with different types of dementia compared to controls in a longitudinal study. METHOD: In 199 patients with Alzheimer's disease (AD), 10 with vascular dementia (VaD), 26 with dementia with Lewy bodies (DLB), 20 with behavioural variant frontotemporal dementia (bvFTD), 15 with language variant frontotemporal dementia (lvFTD) and 112 controls we assessed five cognitive domains: memory, language, attention, executive and visuospatial functioning, and global cognition (Mini-Mental State Examination, MMSE). All subjects had at least two neuropsychological assessments (median 2, range 2-7). Neuropsychological data were standardized into z scores using baseline performance of controls as reference. Linear mixed models (LMMs) were used to estimate baseline cognitive functioning and cognitive decline over time for each group, adjusted for age, gender and education. RESULTS: At baseline, patients with dementia performed worse than controls in all cognitive domains (p < 0.05) except visuospatial functioning, which was only impaired in patients with AD and DLB (p < 0.001). During follow-up, patients with AD declined in all cognitive domains (p < 0.001). DLB showed decline in every cognitive domain except language and global cognition. bvFTD showed rapid decline in memory, language, attention and executive functioning (all p < 0.01) whereas visuospatial functioning remained fairly stable. lvFTD declined mostly in attention and executive functioning (p < 0.01). VaD showed decline in attention and executive functioning. CONCLUSIONS: We show cognitive trajectories of different types of dementia. These estimations of natural disease course have important value for the design of clinical trials as neuropsychological measures are increasingly being used as outcome measures.

Mutation frequency of PRKAR1B and the major familial dementia genes in a Dutch early onset dementia cohort.

Genetic factors are important in all forms of dementia, especially in early onset dementia. The frequency of major gene defects in dementia has not been investigated in the Netherlands. Furthermore, whether the recently in a FTD family identified PRKAR1B gene is associated with an Alzheimer's disease (AD) like phenotype, has not been studied. With this study, we aimed to investigate the mutation frequency of the major AD and FTD genes and the PRKAR1B gene in a well-defined Dutch cohort of patients with early onset dementia. Mutation analysis of the genes PSEN1, APP, MAPT, GRN, C9orf72 and PRKAR1B was performed on DNA of 229 patients with the clinical diagnosis AD and 74 patients with the clinical diagnosis FTD below the age of 70 years. PSEN1 and APP mutations were found in, respectively 3.5 and 0.4 % of AD patients, and none in FTD patients. C9orf72 repeat expansions were present in 0.4 % of AD and in 9.9 % of FTD patients, whereas MAPT and GRN mutations both were present in 0.4 % in AD patients, and in 1.4 % resp. 2.7 % in FTD patients. We did not find any pathogenic mutations in the PRKAR1B gene. PSEN1 mutations are the most common genetic cause in Dutch AD patients, whereas MAPT and GRN mutations were found in less than 5 percent. C9orf72 repeat expansions were the most common genetic defect in FTD patients. No pathogenic PRKAR1B mutations were found in the early onset AD and FTD patients of our study.

The added value of 18-fluorodeoxyglucose-positron emission tomography in the diagnosis of the behavioral variant of frontotemporal dementia.

UNLABELLED: Characteristic frontotemporal abnormalities on structural or functional neuroimaging are mandatory for a diagnosis of probable behavioral variant of frontotemporal dementia (bvFTD) according to the new criteria. 18-Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging is commonly reserved for patients with suspected bvFTD without characteristic structural neuroimaging results. We studied the diagnostic value of 18F-FDG-PET in these patients. METHODS: The 18F-FDG-PET was performed in 52 patients with suspected bvFTD but lacking characteristic structural neuroimaging results. The clinical diagnosis of bvFTD in the presence of functional decline (bvFTD/fd+) after a follow-up period of 2 years was used as a golden standard. RESULTS: The sensitivity of 18F-FDG-PET for bvFTD/fd+ was 47% at a specificity of 92%. The differential diagnosis comprised alternative neurodegenerative and psychiatric disorders and a benign phenocopy of bvFTD. CONCLUSIONS: The 18F-FDG-PET is able to identify nearly half of the patients with bvFTD who remain undetected by magnetic resonance imaging. In our selected group, high specificity enables exclusion of psychiatric and other neurodegenerative disorders.

Time to diagnosis in young-onset dementia as compared with late-onset dementia.

BACKGROUND: The extent to which specific factors influence diagnostic delays in dementia is unclear. Therefore, the aim of the present study was to compare duration from symptom onset to diagnosis for young-onset dementia (YOD) and late-onset dementia (LOD) and to assess the effect of age at onset, type of dementia, gender, living situation, education and family history of dementia on this duration. METHOD: Data on 235 YOD and 167 LOD patients collected from caregivers from two prospective cohort studies were used. Multiple linear regression analysis was performed. RESULTS: The duration between symptom onset and the diagnosis of YOD exceeded that of LOD by an average of 1.6 years (2.8 v. 4.4 years). Young age and being diagnosed with frontotemporal dementia were related to increases in the time to diagnosis. Subjects with vascular dementia experienced shorter time to diagnosis. CONCLUSIONS: There is a need to raise special awareness of YOD to facilitate a timely diagnosis.