The natural history of primary progressive aphasia: beyond aphasia

Introduction: Primary progressive aphasia (PPA) is divided into three prototypical subtypes that are all characterized by their single core symptom of aphasia. Although later in their course, other cognitive, behavioral, and motor domains may become involved, little is known about the progression profile of each subtype relative to the other subtypes. Methods: In this longitudinal retrospective cohort study, based on the recent biomarker-supported diagnostic criteria, 24 subjects diagnosed with semantic variant (svPPA), 22 with non-fluent variant (nfvPPA), and 18 with logopenic variant (lvPPA) were collected and followed up for 1–6 years. Symptom distribution, cognitive test and neuropsychiatric inventory scores, and progression into another syndrome were assessed. Results: Over time, lvPPA progressed with broader language problems (PPA-extended) and nfvPPA progressed to mutism, whereas semantic impairment remained the major problem in svPPA. Apart from linguistic problems, svPPA developed pronounced behavioral disturbances, whereas lvPPA exhibited a greater cognitive decline. By contrast, in nfvPPA motor deficits were more common. Furthermore, within 5 years (IQR = 2.5) after clinical onset, 65.6% of the patients additionally fulfilled the clinical criteria for another neurodegenerative syndrome (PPA-plus). Fourteen out of 24 (58%) svPPA patients additionally met the diagnostic criteria of behavioral variant frontotemporal dementia (5.1 years, IQR = 1.1), whereas the clinical features of 15/18 (83%) lvPPA patients were consistent with Alzheimer disease dementia (4.5 years IQR = 3.4). Furthermore, 12/22 (54%) of the subjects with the nfvPPA progressed to meet the diagnostic criteria of corticobasal syndrome, progressive supranuclear palsy, or motor neuron disease (5.1 years IQR = 3.4). Discussion: Despite aphasia being the initial and unique hallmark of the syndrome, our longitudinal results showed that PPA is not a language limited disorder and progression differs widely for each subtype, both with respect to the nature of symptoms and disease duration

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 (βHinting-Task = 1.20, p<0.01) and LON (βHinting-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 (βHinting-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

Late life bipolar disorder evolving into frontotemporal dementia mimic

Annemiek Dols,1 Welmoed Krudop,2 Christiane M&ouml;ller,2 Kenneth Shulman,3 Martha Sajatovic,4 Yolande AL Pijnenburg2 1Department of Old Age Psychiatry, GGZInGeest, 2Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, the Netherlands; 3Department of Geriatric Psychiatry, Sunnybrook Health Science Centre, Faculty of Medicine, University of Toronto, Toronto, Canada; 4Department of Psychiatry and Neurology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA Objectives: Although bipolar disorder has been understood classically as a cyclic disease with full recovery between mood episodes, in the last decade, evidence has accumulated supporting progressive features. The clinical picture of advanced or end-stage bipolar disorder is heterogeneous with possible deficits in cognition and behavior, as illustrated by our case series.Cases: From our neuropsychiatric outpatient clinic, we describe four cases with bipolar disorder gradually developing a clinical syndrome, including apathy, disinhibition, loss of empathy, stereotypical behavior, and compulsiveness, fulfilling the criteria for possible behavioral variant frontotemporal dementia. All cases were diagnosed with bipolar 1 disorder at least 10 years before the onset of the current symptoms, which were not due to recent mood episodes or switches of medication. In all cases, 3&ndash;7 years of follow-up yielded no progression. Repeated neuroimaging was within normal limits. Cerebrospinal fluid biomarker studies were not supportive of underlying neurodegenerative pathology. C9orf72 mutation status was negative in all cases.Conclusion: Symptoms fitting the criteria for possible behavioral variant frontotemporal dementia may be present in end-stage of bipolar disorder. An alternative neurodegenerative nature seems unlikely based on repeated normal neuroimaging and the absence of clinical progression. Functional involvement of the frontal-subcortical networks might play a role. Keywords: bipolar disorder, older, staging, bvFTD, benign phenocopy syndrom

Psychosis in behavioral variant frontotemporal dementia

Flora T Gossink,1,2 Everard GB Vijverberg,2,3 Welmoed Krudop,2 Philip Scheltens,2 Max L Stek,1 Yolande AL Pijnenburg,1,2 Annemiek Dols1,2 1Department of Old Age Psychiatry, GGZinGeest, 2Alzheimer Center &amp; Department of Neurology, VU University Medical Center, Amsterdam, 3Department of Neurology, HagaZiekenhuis, The Hague, the Netherlands Background: Dementia is generally characterized by cognitive impairment that can be accompanied by psychotic symptoms; for example, visual hallucinations are a core feature of dementia with Lewy bodies, and delusions are often seen in Alzheimer&rsquo;s disease. However, for behavioral variant of frontotemporal dementia (bvFTD), studies on the broad spectrum of psychotic symptoms are still lacking. The aim of this study was to systematically and prospectively subtype the wide spectrum of psychotic symptoms in probable and definite bvFTD.Methods: In this study, a commonly used and validated clinical scale that quantifies the broad spectrum of psychotic symptoms (Positive and Negative Symptom Scale) was used in patients with probable and definite bvFTD (n=22) and with a primary psychiatric disorder (n=35) in a late-onset frontal lobe cohort. Median symptom duration was 2.8 years, and the patients were prospectively followed for 2 years.Results: In total, 22.7% of bvFTD patients suffered from delusions, hallucinatory behavior, and suspiciousness, although the majority of the patients exhibited negative psychotic symptoms such as social and emotional withdrawal and blunted affect (95.5%) and formal thought disorders (81.8%). &ldquo;Difficulty in abstract thinking&rdquo; and &ldquo;stereotypical thinking&rdquo; (formal thought disorders) differentiated bvFTD from psychiatric disorders. The combined predictors difficulty in abstract thinking, stereotypical thinking, &ldquo;anxiety&rdquo;, &ldquo;guilt feelings,&rdquo; and &ldquo;tension&rdquo; explained 75.4% of variance in the diagnosis of bvFTD versus psychiatric diagnoses (P&lt;0.001).Conclusion: Delusions, hallucinatory behavior, and suspiciousness were present in one-fifth of bvFTD patients, whereas negative psychotic symptoms such as social and emotional withdrawal, blunted affect, and formal thought disorders were more frequently present. This suggests that negative psychotic symptoms and formal thought disorders have an important role in the psychiatric misdiagnosis in bvFTD; misdiagnosis in bvFTD might be reduced by systematically exploring the broad spectrum of psychiatric symptoms. Keywords: frontotemporal dementia, psychosis, schizophrenia, formal thought disorders&nbsp

Een 51-jarige man met primaire progressieve afasie

Primary progressive aphasia (PPA) is a form of dementia in which brain circuits responsible for language and speech show progressive impairments. Based on consensus criteria PPA is divided into 3 main variants: a nonfluent/agrammatic, a semantic and a logopenic variant. Each variant has specific clinical characteristics, including neuropsychiatric symptoms, and is associated with different neuropathological findings. We describe a 51-year-old man with neuropsychiatric symptoms and progressive language disturbances. The diagnosis PPA was established after an extensive work-up in a psychiatric clinic. We describe which factors contributed to this complex diagnostic process and discuss why knowledge of this disorder is relevant for psychiatrists

Een pijnlijke hals door acute suppuratieve thyreoïditis veroorzaakt door Salmonella

A 53-year-old woman presented with fever accompanied by chills and an extremely painful swelling of her right thyroid lobe. She was initially diagnosed as having subacute thyroiditis, but after 14 days her disease appeared to be caused by a destructive suppurative thyroiditis due to Salmonella group C. A pre-existing hyperplastic nodule in the right thyroid lobe was the predisposing factor. Antibiotics were given for several weeks and surgical drainage was performed. Finally a hemithyroidectomy was done to eliminate the predisposing factor

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

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) (χ2 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

Schizophrenia as a mimic of behavioral variant frontotemporal dementia.

Recently, the diagnostic criteria for the behavioral variant of frontotemporal dementia were revised. Although these criteria offer a relatively high sensitivity, their specificity is yet unknown. We describe a 54-year-old woman fulfilling criteria for both late-onset schizophrenia and probable behavioral variant frontotemporal dementia. Following an initial presentation with psychosis, she developed progressive apathy, compulsiveness, and executive dysfunction. Moreover, bilateral frontotemporal hypometabolism was seen on [(18)F]fludeoxyglucose-positron emission tomography. A post-mortem diagnosis of schizophrenia was established, given the clinical picture combined with the pathological exclusion of a neurodegenerative cause. Our case suggests that patients with other brain disorders may meet the current diagnostic criteria for probable frontotemporal dementia. Further clinicopathological validation of these criteria is needed to determine their exact specificity

Schizophrenia as a mimic of behavioral variant frontotemporal dementia.

Recently, the diagnostic criteria for the behavioral variant of frontotemporal dementia were revised. Although these criteria offer a relatively high sensitivity, their specificity is yet unknown. We describe a 54-year-old woman fulfilling criteria for both late-onset schizophrenia and probable behavioral variant frontotemporal dementia. Following an initial presentation with psychosis, she developed progressive apathy, compulsiveness, and executive dysfunction. Moreover, bilateral frontotemporal hypometabolism was seen on [(18)F]fludeoxyglucose-positron emission tomography. A post-mortem diagnosis of schizophrenia was established, given the clinical picture combined with the pathological exclusion of a neurodegenerative cause. Our case suggests that patients with other brain disorders may meet the current diagnostic criteria for probable frontotemporal dementia. Further clinicopathological validation of these criteria is needed to determine their exact specificity