Search

Background: Distinguishing a dementia syndrome from a primary psychiatric disease in younger patients can be challenging and may lead to diagnostic change over time. The aim of this study was to examine diagnostic stability in a cohort of patients with younger‐onset neurocognitive disorders. Method: We retrospectively reviewed records of patients that were admitted to our unit between 2000 and 2019, were followed‐up for ≥12 months and received a diagnosis of young onset dementia at any time point. Initial diagnosis included Alzheimer disease (AD)‐type dementia (n= 30), frontotemporal dementia (FTD) syndromes (n=44), vascular dementia (VaD, n=7), mild cognitive impairment (MCI, n= 10), primary psychiatric diseases (n=6) and other conditions such as Lewy Body Dementia (n=30). Result: In a total of n=127 patients, 49 (39%) changed their initial diagnoses during follow‐up. Behavioural variant FTD (bvFTD) was the least stable diagnosis, followed by dementia not otherwise specified and MCI. Compared to patients with a stable diagnosis, those who changed exhibited: a higher cognitive score at baseline, a longer follow‐up period, greater delay to final diagnosis, and no family history of dementia. Patients switching from a neurodegenerative to a psychiatric diagnosis more likely had a long psychiatric history, while those changing from a psychiatric to a neurodegenerative diagnosis had a recent manifestation of psychiatric symptoms. Conclusion: Misdiagnosis in younger patients with neurocognitive disorders is not uncommon, especially in cases of behavioural variant FTD. Late‐onset psychiatric symptoms may be the harbinger to a neurodegenerative disease. Close follow‐up and monitoring of these patients are necessary. [ABSTRACT FROM AUTHOR]

Background: There are currently 28000 people in Australia with younger‐onset dementia (YOD). A recent review of younger‐onset dementia cohorts (Loi SM et al. submitted) suggested that there needs to be more detailed study in this heterogenous group in order to glean more clinically relevant information. For example, our group (Eratne D et al. 2020) investigated the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) chain in a group of people with a range of psychiatric and neurodegenerative disorders and reported that NfL could distinguish between these two broad disorders, demonstrating the benefits in studying a large range of YODs. BeYOND (Biomarkers in younger‐onset neurocognitive disorders) was established as a longitudinal cohort of younger people presenting with neurocognitive symptoms to a clinical diagnostic service, with the aim of identifying clinical and investigational biomarkers which can inform diagnostic and psychosocial outcomes in a clinically heterogenous population. Method: Patients are prospectively recruited during their index presentation to Neuropsychiatry, Royal Melbourne Hospital, Australia. Neuropsychiatry is a tertiary specialist service which provides diagnostic work‐up for patients with cognitive, psychiatric and neurological symptoms. The diagnostic process includes baseline and 18 month assessments of clinical and diagnostic outcomes including CSF and blood biomarkers, cognition, neuroimaging and psychosocial (including caregiver). Results: To date, 50 participants have been recruited (17 females, mean age 55). Thirty of had a dementia diagnosis (including Alzheimer's dementia, frontotemporal dementia and Huntington's disease), with the remainder having a psychiatric disorder (including depression and schizophrenia) as principle diagnosis. All participants have had clinical, neuropsychology and imaging. Eleven have had a lumbar puncture. Twenty participants have had a research blood panel for genetic analysis)and 12 had quantitative susceptibility mapping imaging. Conclusion: The diagnosis of neurodegenerative disorders in younger people can be difficult and is often associated with diagnostic delays (Draper B et al. 2016). The BeYOND study aims to longitudinally assess younger patients with suspected neurodegenerative disease in order to improve diagnostic and psychosocial outcomes for this population. References: Loi SM et al. J Neuropsychiatry Clin Neuroscience. Submitted 23/1/2020. Eratne D et al. ANZJP. 54 (1): 57‐67. 2020. Draper B et al. Int J Geriatr Psychiatry. 31 (11): 1217‐1224. 2016. [ABSTRACT FROM AUTHOR]

Background: Distinguishing primary psychiatric disorders (PPD) from neurological/neurodegenerative disorders (NND) is a common diagnostic dilemma in clinical practice. Numerous studies have focused on whether cognitive, neuroimaging or blood/ cerebrospinal fluid (CSF) are of assistance in this clinical scenario. Olfactory impairment has not however been systematically examined as a clinical tool for this purpose. The aim of this study was to identify whether performance in olfactory identification can distinguish NND and PPD. Method: This was a cross‐sectional retrospective study of inpatients assessed in Neuropsychiatry, Royal Melbourne Hospital (RMH) over the period 2015‐2019. Neuropsychiatry is a tertiary / quaternary service which provides diagnostic work up for patients with cognitive, psychiatric and neurological symptoms. Data extracted from the admission records included: demographics, tobacco use, medical comorbidities, cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), and odour identification assessed using the Sniffin' Sticks Screening 12 Test (SS12). The final discharge diagnosis for all patients was informed by established diagnostic criteria. Result: 121 patients were identified who had valid Sniffin Stick testing over this period. 88 patients (72.7%) were diagnosed with NND (mean age‐ 60, including Alzheimer's dementia, frontotemporal dementia, Lewy body parkinsonian‐related dementias [Parkinson's disease, Multiple Systematic Atrophy, Dementia with Lewy bodies] and other neurological causes of dementia), 33 patients (27.3%) were diagnosed with PPD (mean age=57 years, including mood and psychotic disorders). Patients who scored ≤8 in SS12 were more likely to have NND than PPD, even after adjustment for age, gender and tobacco use [(p=0.005, unadjusted OR=3.51, 95% CI=1.463,8.410), (p=0.009, adjusted OR=3.848, 95% CI=1.395,10.617)]. Receiver Operating Curve (ROC) analyses demonstrated that a score of ≤8 differentiated NND from PSY with sensitivity of 56.8% and specificity of 72.7% (ROC area under the curve of 0.672, p=0.004). Conclusion: Patients presenting with diagnostically complex neurocognitive / neuropsychiatric difficulties who score 8 or less on Sniffin' Sticks are more likely to have a neurodegenerative illness. A cut‐off score of 8 is potentially a "red‐flag" for clinicians faced with the diagnostic question of PPD versus NND. [ABSTRACT FROM AUTHOR]

Background: Accurate diagnosis of a neurodegenerative disorder, in particular distinguishing primary psychiatric from neurological disorders, can be challenging. There is a need for biomarkers to reduce the diagnostic odyssey and improve outcomes. Neurofilament light (NfL) has shown promise as a biomarker for diagnosis, staging and prognosis in a wide range of disorders. Our 'Biomarkers in Younger Onset Neurocognitive Disorders' (BeYOND) and 'Markers in Neuropsychiatric Disorders' (MiND) studies aim to build on our pilot study (Eratne et al, 2019, ANZJP), to explore the diagnostic and broader utility of plasma and cerebrospinal fluid (CSF) NfL, in a broad range of psychiatric and neurodegenerative/neurological disorders. Method: These studies assess plasma and/or CSF NfL concentrations using Simoa technology in a broad range of cohorts, including: patients assessed for neurocognitive/psychiatric symptoms at Neuropsychiatry and Melbourne Young Onset Dementia service; Australian National Creutzfeldt‐Jakob Disease Registry (ANCJDR); treatment trials in Alzheimer's disease (AD) and frontotemporal dementia (FTD); treatment‐resistant schizophrenia (TRS) biobank; FTD; autoimmune encephalitis; Niemann‐Pick Type C; epilepsy; and patients in primary care with cognitive or psychiatric symptoms. The most recent primary consensus diagnosis informed by established diagnostic criteria is categorised: psychiatric disorder (PSY), neurodegenerative/neurological disorder (NND), or healthy controls (HC). Result: As of January 2020, data from 485 patients/participants (NND:325, PSY:100, HC:60) demonstrates significantly elevated plasma and/or CSF NfL levels in a broad range of NND compared to a broad range of PSY, and HC, with areas under the curve of>0.90 and sensitivity and specificity>90%: improving on results from our pilot study. As recruitment, sample analysis, data collection is ongoing, more detailed, up to date results will be presented from over 600 patients/participants, including in‐depth findings from TRS, ANCJDR, AD and FTD treatment trials, and general practice cohorts. Conclusion: NfL shows great promise as a diagnostic test to assist with the common, but challenging diagnostic dilemma of distinguishing psychiatric from neurodegenerative and neurological disorders. A significantly elevated NfL concentration in a patient with a psychiatric diagnosis should prompt consideration of neurological or neurodegenerative differentials. Plasma NfL could dramatically alter clinical care of patients with neurological/neurodegenerative and psychiatric disorders, improving outcomes for patients, their families, the healthcare system, and clinical trials. [ABSTRACT FROM AUTHOR]

THEME: Clinical manifestations TOPIC: Neuropsychiatry & beh neurology SUBTOPIC: Neuropsychiatry Background: Survival duration in frontotemporal dementia (FTD) remains inconsistent, depending on the clinical phenotype with different risk factors identified. Risk factors to mortality include the FTD‐MND presentation, a genetic predisposition (Agarwal S et al. 2019), deficits in neuropsychological tests, imaging changes (Agarwal et al. 2019; Hodges et al. 2003) and non‐tau pathology (Roberson et al. 2005; Hodges et al. 2003). We aimed to identify survival duration and cause of death in this group. Method: All inpatients admitted to Neuropsychiatry, based at the Royal Melbourne Hospital, in metropolitan Australia from 1992 – 2014, who were diagnosed with probably FTD of any subtype were included. Linkage data was obtained by the Australian Institute of Health and Welfare (AIHW). We reviewed their clinical information including demographics, age of symptom onset, type of presenting symptom, neuroimaging and diagnosis. Result: Of the 528 individual inpatients identified with a dementia, there were n=100 who had a diagnosis of probable FTD. There were n=76 who had a behavioural‐variant FTD (bv‐FTD), n=14 who had a language‐variant FTD (lang‐FTD) and n=10 who had FTD‐MND. 67% of the group had died. Overall median duration of survival was 10.5 years (95% CI 7.9, 12.2). There were no differences in age of death nor age onset between the three FTD‐subtypes (p=0.479, p=0.289, respectively). As expected, there were significant differences in the median survival duration of the three FTD subtypes, with FTD‐MND having the shortest duration (p=0.004). Causes of death based on ICD‐10 were predominantly dementia‐related (26.3% Other degenerative diseases of nervous system; 17.5% unspecified dementia) but also included acute myocardial infarction (7%) and alcohol‐related (7%). Standardised mortality ratios (SMRs) revealed that compared to population norms, people with FTD had 8x mortality rate. Conclusion: Not unsurprisingly, FTD‐MND had the shortest duration compared to the other subtypes of FTD. The duration of survival was comparable to other studies. Causes of death revealed that a dementia was identified in almost half of cases. High SMRs suggest that FTD is a particularly "fatal" type of dementia in younger people. Investigation into risk factors to death is required. [ABSTRACT FROM AUTHOR]