Prodromal Features Research Articles

Prospective Study of Lung Function with Prodromal, Clinical Parkinson's Disease, and Mortality.

The association of lung function with the risk of developing prodromal and clinical-diagnosed Parkinson's disease (PD) and with the risk of mortality among individuals with PD remains unknown. To prospectively examine the associations of lung function with the risk of prodromal, clinical-diagnosed PD, and PD-related mortality in participants of the UK Biobank. Included were 452,518 participants free of PD at baseline. Baseline lung function, including forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and FEV1/FVC ratio, was assessed. Eight prodromal features were measured using self-reported diagnoses, hospital admission, and primary care data. Incident PD cases were identified using linkages with hospital admission, death register, and self-report. Vital status and date of death were provided by the UK National Health Service (NHS) and the NHS Central Register. We used Cox proportional hazard models to evaluate these associations. Poor lung function was associated with higher risk of PD in a dose-response relationship: the adjusted hazard ratio comparing the lowest vs. the highest lung function quintile was 1.18 (95% CI, 1.02- 1.37) for FEV1, 1.14 (95% CI, 0.99- 1.29) for FVC, and 1.23 (95% CI, 1.08- 1.41) for PEF (p-trend <0.05 for all). Similar results were obtained for risk of prodromal PD and mortality among individuals with PD. The current study showed that individuals with poor lung function had a high future risk of prodromal and clinical PD and a higher rate of PD-related mortality.

The relationship between prodromal symptom levels and affective temperament features and emotional dysregulation in patients diagnosed with bipolar disorder and their first-degree relatives: A controlled study

BackgroundThe frequency of developing psychiatric symptoms is higher in the first-degree relatives of bipolar patients compared to the healthy population. This study aims to determine the possible diagnosis of bipolarity by revealing the bipolar prodromal features, temperament changes, and emotional disregulation in the first-degree relatives of bipolar patients and their interrelationships. MethodsA total of 150 patients, including bipolar disorder patients, their first-degree relatives, and a healthy control group, aged 18–65 who met the study inclusion criteria, were included in the study. Sociodemographic data form, Bipolar Prodromal Symptom Scale (BPSS), Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire (TEMPS-A), and Difficulty in Emotion Regulation Scale (DERS) were administered to all participants. ResultsSignificant differences were found between the BPSS, TEMPS-A, and DERS total and subscale scores of the bipolar patient group, first-degree relatives, and healthy control group (p < 0.001). There were significant differences in BPSS frequency and severity subscale scores, TEMPS-A hyperthymic and cyclothymic subscale scores, and DERS strategy, goal-oriented, and awareness subscale scores between patients and their first-degree relatives (p < 0.001). Additionally, all scale scores of the patient relatives were significantly different from the healthy control group (p < 0.001). A significant relationship was found between the prodromal scores and temperament scores of the patient relatives, and between the temperament scores and DERS scores (p < 0.001). ConclusionIt has been observed that the severity and frequency of bipolar prodromal symptoms, temperament changes, and difficulty in mood regulation are higher in bipolar patients and their first-degree relatives compared to the healthy population. Differences were found in hyperthymic and cyclothymic temperament features and difficulty in mood regulation scores between bipolar patients and their first-degree relatives. Patient relatives showed significant changes in all parameters compared to the healthy group. The severity of bipolar prodromal symptoms in patient relatives was associated with cyclothymic and anxious temperament features, while the frequency of bipolar symptoms was associated with anxious temperament. Relationships were found between some temperament and mood regulation difficulty sub-scores. In light of these findings, evaluating clinical variables such as the frequency and severity of prodromal symptoms, temperament features, and difficulty in mood regulation in the first-degree relatives of bipolar patients may be an appropriate approach for diagnosing mood disorders.

Neurotoxic effects of coronavirus: Potential implications in Alzheimer's onset and progression

The COVID-19, caused by SARS-CoV-2, first affects the respiratory tract but evidence is emerging that the virus, reaching the central nervous system (CNS), can lead to severe neurological disorders. In particular, CoV infection could cause an acceleration of the neurodegenerative process. On the other hand, patients diagnosed with Alzheimer's disease (AD) develop more serious forms of COVID-19 with worse relapses. Therefore, understanding the connection between the two pathologies, AD and infection by coronavirus, could help in the development of new therapeutic approaches to counter them.We used the SH-SY5Y cell line differentiated into neurons, as widely used in studies of AD if supplemented with exogenous fibrillary β-amyloid (Aβ). As a glial counterpart, human microglia (HMC3) and astrocytic (D54MG) cell lines were used to create co-cultures with neurons via transwell systems. In these experimental models, we generated infection with the Human Coronavirus OC43 (HCoV-OC43), a low-risk model of SARS-CoV-2.Our results suggest that the infection by HCoV-OC43 leads to a neurotoxic effect not depending on an already present event of Aβ deposition. Indeed, unlike microglia, neurons and even more astrocytes are susceptible to CoV infection and, although the infection does not show a cytotoxic effect in the neurons in the first few days, significant alterations at a biochemical and morphological level have been observed, suggesting that the neurons are reacting to a stressful condition, including the prodromal and neurodegenerative features of AD. Interestingly, the interaction of infected astrocytes with the neurons resulted in the manifestation of signs of neurodegeneration, such as amyloid-beta deposition.By using exogenous fibrillary Aβ, as an AD in vitro model, our data suggest that there is an aggravating effect both on the infection itself and on the neurological disease progression.In conclusion, the results of this study suggest a causal interplay between HCoV-OC43 and neurological diseases and demonstrate that the co-presence of different CNS cell populations is the necessary condition to study the pathogenic effects in vitro as a whole.

The lived experience of mental disorders in adolescents: a bottom-up review co-designed, co-conducted and co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involvingnumerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life.

A transdiagnostic prodrome for severe mental disorders: an electronic health record study.

Effective prevention of severe mental disorders (SMD), including non-psychotic unipolar mood disorders (UMD), non-psychotic bipolar mood disorders (BMD), and psychotic disorders (PSY), rely on accurate knowledge of the duration, first presentation, time course and transdiagnosticity of their prodromal stages. Here we present a retrospective, real-world, cohort study using electronic health records, adhering to RECORD guidelines. Natural language processing algorithms were used to extract monthly occurrences of 65 prodromal features (symptoms and substance use), grouped into eight prodromal clusters. The duration, first presentation, and transdiagnosticity of the prodrome were compared between SMD groups with one-way ANOVA, Cohen's f and d. The time course (mean occurrences) of prodromal clusters was compared between SMD groups with linear mixed-effects models. 26,975 individuals diagnosed with ICD-10 SMD were followed up for up to 12 years (UMD = 13,422; BMD = 2506; PSY = 11,047; median[IQR] age 39.8[23.7] years; 55% female; 52% white). The duration of the UMD prodrome (18[36] months) was shorter than BMD (26[35], d = 0.21) and PSY (24[38], d = 0.18). Most individuals presented with multiple first prodromal clusters, with the most common being non-specific ('other'; 88% UMD, 85% BMD, 78% PSY). The only first prodromal cluster that showed a medium-sized difference between the three SMD groups was positive symptoms (f = 0.30). Time course analysis showed an increase in prodromal cluster occurrences approaching SMD onset. Feature occurrence across the prodromal period showed small/negligible differences between SMD groups, suggesting that most features are transdiagnostic, except for positive symptoms (e.g. paranoia, f = 0.40). Taken together, our findings show minimal differences in the duration and first presentation of the SMD prodromes as recorded in secondary mental health care. All the prodromal clusters intensified as individuals approached SMD onset, and all the prodromal features other than positive symptoms are transdiagnostic. These results support proposals to develop transdiagnostic preventive services for affective and psychotic disorders detected in secondary mental healthcare.

The Non-Motor Prodromal Symptoms of Parkinson's Disease: A Review

Parkinson's disease is a common progressive neurodegenerative disorder with both motor and non-motor symptoms. There is no clear etiology, and it has no cure. The non-motor features often precede the motor symptoms by many years, so they are considered prodromal symptoms of the disease. These symptoms include olfactory dysfunction, constipation, sleep problems, and depression. The purpose of this study is to review the literature on Parkinson's disease non-motor prodromal symptoms and their role from the early stages throughout the disease's development. The review discusses several aspects related to the prodromal features of Parkinson's disease: their prevalence in Parkinson's disease patients, the pathophysiology, the treatment, if it is possible, and the prodromal symptoms' effect on the diagnosis, prognosis, and management of the disease, in addition to their impact on patients' quality of life. More studies are required to precisely pinpoint the timing of non-motor prodromal symptoms onset and modify the diagnostic criteria for Parkinson's disease accordingly. KEYWORDS constipation, depression, gastrointestinal dysfunctions, hyposmia, olfactory dysfunction, sleep disturbances

Validation of Polish version of Gastrointestinal Dysfunction Scale for Parkinson's Disease.

The Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) is a novel, disease-specific self-report questionnaire used to quantitatively assess features of gastrointestinal dysfunction symptoms in patients with Parkinson's Disease. The aim of this paper was to validate the Polish translation of the scale, to summarise its consistency with the English language version, and to assess its clinimetric properties. Gastrointestinal dysfunction is a common and often debilitating manifestation of Parkinson's Disease (PD). Gastrointestinal symptoms are also considered to be prodromal features of this disease. To date, there has been no scale in Polish that has precisely assessed gastrointestinal symptoms in patients with PD. The GIDS-PD was translated into Polish by two investigators (M.K. and J.N.). A back-translation was completed by two separate investigators (M.F. and A.A.) who were not involved in the original translation. Afterwards, 10 Polish PD patients underwent cognitive pre-testing. After the final translation was officially approved by the Movement Disorder Society, it was tested on 64 individuals with PD during field testing. For the purpose of testing scale reliability, 20 of the patients recruited for field testing underwent the GIDS-PD for a second time after 8-12 weeks. The GIDS-PD demonstrated overall good consistency (Cronbach's alpha of 0.74, ICC of 0.74). Regarding the individual domains, the constipation subscore demonstrated good reliability, the bowel irritability subscore demonstrated moderate reliability, and the upper GI subscore demonstrated poor reliability. Upper GI symptoms seem to be less pronounced, and also more varied, in the Polish PD population than in its English language counterpart. This paper provides a validated Polish translation of the GIDS-PD questionnaire. We highly recommend using the GIDS-PD for research purposes, as well as everyday clinical practice in the Polish PD population.

Loneliness and Risk of Parkinson Disease

Loneliness is associated with morbidity and mortality, including higher risk of neurodegenerative diseases. To our knowledge, no study has examined whether the association between loneliness and detrimental outcomes extends to Parkinson disease (PD). To assess whether loneliness is associated with risk of incident PD and whether the association is independent of other risk factors or modified by age, sex, and genetic vulnerability. This prospective cohort study included a population-based sample of UK Biobank participants aged 38 to 73 years with loneliness data and without a diagnosis of PD at baseline who were first assessed from March 13, 2006, to October 1, 2010, and followed up to October 9, 2021. Feeling lonely and covariates that are known risk factors for or prodromal features of PD. Incident PD was ascertained through UK National Health Service health records. Of 491 603 participants (mean [SD] age, 56.54 [8.09] years; 54.4% female), 2822 developed PD during the 15-year follow-up. Individuals who reported being lonely had a higher risk of PD (hazard ratio [HR], 1.37; 95% CI, 1.25-1.51), an association that remained after accounting for demographic factors, socioeconomic status, social isolation, PD polygenetic risk score, smoking, physical activity, body mass index, diabetes, hypertension, stroke, myocardial infarction, depression, and ever seeing a psychiatrist (fully adjusted model: HR 1.25; 95% CI, 1.12-1.39). The association between loneliness and incident PD was not moderated by sex (HR for interaction, 0.98; 95% CI, 95% CI, 0.81-1.18), age (HR for interaction, 0.99; 95% CI, 0.98-1.01), or polygenic risk score (HR for interaction, 0.93; 95% CI, 0.85-1.02). Contrary to expectations for a prodromal syndrome, when stratified by time, loneliness was not associated with risk for incident PD during the first 5 years (HR, 1.15; 95% CI, 0.91-1.45) but was associated with PD risk during the subsequent 10 years (HR, 1.32; 95% CI, 1.19-1.46). This large cohort study found that loneliness was associated with risk of incident PD across demographic groups and independent of depression and other prominent risk factors and genetic risk. The findings add to the evidence that loneliness is a substantial psychosocial determinant of health.

0894 Impulsivity across early stages of synucleinopathy: from high-risk relatives, REM sleep behavior disorder to Parkinson’s disease

Abstract Introduction Increased impulsivity is a common neuropsychiatric feature in patients with Parkinson’s disease (PD), especially attributed to the use of dopaminergic medications. Interestingly, emerging evidence suggested that impulsivity had changed in drug-naïve PD patients. However, it remains unclear whether impulsivity has been altered in prodromal stage of PD, namely isolated rapid eye movement sleep behavior disorder (iRBD) and their high-risk relatives. Methods This was a cross-sectional study with four groups of subjects, including early drug-naive PD patients, patients with iRBD and their first-degree relatives (iRBD-FDRs, a high-risk group with potential prodromal RBD features), and controls. A panel of neuropsychological computerized tasks, including go/no-go task, four-choice serial reaction time task (4CSRTT), beads task, balloon analogue risk task (BART) and delay/effort discounting task, would measure various dimensions of motor and decisional impulsivity. Results A total of 331 subjects were recruited, including 27 early drug-naïve PD patients (mean age ± SD: 70.1 ± 5.8 years, 77.8% man), 152 iRBD patients (67.2 ± 6.6 years, 77.6% man), 68 iRBD-FDRs (63.2 ± 6.4 years, 51.5% man), and 84 controls (67.4 ± 8.1years, 61.9% man). Early drug-naïve PD and iRBD patients had fewer numbers of extracted beads in beads task 1 (P&amp;lt; 0.001) and task 2 (P&amp;lt; 0.001) in making decisions and fewer numbers of pumps of unexploded blue balloons in BART (P&amp;lt; 0.001) than controls and iRBD-FDRs, suggesting a higher level of reflection impulsivity and a lower level of risk taking, respectively. In addition, early drug-naïve PD and iRBD patients had more no-go errors in go/no-go task (P=0.023), suggesting a marginally lower level of response inhibition in PD and iRBD groups. Early drug-naïve PD and iRBD patients had more premature responses in 4CSRTT than iRBD-FDRs (P=0.008). The delay and effort discounting indexes were comparable among four groups. Conclusion While risk taking and response inhibition decreased, reflection impulsivity actually increased in iRBD and drug-naïve PD patients. These novel findings indicated that a complex construct of altered impulsivity has already occurred at the earlier stage (at iRBD) of α-synucleinopathy, which will have implications for pathophysiology and clinical management. Support (if any) This study has been supported by the General Research Fund (14116119).

Proposal for a Biologic Staging System of Parkinson's Disease.

The Parkinson's disease (PD) research field has seen the advent of several promising biomarkers and a deeper understanding of the clinical features of the disease from the earliest stages of pathology to manifest disease. Despite progress, a biologically based PD staging system does not exist. Such staging would be a useful framework within which to model the disease, develop and validate biomarkers, guide therapeutic development, and inform clinical trials design. We propose that the presence of aggregated neuronal α-synuclein, dopaminergic neuron dysfunction/degeneration, and clinical signs and symptoms identifies a group of individuals that have Lewy body pathology, which in early stages manifests with what is now referred to as prodromal non-motor features and later stages with the manifestations of PD and related Lewy body diseases as defined by clinical diagnostic criteria. Based on the state of the field, we herein propose a definition and staging of PD based on biology. We present the biologic basis for such a staging system and review key assumptions and evidence that support the proposed approach. We identify gaps in knowledge and delineate crucial research priorities that will inform the ultimate integrated biologic staging system for PD.

0641 Difficulty Maintaining Sleep and Sleep Quality mediate the Relationship between Sleep Disturbances and Depression

Abstract Introduction Prior epidemiological research has established the relationship between sleep disturbances and depression. Sleep disturbances are also common prodromal features of and comorbid with depression. However, limitations exist across past studies, including the frequent focus on “sleep disturbances” over well-defined facets of sleep, inattention to mediators, and a lack of focus on special populations. As such, there is a need to delineate the relationship between sleep disturbances and depression across specific facets of sleep, particularly in special populations. The current study examined multiple sleep facets as mediators of the relationship between general sleep disturbances and depression severity in college student athletes. Methods Student athletes (N = 993) from the Pacific Athlete Conference-12 completed the Athlete Sleep Screening Questionnaire-Sleep Difficulty Subscale (ASSQ-SDS) and Patient Health Questionnaire-9 (PHQ-9). Parallel multiple mediator models were conducted to examine whether the relationship between sleep disturbances and depression severity was mediated by sleep duration, sleep quality, sleep onset latency, and difficulty maintaining sleep. Results Using bootstrapping with 5,000 resamples, the indirect effect of sleep disturbances on depression severity was significantly different from zero through sleep quality (indirect effect = .17, SE = .07, 95% CI [.04, .31]) and difficulty maintaining sleep (indirect effect = .12, SE = .03, 95% CI [.06, .19]). Sleep disturbances were associated with sleep quality (b = .29, SE = .01, p &amp;lt; .001) and difficulty maintaining sleep (b = .16, SE = .01, p &amp;lt; .001). Sleep quality (b = .59, SE = .16, p &amp;lt; .001) and difficulty maintaining sleep (b = .78, SE = .17, p &amp;lt; .001) were associated with depression severity. No other mediators reached statistical significance. Conclusion Results demonstrate that perceived sleep quality and difficulty maintaining sleep mediate the relationship between general sleep disturbances and depression severity in college student athletes. Findings suggest that sleep quality and difficulty maintaining sleep may be more impactful on depression than other facets of sleep and may be clinically useful targets of intervention for depression. Support (if any)

Composite Measures of Prodromal Parkinson’s Disease and the Probability of Phenoconversion at 3 Years (S37.003)

<h3>Objective:</h3> To assess the ability of composite measures of prodromal Parkinson’s disease (PD) to predict phenoconversion at 3 years. <h3>Background:</h3> Features suggestive of prodromal PD are individually insufficient for early disease detection. Using composite measures may improve predictive validity and capture a more representative patient population. <h3>Design/Methods:</h3> The study population comprised 19,757 individuals without PD at baseline (2014–2015). Two composite measures were created: i) the co-occurrence of probable REM sleep behavior disorder (pRBD), constipation and hyposmia, 3 major features of prodromal PD, and ii) a probability score which incorporated information on 8 risk (e.g., sex, physical inactivity) and 7 prodromal markers following the MDS research criteria. For each composite measure we calculated the positive predictive value (PPV) of being diagnosed with PD within 3 years. We additionally calculated the PPV for pRBD, constipation and hyposmia independently, and that of all 3 features along with parkinsonism. We repeated analyses restricting to participants &lt;70 years old. <h3>Results:</h3> Between 2014–15 and 2017–18, we identified a total of 86 incident PD cases. The PPV of being diagnosed with PD within 3 years was 2.48% for those with the 3 prodromal features, 2.62% for those with possible prodromal PD (score≥0.5) and 4.55% for those with probable prodromal PD (score≥0.8). The PPV of individual features was lower than those of the composite measures. Parkinsonism plus the co-occurrence of 3 features resulted in the highest PPV (11.8%). Measures based on the presence of 3 features performed somewhat better among men than women. The PPVs of measures based on the MDS score or parkinsonism were higher among those aged &lt;70 years. <h3>Conclusions:</h3> The ability to predict phenoconversion at 3 years was comparable between the two composite measures evaluated. The performance of composite measures was superior to that of individual features. Longer follow-up may be needed to better understand the validity of these measures. <b>Disclosure:</b> Mr. Torres has nothing to disclose. Dr. Hughes has received personal compensation for serving as an employee of Optum. The institution of Dr. Bjornevik has received research support from Michael J. Fox Foundation. The institution of Dr. Bjornevik has received research support from National Multiple Sclerosis Society. The institution of Dr. Bjornevik has received research support from Department of Defense. Dr. Cortese has received personal compensation in the range of $500-$4,999 for serving as a speaker at educational event with Roche. The institution of Dr. Hung has received research support from Parkinson’s Foundation. The institution of Dr. Hung has received research support from Rho, Inc.. The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB (indirectly, as a service of the Parkinson Study Group service). Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Schwarzschild has received research support from NIH. The institution of Dr. Schwarzschild has received research support from Parkinson’s Foundation. The institution of Dr. Schwarzschild has received research support from Michael J Fox Foundation. The institution of Dr. Schwarzschild has received research support from Farmer Family Foundation. Dr. Schwarzschild has a non-compensated relationship as a Chair, Executive Committee with the Parkinson Study Group that is relevant to AAN interests or activities. The institution of Dr. Ascherio has received research support from NIH and US Department of Defense .

Memory Performance in Asymptomatic and Prodromal Familial Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium (P13-6.001)

Memory Performance in Asymptomatic and Prodromal Familial Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium (P13-6.001)

Case Report of Anti-DPPX Encephalitis: Diagnostic Challenges in Hematologic-Oncologic Comorbidities (P5-5.024)

<h3>Objective:</h3> Describe a case of anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis with attention to hematologic-oncologic comorbidities. <h3>Background:</h3> Anti-DPPX encephalitis is a rare autoimmune encephalitis with prodromal features of weight loss and gastrointestinal symptoms, followed by cognitive impairment and central nervous system hyperexcitability. Due to atypical and variable presentation, diagnosis is frequently delayed. Autoimmune encephalitis is associated with malignancies, and three cases of anti-DPPX encephalitis have been linked to hematologic malignancies. <h3>Design/Methods:</h3> Consent was obtained from patient’s wife. PubMed and Ovid databases were searched using terms (“DPPX” and “lymphoma”) as well as “DPPX”. <h3>Results:</h3> A 54-year-old male presented with two months of metallic taste and unintentional weight loss followed by confusion, memory impairment, hallucinations, and sleep disturbances. Neurologic exam was significant for encephalopathy, ataxia, and stimulus-induced myoclonus. Initial workup revealed mildly elevated protein in cerebrospinal fluid but no pleocytosis, MRI brain with nonspecific white matter hyperintensities, and electroencephalogram without epileptiform activity. Initial basic chemistries were within normal limits, and no vitamin deficiencies were identified. Intravenous methylprednisolone (1000 mg) was initiated for suspected autoimmune encephalitis. After anti-DPPX antibody returned positive, he received additional first- and second-line treatment with intravenous immunoglobulins, plasmapheresis and rituximab with modest improvements in encephalopathy and myoclonus. The patient had a history of monoclonal gammopathy of undetermined significance (MGUS) and tobacco use. He underwent serum protein electrophoresis, confirming IgM MGUS with low to intermediate risk of malignant transformation. However, peripheral flow cytometry revealed an indeterminate kappa monotypic restricted B cell population (CD19 positive, CD5 and CD10 negative) without corresponding findings in the CSF or lymphadenopathy. In discussion with hematology-oncology, the B cell population was favored to be reactive to the anti-DPPX encephalitis, rather than a primary malignant hematologic condition. Other malignancy screening was performed and negative. <h3>Conclusions:</h3> This case highlights the challenges of determining association of anti-DPPX encephalitis with hematologic malignancy and importance of interdisciplinary collaboration. <b>Disclosure:</b> Dr. Fisher has nothing to disclose. Dr. Misiolek has nothing to disclose. Dr. Buckley has nothing to disclose.

Advances in the Diagnosis and Management of Psychotic Symptoms in Neurodegenerative Diseases: A Narrative Review.

Background: Approximately 15% of older adults may experience psychotic phenomena. Primary psychiatric disorders that manifest with psychosis (delusions, hallucinations, and disorganized thought or behavior) account for less than half. Up to 60% of late-life psychotic symptoms are due to systemic medical or neurological conditions, particularly neurodegenerative diseases. A thorough medical workup including laboratory tests, additional procedures if indicated, and neuroimaging studies is recommended. This narrative review summarizes current evidence regarding the epidemiology and phenomenology of psychotic symptoms encountered as part of the neurodegenerative disease continuum (including prodromal and manifest stages). Results: Prodromes are constellations of symptoms that precede the onset of overt neurodegenerative syndromes. Prodromal psychotic features, particularly delusions, have been associated with an increased likelihood of receiving a neurodegenerative disease diagnosis within several years. Prompt prodrome recognition is crucial for early intervention. The management of psychosis associated with neurodegenerative diseases includes behavioral and somatic strategies, although evidence is scarce and mostly limited to case reports, case series, or expert consensus guidelines, with few randomized controlled trials. Conclusion: The complexity of psychotic manifestations warrants management by interprofessional teams that provide coordinated, integrated care.

Updated Percentiles for the University of Pennsylvania Smell Identification Test in Adults 50 Years of Age and Older.

The University of Pennsylvania Smell Identification Test (UPSIT) is commonly used to assess olfaction and screen for early detection of disorders including Parkinson (PD) and Alzheimer disease. Our objective was to develop updated percentiles, based on substantially larger samples than previous norms, to more finely discriminate age- and sex-specific UPSIT performance among ≥50-year-old adults who may be candidates for studies of prodromal neurodegenerative diseases. The UPSIT was administered cross-sectionally to participants recruited between 2007-2010 and 2013-2015 for the Parkinson Associated Risk Syndrome (PARS) and Parkinson's Progression Markers Initiative (PPMI) cohort studies, respectively. Exclusion criteria included age <50 years and a confirmed or suspected PD diagnosis. Demographics, family history, and prodromal features of PD including self-reported hyposmia were collected. Normative data including mean, SDs, and percentiles were derived by age and sex. The analytic sample included 9,396 individuals (5,336 female and 4,060 male), aged 50-95 years, who were predominantly White, non-Hispanic US residents. UPSIT percentiles were derived and are provided across 7 age categories (50-54, 55-59, 60-64, 65-69, 70-74, 75-79, and ≥80 years) for female and male participants separately; relative to existing norms, subgroups included between 2.4 and 20 times as many participants. Olfactory function declined with age and was better among women than men; accordingly, the percentile corresponding to a given raw score varied markedly by age and sex. UPSIT performance was comparable among individuals with vs without first-degree family history of PD. Comparisons of self-reported hyposmia vs UPSIT percentiles indicated a strong association (χ2 p < 0.0001) but minimal agreement (Cohen simple kappa [95% CI]: = 0.32 [0.28-0.36] for female participants; 0.34 [0.30-0.38] for male participants). Updated age/sex-specific UPSIT percentiles are provided for ≥50-year-old adults who reflect a population likely to be recruited into studies of prodromal neurodegenerative diseases. Our findings highlight the potential advantages of evaluating olfaction relative to age and sex instead of in absolute terms (i.e., based on raw UPSIT scores) or based on subjective (i.e., self-reported) measures. This information addresses the need to support studies of disorders including PD and Alzheimer disease by providing updated normative data from a larger sample of older adults. NCT00387075 and NCT01141023.

Relationship between depression and lifestyle factors in Chinese adults using multi-level generalized estimation equation model.

Relationship between depression and lifestyle factors in Chinese adults using multi-level generalized estimation equation model.

A rare rapidly progressive presentation of tuberculous meningitis

Tubercular Meningitis (TBM) usually presents as a sub-acute to chronic illness, with duration of symptoms ranging from weeks to months before clinical presentation. The course of disease is divided into 3 clinical stages- the stage of prodrome, phase of neurological symptoms and paretic stage, which usually progresses gradually over a period.Here we report an unusual case of TB meningitis in young female, which progressed rapidly over a period of 7-10 days from symptom onset, without any prodromal features or previous evidence of Koch’s, to reach a non-salvageable stage despite all the available diagnostic and therapeutic modalities.

Translation and cross-cultural adaptation to Brazilian Portuguese of two brief screening tools for at-risk psychosis youth: the Prodromal Questionnaire (PQ-16) and the PRIME-Screen.

Prodromal characteristics of psychosis have been described for more than a century. Over the last three decades, a variety of studies have proposed methods to prospectively identify individuals (and youth in particular) who are at high risk of developing a psychotic disorder. These studies have validated various screening instruments and made them available in several languages. Here, we describe the translation into Brazilian Portuguese and cross-cultural adaptation of two such screening tools - the Prodromal Questionnaire-16 (PQ-16) and the Prevention through Risk Identification, Management, and Education (PRIME)-Screen. Two bilingual native speakers of Brazilian Portuguese translated the questionnaires from English. A native English speaker then performed back-translations into English. These back-translated versions were submitted to the original authors. They provided feedback and later approved the final versions. After translation and cross-cultural adaptation, no items needed to be changed in the adapted PQ-16 and four items were revised in the PRIME-Screen. After the peer-review process, we included two suggestions in the PQ-16 to facilitate use of the tool in our cultural and social contexts. The PRIME-Screen did not need further changes. These new instruments can help screen Brazilian Portuguese-speaking patients who are at risk of psychosis in primary care.

Widening the Spectrum of Risk Factors, Comorbidities, and Prodromal Features of Parkinson Disease

The prodromal phase of Parkinson disease (PD) may last for more than 10 years. Recognition of the spectrum and occurrence of risk factors, comorbidities, and prodromal features of PD can increase understanding of the causes and development of the disease and help identify individuals at risk. To identify the association of a subsequent diagnosis of PD with a range of risk factors and prodromal features, including lifestyle factors, comorbidities, and potential extracerebral manifestations of PD. This was a case-control study using insurance claims of outpatient consultations of patients with German statutory health insurance between January 1, 2011, and December 31, 2020. Included were patients with incident diagnosis of PD without a previous diagnosis of parkinsonism or dementia and controls matched 1:2 for age, sex, region, and earliest year of outpatient encounter. Exposures were selected based on previous systematic reviews, case-control and cohort studies reporting on risk factors, comorbidities, and prodromal features of PD. Previously postulated risk factors and prodromal features of PD, using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding. A total of 138 345 patients with incident PD (mean [SD] age, 75.1 [9.8] years; 73 720 male [53.3%]) and 276 690 matched controls (mean [SD] age, 75.1 (9.8) years; 147 440 male [53.3%]) were identified. Study participants were followed up for a mean (SD) of 6.0 (2.0) years. Consistent with previous reports, risk factors and prodromal features associated with PD included traumatic brain injury, odds ratio (OR), 1.62; 95% CI, 1.36-1.92; alcohol misuse, OR, 1.32; 95% CI, 1.21-1.44; hypertension, OR, 1.29; 95% CI, 1.26-1.31; anosmia, OR, 2.16; 95% CI, 1.59-2.93; and parasomnias (including RBD), OR, 1.62; 95% CI, 1.42-1.84. In addition, there were associations with restless legs syndrome (OR, 4.19; 95% CI, 3.91-4.50), sleep apnea (OR, 1.45; 95% CI, 1.37-1.54), epilepsy (OR, 2.26; 95% CI, 2.07-2.46), migraine (OR, 1.21; 95% CI, 1.12-1.29), bipolar disorder (OR, 3.81; 95% CI, 3.11-4.67), and schizophrenia (OR, 4.48; 95% CI, 3.82-5.25). The following diagnoses were also found to be associated with PD: sensory impairments beyond anosmia, such as hearing loss (OR, 1.14; 95% CI, 1.09-1.20) and changes of skin sensation (OR, 1.31; 95% CI, 1.21-1.43). There were also positive associations with skin disorders (eg, seborrheic dermatitis, OR, 1.30; 95% CI, 1.15-1.46; psoriasis, OR, 1.13; 95% CI, 1.05-1.21), gastrointestinal disorders (eg, gastroesophageal reflux, OR, 1.29; 95% CI, 1.25-1.33; gastritis, OR, 1.28; 95% CI, 1.24-1.33), conditions with a potential inflammatory component (eg, seronegative osteoarthritis, OR, 1.21; 95% CI, 1.03-1.43), and diabetes types 1 (OR, 1.32; 95% CI, 1.21-1.43) and 2 (OR, 1.24; 95% CI, 1.20-1.27). Associations even 5 to 10 years before diagnosis included tremor (odds ratio [OR], 4.49; 95% CI, 3.98-5.06), restless legs syndrome (OR, 3.73; 95% CI, 3.39-4.09), bipolar disorder (OR, 3.80; 95% CI, 2.82-5.14), and schizophrenia (OR, 4.00; 95% CI, 3.31-4.85). Results of this case-control study suggest that the associations found between PD and certain risk factors, comorbidities, and prodromal symptoms in a representative population may reflect possible early extrastriatal and extracerebral pathology of PD. This may be due to shared genetic risk with PD, medication exposure, or direct causation, or represent pathophysiologically relevant factors contributing to the pathogenesis of PD.