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Abstract Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolving RBD are present, but do not yet meet established diagnostic criteria for RBD. However, the boundary between prodromal and definite RBD is still unclear. As a common effort of the Neurophysiology Working Group of the International RBD Study Group, this manuscript addresses the need for comprehensive and unambiguous v-PSG recommendations to diagnose RBD and identify prodromal RBD. These include: (1) standardized v-PSG technical settings; (2) specific considerations for REM sleep scoring; (3) harmonized methods for scoring REM sleep without atonia; (4) consistent methods to analyze video and audio recorded during v-PSGs and to classify movements and vocalizations; (5) clear v-PSG guidelines to diagnose RBD and identify prodromal RBD. Each section follows a common template: The current recommendations and methods are presented, their limitations are outlined, and new recommendations are described. Finally, future directions are presented. These v-PSG recommendations are intended for both practicing clinicians and researchers. Classification and quantification of motor events, RBD episodes, and vocalizations are however intended for research purposes only. These v-PSG guidelines will allow collection of homogeneous data, providing objective v-PSG measures and making future harmonized multicentric studies and clinical trials possible.

BackgroundDepression is a highly prevalent non-motor symptom in Parkinson’s disease (PD) that can manifest several years prior to the clinical diagnosis of PD. The study was aimed to investigate the clinical characteristics and related risk factors of depression in prodromal PD (pPD) subjects.MethodsA total of 47 pPD participants from community population of East China and 39 healthy controls (HCs) were enrolled in the study. The pPD people were divided into two groups (pPD with depression and pPD without depression) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. The severity of depression was assessed via the 24-item Hamilton Depression Rating Scale (HAMD-24), and the clinical features of depression were assessed by calculating seven factors of the HAMD-24. Comparisons between the two pPD subgroups were conducted to evaluate the clinical characteristics of depression in the prodromal phase of PD. Risk factors for depression in prodromal PD were analyzed by multivariate Logistic regression analysis.ResultsThe prevalence of depression in prodromal PD was 25.53%. pPD group with depression (dpPD) had significantly less years of education and higher HAMD overall scores, Hamilton Anxiety Rating Scale (HAMA) scores, PD non-motor questionnaire scores compared with pPD without depression (ndpPD). The dpPD group obtained significantly higher scores than the ndpPD group across several domains, including anxiety/somatization, cognitive impairment, day/night changes, retardation, and despair. Multivariate Logistic regression analysis showed that anxiety was an independent risk factor for depression in pPD.ConclusionDepression is common in prodromal PD and exhibit a multifaceted nature. pPD subjects with depression are vulnerable to comorbid with other non-motor symptoms. Anxiety is an established risk factor for ndPD, which indicates the critical value of early mood management in early disease intervention.

Traditional measures for assessing functioning with adult patients with schizophrenia have been shown to be insufficient for assessing the issues that occur in adolescents and young adults at clinical high risk (CHR) for psychosis. The current study provides an expanded validation of the Global Functioning: Social (GF:Social) and Role (GF:Role) scales developed specifically for use with CHR individuals and explores the reliability and accuracy of the ratings, the validity of the scores in comparison to other established clinical measures, stability of functioning over a 2-year period, and psychosis predictive ability. Seven hundred fifty-five CHR individuals and 277 healthy control (HC) participants completed the GF:Social and Role scales at baseline as part of the North American Prodrome Longitudinal Study (NAPLS2). Inter-rater reliability and accuracy were high for both scales. Correlations between the GF scores and other established clinical measures demonstrated acceptable convergent and discriminant validity. In addition, GF:Social and Role scores were unrelated to positive symptoms. CHR participants showed large impairments in social and role functioning over 2-years, relative to the HCs, even after adjusting for age, IQ, and attenuated positive symptoms. Finally, social decline prior to baseline was more pronounced in CHR converters, relative to non-converters. The GF scales can be administered in a large-scale multi-site study with excellent inter-rater reliability and accuracy. CHR individuals showed social and role functioning impairments over time that were not confounded by positive symptom severity levels. The results of this study demonstrate that social decline is a particularly effective predictor of conversion outcome.

The rising incidence and death rates linked to Alzheimer's disease (AD) highlight an urgent issue. Genetic screening is celebrated as a significant advancement for its early detection capabilities, pinpointing those at risk before the emergence of symptoms. Yet, the limited availability of these technologies highlights a critical gap in widespread application. This review pivots to the potential of presymptomatic clinical assessments as a readily available, economical, and simple strategy for early detection. Traditionally, AD diagnosis relies on the late‐stage identification of cognitive deterioration, functional impairments, and neuropsychiatric symptoms, coinciding with advanced brain degeneration. Conversely, emerging research identifies early indicators preceding significant degeneration, manifesting years before clinical symptoms. We introduce a mnemonic, MEMORIES, to categorize these prodromal: Metabolism changes, Eye/visual impairments, March (refer to gait disturbances), Olfactory dysfunction, Rhythm (blood pressure and heart rate), Insensitivity of the tongue, Ears (hearing loss), and Stool alterations. Recognizing these prodromal through clinical examinations provides a valuable strategy for initiating preventative actions against brain degeneration. This approach advocates for broadening the screening lens beyond genetic screening to encompass clinical evaluations, enhancing early detection and intervention opportunities for AD. The MEMORIES Mnemonic for Identifying Prodromal Symptoms of Alzheimer's disease. This acronym encapsulates key early indicators associated with the onset of Alzheimer's, including Metabolism change, Eye/visual impairments, gait disturbances (March), Olfactory dysfunction, alterations in physiological Rhythms (specifically blood pressure and heart rate variations), Insensitivity of the tongue to tastes, Ears (hearing loss), and Stool alteration. Highlights Prodromal AD: An alternative when genetic screening is unavailable. Prodromal stages precede brain degeneration in AD. MEMORIES: A tool for early prodromal AD assessment.

The duration of untreated psychosis (DUP) has been widely studied. However, for individuals with attenuated psychosis syndrome (APS), it is unclear whether the duration of untreated prodromal symptoms (DUPrS) also has a negative effect on the progression of psychosis. Our aim was to identify demographic and clinical factors contributing to the DUPrS in a large sample of individuals with APS, and to evaluate the association between DUPrS and the conversion to psychosis. A sample of 391 individuals with APS, who were identified through a structured interview for prodromal syndromes, were included in this study, of whom a total of 334 patients had completed at least a 1-year clinical follow-up. A total of 57 individuals had converted to psychosis. The average DUPrS was 4.8 months for the whole sample. Individuals with a longer DUPrS were likely to be men, non-local residents, with abnormal thought symptoms, a higher severity level of negative symptoms, the lower severity level of general symptoms, and lower level of general function before the onset of attenuated positive symptoms. A DUPrS of less than 2 months, or more than 6 months, lowered the risk for conversion to psychosis. Our data suggested that the association between the DUPrS and outcome in individuals with APS were likely to be different, which is either long or short DUPrS was not related to future psychosis onset. Individuals with APS were more likely to have a group of features associated with a longer DUPrS.

Background People with multiple sclerosis (MS) have an increased risk of migraine. However, little is known about migraine and other headaches during the prodromal phase (before MS symptom onset). Our objective was to study the risk of migraine in women with MS before MS onset. Methods A nationwide, prospective cohort study of women participating in the Norwegian Mother, Father, and Child cohort study 1999–2008. The women reported the occurrence of migraine and other headaches prior to or during pregnancy. We identified women who later developed MS through data linkage with national health registries in 2018. We excluded women with an established MS diagnosis ( n  = 125) and women who had experienced their first clinical symptom of MS, but not yet received an MS diagnosis ( n  = 91). The reference group comprised all other women in the cohort ( n  = 85,292). We used logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs). Results Two hundred and forty-six women developed MS during follow-up. Of these, 116 women had MS symptom onset after 1–5 years, 92 after 6–10 years, and 38 after 10 years. Migraine was more common among women who developed MS compared to the reference group, 18% vs 11%, aOR 1.6 (1.2–2.3), adjusted for age, smoking, socioeconomic status and overweight. The risk of other headaches was similar for women who developed MS compared to the reference group, 29% vs 27%, aOR 1.1 (0.8–1.4). Migraine was reported by 21 of 116 (18%) women with ≤ 5 years until MS symptom onset (aOR 1.7 [1.1–2.8]) and 19 of 92 (21%) women with 6–10 years until MS symptom onset (aOR 1.9 [1.1–2.8]. Only three of 38 (8%) women with > 10 years until MS symptom onset reported migraine, aOR 0.7 (0.2–2.2). Conclusions Women with MS have increased risk of migraine, but not other headaches, up to a decade before the onset of classical MS symptoms. This supports that migraine can be a symptom of the MS prodrome. Special attention in people with migraine may lead to earlier recognition of MS.

Background Little is known about the patterns of brain atrophy in prodromal dementia with Lewy bodies (pro-DLB). Methods In this study, we used SPM8 with diffeomorphic anatomical registration through exponentiated lie algebra to measure grey matter (GM) volume and investigate patterns of GM atrophy in pro-DLB ( n  = 28) and prodromal Alzheimer’s disease (pro-AD) ( n  = 27) and compared and contrasted them with those in elderly control subjects ( n  = 33) ( P  ≤ 0.05 corrected for family-wise error). Results Patients with pro-DLB showed diminished GM volumes of bilateral insulae and right anterior cingulate cortex compared with control subjects. Comparison of GM volume between patients with pro-AD and control subjects showed a more extensive pattern, with volume reductions in temporal (hippocampi and superior and middle gyri), parietal and frontal structures in the former. Direct comparison of prodromal groups suggested that more atrophy was evident in the parietal lobes of patients with pro-AD than patients with pro-DLB. In patients with pro-DLB, we found that visual hallucinations were associated with relative atrophy of the left cuneus. Conclusions Atrophy in pro-DLB involves the insulae and anterior cingulate cortex, regions rich in von Economo neurons, which we speculate may contribute to the early clinical phenotype of pro-DLB.

Our previous study has found that a long duration of untreated prodromal symptoms (DUPrS) does not increase the conversion risk to psychosis in individuals with attenuated psychosis syndrome (APS). However, whether a long DUPrS will lead to other poor outcomes remains unknown. The purpose of this study was to analyse the association between the DUPrS and outcomes (symptomatic and functional recovery) in APS population. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. A post hoc analysis was performed in 391 individuals with APS as identified by the structured interview. APS subjects had follow-up interviews every 6 months for 2 years following diagnosis. Poor functional outcome was defined as a Global Assessment of Functioning (GAF) score less than 60 at the time of follow-up. Poor symptomatic outcome was defined as at least one of the positive symptoms rated scores of 3 or higher. Of total 391 individuals, 334 were followed up for 2 years to assess clinical outcome, 82 (24.6%) had shown conversion to psychosis, 79 (23.7%) met the criteria of poor functioning outcome, and 145 (43.4%) met the criteria of poor symptomatic outcome. A significant correlation between GAF scores and DUPrS was observed in the non-converter group, but not in the converters. Individuals with APS who had a longer DUPrS were correlated with poorer functional outcome. However, it was not correlated with poorer symptomatic outcome. While a longer DUPrS was not related to poor symptomatic outcome, it was significantly related to poor functional outcome. Our findings highlight the importance of reducing DUPrS to decrease future functional impairment in populations at risk for psychosis.

Alzheimer's disease (AD) is associated with a range of non-cognitive symptoms that can be early or even presenting features. Better recognition of pre-diagnostic symptoms of AD would support improved early detection and diagnosis. To identify possible prodromal symptoms of AD, we systematically searched three electronic databases for prospective longitudinal studies to March 2023, that reported the risk of AD diagnosis associated with non-cognitive symptoms. Meta-analyses were performed to assess the associations between a commonly reported symptom and AD. We estimated pooled odds ratios (OR) using random-effects model. Thirty studies were included with the majority focused on neuropsychiatric symptoms. Quantitative analysis of fourteen studies showed depression to be associated with subsequent AD diagnosis (pooled OR = 1.80; 95% CI: 1.29 to 2.50; I = 95.8%) and individual reports of the association showed it to be stronger later in life and closer to AD diagnosis. In contrast with the literature, the evidence on the association between anxiety, sleep difficulties, personality changes and psychotic symptoms, and incident AD was inconsistent. We found evidence that autonomic symptoms including urinary dysfunction, constipation, fatigue, syncope and collapse might be pre-diagnostic symptoms of AD recorded up to 10 years before receiving an AD diagnosis, and there was strong evidence of an association between hypotension and incident AD (pooled OR = 1.94; 95% CI: 1.88 to 2.01; I = 0.0%). We were also able find evidence for the association between weight loss and subsequent AD diagnosis within 10 years (pooled OR = 1.46; 95% CI: 1.22 to 1.74; I = 57.5%). Furthermore, the quantitative synthesis of the evidence on hearing loss (pooled OR = 1.47; 95% CI: 1.14 to 1.89; I = 87.6%) and spondylosis (pooled OR = 1.55; 95% CI: 1.34 to 1.80; I = 68.2%) showed both to be associated with AD diagnosis up to 10 years after identification of these sensory symptoms. Our findings suggest that improved recognition of early non-cognitive presentations is key in facilitating access to timely diagnosis of AD, especially as the emergence of disease-modifying therapies for AD increases the importance of early detection.

Background Recent consensus research criteria have identified a ‘psychiatric onset’ form of prodromal dementia with Lewy bodies (DLB) characterised by prominent late-onset psychiatric symptoms. Although recognised as important to raise the index of diagnostic suspicion, evidence regarding this cohort was deemed too limited to impose formal criteria. We reviewed the published literature on psychiatric-onset DLB to identify key clinical characteristics and evidence gaps to progress our understanding of this entity. Methods Medline, PubMed and Embase were searched for relevant articles containing longitudinal follow-up of patients initially presenting with a psychiatric illness who subsequently developed DLB according to the diagnostic criteria available at the time. Results Two cohort studies (18 and 21 patients) along with 12 case series (13 cases) were identified totalling 52 patients (63% female). Initial psychiatric presentation occurred at a mean of 63 years (range 53–88), with depression being the most frequently reported psychiatric presentation (88%). Psychotic presentations were less common on presentation (11%) but became more prevalent throughout the prodromal period before the diagnosis of DLB (83%). Relapses of the psychiatric disease were common occurring in 94% (32/34) of patients. Parkinsonism, cognitive fluctuations, visual hallucinations, and REM sleep behaviour disorder were uncommonly reported at initial presentation (3.8%). Conclusions Psychiatric-onset DLB is characterized by a female predominant relapsing–remitting psychiatric illness presenting with affective symptoms but later developing psychotic features prior to the onset of DLB. Additional prospective studies including other neurodegenerative cohorts with harmonised assessments are required to inform definitive diagnostic criteria for this condition.