Several modifiable factors affect Alzheimer’s disease (AD) risk. However, evidence on how these factors interact remains scarce, limiting our understanding of their role in AD development. This study aims to assess interactions between chronic stress exposure and insomnia in relation to AD biomarkers beta-amyloid (Aβ42), total tau, and phosphorylated tau. The present study included 124 memory clinic patients without dementia from the Cortisol and Stress in Alzheimer’s disease (Co-STAR) cohort study. Insomnia symptoms, stressful life events (SLEs) and current perceived stress were self-reported via questionnaires, while AD biomarkers were assessed from the cerebrospinal fluid (CSF). Cross-sectional interactions between stress and insomnia in relation to AD biomarkers were examined using linear regression models. Insomnia and SLEs interacted in relation to Aβ42. Greater stressor exposure was associated with reduced CSF Aβ42 levels, reflecting greater brain amyloid accumulation, only in those with moderate-to-high insomnia scores. No interactions were found for total or phosphorylated tau. This study suggests that chronic stress and sleep disturbances exhibit an interactive relationship in their associations with AD pathology, and highlights the need for further research into interactive effects of multiple modifiable risk factors in the development of AD.
Myotonia is delayed muscle relaxation after forceful contraction. It is due to hyperexcitability of the skeletal muscle membrane. It can arise from primary skeletal muscle ion channel dysfunction, involving chloride or sodium channels, but is also a prominent clinical feature in myotonic dystrophies where altered RNA splicing leads to secondary ion channel dysregulation amongst other systemic manifestations. Clinically, myotonia can range from delayed eye opening to a disabling symptom causing impaired mobility, functional difficulty and sometimes pain. It can also be a “hidden disability” with many patients feeling socially embarrassed by “looking healthy”, yet being unable to do everyday physical tasks or to do them as effortlessly as their peers. It is a symptom that almost always indicates a genetic diagnosis, although it can occur in acquired conditions, including metabolic and drug-induced causes. To experience myotonia without knowing what it is can be baffling. To receive a genetic diagnosis associated with it can be life changing. Although there is no cure, there are many effective and available symptomatic treatments for myotonia and currently we are in an exciting era of clinical trials for new molecular disease-modifying therapies for myotonic dystrophy type 1. In this review, we consider recent developments in the treatment of myotonic disorders and how they may change clinical practice.
Optic neuritis (ON) diagnosis is challenging due to variable clinical presentations and the limited prospective validation of current criteria. This study evaluates the 2022 international consensus criteria for optic neuritis (ICON) criteria, and the impact of adding visual evoked potentials (VEPs) and new clinical definitions to improve diagnostic accuracy. We introduced modifications to the ICON 2022 criteria, including a less strict clinical category allowing ON diagnosis with incomplete clinical features and the incorporation of VEPs as an additional paraclinical test. We then prospectively studied 46 patients with a first episode of unilateral subacute ON. Alongside standard clinical, MRI, OCT, and laboratory assessments, diagnostic classifications were compared between the original and modified criteria. Using the original ICON 2022 criteria, 20 patients (43.5
Cerebral amyloid angiopathy (CAA) has long been regarded as a hemorrhagic age-related small vessel disease (SVD). However, cerebral ischemia, indicated by symptomatic and incidental diffusion-weighted imaging (sDWI and iDWI) hyperintensities, remains controversial regarding its clinical relevance and pathological mechanisms. This study aimed to investigate the prevalence, distributing characteristics, and risk factors of sDWI and iDWI lesions in patients with CAA. Participants meeting the criteria for probable CAA (Boston criteria version 1.5) were recruited from a prospective cohort of cerebral small vessel disease at Peking Union Medical College Hospital between March 2017 and February 2026. Baseline clinical data and neuroimaging markers of SVD were collected. sDWI lesions and iDWI lesions were recorded at any MRI time point, with topography showing via lesion probability maps. Cumulative incidence was estimated using Kaplan–Meier method. The characteristics were compared between patients with sDWI lesions or iDWI lesions and those without any DWI lesion at baseline. The prospective Cox regression analyses were performed to identify risk factors for sDWI lesions and iDWI lesions, respectively. We enrolled 185 patients with probable CAA, of whom 99 underwent follow-up MRI with a total of 163 scans. sDWI lesions were detected in 29 patients and iDWI lesions in 49 patients. sDWI lesions predominantly involved deep regions (72.7
Immune-mediated necrotizing myopathy (IMNM) is a distinct entity with limited large-cohort data. We aimed to characterize clinico-serological features and treatment outcomes of anti-SRP, anti-HMGCR, and seronegative IMNM in a large Italian cohort. Retrospective multicenter study of adults diagnosed with IMNM (224th ENMC criteria) across 14 Italian neuromuscular centers between 2019 and 2022 was performed. We included 159 subjects (57
Alzheimer’s disease (AD) is increasingly conceptualised as a biological and clinical continuum that includes Subjective cognitive decline (SCD), mild cognitive impairment (MCI), and overt dementia. We conducted a systematic review and meta-analysis to assess the prevalence of APOE ε4 allele in individuals with SCD. Main databases were searched to identify studies published up to 15 April 2026, plus citation checking. Eligible studies included participants with SCD defined according to standardized criteria, with available APOE genotype data. Application of SCD-plus criteria was also recorded. Of 474 screened records, 49 studies were included in the quantitative synthesis. The pooled prevalence of APOE ε4 allele carriers was 28.3
Tiletamine–zolazepam (Zoletil) is a veterinary anesthetic, which is increasingly being abused by humans. However, the chronic neurotoxicity of this compound in humans and its long-term clinical outcomes have rarely been reported. To characterize the neurological and systemic injury following recreational Zoletil 50 inhalation, including relapse behavior and persistent deficits. We performed a retrospective case series of patients presenting to our institution with Zoletil 50 toxicity. We analyzed the clinical features, laboratory results, and neuroimaging findings, and assessed long-term outcomes and relapse rates during a two-year observation period. All 36 subjects (100
Multiple sclerosis (MS) is associated with cognitive impairments affecting attention, processing speed, executive functions, and episodic memory. Social cognition (SC), encompassing emotional processing and theory of mind (ToM), is also impaired in MS. However, its relationship with common cognitive functioning is not well defined. The objective of this study was to investigate the relationships between social and non-social cognitive impairments, focusing on episodic memory, executive functions, and information processing speed in people with MS. We assessed 58 relapsing–remitting MS patients and 30 healthy controls using neuropsychological and SC tests to explore these associations. MS patients showed significant deficits in emotional recognition and ToM, which correlated strongly with episodic memory performance but showed weak correlations with executive functions and not with processing speed. Multivariate analyses indicated that episodic memory accounted for a significant portion of the variance in emotional processing and ToM abilities. These results suggest that episodic memory deficits represent an important cognitive correlate of SC in MS, underscoring the need to consider memory function in understanding and addressing SC difficulties in this population. Clinical Trails gov ID NCT02708927) This study received approval from the ethics committee (Comité de Protection des Personnes [CPP] Sud-Ouest et Outre-Mer III) (ID-RCB: 2015-A01282-47).
Oral anticoagulants (OACs), including vitamin K antagonists and direct OACs, reduce stroke risk in atrial fibrillation (AF), yet breakthrough ischemic stroke still occurs in 1–2
Digital screen exposure has risen sharply across paediatric, adolescent, and adult populations, and many individuals with migraine report that screen use triggers or worsens attacks. To systematically review and meta-analyse the association between digital screen exposure and migraine/headache burden, including frequency, severity, disability, and related secondary outcomes, and to summarise the proposed neurobiological mechanisms. This review was prospectively registered on PROSPERO (CRD420261404162) and conducted in accordance with PRISMA 2020 guidance. Embase, MEDLINE, PubMed, Scopus, and Google Scholar were searched without date restrictions for English-language observational and interventional studies of adolescents or adults with migraine or primary headache and a quantifiable measure of digital screen exposure. Two reviewers independently screened records, extracted data, and assessed risk of bias using a modified Joanna Briggs Institute (JBI)/AHRQ checklist for cross-sectional and observational studies. When ten or more studies reported an odds ratio (OR) with a 95
Dizziness and vertigo are common and debilitating neurological symptoms among patients visiting the emergency department (ED). Possibly because the symptoms are not captured by standard stroke severity tools such as the NIHSS (National Institutes of Health Stroke Scale), their network-level neuroanatomical correlates—particularly potential supratentorial contributions—remain incompletely characterized. Therefore, we aim to investigate the neuroanatomical substrates of post-stroke dizziness and vertigo. This retrospective analysis included patients with acute ischemic stroke from the randomized controlled INSPiRE-TMS trial. Each patient underwent MRI within seven days of symptom onset, and stroke severity was assessed using the NIHSS at hospital admission. Patients were assessed for broadly defined new-onset dizziness/vertigo associated with the acute cerebrovascular event. Lesion symptom mapping (LSM) and lesion network mapping (LNM) were used to investigate associations between lesion location, functional connectivity, and dizziness/vertigo. Among 484 patients, 32 https://clinicaltrials.gov/ct2/show/NCT01586702 ); first registry in April 2012; first patient recruitment: September 2011.
Essential tremor has been associated with cognitive impairment. Mild action tremor labelled physiological tremor is present in all humans. Tremor increases with age. It is unknown if mild action tremor is associated with cognitive performance in older people. To test the hypothesis that mild—mostly non-pathological—action tremor is associated with reduced cognitive performance in community-dwelling older adults. The Cooperative Health Research in the Region of Augsburg (KORA)-Age study assessed health-related parameters including cognition in individuals between 65 and 93 years of age. We measured tremor using semi-quantitative ratings of Archimedes-spiral drawings. Participants taking Parkinson medication, with a self-reported neurologic disease or with a spiral rating > 5 indicating certainly pathologic tremor were excluded. The modified Telephone Interview for Cognitive Status (TICS-m) was used to measure cognition. We analyzed the association between tremor and cognition using multivariable adjusted regression models in the whole population and after exclusion of participants with a spiral rating > 3. We employed stepwise backward variable selection to build a final regression model. Tremor severity was associated with cognitive performance. Age, sex, Parkinson score, frailty, tremor score, physical activity, sleep-duration and previous stroke entered the final statistical model. Judged by the differences of adjusted r-squared between models, age was the most important predictor of cognition followed by sex, Parkinson score, frailty, and tremor severity. Sensitivity analyses excluding participants with likely pathological tremors did not attenuate the association between tremor severity and cognitive performance. Even mild action tremor severity is associated with reduced cognitive performance in older people. We hypothesize that aging-related brain changes are a common cause of cognitive impairment and tremor.
Tardive syndromes may present with variable movement disorders. Blepharospasm (BSP), while typically idiopathic in origin, may be drug-induced, but there is little information regarding frequency and phenomenology of tardive BSP. We aimed to assess the clinical features of tardive BSP and compare them with patients with idiopathic BSP. The Abnormal Involuntary Movement Scale (AIMS) was used to assess the severity of movements and the Jankovic Rating Scale (JRS) was used to evaluate the severity of BSP. Among 72 consecutive patients with tardive syndromes, 15 (20.8
Gastrointestinal (GI) dysfunction has been reported in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, GI dysfunction in GFAP-A has not been sufficiently investigated. This study aimed to analyze the clinical features of GFAP-A patients with GI dysfunction and explore potential pathogenic mechanisms. From January 1, 2016, to April 30, 2024, patients diagnosed with GFAP-A based on CSF GFAP-IgG positivity at the Third Affiliated Hospital of Sun Yat-sen University were enrolled. Clinical parameters and GI dysfunction assessed by the I-FEED scoring system were collected. Pathological examination was performed in a subset of patients. And the preliminary role of GFAP-IgG in the enteric plexus was investigated. Among 92 enrolled individuals (male:female = 68:24; median age 39.5 years), gastrointestinal dysfunction occurred in 72 cases (78.3
The right-temporal variant of frontotemporal dementia (FTD) is well characterised. Whether it should be considered a distinct clinical entity, separate from other syndromes of FTD, remains an open question. The study addressed the issue through a retrospective comparison of clinical characteristics of patients with predominant atrophy in right or left anterior temporal lobe (R-ATL vs. L-ATL). Patients were identified from a clinical database, diagnosed with FTD, and reported to show temporal lobe atrophy on imaging. Fifty-one patients were selected in whom independent ratings of atrophy were greatest in right or left anterior temporal lobe. Presenting symptoms, cognitive and behavioural characteristics, neuropsychological findings, and diagnostic classification were recorded. Difficulty recognising people, impaired decision-making, perseverative preoccupations, disinhibition, and loss of empathy characterised the R-ATL group, in keeping with the previous reports. There was, however, overlap in cognitive and behavioural symptomatology in R-ATL and L-ATL, and sensitivity and specificity values were modest. Group differences diminished with disease progression. The most common clinical classification at first assessment in both groups was semantic dementia (SD), with other patients being classified as behavioural-variant FTD (bvFTD), FTD with amyotrophic lateral sclerosis or mixed FTD/SD. Not all patients with L-ATL met criteria for semantic variant primary progressive aphasia (svPPA). The data question the notion that R-ATL and L-ATL presentations are separate entities. We argue that a common diagnostic framework for the two is warranted, with classification being based on cognitive/behavioural characteristics rather than neuroradiological grounds.
Optical coherence tomography (OCT) quantifies retinal neuroaxonal loss related to neurodegeneration in people with multiple sclerosis (pwMS) and is associated with physical and cognitive disability. However, no data exist on the relationship between OCT metrics and cognitive progression independent of relapse activity (cognitive PIRA). To assess if OCT can prognosticate cognitive PIRA events in pwMS. Prospective study with baseline OCT (peripapillary retinal nerve fiber- (pRNFL), macular ganglion cell-inner plexiform- (mGCIPL) and inner nuclear layers (mINL)) and brief international cognitive assessment for MS (BICAMS) at yearly visits. Cognitive PIRA in each test was defined as more than 10
