The neuropsychiatric features of Long COVID in older adults and the potential association with neuroinflammation: Preliminary observations in a small cohort.

Data on the manifestation and progression of neurological and psychiatric symptoms in adult patients with late-onset Tay-Sachs (LOTS) disease after the age of 2years are scarce and not available for Germany. In this cross-sectional study data from the "8 in 1" register study for gangliosidoses of 16 adult patients with LOTS were retrospectively evaluated with respect to the manifestation and the occurrence of neurological and psychiatric symptoms. The LOTS can be manifested in preschool age with aneurodevelopmental disorder, in school age and adolescence with cerebellar symptoms or in adolescence and adulthood with leg dominant muscle weakness and muscle atrophy in the sense of a motor neuron disease (MND). The initial symptoms of LOTS begin insidiously, are variable and often go unrecognized. Severe psychiatric disorders regularly occur in the course of the disease, particularly in those patients who have neurological developmental disorders and manifestation of cerebellar symptoms. The prevalence of psychiatric disorders is 62.5%. In 10 of the 16adult patients, psychoses occurred that were diagnosed as severe depression, bipolar affective disorder, as polymorphic psychotic disorder or as schizoaffective disorder. The patients were treated in particular with atypical antipsychotic drugs, benzodiazepines and mood stabilizers. Neuropsychiatric symptoms in LOTS were explained with the concept of a cerebellar cognitive affective syndrome (CCAS) as an organic brain disease of the cerebellum; however, symptoms such as massive psychomotor agitation, anxiety, rapid mood swings, confusion, formal and content-related thought disorder as well as hallucinations cannot be completely explained by CCAS and are consistent with concepts that describe a role of cerebellar network dysfunctions in psychoses. Our data can help to include LOTS as adifferential diagnosis in patients with psychiatric and neurological symptoms.

BackgroundThe decision between home-based (HC) and institutional care (IC) for Alzheimer's disease (AD) is critical for patients, families, and healthcare systems, yet evidence on long-term trade-offs remains insufficient.ObjectiveThis study comprehensively compare the 5-year clinical, economic, and family-related outcomes between HC and IC for AD patients.MethodsWe conducted a prospective-retrospective cohort study involving 252 AD patients (HC = 124; IC = 128) and their families. Outcomes included cognitive and functional status (using Mini-Mental State Examination and Barthel index), neuropsychiatric symptoms (Neuropsychiatric Inventory), medication adherence (Medication Possession Ratio and Morisky Medication Adherence Scale), healthcare costs, and family impact (Depression, Anxiety and Stress Scales and General Health Questionnaire).ResultsAnalysis revealed a critical dichotomy: HC showed better early cognitive preservation but later accelerated decline, contrasting with IC's stable trajectory. IC demonstrated superior control of harmful behaviors and prevention of consequential events, while HC was associated with more significant medical complications. Medication adherence was sustainably higher in IC but progressively deteriorated in HC. Economically, HC's lower initial direct costs were offset by substantial indirect costs, while IC incurred higher but predictable direct expenditures. Crucially, the psychological and health impact on family progressed substantially in HC but remained low and stable in IC.ConclusionsNo single care model was universally superior. The HC versus IC decision involves strategic trade-offs across clinical, economic, and family domains. These findings advocate for personalized, dynamic care models that facilitate timely transitions, guided by patient needs and family capacity, to optimize long-term outcomes for both patients and their families.

Mania and psychosis following chimeric antigen receptor T-cell therapy: A report of two cases and mechanistic discussion.

Global aging and health care workforce shortages are increasing demand for therapeutic support among older adult and pediatric populations. Care robots, an umbrella term for socially assistive robots, companion and pet platforms, and therapeutic humanoids sharing a social interaction component, have been proposed as embodied digital health adjuncts, but prior syntheses have remained population- or platform-specific, leaving cross-population and cross-platform effects unquantified. This review quantifies the pooled effects of care-robot interventions across 7 prespecified outcome domains, examines robot platform, target population, and intervention-duration moderators, and grades evidence certainty. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020, we searched 5 databases (PubMed, including MEDLINE, Embase, Cochrane CENTRAL, CINAHL, APA PsycINFO) and 2 trial registries (ClinicalTrials.gov; World Health Organization International Clinical Trials Registry Platform) through April 29, 2026, with no language restriction. Eligible studies were randomized controlled trials of embodied care robots versus standard care, active controls, or waitlist. Random-effects meta-analysis used Hedges g with Hartung-Knapp-Sidik-Jonkman correction; for domains with k≥4, we report 95% CIs and prediction intervals (PIs). Risk of bias used the Cochrane Risk of Bias 2 tool; certainty used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. A total of 34 randomized controlled studies (n=2476; 17 countries; 2015-2024) met inclusion criteria; 20 contributed to at least 1 meta-analysis, and 14 entered narrative synthesis. Under Hartung-Knapp-Sidik-Jonkman pooling, only neuropsychiatric symptoms reached significance: Hedges g=0.44 (95% CI 0.03-0.84; 95% PI -0.42 to 1.30; k=6; P=.04). The remaining 6 domains were favorable but nonsignificant: quality of life Hedges g=0.15 (95% CI -0.41 to 0.71; 95% PI -0.86 to 1.16; k=5); depression Hedges g=0.20 (95% CI -0.08 to 0.49; 95% PI -0.36 to 0.76; k=7); agitation Hedges g=0.32 (95% CI -0.07 to 0.71; 95% PI -0.26 to 0.89; k=4); stress and pain Hedges g=0.53 (95% CI -0.48 to 1.53; 95% PI -1.57 to 2.62; k=6); social-communicative skills Hedges g=0.45 (95% CI -0.52 to 1.42; 95% PI -1.66 to 2.56; k=5); and cognitive function Hedges g=0.18 (95% CI -0.62 to 0.98; 95% PI -1.11 to 1.47; k=4). All 7 PIs encompassed the null, indicating no assured effect in new settings. The neuropsychiatric symptom result was fragile: significance was lost in 5 of 6 leave-one-out iterations and on excluding Petersen 2016 (data extraction ambiguity), yielding a Hedges g of 0.40 (P=.10). GRADE certainty was low for neuropsychiatric symptoms and very low for the remaining 6 domains. Across cross-population, cross-platform randomized controlled trial pooling, the evidence does not yet support routine clinical adoption of care robots. Potential benefits are narrow, of low certainty, and contingent on adequately powered multicenter confirmatory trials with PI-informed sample sizes. Care robots are best framed as facilitator-supported adjuncts that augment, rather than substitute for, human-delivered care.

Evidence for hippocampal globotriaosylceramide (Gb3) accumulation and spatial memory impairment in a mouse model of Fabry disease.

BackgroundThe associations between agitation, cerebrospinal fluid (CSF) biomarkers, and cognitive decline, and whether these relationships vary by APOE genotype, remain unclear in Alzheimer's disease (AD) and mild cognitive impairment (MCI).ObjectiveTo investigate the association between CSF biomarkers and agitation in cognitively impaired individuals, with a focus on the potential moderating role of APOE ε4 status.MethodsWe analyzed 491 cognitively impaired individuals (359 MCI and 132 AD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with available CSF biomarker data. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI), focusing on agitation.ResultsAmong APOE ε4 carriers, agitation was significantly associated with higher CSF GAP-43 (OR = 1.584, 95% CI: 1.159-2.195, p = 0.005) and p-tau levels (OR = 1.49, 95% CI: 1.073-2.101, p = 0.02). These associations were not observed in non-carriers. In addition, APOE ε4 carriers with agitation showed a higher risk of progression to dementia compared with other groups (HR = 4.422, 95% CI: 2.542-7.692, p < 0.001).ConclusionsCSF GAP-43 and p-tau levels are associated with agitation in APOE ε4 carriers. Agitation in this subgroup is also associated with an increased risk of progression to dementia, suggesting that it may reflect underlying disease-related processes.

Bilateral symmetrical calcification of striatum and pallidum with or without involvement of other brain structures is a rare radiological finding. Genetic causes predominates once hypoparathyroidism is ruled out. Clinical features include a variable combination of neuropsychiatric and motor symptoms, including dystonia, Parkinsonism, ataxia, psychosis, dementia, chorea, and frontal-subcortical cognitive dysfunction. One third of primary familial brain calcification is asymptomatic. Solute carrier 20 A2 gene mutation accounts for the majority of primary familial brain calcification. Here we describe a case of primary brain calcification due to a novel mutation in Solute carrier 20A gene in a 55-year-old woman.

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by the abrupt onset of neuropsychiatric symptoms, including obsessive-compulsive disorder and/or restricted food intake, in response to infection or other triggers. This mixed methods systematic review synthesized evidence on the lived experience and psychosocial impacts of caring for a child with PANS. Seventeen publications of moderate to high quality met eligibility criteria. Four synthesized findings emerged from the qualitative meta-aggregation: (i) broad psychosocial impacts on caregivers and families; (ii) shock and ongoing uncertainty arising from the sudden, severe onset and unpredictable symptom flares; (iii) pervasive systemic barriers to timely diagnosis, treatment, and educational support; and (iv) caregivers' proactive responses to the challenges of navigating PANS. Narrative synthesis of quantitative findings highlighted increased caregiver burden, and elevated psychological distress and relationship dissatisfaction. Disease activity, diagnostic and treatment delays, and disruption to schooling and employment were associated with greater impact. Implications for improving clinical recognition and supporting caregiver and family wellbeing are discussed.

Psychosocial interventions are widely used in dementia care, yet standardized outcome measurement remains highly variable, and recent frameworks emphasize outcomes prioritized by people living with dementia and their care partners. This narrative, measurement-focused review does not appraise or synthesize treatment effects. Instead, it aims to map outcome measures to the International Consortium for Health Outcomes Measurement (ICHOM) dementia set plus an additional carer-wellbeing domain, to organize them into a taxonomy of wellbeing domains that highlights patterns and gaps in measurement practice. Eligible studies included participants with Alzheimer's disease and related dementias, evaluated a psychosocial intervention, and reported standardized pre- and post-intervention outcome measures at short and/or long-term follow-up. A total of 136 studies met inclusion criteria. Interventions encompassed arts and creative therapies, cognitive and reminiscence approaches, education and psychosocial support, physical and movement-based therapies, sensory and relaxation therapies, environmental and daily living support, and animal/robot-assisted programs. Outcome measures clustered on neuropsychiatric symptoms (205 instances) and cognitive functioning (146 instances), with fewer measures of social functioning (22 instances) and health-related quality of life (13 instances). Measurement approaches were highly variable (43 distinct neuropsychiatric measures, 47 cognitive measures, 14 social functioning measures). Outcomes were predominantly assessed using short-term measures, with some long-term follow-up, and few observational in-the-moment measures capturing engagement, enjoyment, reciprocity or mastery. This review presents a taxonomy of outcome measures that highlights the mismatch between current evaluation practices and person-centered psychosocial priorities in dementia care, and guides more purposeful measure selection.

Background and AimsAnti‐NMDAR encephalitis is a severe autoimmune encephalitis that is frequently associated with ovarian teratomas, whereas infectious triggers remain incompletely understood. We report a case of ovarian teratoma–associated anti‐NMDAR encephalitis in a young woman with concurrent Group A Streptococcus infection presenting with prominent psychiatric symptoms and subsequent neurologic decline.MethodsWe describe the clinical course, diagnostic evaluation, and multidisciplinary management of a 25‐year‐old African American woman with acute‐onset neuropsychiatric symptoms, confirmed anti‐NMDAR encephalitis, bilateral ovarian teratomas, and concurrent Group A Streptococcus infection. Verbal informed consent was obtained from the patient for publication of this case report and any accompanying images.ResultsThe patient initially presented with acute psychiatric symptoms and was treated for suspected schizoaffective disorder. Further evaluation following clinical deterioration revealed anti‐NMDAR antibodies in the cerebrospinal fluid and bilateral ovarian teratomas on imaging. She was treated with IVIG, high‐dose corticosteroids, bilateral ovarian cystectomy, and plasma exchange, with subsequent clinical improvement and discharge after prolonged hospitalization.ConclusionThis case underscores the importance of considering anti‐NMDAR encephalitis in young women presenting with acute psychiatric symptoms and neurologic decline. It also highlights the importance of pelvic imaging for ovarian teratoma and careful infectious evaluation, including for streptococcal infection when clinically indicated. The observed association between Group A Streptococcus infection preceding symptom onset suggests a possible infectious trigger leading to an immunologic response and subsequent anti‐NMDAR encephalitis; however, there is limited evidence of a causal relationship in the literature.

BackgroundDeep brain stimulation (DBS) for Parkinson's disease (PD) primarily improves motor symptoms but leaves non-motor symptoms (NMS) largely unattended. Neurophysiological markers associated with specific symptoms could improve DBS programming. We systematically reviewed the evidence linking basal ganglia local field potentials (LFP) to NMS in PD.MethodsThe literature search (Medline, Embase, Scopus, and Web of Science) on August 20, 2024 yielded 1066 records. Studies were included if they focused on patients with idiopathic PD treated with DBS of the subthalamic nucleus (STN) or globus pallidus interna (GPi) and reported on the relationship between LFP data and NMS. The study risk of bias was evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST). A narrative synthesis of results was provided.ResultsTwenty-one studies were included, focusing on impulse control disorders (n = 8), sleep-wake disorders (n = 5), depressive symptoms (n = 4), cognitive dysfunction (n = 3), hypomania (n = 1) and lower urinary tract symptoms (n = 1). Seven studies had a high risk of bias. Theta and alpha power in the STN were frequently associated with neuropsychiatric symptoms and cognitive function. Beta power in the STN and GPi was linked to sleep-wake disorders and urinary dysfunction.ConclusionsOverall, evidence on basal ganglia physiomarkers of NMS in PD remains limited. Further research is essential to develop patient-specific stimulation paradigms targeting NMS, which could significantly improve the quality of life of individuals with PD.OtherThis systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42024495284). There was no specific funding for this study.

BackgroundResearch on the cognitive profile in progressive supranuclear palsy (PSP) has been scarce in Latin America.ObjectiveTo outline the demographic, clinical, and cognitive profile of Peruvian PSP patients living in Lima, Peru. We sought to determine the relationship between first clinical symptoms and specific cognitive abilities.MethodsA cross-sectional study of 34 PSP subjects. We used the Uniform Data Set Version 3 Neuropsychological Battery (UDS3-NB), which possesses normative data for the Peruvian population, to assess global and specific cognitive functions. We also performed correlation analyses to determine the relationship between presenting clinical symptoms (parkinsonism, postural instability, and cognitive impairment) and cognitive functioning.ResultsThe mean age was 68 years, and mean schooling was 12.1 years in this cohort. The most common initial clinical symptom was parkinsonism (55.9%), followed by postural instability (23.5%) and dementia (20.6%). Our cohort showed poor performance on global cognition, with selective impairment of processing speed, executive function, and episodic memory. Attentional and visuospatial skills were mildly affected, with partial preservation of naming. There was no significant relationship between the initial clinical symptoms and global cognition, except for a slight correlation between parkinsonism and visuospatial function (r = 0.18;p < 0.05).ConclusionWe found that PSP patients in Peru had extensive impairment in executive function, processing speed, and episodic memory, with relatively preserved naming, consistent with other international cohorts. We did not find a correlation between initial clinical signs and cognitive profile, suggesting that an interdisciplinary approach is needed to evaluate patients with suspicion for PSP. Longitudinal studies are needed to more clearly define the progression of neuropsychiatric symptoms in PSP patients.

The earliest stages of Alzheimer's disease (AD) are frequently characterized by neuropsychiatric symptoms (NPS) such as anxiety, agitation, depression, compulsivity, appetite dysregulation, and sleep disturbances, often preceding measurable cognitive decline. Evidence from clinical and animal studies implicates hyperactivity of the locus coeruleus-norepinephrine (LC-NE) system as a mechanistic driver of these behaviors. Here, we review noradrenergic circuits that can potentially underlie psychiatric disturbances to identify therapeutic targets for preventing and delaying onset of AD. Given that this system influences attention, arousal, mood, and stress responses, LC-NE hyperactivity across circuitry involving amygdala, thalamus, hypothalamus, anterior cingulate cortex, prefrontal cortex, and olfactory areas can contribute to NPS features in early AD. Advances in neuroimaging and physiological measures of noradrenergic function have enabled in vivo tracking of LC integrity and NE transmission, offering the opportunity to detect LC-NE dysfunction early in disease progression and potentially implement targeted pharmacologic and neuromodulatory interventions to restore optimal LC-NE tone. Overall, dissection of LC-NE circuitry and its clinical translation hold promise for developing biomarker-driven, stage-specific interventions to reduce NPS burden and enhance the efficacy of disease-modifying therapies in AD.

Parkinsonian syndromes in institutionalized older adults in the French Caribbean: Clinical characteristics and one-year mortality.

Dementia with Lewy bodies (DLB)is a multisystem neurodegenerative disorder often accompanied by autonomic and neuropsychiatric symptoms. Nutritional impairment is increasingly recognized yet under-characterized in DLB. DLB was chosen due to its early multisystem involvement, including brainstem-mediated autonomic and sleep disturbances, which may uniquely affect nutrition. This study evaluated nutritional status and its associations with cognitive, mood, autonomic, and sleep-related features. Seventy patients with probable DLB (2017 McKeith criteria) were retrospectively included. Cases of Parkinson's disease dementia or other Lewy body-related conditions were excluded. Nutritional status was assessed with the Mini Nutritional Assessment-Short Form (MNA-SF). Cognitive function (Addenbrooke's Cognitive Examination, ACE-III), depressive symptoms (Geriatric Depression Scale, GDS), motor severity (Hoehn and Yahr staging), sleep disturbances (Rapid Eye Movement Sleep Behavior Disorder, RBD, insomnia), and autonomic symptoms (urinary incontinence, constipation, orthostatic hypotension) were extracted from clinical records. Multivariable logistic, ordinal regression, and hierarchical cluster analyses were performed. Normal nutrition was observed in 14.3% of patients, 60.0% were at risk, and 25.7% were malnourished. Malnutrition was significantly associated with lower ACE-III and higher GDS scores (p < 0.05). RBD and urinary incontinence differed across nutritional groups. Ordinal regression showed age and female sex independently associated with worse nutritional status. Cluster analysis identified a high-risk phenotype with greater cognitive, depressive, autonomic, and sleep-related burden linked to malnutrition. Malnutrition is highly prevalent in DLB and correlates with cognitive, psychiatric, autonomic, and sleep-related features. These associations support that nutritional impairment reflects the multisystem disease burden. Early identification of patients with combined deficits may help target those at risk and guide comprehensive management.

The intersection of immunity and mental health: Immunotherapy's role in modulating depression and neuropsychiatric disorders.

Alzheimer's disease (AD) accounts for a significant proportion of health and social care costs. We studied family caregiver (FC), care recipient (CR), and formal care provider-related factors, which are associated with the cost of care in different stages of AD in Finland. A 5-year follow-up was conducted with 231 individuals with AD (CRs) and their FCs as a part of the ALSOVA project. The data was collected between 2002 and 06. Significant factors associated with costs were identified using a stepwise backward elimination procedure. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory (NPI). Across all stages of AD, each additional year of CR's education was associated with a 3.4% reduction in costs (rate ratio [RR] 0.966, 95% CI 0.940-0.993). Conversely, a one-point increase on the Neuropsychiatric Inventory was associated with a 1.8% increase in costs (RR 1.018, 95% CI 1.011-1.025). CR's neuropsychiatric symptoms (RR 1.028, 95% CI 1.010-1.047) and male FC (RR 1.756, 95% CI 1.266-2.437) were associated with increased total costs in early AD, CR's comorbidities (RR 1.138, 95% CI 1.068-1.212) and FC's burden (RR 1.032, 95% CI 1.012-1.053) in mild AD and FC being a spouse (RR 1.451, 95% CI 1.105-1.905) in moderate AD. No formal care provider-related factors were associated with total costs in any stage of AD. This study reveals several factors that may be manageable to control the costs of AD. Comprehensive prevention, evaluation, and treatment of a CR's neuropsychiatric symptoms and comorbidities should be executed early. Informal care can act as a substitute for formal care in early-stage AD, and supportive measures toward FCs should be considered.

Efficacy of targeted multimodal psychosocial rehabilitation on residual neuropsychiatric symptoms in Wilson's disease: A propensity score-matched cohort study.

Hypercalcemic crisis from a functioning parathyroid adenoma (PA) is exceptionally rare in prepubertal children and typically presents with a non-specific complaint such as polyuria or lethargy. We report a 7-year-old girl who was urgently referred for acute, colicky abdominal pain and repeated vomiting, which clinically mimicked acute appendicitis. During the work-up, extensive metabolic tests incidentally revealed severe hypercalcemia and elevated intact parathyroid hormone (PTH), which led to the diagnosis of PA-induced hypercalcemic crisis.Her initial manifestation was an acute abdomen rather than renal or neuropsychiatric symptoms. The case underscores that functioning PA should be included in the differential diagnosis of children presenting with unexplained gastrointestinal distress, and illustrates that timely diagnosis and focused parathyroidectomy can effectively reverse biochemical abnormalities, alleviate skeletal symptoms, and mitigate the risk of serious long-term complications. We report the case of a seven-year-old female patient who was hospitalized due to complaints of abdominal discomfort accompanied by episodes of recurrent vomiting.Subsequent analysis revealed that these symptoms may represent acute gastrointestinal syndrome in the context of a hypercalcemic crisis.We describe her clinical course, diagnostic workup, and treatment. Laboratory tests revealed severe hypercalcemia (4.67 mmol/L; reference range: 2.1-2.7mmol/L), along with hypophosphatemia, hypomagnesemia, and markedly elevated PTH (268.1 pg/mL).Thyroid ultrasound revealed a nodule in the inferior aspect of the right lobe of the thyroid gland, which was subsequently confirmed by contrast-enhanced CT.After urgent management of hypercalcemia-including intravenous fluids, furosemide, salmon calcitonin, and pamidronate-the patient underwent surgical excision of the right inferior parathyroid gland.Histopathological examination confirmed the diagnosis of a benign PA. Serum calcium and PTH levels normalized within 24 hours postoperatively, with complete resolution of clinical symptoms. Marked hypocalcemia developed within several days postoperatively and was corrected. During follow-up to date, serum calcium,PTH levels, and ultrasound examination of the parathyroid have been normal. PA represents an uncommon yet manageable cause of hypercalcemic crisis in pediatric patients. Timely assessment of serum calcium and PTH levels in individuals presenting with unexplained gastrointestinal symptoms-such as nausea, vomiting, or abdominal pain-facilitates swift diagnosis, thereby reducing the need for unnecessary diagnostic procedures like extensive imaging or invasive tests.Surgical resection of the PA is the first-line treatment. Postoperatively, prevention of hungry bone syndrome and long-term follow-up are required.