ArticleJAMA network open2023
Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease.
Article in JAMA network open, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Neuroinflammatory fluid biomarkers in patients with Alzheimer's disease: a systematic literature review.Molecular psychiatry · 2025Pooled it
- Investigating neuropathological correlates of hyperactive and psychotic symptoms in dementia: a systematic review.Frontiers in dementia · 2025Pooled it
- Pooled it
- Trial
- Tau-PET correlates of mild behavioral impairment in preclinical and prodromal Alzheimer's disease: A head-to-head comparison of Flortaucipir and MK6240.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Toward Precision Neuropsychiatry of Dementia: Neuropsychiatric Symptoms as Multidimensional Clinical Phenotypes.Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society · 2026Review
- Depression in neurodegenerative disease: neurobiological mechanisms and emerging treatments.Molecular psychiatry · 2026Review
- Plasma neurofilament light chain and regional brain atrophy mediate the association of neuropsychiatric symptoms with cognition in Alzheimer's disease: evidence from two population-based studies.Psychological medicine · 2026Article
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Dynamic trajectories of neuropsychiatric symptoms predict Alzheimer's disease risk and clinical phenotypes.General psychiatry · 2026Article
- Dual association patterns between microglial activation and neuronal health in Alzheimer's disease: a whole-brain MRSI/PET study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A community screening tool for neuropsychiatric symptoms in the elderly: integrating cortisol, microbiome, and social factors with machine learning.Translational psychiatry · 2026Observational
- The prefrontal cortex as a target of HIV-1 neurotoxicity: molecular mechanisms of viral protein-mediated neurodegeneration and executive dysfunction.Frontiers in cellular neuroscience · 2026Review
- Multimodal Neuroimaging Mechanisms of Apathy in Alzheimer's Disease: A Narrative Review of Structural, Functional, and Molecular Evidence.International journal of general medicine · 2026Review
- Microglia-Neuron Interactions in Alzheimer's Disease.Current neuropharmacology · 2026Review
- Neuropsychiatric symptoms in Alzheimer's disease: Bridging mechanisms, management, and emerging innovations.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Rosiglitazone Adjunct to Risperidone for Irritability in Autistic Children: A Randomized, Double-Blind, Placebo-Controlled Trial.Journal of autism and developmental disorders · 2025Article
- Patient-reported characteristics of pernicious anaemia: a first step to initiate James Lind Alliance Priority Setting Partnership driven research.BMC primary care · 2025Article
- Review
- Midbrain degeneration triggers astrocyte reactivity and tau pathology in experimental Alzheimer's Disease.Molecular neurodegeneration · 2025Article
Corrections and comments
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Authors and funding
39 authors at 9 institutions in 5 countries.
Funding
Abstract
Importance: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms. Objective: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum. Design, Setting, and Participants: This cross-sectional study was conducted from January to June 2023, leveraging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University, Canada. Recruitment was based on referrals of individuals from the community or from outpatient clinics. Exclusion criteria included active substance abuse, major surgery, recent head trauma, safety contraindications for positron emission tomography (PET) or magnetic resonance imaging, being currently enrolled in other studies, and having inadequately treated systemic conditions. Main Outcomes and Measures: All individuals underwent assessment for neuropsychiatric symptoms (Neuropsychiatry Inventory Questionnaire [NPI-Q]), and imaging for microglial activation ([11C]PBR28 PET), amyloid-β ([18F]AZD4694 PET), and tau tangles ([18F]MK6240 PET). Results: Of the 109 participants, 72 (66%) were women and 37 (34%) were men; the median age was 71.8 years (range, 38.0-86.5 years). Overall, 70 had no cognitive impairment and 39 had cognitive impairment (25 mild; 14 Alzheimer disease dementia). Amyloid-β PET positivity was present in 21 cognitively unimpaired individuals (30%) and in 31 cognitively impaired individuals (79%). The NPI-Q severity score was associated with microglial activation in the frontal, temporal, and parietal cortices (β = 7.37; 95% CI, 1.34-13.41; P = .01). A leave-one-out approach revealed that irritability was the NPI-Q domain most closely associated with the presence of brain microglial activation (β = 6.86; 95% CI, 1.77-11.95; P = .008). Furthermore, we found that microglia-associated irritability was associated with study partner burden measured by NPI-Q distress score (β = 5.72; 95% CI, 0.33-11.10; P = .03). Conclusions and Relevance: In this cross-sectional study of 109 individuals across the AD continuum, microglial activation was associated with and a potential biomarker of neuropsychiatric symptoms in Alzheimer disease. Moreover, our findings suggest that the combination of amyloid-β- and microglia-targeted therapies could have an impact on relieving these symptoms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.