2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T72b,The socioeconomic burden of early onset dementia (EOD) defined as disease onset before the age of 65 years, is substantial due to its widespread disabling effects in relatively young individuals. While dementia is widely recognised as a major contributor to mortality among the elderly, only a limited number of studies have assessed survival and factors associated with prognosis specifically in EOD. A population-based cohort study, encompassing all incident EOD cases from two defined regions in Finland. The survival and all-cause mortality rates in EOD and its subtypes were evaluated from January 2010 to December 2021. All visits at the dementia outpatient clinics were reviewed and manually re-assessed (n=12 490), resulting in 794 validated EOD cases of Alzheimer's disease (AD), frontotemporal dementia (FTD), alpha-synucleinopathy (α-SYNU) and other EOD spectra. Region-, age- and sex-matched control groups without neurodegenerative diseases were created from nonselective general population data registers (1:10 case to control ratio, 7930 controls in total). The median survival for EOD was 8.7 years, with the shortest survival in the FTD (6.9 years) and α-SYNU groups (7.0 years), followed by the AD group (9.9 years). Compared with controls, mortality was significantly higher in the total EOD group (HR=6.56, 95% CI=5.56-7.74, p<0.001). Among the dementia subtypes, FTD spectrum patients had the highest all-cause mortality risk compared with controls (HR=13.75, 95% CI=10.25-18.43, p<0.001). Male sex, older age, several comorbidities and lower level of education were associated with increased mortality, but these were not EOD-specific. EOD diagnosis significantly deteriorates patients' survival, with significant variation between different diagnostic groups and in relation to patients' demographic factors.31:T983, Background The socioeconomic burden of early onset dementia (EOD) defined as disease onset before the age of 65 years, is substantial due to its widespread disabling effects in relatively young individuals. While dementia is widely recognised as a major contributor to mortality among the elderly, only a limited number of studies have assessed survival and factors associated with prognosis specifically in EOD. Methods A population-based cohort study, encompassing all incident EOD cases from two defined regions in Finland. The survival and all-cause mortality rates in EOD and its subtypes were evaluated from January 2010 to December 2021. All visits at the dementia outpatient clinics were reviewed and manually re-assessed (n=12 490), resulting in 794 validated EOD cases of Alzheimer’s disease (AD), frontotemporal dementia (FTD), alpha-synucleinopathy (α-SYNU) and other EOD spectra. Region-, age- and sex-matched control groups without neurodegenerative diseases were created from nonselective general population data registers (1:10 case to control ratio, 7930 controls in total). Results The median survival for EOD was 8.7 years, with the shortest survival in the FTD (6.9 years) and α-SYNU groups (7.0 years), followed by the AD group (9.9 years). Compared with controls, mortality was significantly higher in the total EOD group (HR=6.56, 95% CI=5.56–7.74, p<0.001). Among the dementia subtypes, FTD spectrum patients had the highest all-cause mortality risk compared with controls (HR=13.75, 95% CI=10.25–18.43, p<0.001). Male sex, older age, several comorbidities and lower level of education were associated with increased mortality, but these were not EOD-specific. Conclusion EOD diagnosis significantly deteriorates patients’ survival, with significant variation between different diagnostic groups and in relation to patients’ demographic factors. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Frontotemporal Dementia: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Frontotemporal Dementia (condition). Clinician-written summaries and actionable practice insights. 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The meta-analyses themselves included 299–382 patients across 8 studies each.","value_numeric":null},{"paper_doi":"10.1007/s11065-026-09700-1","tag_type":"warning","value":"The level of evidence (2) reflects the systematic review design; the underlying studies are all cross-sectional observational, limiting causal conclusions.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and meta-analysis examined the relationship between social cognition (SC) — measured with performance-based tests of emotion recognition and theory of mind (ToM) — and social behavior (disinhibition, apathy, irritability, agitation) rated by proxies, across adult patients with neurodegenerative diseases (AD, FTD, PD, HD, and others). Twenty-one cross-sectional studies published up to September 2023 were included.","key_result":"Evidence for a consistent SC–social behavior link was weak. Meta-analyses found only small pooled effects: better emotion recognition correlated with fewer total behavioral symptoms (r = −.23, 95% CI [−0.42, −0.02]) and less apathy (r = −.24, 95% CI [−0.46, 0.01]), the latter non-significant. Disinhibition was most often associated with SC deficits (~50% of studies for total emotion recognition score); affective ToM was more consistently linked to behavioral symptoms than cognitive ToM. No associations were found between SC and irritability or agitation.","limitations":"- Only 21 cross-sectional studies with small samples (median n = 26) were available, limiting meta-analytic power and causal inference.\n- High heterogeneity across studies in SC and social behavior instruments (I² = 69–75%) prevented broader meta-analyses.\n- Proxy ratings of behavior are subjective and may be influenced by caregiver burden; no correction for multiple comparisons was applied in the qualitative synthesis.","practice_takeaway":"Clinicians should not rely on SC test scores alone to predict or explain social behavioral changes in neurodegenerative disease — the link is weak and inconsistent. Standardized, ecologically valid SC and behavioral measures are needed before SC testing can serve as a reliable early indicator of behavioral deterioration."}},{"doi":"10.1001/jamaneurol.2026.2812","pmid":"42636000","title":"TDP-43–Associated Neurodegenerative Disease Conceptualization and Integrated Staging","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-08-24T00:00:00.000Z","url":"https://doi.org/10.1001/jamaneurol.2026.2812","source_score":25,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-30T06:19:48.977Z","updated_at":"2026-08-30T06:19:48.977Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"condition","value":"Inclusion Body Myositis","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"condition","value":"Limbic-Predominant Age-Related TDP-43 Encephalopathy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"condition","value":"Multisystem Proteinopathy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"condition","value":"TDP-43 Proteinopathy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"generic","value":"TDP-43","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"modality","value":"Biomarker Development","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"study_design","value":"Expert Consensus / Conceptual Framework","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"warning","value":"The DOI year (2026) is consistent with the provided publication date; flagging in case of early-access or preprint status at time of indexing.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the proposed paradigm shift in disease classification, not a clinical trial outcome.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.2812","tag_type":"warning","value":"This paper is a conceptual/opinion piece published in JAMA Neurology; no primary data, cohort, or sample size is reported — level of evidence is set to 7 (expert opinion/narrative).","value_numeric":null}],"summaries":{"what_studied":"This paper proposes a pathobiology-based framework for classifying TDP-43–associated neurodegenerative diseases — including LATE, ALS, FTD, inclusion body myositis, and multisystem proteinopathy — shifting away from clinical phenotype as the organizing principle and introducing an integrated staging system that accounts for presymptomatic disease.","key_result":"The authors argue that TDP-43 pathology underlies a spectrum of clinically distinct disorders and that recognizing this shared biology — with clinical labels like ALS, FTD, or LATE recast as phenotypic manifestations — provides a clearer road map for biomarker development and therapy targeting fundamental disease mechanisms.","limitations":"This is a conceptual/opinion paper without primary data; no clinical outcomes, biomarker validation cohorts, or staging criteria are empirically tested here.","practice_takeaway":"Clinicians should be aware that ALS, FTD, LATE, and related disorders may share a common TDP-43 pathobiology, which has direct implications for how future biomarkers and disease-modifying therapies will be developed and trialed across these conditions."}},{"doi":"10.1016/j.immuni.2026.07.009","pmid":"42546695","title":"Progranulin deficiency-induced lysosomal dysfunction drives maladaptive myeloid cell states through the MITF/TFE transcription factors","journal_title":"Immunity","journal_issn":"1074-7613","published_at":"2026-08-03T00:00:00.000Z","url":"https://doi.org/10.1016/j.immuni.2026.07.009","source_score":22,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-09T13:25:02.629Z","updated_at":"2026-08-09T13:25:02.629Z","tags":[{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"condition","value":"Lysosomal Dysfunction","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"condition","value":"Neurodegeneration","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"condition","value":"Progranulin Deficiency","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"generic","value":"progranulin","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"modality","value":"Lysosomal Biology / Gene Knockout","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"study_design","value":"Animal Study with Multi-Omic Profiling (scRNA-seq + Epigenomics)","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"warning","value":"DOI publication date (2026-08-03) is recent; findings have not yet been independently replicated.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"warning","value":"Study design label reflects a preclinical mouse model with multi-omic methods; no standard RCT or observational design applies.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"warning","value":"The impact_flag 'practice_changing' reflects mechanistic novelty (GPNMB/MITF-TFE axis); no clinical trial or human intervention data are present.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.07.009","tag_type":"warning","value":"The 'older_adult' age group tag refers to aged mice used in the model, not human older adults — direct clinical translation is uncertain.","value_numeric":null}],"summaries":{"what_studied":"Multi-omic profiling (scRNA-seq + epigenetic) of myeloid cells from aged progranulin-deficient (Grn-/-) mouse brains was used to map how lysosomal dysfunction shapes microglial cell states and identify the transcription factors driving maladaptive responses.","key_result":"A GPNMB+ microglial subpopulation emerged in Grn-/- mice with hallmarks of lysosomal stress (lipofuscinosis, metabolic and lipid dysregulation); MITF/TFE transcription factor motifs were enriched at active enhancers, and their deletion reversed the Grn-/--specific transcriptional signature. Compensatory GPNMB upregulation promoted lysosomal acidification, while myeloid-specific GPNMB loss worsened neurotoxicity.","limitations":"Findings are based on a mouse (Grn-/-) model, limiting direct translation to human neurodegeneration. The study does not test therapeutic rescue of lysosomal function in vivo beyond genetic manipulations. Causal ordering between epigenetic changes and lysosomal dysfunction in human disease remains unestablished.","practice_takeaway":"GPNMB and MITF/TFE signaling in microglia are candidate therapeutic targets for progranulin-linked neurodegeneration (e.g., frontotemporal dementia). Lysosomal deacidification broadly recapitulates the maladaptive microglial state, suggesting lysosomal pH restoration as a potential intervention strategy."}},{"doi":"10.1212/wnl.0000000000218296","pmid":"42447421","title":"Legal Protections to Mitigate Discrimination due to Neurodegenerative Biomarker Status","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-07-14T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218296","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-23T07:33:14.580Z","updated_at":"2026-08-23T07:33:14.580Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"modality","value":"Biomarker Testing","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"study_design","value":"Policy Analysis / Legal Review","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"warning","value":"No primary empirical data are presented; this is a legal/policy opinion piece, not a clinical study — sample size and statistical outcomes are not applicable.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"warning","value":"Study design label is non-standard; the article is a legal and policy analysis published in a clinical neurology journal, which may not map cleanly onto conventional evidence hierarchies.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218296","tag_type":"warning","value":"The 'impact_flag' of safety_signal is applied in the context of patient legal and privacy risk, not a pharmacologic or procedural safety signal in the traditional sense.","value_numeric":null}],"summaries":{"what_studied":"This policy analysis evaluates gaps in U.S. federal legal protections (GINA, ADA, ACA, HIPAA) for individuals undergoing neurodegenerative biomarker testing (AD, PD, ALS) — particularly those in preclinical or prodromal disease stages — and proposes an evidence-informed framework for building biomarker-specific privacy and antidiscrimination policy.","key_result":"Existing federal laws leave critical gaps: GINA excludes life, long-term care, and disability insurance; the ADA requires overt symptoms to qualify as a disability; and HIPAA allows health information disclosure for treatment and payment purposes. Preclinical/prodromal individuals — who may still be employed or seeking insurance — are most exposed. A proposed 'BINA' (Biomarker Information Non-Discrimination Act) modeled on GINA is identified as a potential but imperfect solution.","limitations":"This is a legal and policy analysis with no primary empirical data; evidence on actual observed discrimination against biomarker-tested individuals is currently lacking. State-level legal variation and research-record protections are explicitly outside the article's scope.","practice_takeaway":"Until stronger protections exist, clinicians should inform patients and research participants about privacy and discrimination risks tied to biomarker testing — including the option to keep research results out of the clinical medical record. Consent documents for neurodegenerative biomarker research should explicitly address these legal gaps."}},{"doi":"10.1212/wnl.0000000000218268","pmid":"42418748","title":"Long-Term Income and Productivity Losses in Individuals With Early-Onset Dementia","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218268","source_score":64,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:33.922Z","updated_at":"2026-08-17T13:33:33.922Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"condition","value":"Alpha-Synucleinopathy","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"condition","value":"Early-Onset Dementia","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"condition","value":"Vascular Cognitive Disorder","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"sample_size","value":"n=793","value_numeric":793},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"study_design","value":"Retrospective Population-Based Longitudinal Cohort Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"warning","value":"Findings are based on the Finnish universal health care and social security system; magnitude and timing of productivity loss may not be directly transferable to other countries with different labor market structures or social safety nets.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"warning","value":"Study funding came from Roche Oy; several authors report advisory or consulting relationships with pharmaceutical companies (Eisai, Eli Lilly, Novartis, BioArctic, Roche), which may introduce potential conflict of interest.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"warning","value":"The 'impact_flag' of practice_changing reflects the unusually long (15-year) prediagnostic window of detectable productivity loss, which has direct implications for early intervention policy, though the study is observational and does not establish causality.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218268","tag_type":"warning","value":"The α-synucleinopathy subgroup (n=46) is underpowered; subgroup results should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"This retrospective, population-based longitudinal cohort study evaluated income trajectories and societal productivity loss in 793 adults with early-onset dementia (EOD; onset <65 years) — including AD, FTD spectrum, α-synucleinopathies, and other EODs — compared with 7,926 age- and sex-matched controls, using Finnish national tax records and the Human Capital Approach across 15 years before diagnosis (2010–2021).","key_result":"Cumulative productivity loss reached **€74,577 per patient** over 15 years. Loss was detectable 15 years before diagnosis (€2,774/year; p=0.008) and averaged €12,021/year at diagnosis. By subtype: FTD showed loss from 11 years pre-diagnosis (€4,799/year) rising to €16,116/year at diagnosis; AD from 6 years pre-diagnosis (€2,767/year) rising to €11,431/year; α-synucleinopathies only at diagnosis (€11,284/year); and the vascular/mixed \"other EOD\" group had consistently high losses throughout (€8,322–€8,744/year).","limitations":"- Residual confounding from unmeasured baseline socioeconomic status, occupation type, and psychiatric comorbidity cannot be excluded.\n- The α-synucleinopathy subgroup (n=46) is small, limiting statistical power.\n- HCA captures only wage-based productivity loss, excluding unpaid caregiving and housework; findings may not generalize beyond Finland's universal health care and social security context.","practice_takeaway":"Clinicians should be aware that EOD — especially FTD — causes measurable income and work-capacity decline up to a decade before diagnosis, which can help frame discussions with patients and families about early financial and workplace planning. Earlier diagnostic pathways and workplace support systems are warranted to reduce the substantial socioeconomic burden on individuals and society."}},{"doi":"10.1038/s41593-026-02348-3","pmid":"42420559","title":"Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice","journal_title":"Nature Neuroscience","journal_issn":"1097-6256","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1038/s41593-026-02348-3","source_score":73,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-11T13:33:10.361Z","updated_at":"2026-07-11T13:33:10.361Z","tags":[{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"condition","value":"Myelin Abnormalities","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"condition","value":"TDP-43 Proteinopathy","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"generic","value":"TDP-43 (TARDBP)","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"modality","value":"Gene Knockout / Conditional Knockout","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"study_design","value":"Animal Study (Mouse Knockout Model)","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"warning","value":"Sample sizes were not statistically predetermined; breeding constraints drove group sizes, which may affect statistical power for some outcomes.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"warning","value":"The 'practice_changing' impact flag reflects mechanistic novelty (new TREM2-DAP12-TDP-43 axis), not a clinical intervention; this is a preclinical mouse study only.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02348-3","tag_type":"warning","value":"The study is a Nature Portfolio reporting summary (supplementary document), not the full manuscript; quantitative results cited in the summary are drawn from the abstract only, as the main figures and results sections were not included in the provided text.","value_numeric":null}],"summaries":{"what_studied":"This mouse study examined the role of microglial TDP-43 (encoded by *Tardbp*) in early postnatal brain development and adult motor function, using a conditional knockout (cKO) model (Cx3cr1-CreERT2;Tardbp-flox) assessed by MRI, confocal and electron microscopy, spatial transcriptomics, bulk RNA-seq, proteomics, and behavioral testing.","key_result":"Loss of microglial TDP-43 caused structural myelin abnormalities in the early postnatal brain, impaired microglial myelin engulfment and degradation, led to motor deficits in adult mice, and—mechanistically—produced cryptic exon inclusion in *Tyrobp* mRNA, generating a truncated DAP12 protein that disrupted TREM2 signaling. Spatial transcriptomics revealed an enriched interferon-responsive signature linked to oligodendrocyte dysfunction.","limitations":"- Study is entirely in mice; direct relevance to human TDP-43 proteinopathy (ALS, FTD) is inferential.\n- Sample sizes were not statistically predetermined; they depended on breeding capacity and litter sizes.\n- Some experiments used only one sex (electron microscopy and P12 analysis: males only; bulk RNA-seq: females only), limiting sex-generalizability.","practice_takeaway":"This is a basic science study in mice and has no immediate clinical practice implications. However, it identifies a novel TREM2-DAP12 regulatory axis controlled by TDP-43 in microglia that may inform future therapeutic targets in ALS and FTD."}},{"doi":"10.1001/jamaneurol.2026.1927","pmid":"42329632","title":"Clinical Associations of Cerebrospinal Fluid TMEM106B in Familial and Sporadic Frontotemporal Dementia","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-06-22T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13288190/","source_score":21,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-02T13:33:06.806Z","updated_at":"2026-07-02T13:33:06.806Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"condition","value":"Frontotemporal Lobar Degeneration","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"generic","value":"neurofilament light chain","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"generic","value":"TMEM106B protein","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"modality","value":"CSF Biomarker","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"sample_size","value":"n=654","value_numeric":654},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"warning","value":"Full text is under PMC embargo until June 22, 2027; summary is based solely on the abstract and results excerpt.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"warning","value":"Sample size of n=654 reflects combined discovery and validation cohorts; they were analyzed independently and should not be pooled without caution.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"warning","value":"Study design is cross-sectional for the primary analysis; the 2-year follow-up for progression data is a secondary component and its scope is unclear from the abstract.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1927","tag_type":"warning","value":"TMEM106B was quantified via two different SomaScan versions (v3.0 vs v4.1) across cohorts, which may introduce inter-assay variability not fully addressable from the abstract alone.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study examined CSF TMEM106B protein levels and their clinical associations in two independent cohorts (discovery n=271; validation n=383) of patients with sporadic neuropathology-confirmed FTLD, familial FTLD (C9orf72, GRN, MAPT variant carriers), Alzheimer disease, and controls, with a 2-year follow-up for progression data.","key_result":"Lower CSF TMEM106B was associated with greater disease severity (β=−0.15; P=.003), smaller frontotemporal brain volumes (β=0.42; P<.001), and faster clinical progression (β=−2.21; P=.001), independently of neurofilament light chain; the protective rs1990622 G/G genotype was linked to lower TMEM106B levels than the risk A/A genotype, and CSF TMEM106B did not distinguish FTLD subtypes from each other or from AD.","limitations":"Cross-sectional design limits causal inference; TMEM106B was measured by aptamer proteomics (SomaScan), which may not capture all protein isoforms; full text is embargoed, so methodological details and subgroup analyses could not be fully reviewed.","practice_takeaway":"CSF TMEM106B tracks disease severity and brain atrophy in both sporadic and genetic FTLD, but it cannot differentiate FTLD subtypes or distinguish FTLD from AD — so it is not yet a stand-alone diagnostic biomarker. Clinicians should note that rs1990622 genotype influences TMEM106B levels and would need to be accounted for in any future clinical application."}},{"doi":"10.1002/alz.71450","pmid":"42187024","title":"Systemic delivery of synapsin‐promoted caveolin‐1 overexpression ameliorates pathological TDP‐43–induced cognitive decline and neurodegenerative changes","journal_title":"Alzheimer's & Dementia","journal_issn":"1552-5260","published_at":"2026-05-26T00:00:00.000Z","url":"https://doi.org/10.1002/alz.71450","source_score":50,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-31T13:35:29.310Z","updated_at":"2026-05-31T13:35:29.310Z","tags":[{"paper_doi":"10.1002/alz.71450","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"condition","value":"TDP-43 Proteinopathy","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"generic","value":"caveolin-1 (AAV-PhP.eB-SynCav1)","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"modality","value":"AAV Vector","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"modality","value":"Gene Therapy","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"study_design","value":"Preclinical Animal Study","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"warning","value":"AAV-PhP.eB is a research-grade capsid with variable CNS transduction efficiency across species; clinical translatability is not established.","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"warning","value":"No specific sample sizes (n) or quantitative cognitive outcome metrics are reported in the available abstract/results text — numeric findings may be present in the full paper.","value_numeric":null},{"paper_doi":"10.1002/alz.71450","tag_type":"warning","value":"Study is entirely preclinical (mouse model); extrapolation to human FTD or AD should be made with caution.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated systemic delivery of AAV-PhP.eB-SynCav1 (synapsin-promoted caveolin-1) in TDP-43A315T transgenic mice — a model of TDP-43 proteinopathy — assessing effects on cognition, membrane lipid raft (MLR) stability, synaptic ultrastructure, and mitochondrial dynamics.","key_result":"SynCav1 delivery reduced pathological TDP-43 mislocalization to MLRs, restored MLR-associated GluN2A expression, preserved synaptic ultrastructure, and mitigated mitochondrial hyper-fragmentation and excessive fission signaling, resulting in improved cognitive outcomes.","limitations":"This is a preclinical mouse study (TDP-43A315T model), so translation to human disease is uncertain. Specific sample sizes and quantitative cognitive outcome data are not reported in the abstract. Long-term safety and durability of AAV-PhP.eB systemic delivery were not discussed.","practice_takeaway":"While not yet clinically applicable, SynCav1 gene therapy represents a novel neuron-targeted approach linking TDP-43 proteinopathy to lipid raft instability — a mechanistic angle worth monitoring for future FTD and AD therapeutic development."}},{"doi":"10.1016/j.inpsyc.2026.100221","pmid":"42185186","title":"Automating collateral histories in dementia: Development and proof‑of‑concept evaluation of the LUMEN conversational AI","journal_title":"International Psychogeriatrics","journal_issn":"1041-6102","published_at":"2026-05-25T00:00:00.000Z","url":"https://doi.org/10.1016/j.inpsyc.2026.100221","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-31T13:35:37.742Z","updated_at":"2026-05-31T13:35:37.742Z","tags":[{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"condition","value":"Dementia with Lewy Bodies","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"condition","value":"Mild Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"condition","value":"Vascular Dementia","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"generic","value":"Qwen3-30B-A3B","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"modality","value":"Conversational Artificial Intelligence","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"modality","value":"Large Language Model","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"sample_size","value":"n=54","value_numeric":54},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"study_design","value":"Proof-of-Concept Study","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"warning","value":"All 54 dialogues were synthetic — either clinician role-played or GPT-4 generated — so reported AUROC and κ values reflect performance on artificial data only, not real patient or carer interactions.","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"warning","value":"Qwen3-30B-A3B is an open-source LLM used as the backbone; it is not a licensed clinical device and its tag as 'generic' is an approximation given no standard drug/device classification applies.","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"warning","value":"Study design is best described as a proof-of-concept/feasibility evaluation; it does not fit neatly into standard evidence hierarchy levels — level 5 is an approximation.","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2026.100221","tag_type":"warning","value":"The sample size tag reflects the number of synthetic dialogues (n=54), not a patient cohort; the stakeholder co-design programme involved ~232 participants but these were not diagnostic test subjects.","value_numeric":null}],"summaries":{"what_studied":"The LUMEN conversational AI system was developed and evaluated as a tool to automate structured collateral history collection from carers for dementia diagnosis, using 54 synthetic dialogues generated from 6 clinician-authored vignettes covering Alzheimer's disease, dementia with Lewy bodies, vascular dementia, frontotemporal dementia, mild cognitive impairment, and normal cognition.","key_result":"In a closed-loop synthetic proof-of-concept, macro-average AUROC was 0.95; AUROC was highest for Alzheimer's disease and vascular dementia (1.00) and lowest for mild cognitive impairment (0.77). Rule-based rubric vs. clinician rating agreement was κ = 0.88 (95% CI 0.83–0.93). Mean System Usability Scale score was 78.1/100.","limitations":"All testing used synthetic vignettes and AI-generated dialogues, not real patients or carers — results cannot be generalised to real-world diagnostic performance. The dataset was small (54 dialogues) and closed-loop, meaning the same LLM ecosystem generated and evaluated content. No prospective clinical validation has been performed.","practice_takeaway":"LUMEN shows early promise as a structured collateral history tool for memory services, but clinicians should treat these findings as proof-of-concept only. Real-world clinical trials are needed before this system can be considered for routine use."}},{"doi":"10.1001/jamapsychiatry.2026.0171","pmid":"41920573","title":"Dementia in Severe Schizophrenia","journal_title":"JAMA Psychiatry","journal_issn":"2168-622X","published_at":"2026-04-01T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13044795/","source_score":97,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:23:50.890Z","updated_at":"2026-06-10T14:23:50.890Z","tags":[{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"condition","value":"Lewy Body Dementia","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"condition","value":"Schizophrenia","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"generic","value":"Montreal Cognitive Assessment","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"modality","value":"Cognitive Assessment","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"sample_size","value":"n=155","value_numeric":155},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"warning","value":"MoCA is used both as a clinical screening tool and as the primary outcome measure here — potential ceiling/floor effects in this severely impaired group should be noted.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously: findings challenge prevailing etiologic assumptions but are observational and require replication with neuropathological data.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.0171","tag_type":"warning","value":"The SETRS cohort is highly selected (continuously hospitalized ≥5 years, New York state hospitals only), which may limit applicability to broader schizophrenia populations.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cohort study characterized cognitive, clinical, and genetic features of dementia in 155 adults with severe, extremely treatment-resistant schizophrenia (SETRS) continuously hospitalized ≥5 years at New York state hospitals (data collected December 2017–July 2019; analyzed January–December 2025), comparing MoCA profiles and genetic markers to NACC datasets of AD, FTD, LBD, VD, and healthy controls.","key_result":"98.7% (153/155) scored below the MoCA cutoff for mild cognitive impairment; 47.1% (73/155) scored below 10 (severe dementia; mean MoCA 9.8). The cognitive profile mirrored community-dwelling schizophrenia (r = 0.86, P < .001) rather than AD or FTD. No pathogenic Mendelian dementia variants were found; APOE4 frequency was markedly lower in SETRS (14.4%) vs. AD (33.6%; OR 0.33) and LBD (24.7%; OR 0.51).","limitations":"- Retrospective design with a highly selected, institutionalized sample limits generalizability to outpatient or less severe schizophrenia.\n- No neuropathological or neuroimaging data to directly assess underlying brain pathology.\n- Cross-sectional cognitive assessment cannot establish trajectory or causality of cognitive decline.","practice_takeaway":"Clinicians should not assume comorbid Alzheimer disease or vascular risk factors explain dementia in treatment-resistant schizophrenia — the cognitive signature is distinct and APOE4 burden is low. Patients with SETRS warrant proactive cognitive monitoring using tools like the MoCA, independent of standard dementia workups."}},{"doi":"10.1136/jnnp-2025-336805","pmid":"41188051","title":"Survival and mortality rates in early onset dementia","journal_title":"Journal of Neurology, Neurosurgery & Psychiatry","journal_issn":"0022-3050","published_at":"2025-11-05T00:00:00.000Z","url":"https://doi.org/10.1136/jnnp-2025-336805","source_score":79,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-11-05","doi":"10.1136/jnnp-2025-336805","days":"30","issn":"0022-3050","rank":"9","field":"Clinical Medicine","score":"79","category":"Surgery","categories":["Surgery"],"_categories":["Surgery"]},"pubmed":{"doi":"10.1136/jnnp-2025-336805","title":"Survival and mortality rates in early onset dementia.","journal":"Journal of neurology, neurosurgery, and psychiatry","methods":"","results":"The median survival for EOD was 8.7 years, with the shortest survival in the FTD (6.9 years) and α-SYNU groups (7.0 years), followed by the AD group (9.9 years). Compared with controls, mortality was significantly higher in the total EOD group (HR=6.56, 95% CI=5.56-7.74, p<0.001). Among the dementia subtypes, FTD spectrum patients had the highest all-cause mortality risk compared with controls (HR=13.75, 95% CI=10.25-18.43, p<0.001). Male sex, older age, several comorbidities and lower level of education were associated with increased mortality, but these were not EOD-specific.","abstract":"$30","keywords":["ALZHEIMER'S DISEASE","EPIDEMIOLOGY","FRONTOTEMPORAL DEMENTIA","Prognosis","VASCULAR DEMENTIA"],"pubmed_id":"41188051","conclusions":"EOD diagnosis significantly deteriorates patients' survival, with significant variation between different diagnostic groups and in relation to patients' demographic factors.","publication_date":"2025-11-05T00:00:00"},"crossref":{"DOI":"10.1136/jnnp-2025-336805","URL":"https://doi.org/10.1136/jnnp-2025-336805","ISSN":["0022-3050","1468-330X"],"link":[{"URL":"https://syndication.highwire.org/content/doi/10.1136/jnnp-2025-336805","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"jnnp-2025-336805","type":"journal-article","issue":null,"score":1,"title":["Survival and mortality rates in early onset dementia"],"author":[{"given":"Kasper","family":"Katisko","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland"}]},{"given":"Mikko","family":"Aaltonen","sequence":"additional","affiliation":[{"name":"Law School, University of Eastern Finland, Joensuu, Finland"}]},{"given":"Kalle","family":"Aho","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland"}]},{"given":"Sami","family":"Heikkinen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland"}]},{"given":"Ave","family":"Kivisild","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland"}]},{"given":"Adolfina","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland"}]},{"given":"Laura","family":"Leppänen","sequence":"additional","affiliation":[{"name":"Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland"}]},{"given":"Iina","family":"Rinnankoski","sequence":"additional","affiliation":[{"name":"Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland"}]},{"given":"Helmi","family":"Soppela","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland"}]},{"given":"Laura","family":"Tervonen","sequence":"additional","affiliation":[{"name":"Research Unit of Clinical Medicine, Neurology, University of Oulu, Oulu, Finland"},{"name":"MRC, Oulu University Hospital, Oulu, Finland"}]},{"given":"Noora Maria","family":"Suhonen","sequence":"additional","affiliation":[{"name":"Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland"}]},{"given":"Annakaisa","family":"Haapasalo","sequence":"additional","affiliation":[{"name":"A.I. 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Mortality was higher than controls in all EOD (HR 6.56, 95% CI 5.56–7.74), with the highest risk in frontotemporal dementia (HR 13.75, 95% CI 10.25–18.43); male sex, older age, comorbidities, and lower education were linked to higher mortality.","limitations":"Data come from only two regions in Finland, which may limit generalizability. The abstract does not give absolute death counts or detail the composition of the “other EOD” subgroup.","practice_takeaway":"Expect shorter survival in EOD (about 9 years), with frontotemporal and alpha‑synucleinopathy subtypes faring worst; Alzheimer’s disease has longer survival among EOD. Discuss prognosis and planning with patients and families, noting higher mortality with male sex, older age, comorbidity burden, and lower education."}},{"doi":"10.1016/j.inpsyc.2025.100078","pmid":"40312204","title":"Nation-wide Japanese FTD consortium FTLD-J: Utility of case review meetings","journal_title":"International Psychogeriatrics","journal_issn":"1041-6102","published_at":"2025-05-01T00:00:00.000Z","url":"https://doi.org/10.1016/j.inpsyc.2025.100078","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-13T15:34:38.383Z","updated_at":"2026-06-13T15:34:38.383Z","tags":[{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"condition","value":"Behavioral Variant Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"condition","value":"Frontotemporal Dementia","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"condition","value":"Frontotemporal Lobar Degeneration","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"condition","value":"Progressive Nonfluent Aphasia","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"condition","value":"Semantic Dementia","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"sample_size","value":"n=269","value_numeric":269},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"study_design","value":"Multicenter Registry Study","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"warning","value":"No neuropathological confirmation data were described; revised clinical diagnoses after review meetings are used as the reference standard, which may overestimate true diagnostic accuracy gains.","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"warning","value":"Sex distribution of the study population was not reported in the abstract or results; sex tag omitted.","value_numeric":null},{"paper_doi":"10.1016/j.inpsyc.2025.100078","tag_type":"warning","value":"The study design is a registry/observational study — 'case review meetings' are an internal quality-control process, not a clinical intervention in the traditional sense; study design label reflects closest standard category.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated the utility of structured case review meetings for improving diagnostic consistency in a Japanese nationwide multicenter FTD registry (FTLD-J), enrolling 269 patients with bvFTD, semantic dementia (SD), or progressive nonfluent aphasia (PNFA) between February 2016 and August 2024.","key_result":"Diagnostic changes occurred in 40% of bvFTD cases (51/126), 19% of SD cases (18/95), and 12% of PNFA cases (2/17) after case review meetings; bvFTD had a significantly higher rate of diagnostic change than SD (p < 0.001).","limitations":"- PNFA group was small (n=17), limiting comparisons with that subtype.\n- No blinded re-diagnosis or gold-standard pathological confirmation reported, so the 'corrected' diagnoses may still carry uncertainty.\n- Single-nation registry (Japan) may limit generalizability to other populations.","practice_takeaway":"bvFTD is particularly prone to misdiagnosis at initial assessment — nearly 4 in 10 cases were reclassified after expert review. Multicenter FTD registries should build in structured case review meetings to improve diagnostic accuracy before enrolling patients in clinical trials or longitudinal studies."}}],"initialOffset":12,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Frontotemporal Dementia"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Frontotemporal Dementia"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Frontotemporal Dementia"}}}]]

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