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:T532,Cognitive impairments are a hallmark of Huntington's disease (HD). Seventy-one participants (43 HD gene-expanded [HDGE], 28 healthy controls) from the HD-Young Adult Study at two timepoints ≈ 4.7 years apart, completed the Cambridge Neuropsychological Test Automated Battery Rapid Visual Information Processing task and underwent resting-state functional magnetic resonance imaging. We focused on predefined regions of interest that are involved in sustained attention. HDGE individuals showed significantly poorer sustained attention than controls (p These findings demonstrate early and persistent attention deficits in HDGE, linked to altered FC in attention-related circuits. This supports the presence of early cognitive dysfunction in HD and highlights potential compensatory and pathological changes in brain networks prior to the onset of clinical motor symptoms. We detail the discovery of early sustained attention deficits in Huntington's disease (HD) gene-expanded (HDGE) young adults. These sustained attention deficits do not measurably decline over a 4.7-year period. Altered functional connectivity was observed in attention-related brain networks. Alterations in regions include occipital, opercular, lentiform, and frontal areas. Findings support attention as an early cognitive biomarker in HDGE young adults.31:Td41,Abstract BACKGROUND Cognitive impairments are a hallmark of Huntington's disease (HD). METHODS Seventy‐one participants (43 HD gene‐expanded [HDGE], 28 healthy controls) from the HD‐Young Adult Study at two timepoints ≈ 4.7 years apart, completed the Cambridge Neuropsychological Test Automated Battery Rapid Visual Information Processing task and underwent resting‐state functional magnetic resonance imaging. We focused on predefined regions of interest that are involved in sustained attention. RESULTS HDGE individuals showed significantly poorer sustained attention than controls ( p adj = 0.007), with no significant change over time. Functional connectivity (FC) analyses revealed group differences in attention‐related networks, including the occipital–operculum and lentiform–orbitalis pathways. Time and group × time effects were also observed in frontal and parietal regions. DISCUSSION These findings demonstrate early and persistent attention deficits in HDGE, linked to altered FC in attention‐related circuits. This supports the presence of early cognitive dysfunction in HD and highlights potential compensatory and pathological changes in brain networks prior to the onset of clinical motor symptoms. Highlights

We detail the discovery of early sustained attention deficits in Huntington's disease (HD) gene‐expanded (HDGE) young adults.

These sustained attention deficits do not measurably decline over a 4.7‐year period.

Altered functional connectivity was observed in attention‐related brain networks.

Alterations in regions include occipital, opercular, lentiform, and frontal areas.

Findings support attention as an early cognitive biomarker in HDGE young adults.

25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Huntington's Disease: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Huntington's Disease (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":"10.1002/alz.71680","pmid":"42626968","title":"A combined artificial intelligence–wet lab approach identifies a pivotal role of the NAD\n ⁺\n –mitophagy axis on aging and neurodegeneration","journal_title":"Alzheimer's & Dementia","journal_issn":"1552-5260","published_at":"2026-08-21T00:00:00.000Z","url":"https://doi.org/10.1002/alz.71680","source_score":29,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-30T06:19:49.491Z","updated_at":"2026-08-30T06:19:49.491Z","tags":[{"paper_doi":"10.1002/alz.71680","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"brand","value":"PandaOmics","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"condition","value":"Brain Aging","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"condition","value":"Huntington's Disease","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"condition","value":"Parkinson's Disease","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"generic","value":"nicotinamide mononucleotide","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"modality","value":"Mitochondrial Fusion Promoter","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"modality","value":"NAD+ Pathway Modulator","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"modality","value":"RNA Interference","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"sample_size","value":"n=3489","value_numeric":3489},{"paper_doi":"10.1002/alz.71680","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"study_design","value":"Translational Study (Multi-Omics + Experimental Validation)","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"warning","value":"PandaOmics is a proprietary AI platform developed by Insilico Medicine, and several co-authors are affiliated with that company, representing a potential conflict of interest in target prioritization findings.","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"warning","value":"Sample size of n=3,489 reflects the combined transcriptomic dataset (patients + controls); the iPSC and C. elegans experiments involved much smaller groups and some endpoints had only 1–2 biological repeats.","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"warning","value":"Study design tag 'Translational Study' is used because this work combines computational transcriptomics with multi-model wet-lab validation and does not fit a single standard design label cleanly.","value_numeric":null},{"paper_doi":"10.1002/alz.71680","tag_type":"warning","value":"The study design is a hybrid of computational and preclinical experimental work; there are no human clinical intervention data. The 'level of evidence 4' reflects this preclinical/translational nature.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated expression of 102 NAD⁺/mitophagy-related genes across 12 human brain regions and blood using 77 public transcriptomic datasets (1,966 neurodegenerative disease patients vs. 1,523 controls) spanning AD, PD, HD, and ALS. Key AI-prioritized targets were then validated in *C. elegans*, a HEK293 Tau-Venus cell model, and APOE4/4 iPSC-derived cortical neurons.","key_result":"The NAD⁺–mitophagy axis was more severely dysregulated in neurodegeneration than in normal brain aging, with CNS samples showing broader gene dysregulation than blood. Five AD-protective genes were prioritized: **ULK1, OPA1, LAMP2, MFN1, and ATP6V0E1**. Knockdown of MFN1 or LAMP2 worsened Tau aggregation in the cell model; neuronal knockdown of eat-3 (OPA1) or fzo-1 (MFN1) impaired cholinergic synaptic function in *C. elegans*. Pharmacological activation of mitochondrial fusion (SML0629/OPA1 pathway) in APOE4/4 cortical neurons reduced p-Tau217 levels.","limitations":"- Experimental validation used lower-organism (*C. elegans*) and non-neuronal cell models; effects in higher organisms remain untested.\n- iPSC cortical neuron experiments were limited to short treatment windows (24 h) and single biological repeats for some endpoints, reducing statistical power.\n- The study is observational/transcriptomic for human data; causality in human brain aging and neurodegeneration cannot be established.","practice_takeaway":"The NAD⁺–mitophagy axis—particularly OPA1, MFN1, LAMP2, and ATP6V0E1—represents a promising but preclinical therapeutic target in AD; no clinical interventions are ready based on this data alone. Clinicians should watch for trials targeting mitochondrial fusion or NAD⁺ pathways as this mechanistic evidence matures."}},{"doi":"10.1002/mdc3.70689","pmid":"42261003","title":"Cerebellar Ataxia and Chorea: Genetic Etiologies and Key Considerations for Diagnosis and Management","journal_title":"Movement Disorders Clinical Practice","journal_issn":"2330-1619","published_at":"2026-06-08T00:00:00.000Z","url":"https://doi.org/10.1002/mdc3.70689","source_score":26,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-21T13:29:45.904Z","updated_at":"2026-06-21T13:29:45.904Z","tags":[{"paper_doi":"10.1002/mdc3.70689","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Ataxia Telangiectasia","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Cerebellar Ataxia","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Chorea","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Dentatorubral-Pallidoluysian Atrophy","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Glucose Transporter Type 1 Deficiency","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Huntington's Disease","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Mitochondrial Cytopathy","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Neurodegeneration With Brain Iron Accumulation","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Niemann-Pick Disease Type C","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Spinocerebellar Ataxia","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"condition","value":"Wilson's Disease","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"warning","value":"No primary patient data are included; all findings are based on a literature review of existing studies, many of which are small or case-level evidence for rare disorders.","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"warning","value":"Sample size tag omitted — this is a review with no single study population.","value_numeric":null},{"paper_doi":"10.1002/mdc3.70689","tag_type":"warning","value":"The 'impact_flag' of practice_changing reflects the clinical utility of the diagnostic framework for treatable conditions, not a new trial result.","value_numeric":null}],"summaries":{"what_studied":"A PubMed literature review (January 2000–January 2025) examining inherited and metabolic disorders that present with both prominent chorea and cerebellar ataxia, with the goal of proposing a structured diagnostic and management approach.","key_result":"A defined set of conditions was identified with this dual phenotype — including spinocerebellar ataxias, Huntington's disease, DRPLA, ataxia telangiectasia, brain iron metabolism disorders, Wilson's disease, Niemann-Pick type C, ataxia with oculomotor apraxia, GLUT1 deficiency, and mitochondrial cytopathies — several of which are treatable if recognized early.","limitations":"Narrative/review design without systematic meta-analysis; no primary patient data; evidence quality depends on the underlying literature, which is largely limited to case series and small studies for rare disorders.","practice_takeaway":"When a patient presents with both progressive ataxia and chorea, prioritize identifying treatable causes (Wilson's disease, GLUT1 deficiency, Niemann-Pick type C) early. A targeted genetic and metabolic workup guided by accompanying clinical features can significantly narrow the differential."}},{"doi":"10.1177/13872877261450168","pmid":"42191653","title":"Nancy Wexler: A personal and scientific memoir","journal_title":"Journal of Alzheimer’s Disease","journal_issn":"1387-2877","published_at":"2026-05-26T00:00:00.000Z","url":"https://doi.org/10.1177/13872877261450168","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-07T13:26:47.882Z","updated_at":"2026-06-07T13:26:47.882Z","tags":[{"paper_doi":"10.1177/13872877261450168","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1177/13872877261450168","tag_type":"condition","value":"Huntington's Disease","value_numeric":null},{"paper_doi":"10.1177/13872877261450168","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1177/13872877261450168","tag_type":"study_design","value":"Memoir / Narrative Review","value_numeric":null},{"paper_doi":"10.1177/13872877261450168","tag_type":"warning","value":"No sample size, population, or quantitative outcomes are reported; most structured tags are not applicable.","value_numeric":null},{"paper_doi":"10.1177/13872877261450168","tag_type":"warning","value":"This is a memoir/tribute article and contains no original clinical or experimental data. Summaries are based on limited metadata only — the full text was not available for detailed extraction.","value_numeric":null}],"summaries":{"what_studied":"A personal and scientific memoir about Nancy Wexler, recounting her contributions to the discovery of the Huntington's disease gene and her advocacy work in neurogenetics.","limitations":"As a memoir, this article reflects a personal perspective and does not present original experimental data or clinical outcomes."}},{"doi":"10.1186/s40035-026-00557-1","pmid":"42186042","title":"Ketogenic diet as a therapeutic strategy for neurodegenerative diseases: from mechanisms to translational challenges","journal_title":"Translational Neurodegeneration","journal_issn":"2047-9158","published_at":"2026-05-25T00:00:00.000Z","url":"https://doi.org/10.1186/s40035-026-00557-1","source_score":37,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-01T13:39:40.006Z","updated_at":"2026-06-01T13:39:40.006Z","tags":[{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"condition","value":"Huntington's Disease","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"condition","value":"Multiple Sclerosis","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"condition","value":"Parkinson's Disease","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"generic","value":"beta-hydroxybutyrate","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"generic","value":"medium-chain triglycerides","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"modality","value":"Dietary Intervention","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"modality","value":"Ketone Supplement","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"warning","value":"Clinical sample sizes are very small (many n<50 or single case studies); effect estimates should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"warning","value":"Most preclinical studies cited used male-only animals, limiting sex-balanced translational conclusions.","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"warning","value":"No original experimental data are presented; all conclusions are derived from cited literature.","value_numeric":null},{"paper_doi":"10.1186/s40035-026-00557-1","tag_type":"warning","value":"This is a narrative review without systematic meta-analytic methods; study selection may reflect author bias.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluates the ketogenic diet (KD) as a therapeutic strategy across five neurodegenerative diseases — Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), ALS, and multiple sclerosis (MS) — synthesizing preclinical and clinical evidence on its effects on mitochondrial function, oxidative stress, neuroinflammation, autophagy, and gut microbiota.","key_result":"Across diseases, KD and its primary ketone body β-hydroxybutyrate (BHB) consistently reduced neuroinflammatory markers (IL-1β, TNF-α, NF-κB, NLRP3), improved energy metabolism, and showed functional benefits in small clinical trials:\n- **AD**: MCT-based KD improved working memory and episodic memory (n=20 and n=52 studies); a randomized crossover trial (n=21 completers) showed improved daily function and quality of life over two 12-week periods.\n- **PD**: A pilot RCT (n=47, 38 completers, 8 weeks) improved non-motor UPDRS scores; a 24-week longitudinal study improved motor and non-motor outcomes.\n- **HD**: One case study (48 weeks) showed 52% motor improvement and 28% gain in daily living activities.\n- **ALS**: One case study (18 months) showed 7% functional improvement and 19% quality-of-life gain.\n- **MS**: A 6-month Phase II trial (n=64) improved fatigue, depression, and reduced leptin; an 18-month RCT sustained tolerability and disability score improvements.","limitations":"- Clinical evidence is largely from small pilots and single case studies, limiting generalizability.\n- Most animal studies used only male subjects, reducing translational relevance to mixed-sex populations.\n- Long-term safety data in neurodegenerative populations are scarce; adherence to the strict regimen remains a major barrier.","practice_takeaway":"KD may offer a metabolic adjunct to standard pharmacotherapy in AD, PD, HD, ALS, and MS — particularly by improving energy metabolism and reducing neuroinflammation — but current evidence is preliminary and should not replace disease-specific treatments. Clinicians considering KD for these patients should supervise nutritional adequacy, monitor for 'keto flu,' cardiovascular risk, and micronutrient deficiencies, and pair dietary initiation with structured adherence support."}},{"doi":"10.1016/j.freeradbiomed.2026.05.285","pmid":"42156213","title":"Dysregulation of arginase and arginine pathways in neurodegenerative diseases: Metabolic and cellular dysfunction and therapeutic implications","journal_title":"Free Radical Biology and Medicine","journal_issn":"0891-5849","published_at":"2026-05-19T00:00:00.000Z","url":"https://doi.org/10.1016/j.freeradbiomed.2026.05.285","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-26T13:34:58.477Z","updated_at":"2026-05-26T13:34:58.477Z","tags":[{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"condition","value":"Huntington's Disease","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"condition","value":"Parkinson's Disease","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"modality","value":"Arginase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"warning","value":"No sample size applies — this is a review article with no primary patient cohort. Sex of subjects is not reported at the review level.","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"warning","value":"The paper was published May 19, 2026; it is very recent and may not yet have undergone broad post-publication scrutiny.","value_numeric":null},{"paper_doi":"10.1016/j.freeradbiomed.2026.05.285","tag_type":"warning","value":"Therapeutic strategies discussed are proposed/preclinical; no approved arginase-targeted treatments for neurodegeneration are described.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates evidence for dysregulation of arginase isoenzymes and arginine metabolic pathways in Alzheimer's, Parkinson's, Huntington's diseases, and ALS, drawing on patient data and experimental models to explore mechanisms and therapeutic strategies.","key_result":"Disrupted arginase activity and arginine metabolism contribute to neurodegeneration via nitrogen metabolism imbalance, oxidative/nitrosative stress, mitochondrial dysfunction, and neuroinflammation across all four diseases reviewed; therapeutic targeting of arginase-related pathways is proposed to slow disease progression.","limitations":"As a narrative review, it synthesizes existing data without systematic meta-analytic methods. Evidence is largely from experimental models, with limited direct clinical trial data. Cell-, stage-, and disease-specific roles of arginase isoenzymes remain incompletely characterized.","practice_takeaway":"No approved arginase-targeted therapies exist yet, but this review highlights arginine metabolic pathways as a potential drug target in neurodegeneration. Clinicians should watch for emerging trials focused on arginase modulation in Alzheimer's, Parkinson's, Huntington's, and ALS."}},{"doi":"10.1080/00952990.2026.2645215","pmid":"42024796","title":"Alcohol and neurodegenerative diseases: a review of mechanistic insights and disease specific effects","journal_title":"The American Journal of Drug and Alcohol Abuse","journal_issn":"0095-2990","published_at":"2026-04-23T00:00:00.000Z","url":"https://doi.org/10.1080/00952990.2026.2645215","source_score":11,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:50:31.225Z","updated_at":"2026-05-07T22:50:31.225Z","tags":[{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"condition","value":"Alcohol Use Disorder","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"condition","value":"Amyotrophic Lateral Sclerosis","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"condition","value":"Huntington's Disease","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"condition","value":"Parkinson's Disease","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"modality","value":"Alcohol Exposure","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"warning","value":"No sample size is applicable as this is a review article with no primary cohort.","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"warning","value":"The 'dose-dependent' relationship described is based on epidemiological associations and should not be interpreted as establishing causality.","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"warning","value":"The review covers four distinct diseases with heterogeneous evidence bases; conclusions about ALS and HD are notably weaker than those for AD and PD.","value_numeric":null},{"paper_doi":"10.1080/00952990.2026.2645215","tag_type":"warning","value":"This is a narrative review without a registered protocol or systematic search strategy, so selective inclusion of studies cannot be excluded.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluated the effects of alcohol consumption on the onset and progression of four major neurodegenerative diseases — Alzheimer's disease (AD), Parkinson's disease (PD), ALS, and Huntington's disease (HD) — integrating human cohort epidemiological data with preclinical mechanistic studies.","key_result":"Chronic heavy alcohol consumption was linked to neurodegeneration via oxidative stress, mitochondrial dysfunction, neuroinflammation, dopaminergic impairment, and gut-brain axis disruption; epidemiological evidence most consistently tied heavy drinking to increased risk or accelerated progression of AD and PD, while evidence in ALS and HD remained inconsistent.","limitations":"As a narrative (not systematic) review, study selection was not protocol-driven and is susceptible to bias. Epidemiological findings are largely observational, limiting causal inference. Evidence for ALS and HD is sparse and inconsistent, reducing generalizability across all four diseases.","practice_takeaway":"Counsel patients — especially those with risk factors for AD or PD — that long-term heavy alcohol use may accelerate neurodegeneration. Minimizing alcohol consumption is a pragmatic, modifiable step that may reduce neurodegenerative risk."}},{"doi":"10.1002/alz.70944","pmid":"41528030","title":"Discovery of disrupted sustained attention and altered functional connectivity in far‐from‐onset Huntington's disease gene‐expanded young adults","journal_title":"Alzheimer's & Dementia","journal_issn":"1552-5260","published_at":"2026-01-13T00:00:00.000Z","url":"https://doi.org/10.1002/alz.70944","source_score":62,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-15","doi":"10.1002/alz.70944","days":"7","issn":"1552-5260","rank":"8","field":"Clinical Medicine","score":"62","category":"Clinical Neurology","categories":["Clinical Neurology"],"_categories":["Clinical Neurology"]},"pubmed":{"doi":"10.1002/alz.70944","title":"Discovery of disrupted sustained attention and altered functional connectivity in far-from-onset Huntington's disease gene-expanded young adults.","journal":"Alzheimer's & 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Resting‑state functional connectivity was altered in attention‑related circuits, including occipital, opercular, lentiform, and frontal regions.","limitations":"Modest sample size (n=71) from a single cohort of far‑from‑onset young adults limits generalizability. Imaging analyses were restricted to predefined regions of interest. Only two timepoints ≈4.7 years apart may miss subtler longitudinal change.","practice_takeaway":"Sustained attention is impaired early in HD gene carriers and remains stable over ~5 years, alongside connectivity changes; attention testing may serve as an early cognitive biomarker before motor onset."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Huntington's Disease"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Huntington's Disease"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Huntington's Disease"}}}]]

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