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:T45b,The concepts of brain health (ie, optimal functioning of the brain across cognitive, emotional, and behavioral domains throughout life) and cognitive resilience (ie, the ability of the brain to recover after an insult) have become increasingly important as the population ages. Previous research has called attention to vascular risk factors underlying cerebrovascular disease, as well as modifiable variables that contribute to premature aging and cognitive dysfunction. In this scientific statement, we focus on the role of nonvascular physical and psychologic variables that affect brain health across the life span. We provide a broad overview of influences such as chronic medical conditions, inflammation, environmental exposures, and socioeconomic drivers that affect the developing brain, along with factors including sleep quality, the gut microbiome, and mental health that contribute to neurodegeneration. We also review the varying strength of evidence supporting biologic mechanisms and mitigating strategies that may help optimize resilience, with the goal of providing a framework for future studies.31:T4cb, The concepts of brain health (ie, optimal functioning of the brain across cognitive, emotional, and behavioral domains throughout life) and cognitive resilience (ie, the ability of the brain to recover after an insult) have become increasingly important as the population ages. Previous research has called attention to vascular risk factors underlying cerebrovascular disease, as well as modifiable variables that contribute to premature aging and cognitive dysfunction. In this scientific statement, we focus on the role of nonvascular physical and psychologic variables that affect brain health across the life span. We provide a broad overview of influences such as chronic medical conditions, inflammation, environmental exposures, and socioeconomic drivers that affect the developing brain, along with factors including sleep quality, the gut microbiome, and mental health that contribute to neurodegeneration. We also review the varying strength of evidence supporting biologic mechanisms and mitigating strategies that may help optimize resilience, with the goal of providing a framework for future studies. 32:T614,While omega-3 fatty acid supplementation is widely used for cognitive protection, its efficacy remains controversial, and its impact on core Alzheimer's disease (AD) pathologies in humans is not well-established. This longitudinal study utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We employed linear mixed-effects models to assess the association between omega-3 supplementation and longitudinal cognitive decline, and mediation analyses to examine whether this relationship was mediated by core AD pathologies (Aβ-PET, tau-PET, T1-MRI, FDG-PET). Omega-3 supplementation was associated with significantly accelerated cognitive decline, as evidenced by a faster decrease in MMSE scores (β = -0.266, p < 0.001) and a faster increase in both ADAS-Cog13 (β = 0.823, p < 0.001) and CDR-SB scores (β = 0.205, p < 0.001). This association was not mediated by Aβ deposition, tau pathology, or gray matter atrophy. Instead, longitudinal FDG hypometabolism within AD-vulnerable regions served as a significant mediating pathway, accounting for 30.8%, 40.8%, and 19.0% of the total effect on the decline in MMSE, ADAS-Cog13, and CDR-SB, respectively. Omega-3 supplementation may be associated with accelerated cognitive decline in older adults, potentially through adverse effects on cerebral synaptic function rather than classical AD proteinopathies. These findings challenge the prevailing view of omega-3 as uniformly beneficial and highlight the need for a cautious reassessment of its widespread use for cognitive protection.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Cognitive Decline: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Cognitive Decline (condition). Clinician-written summaries and actionable practice insights. 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no aggregate N is meaningful.","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06812-4","tag_type":"warning","value":"Study design tagged as 'Narrative Review'; level of evidence set to 5 (expert opinion/narrative review) per standard hierarchy.","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06812-4","tag_type":"warning","value":"The review is not systematic and explicitly uses a convenience sample of cohorts, so publication and selection bias in cohort inclusion cannot be ruled out.","value_numeric":null},{"paper_doi":"10.1007/s00125-026-06812-4","tag_type":"warning","value":"Two authors (FR and AB) are Associate Editors of Diabetologia, the publishing journal; potential editorial conflict of interest is disclosed but should be noted.","value_numeric":null}],"summaries":{"what_studied":"This narrative review synthesizes 50 years of observational cohort research on type 2 diabetes (T2D), drawing on data from general population-based, disease-based, intervention-based, and registry-based cohorts across every continent, organized around four themes: diagnosis/screening, complications, risk factors, and pathophysiology.","key_result":"Key findings include: ≥50% of adults with T2D were previously undiagnosed in multiple cohorts; HbA1c ≥48 mmol/mol (6.5%) is validated as a diagnostic threshold via retinopathy association; screen-detected T2D carries a ~twofold lower all-cause mortality than clinically diagnosed T2D; T2D confers ~double the CVD risk in men and ~triple in women vs. those without T2D; 91% (95% CI 83–95%) of T2D cases were attributed to modifiable lifestyle factors in the Nurses' Health Study; and five reproducible T2D subtypes (ANDIS/German Diabetes Study) show distinct complication profiles.","limitations":"- Narrative (not systematic) review; cohort selection was a convenience sample, so many cohorts and findings may be omitted.\n- Historical cohorts systematically under-represent young adults, workers, low-SES groups, and non-European ethnicities, limiting generalizability and risking lead-time bias in screening studies.\n- Observational designs are inherently prone to unmeasured confounding; causal inference requires complementary RCT evidence.","practice_takeaway":"Cohort evidence supports targeted T2D screening using validated risk scores (e.g., Indian Diabetes Risk Score), with HbA1c ≥48 mmol/mol as a reliable diagnostic cut-off. Clinicians should address the full spectrum of T2D comorbidities—including cognitive decline, cancer, mental health, and musculoskeletal disease—not just cardiovascular and microvascular outcomes."}},{"doi":"10.1111/jgh.70695","pmid":"42634002","title":"Methodological Considerations Regarding the Association Between Gastrointestinal Symptoms and Cognitive Decline in Parkinson's Disease","journal_title":"Journal of Gastroenterology and Hepatology","journal_issn":"0815-9319","published_at":"2026-08-23T00:00:00.000Z","url":"https://doi.org/10.1111/jgh.70695","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-01T06:21:14.216Z","updated_at":"2026-09-01T06:21:14.216Z","tags":[{"paper_doi":"10.1111/jgh.70695","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"condition","value":"Gastrointestinal Symptoms","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"condition","value":"Parkinson's Disease","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"study_design","value":"Commentary","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"warning","value":"Full text was not provided; summary is based solely on the title, journal, and DOI metadata. Key arguments and specific methodological concerns could not be extracted.","value_numeric":null},{"paper_doi":"10.1111/jgh.70695","tag_type":"warning","value":"This paper appears to be a methodological commentary or letter, not an original research study — no primary data, sample size, or quantitative results are available from the provided metadata.","value_numeric":null}],"summaries":{"what_studied":"This paper examines methodological issues in studies evaluating the association between gastrointestinal (GI) symptoms and cognitive decline in Parkinson's disease (PD).","limitations":"The paper is a methodological commentary rather than an original study, so it does not provide primary data, effect sizes, or a study population of its own.","practice_takeaway":"Clinicians should interpret findings linking GI symptoms to cognitive decline in PD with caution, given the methodological concerns raised about existing studies in this area."}},{"doi":"10.1002/alz.71689","pmid":"42583866","title":"Social engagement and brain structure‐informed cognitive domain trajectories in older adults: The National Health and Aging Trends Study","journal_title":"Alzheimer's & Dementia","journal_issn":"1552-5260","published_at":"2026-08-12T00:00:00.000Z","url":"https://doi.org/10.1002/alz.71689","source_score":38,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-14T13:24:48.717Z","updated_at":"2026-08-14T13:24:48.717Z","tags":[{"paper_doi":"10.1002/alz.71689","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"condition","value":"Dementia Prevention","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"modality","value":"Social Engagement Intervention","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"sample_size","value":"n=6084","value_numeric":6084},{"paper_doi":"10.1002/alz.71689","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"study_design","value":"Longitudinal Cohort Study","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"warning","value":"Executive function was measured solely by clock drawing test, a single brief task with a narrow score range (0–5), which limits sensitivity to detect gradations of change.","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"warning","value":"Primary analyses used unweighted models to preserve representation of the oldest-old; survey-weighted sensitivity analyses yielded similar results but the choice of unweighted primary analysis should be noted.","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"warning","value":"The social engagement index was adapted from a 12-item version; only 9 items were available in NHATS, which may reduce comparability to the original validated index.","value_numeric":null},{"paper_doi":"10.1002/alz.71689","tag_type":"warning","value":"The study is observational; causal inference is limited by potential reverse causation (cognitively intact individuals may be more socially active at baseline). The authors acknowledge this.","value_numeric":null}],"summaries":{"what_studied":"This longitudinal observational study examined whether a brain-structure-informed social engagement index (9-item Felix Social Engagement Index) at baseline was associated with slower decline in memory, orientation, and executive function over 8 years (2011–2019) among 6,084 dementia-free, community-dwelling Medicare beneficiaries aged ≥65 (mean age 76.4 years), including the oldest-old.","key_result":"Higher baseline social engagement significantly attenuated aging-related cognitive decline across all three domains after 8 years: memory (β = 0.14; p < 0.001), orientation (β = 0.14; p < 0.001), and executive function (β = 0.05; p < 0.001). Benefits were incremental — the highest engagement quartile (scores 8–9) provided the greatest protection across all domains.","limitations":"- Reverse causation cannot be excluded: better baseline cognition may enable greater social engagement rather than the other way around.\n- NHATS lacks neuroimaging, so brain-structural links are inferred from a separate foundational DTI study, not directly measured here.\n- Cognitive assessment relies on brief screening subscales (word recall, clock draw, orientation items), not full neuropsychological batteries, risking ceiling/floor effects.","practice_takeaway":"Encourage older adult patients to engage broadly across multiple social activities — marriage/cohabitation, driving, clubs, volunteering, religious services — as cumulative breadth of engagement (not any single activity) is linked to slower decline in memory, orientation, and executive function over nearly a decade. Even in highly educated populations, incremental gains from greater social engagement are detectable."}},{"doi":"10.1212/wnl.0000000000218380","pmid":"42531540","title":"Association Between Consumption of Low- and No-Calorie Artificial Sweeteners and Cognitive Decline","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-07-30T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218380","source_score":210,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-08-06T13:22:16.718Z","updated_at":"2026-08-06T13:22:16.718Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"modality","value":"Artificial Sweetener","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"study_design","value":"Observational Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"warning","value":"Age group 'adult' is an assumption based on typical cognitive decline research populations; the actual age range is unverified.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"warning","value":"Only the paper title, DOI, journal, and publication date were provided — no abstract or full text. All structured content is based solely on the title and cannot be verified against study methods, results, or conclusions. Key fields such as key_result, sample_size, sex, level_of_evidence, and practice_takeaway could not be populated accurately. Please provide the abstract or full text for a complete extraction.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218380","tag_type":"warning","value":"Study design was inferred from the word 'association' in the title; this has not been confirmed from the source text.","value_numeric":null}],"summaries":{"what_studied":"This study examined the association between consumption of low- and no-calorie artificial sweeteners (LNCS) and cognitive decline, likely in an adult or older adult cohort over a defined follow-up period.","key_result":"The paper's specific findings (e.g., effect size, direction of association, or population subgroups affected) are not available in the provided source text; only the title and metadata were supplied.","limitations":"Full text was not provided, so material limitations specific to this study (e.g., self-reported dietary intake, observational design, confounding) cannot be verified or extracted."}},{"doi":"10.1080/13803395.2026.2703678","pmid":"42489366","title":"Latent variables in cognitive decline: introducing a behavioral-relational factor","journal_title":"Journal of Clinical and Experimental Neuropsychology","journal_issn":"1380-3395","published_at":"2026-07-23T00:00:00.000Z","url":"https://doi.org/10.1080/13803395.2026.2703678","source_score":7,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-07-28T14:02:28.370Z","updated_at":"2026-07-28T14:02:28.370Z","tags":[{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"condition","value":"Mild Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"sample_size","value":"n=422","value_numeric":422},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"warning","value":"RMSEA of 0.091 slightly exceeds the conventional acceptable threshold of 0.08; the authors characterize fit as adequate, but this is worth noting when interpreting model quality.","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"warning","value":"Sex breakdown of the sample is not reported in the abstract or results; the 'mixed' sex tag is inferred from the ADNI dataset's general composition.","value_numeric":null},{"paper_doi":"10.1080/13803395.2026.2703678","tag_type":"warning","value":"The study design is cross-sectional; the tag reflects this, though the ADNI longitudinal wave structure could suggest repeated-measures elements not detailed here.","value_numeric":null}],"summaries":{"what_studied":"This study used confirmatory factor analysis (CFA) on ADNI Wave 4 data (n=422) to test a two-factor latent variable model of cognitive decline: one factor capturing cognitive and functional (CF) performance, and a second capturing caregiver burden and behavioral/psychological symptoms of dementia (BR), across cognitively normal adults, MCI, and dementia groups.","key_result":"CFA supported a good-fitting two-factor model (CFI=0.964; RMSEA=0.091). CF factor loadings ranged r=−0.707 to 0.747 (p<0.0001); BR factor loadings ranged r=0.237 to 0.760 (p<0.0001). Both factors significantly tracked diagnosis severity: CF declined and BR increased from cognitively normal → MCI → dementia.","limitations":"- Cross-sectional ADNI data limits causal or longitudinal inference.\n- RMSEA of 0.091 slightly exceeds the conventional 0.08 threshold, suggesting modest model fit.\n- Sample was ADNI-derived, which skews toward well-educated, predominantly White volunteers, limiting generalizability.","practice_takeaway":"When evaluating patients for cognitive decline, clinicians should assess both cognitive/functional ability **and** caregiver burden plus neuropsychiatric symptoms — these are distinct dimensions that each track disease severity. Tools like the NPI and GDS capture a real, separate signal beyond standard cognitive tests."}},{"doi":"10.1016/s0140-6736(26)01278-x","pmid":"42442374","title":"Multidomain lifestyle intervention for the prevention of cognitive decline in at-risk older adults in Latin America (LatAm-FINGERS): a single-blind, multicentre, randomised controlled trial","journal_title":"The Lancet","journal_issn":"0140-6736","published_at":"2026-07-13T00:00:00.000Z","url":"https://doi.org/10.1016/s0140-6736(26)01278-x","source_score":193,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-17T13:24:17.255Z","updated_at":"2026-07-17T13:24:17.255Z","tags":[{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"condition","value":"Dementia Prevention","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"modality","value":"Multidomain Lifestyle Intervention","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"sample_size","value":"n=1065","value_numeric":1065},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"warning","value":"Cognitive score increases in both arms are likely influenced by practice effects from repeated testing — true neuroprotective benefit is difficult to isolate.","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"warning","value":"The comparator arm (FLI) is general health advice, not a true placebo; the cognitive benefit may partly reflect differential engagement intensity rather than specific intervention components.","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)01278-x","tag_type":"warning","value":"The study was funded solely by the Alzheimer's Association; potential for funder influence on trial design or reporting should be noted.","value_numeric":null}],"summaries":{"what_studied":"This 2-year single-blind RCT across 11 Latin American countries tested whether a culturally adapted, structured multidomain lifestyle intervention (SLI: diet, exercise, cognitive training, vascular risk management) outperformed a flexible lifestyle intervention (FLI: general health advice) on global cognitive function and trial feasibility in 1,065 adults aged 60–77 with elevated dementia risk.","key_result":"Global cognitive composite scores improved significantly more in the SLI group vs. FLI group (mean annual gain: 0.31 SD vs. 0.20 SD; between-group difference 0.11 SD/year, 95% CI 0.06–0.15; p<0.0001). Trial feasibility was supported: recruitment effectiveness 62%, SLI adherence 71.6%, and 2-year follow-up completion 82.3% overall. Adverse events were more frequent in the SLI group (412 vs. 66), mostly musculoskeletal symptoms; no deaths were intervention-related.","limitations":"- No active placebo in the FLI arm; differential contact time may inflate the apparent benefit of SLI.\n- Practice effects likely contributed to cognitive score gains in both groups, complicating interpretation of true prevention.\n- Higher dropout in the FLI group (20.2% vs. 15.2%) could bias between-group comparisons despite blinded outcome assessment.","practice_takeaway":"Clinicians managing older adults at high dementia risk in Latin America can consider structured multidomain lifestyle programs (combining exercise, diet, cognitive training, and vascular risk management) as a feasible, scalable strategy to slow cognitive decline. Musculoskeletal safety monitoring should be built into any physical activity component."}},{"doi":"10.1523/jneurosci.2274-25.2026","pmid":"42409639","title":"Mapping the Heart–Brain Continuum beyond Heart Failure: Why Neurology Matters","journal_title":"The Journal of Neuroscience","journal_issn":"0270-6474","published_at":"2026-07-06T00:00:00.000Z","url":"https://doi.org/10.1523/jneurosci.2274-25.2026","source_score":129,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-12T13:19:51.345Z","updated_at":"2026-07-12T13:19:51.345Z","tags":[{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"condition","value":"Coronary Artery Disease","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"condition","value":"Heart Failure","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"modality","value":"Diffusion-Weighted MRI","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"sample_size","value":"n=73","value_numeric":73},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"study_design","value":"Prospective Observational Cohort Study","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"warning","value":"Small sample size (n=73) and predominantly male cohort (73% male) may limit generalizability, particularly to female patients. The impact_flag 'practice_changing' is applied with caution given these constraints — findings are hypothesis-generating and require replication in larger, more diverse cohorts.","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"warning","value":"The paper is dated July 6, 2026, which is very recent; peer-review status and final publication details should be verified before clinical application.","value_numeric":null},{"paper_doi":"10.1523/jneurosci.2274-25.2026","tag_type":"warning","value":"The study is observational; mediation analysis establishes a statistical pathway but cannot confirm causality between cardiac dysfunction, brain microstructure, and cognitive decline.","value_numeric":null}],"summaries":{"what_studied":"A prospective observational cohort study (n=73; mean age 54.8 years) from the Leipzig Heart Study examined whether baseline cardiac dysfunction (LVEF, NT-proBNP) predicts gray matter microstructural integrity (mean diffusivity on DW-MRI) and whether that integrity mediates the link to cognitive performance, with ~3.5-year follow-up in patients with and without established heart failure.","key_result":"Lower baseline LVEF predicted greater future gray matter mean diffusivity across **all** 73 participants, including those without clinical heart failure. Higher NT-proBNP predicted extensive microstructural damage only in the established heart failure group. Increased mean diffusivity in Alzheimer's-vulnerable regions (cingulate and lingual gyri) significantly **mediated** the cardiac–memory performance association.","limitations":"- Small sample (n=73) limits statistical power and generalizability.\n- Predominantly male cohort (53/73; 73%) restricts sex-specific conclusions.\n- Single-center observational design precludes causal inference and may introduce selection bias.","practice_takeaway":"Routine cardiac biomarkers—particularly LVEF—may flag patients at risk for silent brain microstructural damage years before cognitive symptoms emerge, even without overt heart failure. Clinicians should consider early neurological surveillance in patients with reduced LVEF as a potential window for upstream dementia prevention."}},{"doi":"10.1007/s12529-026-10473-3","pmid":"42270971","title":"Behavioral Components of Life's Essential 8 Are More Strongly Associated with Cognitive Function than Clinical Factors in Chinese Older Adults","journal_title":"International Journal of Behavioral Medicine","journal_issn":"1070-5503","published_at":"2026-06-10T00:00:00.000Z","url":"https://doi.org/10.1007/s12529-026-10473-3","source_score":8,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-12T13:24:28.795Z","updated_at":"2026-06-12T13:24:28.795Z","tags":[{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"category","value":"Psychology, Clinical","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"condition","value":"Cardiovascular Health","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"condition","value":"Mild Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"modality","value":"Lifestyle Intervention","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"sample_size","value":"n=2527","value_numeric":2527},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"warning","value":"Cross-sectional design: associations cannot establish causality between LE8 behavioral components and cognitive outcomes. The paper does not provide longitudinal follow-up data.","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"warning","value":"Subgroup heterogeneity by sex and depressive status is noted but not fully characterized; interaction effects should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1007/s12529-026-10473-3","tag_type":"warning","value":"The study is limited to a single Chinese cohort (Ma'anshan), so findings may not generalize broadly. Cultural dietary patterns and lifestyle norms may differ meaningfully from other populations.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study examined how Life's Essential 8 (LE8) scores — including both behavioral (diet, sleep, physical activity, smoking) and clinical (blood glucose, lipids, blood pressure, BMI) components — relate to cognitive function and mild cognitive impairment (MCI) in 2,527 Chinese adults aged ≥65 from the Ma'anshan Healthy Aging Cohort.","key_result":"Each 10-point rise in LE8 score linked to a 0.532-point higher MMSE score (95% CI: 0.353–0.712, P<0.001) and a 16.5% lower MCI risk (OR=0.835, 95% CI: 0.742–0.945, P=0.004). Behavioral components (diet, sleep, physical activity) showed stronger associations with cognitive outcomes than clinical factors (blood glucose, lipids). Dose-response relationships were linear.","limitations":"- Cross-sectional design prevents causal inference about LE8 and cognitive outcomes.\n- Single Chinese cohort (Ma'anshan) may limit generalizability to other ethnic or geographic groups.\n- Subgroup analyses suggest effect heterogeneity by sex and depressive status, but the study was not powered to confirm these interactions.","practice_takeaway":"Encourage older adults to prioritize modifiable behaviors — especially diet quality, physical activity, and sleep — as these show the strongest links to cognitive health, even beyond managing blood glucose or lipids. Behavior-focused interventions may be the highest-yield strategy for preventing cognitive decline in this age group."}},{"doi":"10.1016/s0140-6736(26)00515-5","pmid":"42208562","title":"Alzheimer's disease neuropathology plasma biomarkers and cognition in midlife: a community-based cohort study","journal_title":"The Lancet","journal_issn":"0140-6736","published_at":"2026-05-28T00:00:00.000Z","url":"https://doi.org/10.1016/s0140-6736(26)00515-5","source_score":336,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-31T13:35:43.854Z","updated_at":"2026-05-31T13:35:43.854Z","tags":[{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"generic","value":"amyloid beta 40","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"generic","value":"amyloid beta 42","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"generic","value":"p-tau217","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"modality","value":"Plasma Biomarker","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"sample_size","value":"n=1350","value_numeric":1350},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"warning","value":"Effect modification by race and sex was noted as inconsistent — subgroup findings should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"warning","value":"Participant age range (53–69 years) spans both middle-aged and older-adult categories; 'midlife' framing used in the paper may not fully align with standard age-group definitions.","value_numeric":null},{"paper_doi":"10.1016/s0140-6736(26)00515-5","tag_type":"warning","value":"The study excluded individuals with probable dementia, so findings apply to a pre-dementia community population and may not generalise to clinical settings.","value_numeric":null}],"summaries":{"what_studied":"This cohort study examined plasma biomarkers of Alzheimer's disease neuropathology (Aβ42/40, p-tau217, and p-tau217/Aβ42 ratio) and their associations with cognitive performance and accelerated decline across five domains in 1,350 midlife adults (mean age 61 years) from the CARDIA study, a racially diverse US community sample assessed at years 30 and 35 (2020–22).","key_result":"AD neuropathology positivity ranged from 4–15% depending on biomarker; it was associated with worse processing speed (standardised difference −0.54 to −0.25) and executive function (−0.42 to −0.19), and with increased odds of accelerated verbal memory decline (Aβ42/40 OR 4.31, 95% CI 1.71–10.9; p-tau217/Aβ42 OR 2.44, 95% CI 1.16–5.13) and processing speed decline (p-tau217 OR 3.98, 95% CI 1.71–9.3; p-tau217/Aβ42 OR 3.35, 95% CI 1.77–6.35), with no association for global cognition or verbal fluency.","limitations":"- Single time-point plasma biomarker measurement limits causal inference and longitudinal tracking of neuropathology progression.\n- Amyloid PET validation cutpoints were applied to a community midlife sample, where their calibration may differ from clinical or older-adult populations.\n- Effect modification findings (stronger associations in women, Black participants, and APOE ε4 carriers) were not consistent across all biomarkers, limiting firm subgroup conclusions.","practice_takeaway":"Plasma AD biomarkers (especially p-tau217/Aβ42) can identify neuropathology in midlife adults before dementia onset, and positivity is linked to measurable cognitive decline in processing speed and verbal memory. Clinicians may consider midlife plasma screening to enable earlier risk-reduction counselling and timely pharmacological intervention."}},{"doi":"10.1001/jamaoto.2026.1050","pmid":"42207546","title":"Speech-in-Noise Ability and Longitudinal Cortical Thinning in Speech-Processing Networks","journal_title":"JAMA Otolaryngology–Head & Neck Surgery","journal_issn":"2168-6181","published_at":"2026-05-28T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13220155/","source_score":22,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:23:46.150Z","updated_at":"2026-06-10T14:23:46.150Z","tags":[{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"condition","value":"Age-Related Hearing Loss","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"condition","value":"Cortical Atrophy","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"modality","value":"Hearing Aid","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"modality","value":"Structural MRI","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"sample_size","value":"n=312","value_numeric":312},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"study_design","value":"Longitudinal Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"warning","value":"Full text was not accessible; structured data were extracted from the abstract and results sections only — fine detail on statistical covariates and subgroup analyses may be incomplete.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"warning","value":"Hearing aid duration data were collected but effect sizes for this variable are not reported in the abstract; the null finding for hearing aids should be interpreted cautiously given potential confounding by duration and adherence.","value_numeric":null},{"paper_doi":"10.1001/jamaoto.2026.1050","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the finding that peripheral audiometry alone is insufficient and SIN testing should be prioritized, but replication in other cohorts is needed before broad clinical adoption.","value_numeric":null}],"summaries":{"what_studied":"In 312 cognitively normal community-dwelling older adults (mean age 73.5 years) from the ASPREE trial, this longitudinal cohort study examined whether peripheral hearing thresholds, speech-in-noise (SIN) performance, or hearing aid use predicted cortical thinning and cognitive change over 3 years (MRI and cognitive data collected 2012–2017).","key_result":"Poorer baseline SIN performance — not peripheral hearing loss or hearing aid use — was independently associated with faster cortical thinning over 3 years in inferior parietal (β = −0.002), precuneus (β = −0.001), middle temporal cortex (β = −0.001), and superior temporal sulcus (β = −0.001) regions. No statistically significant link was found between audiometric hearing loss or hearing aid use and neurostructural change or cognitive decline.","limitations":"- Single cohort from one country (Australia/ASPREE trial) limits generalizability.\n- Cognitive outcomes relied on the Modified Mini-Mental State Examination, which may lack sensitivity to subtle early decline.\n- 3-year follow-up may be too short to detect hearing-aid-related neuroprotective effects.","practice_takeaway":"Speech-in-noise testing may flag neural vulnerability in older adults before cognitive decline becomes measurable — consider it as a routine screening tool alongside standard audiometry. Peripheral hearing thresholds alone appear insufficient to predict accelerated brain aging in this population."}},{"doi":"10.1177/13872877261450646","pmid":"42199003","title":"Differential associations of core and non-core plasma biomarkers with cognitive performance in Black adults","journal_title":"Journal of Alzheimer’s Disease","journal_issn":"1387-2877","published_at":"2026-05-27T00:00:00.000Z","url":"https://doi.org/10.1177/13872877261450646","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-08T13:46:49.856Z","updated_at":"2026-06-08T13:46:49.856Z","tags":[{"paper_doi":"10.1177/13872877261450646","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"generic","value":"glial fibrillary acidic protein","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"generic","value":"neurofilament light chain","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"generic","value":"phosphorylated tau181","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"modality","value":"Plasma Biomarker","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"sample_size","value":"n=334","value_numeric":334},{"paper_doi":"10.1177/13872877261450646","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"warning","value":"Follow-up duration was only 1 year; longitudinal findings should be interpreted cautiously as short-term trajectories may not reflect longer-term cognitive decline patterns.","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"warning","value":"Study design is described as both cross-sectional and longitudinal; the longitudinal component is limited and based on baseline biomarker levels only.","value_numeric":null},{"paper_doi":"10.1177/13872877261450646","tag_type":"warning","value":"The study enrolled only Black adults from a community-based cohort (ARCHES), so results may not generalize to other racial/ethnic groups or clinical settings.","value_numeric":null}],"summaries":{"what_studied":"Cross-sectional and longitudinal associations between core (amyloid, phosphorylated tau181) and non-core (NfL, GFAP) plasma biomarkers and cognitive performance in 334 community-based Black adults (mean age 64.6 years) from the ARCHES study, with up to 1-year follow-up.","key_result":"Cross-sectionally, higher brain-derived p-tau181 was linked to lower MoCA scores (p=0.04) and higher NfL to lower PACC scores (p=0.04). Longitudinally, higher baseline NfL and GFAP were each independently associated with faster cognitive decline (p<0.001 and p=0.018, respectively).","limitations":"- Follow-up was limited to one year, which may underestimate longer-term biomarker-cognition relationships.\n- Cross-sectional design for the primary biomarker analyses limits causal inference.\n- Single-cohort, community-based sample of Black adults may limit generalizability to other settings or subgroups.","practice_takeaway":"In Black adults, non-core plasma biomarkers NfL and GFAP may be especially useful for tracking cognitive aging and decline—consider including them alongside standard amyloid/tau panels in ADRD screening and research. Efforts to increase representation of Black adults in biomarker studies are needed to ensure equitable ADRD detection."}},{"doi":"10.1080/13697137.2026.2671583","pmid":"42166168","title":"Does MHT prevent or treat cognitive decline? Recent data converge on an answer","journal_title":"Climacteric","journal_issn":"1369-7137","published_at":"2026-05-21T00:00:00.000Z","url":"https://doi.org/10.1080/13697137.2026.2671583","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-31T13:35:44.839Z","updated_at":"2026-05-31T13:35:44.839Z","tags":[{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"condition","value":"Menopause","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"generic","value":"menopausal hormone therapy","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"modality","value":"Hormone Therapy","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"study_design","value":"Review","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"warning","value":"Full text of this article was not provided — only the citation metadata is available. All summary fields are based solely on the title and journal context; specific findings, sample sizes, and conclusions could not be verified.","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"warning","value":"Publication date is May 2026; this is a very recently published article and its conclusions may not yet have been incorporated into clinical guidelines.","value_numeric":null},{"paper_doi":"10.1080/13697137.2026.2671583","tag_type":"warning","value":"Study design is inferred as a narrative or literature review based on the title framing ('recent data converge'); this has not been confirmed from the full text.","value_numeric":null}],"summaries":{"practice_takeaway":"Clinicians should monitor emerging consensus data on MHT and cognition when counseling perimenopausal and postmenopausal patients about hormone therapy decisions.","key_result":"Recent data appear to converge toward a clearer answer on MHT's role in cognitive outcomes, though specific effect sizes and study-level numbers are not available from the provided source text.","limitations":"Full text is unavailable; conclusions, effect sizes, and specific study details cannot be verified or extracted from the abstract alone.","what_studied":"This paper reviews recent evidence on whether menopausal hormone therapy (MHT) prevents or treats cognitive decline in women, synthesizing converging data from recent studies."}},{"doi":"10.1212/wnl.0000000000218123","pmid":"42160746","title":"Smoking Cessation, Weight Change, and Risk of Dementia","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-05-20T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000218123","source_score":116,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-24T13:23:17.300Z","updated_at":"2026-05-24T13:23:17.300Z","tags":[{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"modality","value":"Smoking Cessation","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"sample_size","value":"n=32802","value_numeric":32802},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"warning","value":"Age group tagged as 'older_adult' based on mean age 60.5 years; the sample spans a wide range (SD 10.7 years) and may include some middle-aged adults.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"warning","value":"Impact flag 'practice_changing' applied given the large sample, long follow-up, and actionable interaction finding; however, residual confounding in an observational study means causality cannot be confirmed.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000218123","tag_type":"warning","value":"The >10 kg postcessation weight gain subgroup showed a point estimate suggesting increased dementia risk (HR 1.33), but the CI was wide and crossed 1.0 — interpret with caution.","value_numeric":null}],"summaries":{"practice_takeaway":"Counsel patients that quitting smoking reduces dementia risk within years, approaching never-smoker levels by ~7 years post-cessation. Pair cessation support with active weight management, as weight gain of >10 kg after quitting may negate the cognitive benefit.","what_studied":"This prospective cohort study examined whether smoking cessation and postcessation weight gain affect long-term dementia risk and cognitive trajectories in 32,802 dementia-free US adults (mean age 60.5 years) followed for up to 25 years (median 9.9 years) using data from the Health and Retirement Study (1995–2020).","key_result":"Quitting smoking during follow-up was associated with a 16% lower dementia risk vs. current smokers (HR 0.84, 95% CI 0.73–0.95), approaching never-smoker risk (~7 years post-cessation). Benefits were limited to those with ≤5 kg postcessation weight gain; >10 kg gain eliminated the protective effect (HR 1.33, 95% CI 0.87–1.82). Quitting also slowed cognitive decline by 0.19 points/decade (95% CI 0.00–0.38) on a 27-point scale.","limitations":"- Residual confounding cannot be excluded in this observational design.\n- Smoking status and body weight rely on self-report, introducing measurement error.\n- The >10 kg weight-gain subgroup had a wide CI crossing 1.0, limiting conclusions about that specific group."}},{"doi":"10.1002/alz.71477","pmid":"42151737","title":"Associations of the Lifestyle for Brain Health (LIBRA) index with cognitive functioning across adulthood: Variation by sex and socioeconomic status in the German National Cohort (NAKO)","journal_title":"Alzheimer's & Dementia","journal_issn":"1552-5260","published_at":"2026-05-18T00:00:00.000Z","url":"https://pub.dzne.de/record/287287","source_score":245,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-17T13:29:42.915Z","updated_at":"2026-06-17T13:29:42.915Z","tags":[{"paper_doi":"10.1002/alz.71477","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"condition","value":"Dementia","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"condition","value":"Depression","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"condition","value":"Hypertension","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"modality","value":"Lifestyle Risk Index (LIBRA)","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"sample_size","value":"n=149948","value_numeric":149948},{"paper_doi":"10.1002/alz.71477","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"warning","value":"LIBRA in adults under 40 is characterized by the authors as a descriptive tool for modifiable risk factor profiling — not validated as a predictor of future dementia risk in this age group.","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"warning","value":"The ~17% average response rate raises participation bias concerns; the analytic sample likely skews toward healthier, higher-functioning individuals, which could attenuate observed associations.","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"warning","value":"The incremental variance explained by LIBRA after covariate adjustment is small (Cohen f²=0.012), so clinical interpretation of the composite score for individual risk prediction should be tempered.","value_numeric":null},{"paper_doi":"10.1002/alz.71477","tag_type":"warning","value":"The LIBRA score was computed from 10 of 12 original factors (cognitive activity and healthy diet were unavailable), which may underestimate true modifiable risk burden — particularly the protective side of the score. Comparisons with studies using the full 12-factor LIBRA should be made cautiously.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study examined how the LIBRA (Lifestyle for Brain Health) index — a weighted composite of 10 modifiable dementia risk and protective factors — relates to cognitive functioning across adulthood (ages 20–75) in 149,948 community-dwelling Germans from the NAKO cohort baseline (2014–2019), with stratification by age group, sex, and socioeconomic status (SES).","key_result":"Higher (worse) LIBRA scores were consistently linked to lower cognitive functioning across all age groups, including young adults (20–29 years). In the unadjusted model, each 1-point LIBRA increase was associated with −0.129 SD lower cognition (R²=0.067); after full adjustment, the effect attenuated to −0.027 SD (R²=0.349, incremental Cohen f²=0.012). Behavioral/psychosocial risks (smoking 25%, depression 8.7%, physical inactivity 9.6%) peaked in younger adults; cardiovascular risks (hypertension 74.4%, hypercholesterolemia 43.8%) dominated in older adults. Men had higher LIBRA scores than women; lower SES groups had the highest LIBRA scores at every age.","limitations":"- Cross-sectional design prevents causal inference; reverse causation (lower cognition shaping lifestyle) cannot be excluded.\n- Two LIBRA factors (cognitive activity, healthy diet) were unavailable, and hearing impairment was available for <25% of the sample, limiting score completeness.\n- Low response rate (~17% average) and center-based recruitment likely underrepresent individuals with moderate-to-severe cognitive impairment, potentially underestimating LIBRA–cognition associations in older groups.","practice_takeaway":"Modifiable dementia risk factors — especially smoking, depression, obesity, and hypertension — are already common and linked to lower cognitive performance in adults as young as 20, suggesting that brain health prevention efforts should start well before midlife. Clinicians should pay particular attention to low-SES women, who show the steepest cognitive penalties associated with higher LIBRA scores in early adulthood."}},{"doi":"10.1161/strokeaha.125.053444","pmid":"42131939","title":"Prior Myocardial Infarction and Cognitive Decline: The REGARDS Cohort","journal_title":"Stroke","journal_issn":"0039-2499","published_at":"2026-05-14T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13178101/","source_score":107,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-20T13:23:29.265Z","updated_at":"2026-05-20T13:23:29.265Z","tags":[{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"condition","value":"Myocardial Infarction","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"condition","value":"Silent Myocardial Infarction","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"sample_size","value":"n=20923","value_numeric":20923},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"warning","value":"Impact flag 'practice_changing' was applied cautiously — the finding about silent MI and cognition is novel and clinically actionable, but replication in studies with more detailed cognitive assessments is needed.","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"warning","value":"The cognitive outcome measure (6-item telephone screener) is a coarse tool; the clinical significance of a -0.016 point annual difference on this scale is not directly interpretable without context on the scale's range and minimally important difference.","value_numeric":null},{"paper_doi":"10.1161/strokeaha.125.053444","tag_type":"warning","value":"The study enrolled participants from 2003–2007; changes in MI management over time may limit generalizability to current patients.","value_numeric":null}],"summaries":{"what_studied":"This study examined whether prior MI — classified as self-reported, clinical (Q-wave + history), or silent (Q-wave without history) — was associated with longitudinal cognitive decline in 20,923 cognitively intact adults from the biracial REGARDS cohort, followed over a median of 10.1 years.","key_result":"Prior MI was associated with an excess adjusted annual global cognitive decline of -0.016 points (95% CI, -0.021 to -0.012). All three MI subtypes showed similar accelerated decline: self-reported (-0.016), clinical (-0.020), and silent (-0.015), all with P<0.001 or P=0.001.","limitations":"- Cognitive function was measured by a brief 6-item telephone screener, which may lack sensitivity for subtle decline compared to comprehensive neuropsychological testing.\n- 4,884 participants (23%) died during follow-up and were censored, introducing potential survival bias — those with worse outcomes may be underrepresented.\n- Causal mechanisms linking MI subtypes to cognitive decline cannot be established from this observational design.","practice_takeaway":"Patients with a history of MI — including those with silent MI detected incidentally on ECG — face accelerated cognitive decline and may warrant proactive cognitive monitoring. Routine ECG review could help flag at-risk individuals even without a clinical MI history."}},{"doi":"10.1016/j.immuni.2026.04.014","pmid":"42140192","title":"Aged circulating CD8+ T cells and their secreted factors drive cognitive decline","journal_title":"Immunity","journal_issn":"1074-7613","published_at":"2026-05-14T00:00:00.000Z","url":"https://doi.org/10.1016/j.immuni.2026.04.014","source_score":42,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-17T13:21:35.636Z","updated_at":"2026-05-17T13:21:35.636Z","tags":[{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"category","value":"Immunology","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"condition","value":"Brain Aging","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"generic","value":"granzyme K","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"modality","value":"Immune Cell Targeting","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"modality","value":"Serine Protease Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"study_design","value":"Preclinical Animal Study","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"warning","value":"Granzyme K (GZMK) is identified mechanistically but no approved inhibitor exists for clinical use as of the publication date.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"warning","value":"No sample size (n) was reported in the abstract; tag omitted accordingly.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"warning","value":"Study is entirely preclinical (mouse models); clinical relevance in humans is inferred but not yet tested.","value_numeric":null},{"paper_doi":"10.1016/j.immuni.2026.04.014","tag_type":"warning","value":"The 'practice_changing' flag reflects high mechanistic novelty, not yet established clinical practice change — human trials are pending.","value_numeric":null}],"summaries":{"what_studied":"This study investigated whether aged circulating (non-infiltrating) CD8+ T cells and their secreted factors drive hippocampal-dependent cognitive decline in aging, using heterochronic parabiosis, transcriptomics, and targeted inhibition experiments in mice.","key_result":"Systemic exposure of young mice to aged CD8+ T cells caused synaptic hippocampal changes and impaired cognition; inhibiting CD8+ T cell activation (but not brain infiltration) reversed pro-aging effects. Granzyme K (GZMK) was identified as a key secreted pro-aging factor — its inhibition rescued cognition in aged animals.","limitations":"Findings are currently from animal models (parabiosis and mouse experiments); direct translation to human cognitive aging is not yet established. The specific downstream synaptic mechanisms of GZMK are not fully characterized. Study does not address long-term safety of GZMK or CD8+ T cell activation inhibition.","practice_takeaway":"Aged CD8+ T cell activation and their circulating secreted factors — particularly GZMK — are emerging therapeutic targets for age-related cognitive decline. Clinicians should watch for trials targeting peripheral immune aging pathways as a novel strategy to preserve cognition in older adults."}},{"doi":"10.1161/str.0000000000000518","pmid":"42047038","title":"Brain Health Across the Life Span: A Framework for Future Studies: A Scientific Statement From the American Heart Association","journal_title":"Stroke","journal_issn":"0039-2499","published_at":"2026-04-28T00:00:00.000Z","url":"https://doi.org/10.1161/str.0000000000000518","source_score":117,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-01","doi":"10.1161/str.0000000000000518","days":"14","issn":"0039-2499","rank":"3","field":"Clinical Medicine","score":"117","category":"Clinical Neurology","categories":["Clinical Neurology"],"_categories":["Clinical Neurology"]},"pubmed":{"doi":"10.1161/STR.0000000000000518","title":"Brain Health Across the Life Span: A Framework for Future Studies: A Scientific Statement From the American Heart Association.","journal":"Stroke","methods":"","results":"","abstract":"$30","keywords":["AHA Scientific Statements","aging, premature","brain","cognition","mental health","resilience, psychological"],"pubmed_id":"42047038","conclusions":"","publication_date":"2026-04-28T00:00:00"},"crossref":{"DOI":"10.1161/str.0000000000000518","URL":"https://doi.org/10.1161/str.0000000000000518","ISSN":["0039-2499","1524-4628"],"link":[{"URL":"https://www.ahajournals.org/doi/full/10.1161/STR.0000000000000518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Brain Health Across the Life Span: A Framework for Future Studies: A Scientific Statement From the American Heart Association"],"author":[{"given":"Elisabeth Breese","family":"Marsh","sequence":"first","affiliation":[]},{"given":"Helen","family":"Lavretsky","sequence":"additional","affiliation":[]},{"given":"Nadine A.","family":"Kasparian","sequence":"additional","affiliation":[]},{"given":"Nancy A.","family":"Pike","sequence":"additional","affiliation":[]},{"given":"Kristian P.","family":"Doyle","sequence":"additional","affiliation":[]},{"given":"Neelum T.","family":"Aggarwal","sequence":"additional","affiliation":[]},{"given":"Heather J.","family":"Fullerton","sequence":"additional","affiliation":[]},{"given":"Autumn S.","family":"Ivy","sequence":"additional","affiliation":[]},{"given":"Nomazulu","family":"Dlamini","sequence":"additional","affiliation":[]},{"given":null,"family":null,"sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,4,28]]},"member":"276","prefix":"10.1161","source":"Crossref","volume":null,"created":{"date-time":"2026-04-28T09:00:20Z","timestamp":1777366820000,"date-parts":[[2026,4,28]]},"indexed":{"date-time":"2026-05-13T10:07:37Z","timestamp":1778666857098,"date-parts":[[2026,5,13]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.ahajournals.org/doi/10.1161/STR.0000000000000518"}},"subtitle":[],"assertion":[{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":3,"value":"2026-04-28"}],"deposited":{"date-time":"2026-05-13T09:08:38Z","timestamp":1778663318000,"date-parts":[[2026,5,13]]},"issn-type":[{"type":"print","value":"0039-2499"},{"type":"electronic","value":"1524-4628"}],"published":{"date-parts":[[2026,4,28]]},"publisher":"Ovid Technologies (Wolters Kluwer Health)","reference":[{"DOI":null,"key":"e_1_3_1_2_2","year":"2005","issue":null,"author":"Kinsella K","volume":"60","first-page":null,"unstructured":"Kinsella K, Phillips DR. 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Intervening early and across multiple domains offers the best opportunity to preserve cognitive resilience."}},{"doi":"10.1212/wnl.0000000000214803","pmid":"42030516","title":"Association of MRI-Visible Perivascular Spaces With Longitudinal Cognitive Decline Over a Decade","journal_title":"Neurology","journal_issn":"0028-3878","published_at":"2026-04-24T00:00:00.000Z","url":"https://doi.org/10.1212/wnl.0000000000214803","source_score":12,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-05T13:26:51.815Z","updated_at":"2026-06-05T13:26:51.815Z","tags":[{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"condition","value":"Cerebral Small Vessel Disease","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"condition","value":"Mild Cognitive Impairment","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"modality","value":"Neuroimaging Biomarker","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"sample_size","value":"n=750","value_numeric":750},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"study_design","value":"Longitudinal Observational Cohort Study","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"warning","value":"Beta coefficients represent effect per theoretical 0–100% PVS volume fraction increase; actual observed PVS values are much smaller, so absolute clinical effect sizes per individual patient are proportionally smaller than the reported betas.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"warning","value":"Data collection for the expansion cohort is ongoing; the 11-year follow-up had only 18 participants, so long-term estimates are based on sparse data at the latest time points.","value_numeric":null},{"paper_doi":"10.1212/wnl.0000000000214803","tag_type":"warning","value":"Level of evidence set to 2 (prospective cohort); no randomization or intervention was involved — this is observational only, causation cannot be established.","value_numeric":null}],"summaries":{"what_studied":"This longitudinal cohort study (Vanderbilt Memory and Aging Project) examined whether baseline MRI-visible perivascular space (PVS) burden — measured by deep learning on 3T MRI — independently predicts cognitive decline across multiple domains over up to 11 years (mean 4.9 ± 3.1 years) in 750 older adults (age 68 ± 9, 52% female) free of stroke or dementia, while accounting for other SVD markers (WMH, CMBs, lacunes).","key_result":"Higher basal ganglia PVS burden was independently associated with faster decline in executive function (β = −7.47; 95% CI −12.84 to −2.10) and visuospatial skills (Hooper Visual Organization Test β = −22.11; 95% CI −42.38 to −1.85) even after head-to-head adjustment for WMH, CMBs, and lacunes. White matter PVS showed no significant independent associations with longitudinal cognition.","limitations":"- The cohort excluded stroke, dementia, heart failure, and other major illnesses, making it healthier than average and limiting generalizability.\n- Attrition bias is likely, as sicker participants withdrew preferentially, potentially biasing results toward the null.\n- PVS quantification relied on T1-weighted images rather than preferred T2-weighted imaging, and the basal ganglia mask included ventricular regions.","practice_takeaway":"Clinicians reading brain MRIs in older adults should note basal ganglia PVS burden as a marker of future executive function and visuospatial decline, independent of white matter hyperintensities or microbleeds. Tracking PVS alongside other SVD markers may help identify patients at higher risk for domain-specific cognitive decline before symptoms are obvious."}},{"doi":"10.1001/jamaneurol.2026.0832","pmid":"42008251","title":"Brain Imaging Biomarkers and Cognitive Outcomes in a Multidomain Lifestyle Intervention","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-04-20T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13097035/","source_score":43,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-15T13:21:46.591Z","updated_at":"2026-06-15T13:21:46.591Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"modality","value":"Multidomain Lifestyle Intervention","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"sample_size","value":"n=983","value_numeric":983},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"warning","value":"Full text is under PMC embargo until April 20, 2027; summary is based solely on the abstract and reported results sections.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"warning","value":"Study was single-blind, not double-blind — allocation concealment may be imperfect for behavioral outcomes.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0832","tag_type":"warning","value":"The imaging subsample (n=983) represents ~51% of the parent POINTER trial (n=1943), which may limit generalizability due to potential selection bias.","value_numeric":null}],"summaries":{"what_studied":"This 2-year randomized clinical trial (POINTER Imaging ancillary study, n=983, ages 60–79) tested whether a structured high-intensity multidomain lifestyle intervention (physical activity, cognitive activity, nutrition, social engagement, cardiovascular monitoring) vs. a self-guided lower-intensity version affected brain imaging biomarkers (global Aβ burden, entorhinal cortex tau, hippocampal volume, white matter hyperintensity volume) and global cognition, and whether baseline brain characteristics predicted cognitive benefit.","key_result":"No intervention group differences were found in longitudinal cognitive or imaging outcomes. However, participants with lower baseline hippocampal volume showed greater cognitive benefit from the structured vs. self-guided intervention (0.077 SD; 95% CI, 0.022–0.132 vs. 0.002 SD; 95% CI, −0.037–0.041; interaction P = .03). The structured intervention also attenuated the negative association between rising entorhinal cortex tau and cognitive decline seen in the self-guided group (difference in association: 0.289; 95% CI, 0.029–0.550; interaction P = .03).","limitations":"- Only ~51% of parent trial participants underwent neuroimaging, raising the possibility of selection bias.\n- The study was single-blind, which may introduce performance or assessment bias.\n- Full text was not available; findings are based on the abstract and results sections only.","practice_takeaway":"A high-intensity multidomain lifestyle intervention did not change brain biomarker trajectories overall, but older adults with smaller hippocampal volumes at baseline may derive the most cognitive benefit — consider brain imaging to stratify who is most likely to respond to intensive lifestyle programs."}},{"doi":"10.1016/j.tjpad.2026.100569","pmid":"42000571","title":"The association between omega-3 supplementation and cognitive decline in older adults","journal_title":"The Journal of Prevention of Alzheimer's Disease","journal_issn":"2274-5807","published_at":"2026-04-19T00:00:00.000Z","url":"https://doi.org/10.1016/j.tjpad.2026.100569","source_score":167,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-04-19","doi":"10.1016/j.tjpad.2026.100569","days":"30","issn":"2274-5807","rank":"6","field":"Clinical Medicine","score":"167","category":"Clinical Neurology","categories":["Clinical Neurology"],"_categories":["Clinical Neurology"]},"pubmed":{"doi":"10.1016/j.tjpad.2026.100569","title":"The association between omega-3 supplementation and cognitive decline in older adults.","journal":"The journal of prevention of Alzheimer's disease","methods":"","results":"Omega-3 supplementation was associated with significantly accelerated cognitive decline, as evidenced by a faster decrease in MMSE scores (β = -0.266, p < 0.001) and a faster increase in both ADAS-Cog13 (β = 0.823, p < 0.001) and CDR-SB scores (β = 0.205, p < 0.001). This association was not mediated by Aβ deposition, tau pathology, or gray matter atrophy. Instead, longitudinal FDG hypometabolism within AD-vulnerable regions served as a significant mediating pathway, accounting for 30.8%, 40.8%, and 19.0% of the total effect on the decline in MMSE, ADAS-Cog13, and CDR-SB, respectively.","abstract":"$32","keywords":["Alzheimer","Amyloid-β","Cognitive","Omega-3","Tau","synaptic dysfunction"],"pubmed_id":"42000571","conclusions":"","publication_date":"2026-04-19T00:00:00"},"crossref":{"DOI":"10.1016/j.tjpad.2026.100569","URL":"https://doi.org/10.1016/j.tjpad.2026.100569","ISSN":["2274-5807"],"link":[{"URL":"https://api.elsevier.com/content/article/PII:S2274580726000932?httpAccept=text/xml","content-type":"text/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https://api.elsevier.com/content/article/PII:S2274580726000932?httpAccept=text/plain","content-type":"text/plain","content-version":"vor","intended-application":"text-mining"}],"page":"100569","type":"journal-article","issue":"6","score":1,"title":["The association between omega-3 supplementation and cognitive decline in older adults"],"author":[{"given":"Zheng-Bin","family":"Liao","sequence":"first","affiliation":[]},{"given":"Zi-Cheng","family":"Hu","sequence":"additional","affiliation":[]},{"given":"Gui-Hua","family":"Zeng","sequence":"additional","affiliation":[]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Xin-Peng","family":"Li","sequence":"additional","affiliation":[]},{"given":"Yu-Hui","family":"Liu","sequence":"additional","affiliation":[]},{"given":"Xiu-Qing","family":"Yao","sequence":"additional","affiliation":[]},{"given":"Ye-Ran","family":"Wang","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/100016834","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100016834","name":"Chongqing Municipal Health Commission","doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/501100001809","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100001809","name":"National Natural Science Foundation of China","award":["82371435"],"award-info":[{"award-number":["82371435"]}],"doi-asserted-by":"publisher"}],"issued":{"date-parts":[[2026,6]]},"member":"78","prefix":"10.1016","source":"Crossref","volume":"13","created":{"date-time":"2026-04-17T09:20:01Z","timestamp":1776417601000,"date-parts":[[2026,4,17]]},"indexed":{"date-time":"2026-05-11T10:08:21Z","timestamp":1778494101381,"date-parts":[[2026,5,11]]},"license":[{"URL":"https://www.elsevier.com/tdm/userlicense/1.0/","start":{"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000,"date-parts":[[2026,6,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://www.elsevier.com/legal/tdmrep-license","start":{"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000,"date-parts":[[2026,6,1]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"http://creativecommons.org/licenses/by/4.0/","start":{"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000,"date-parts":[[2026,4,7]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":null,"language":"en","relation":{},"resource":{"primary":{"URL":"https://linkinghub.elsevier.com/retrieve/pii/S2274580726000932"}},"subtitle":[],"assertion":[{"name":"publisher","label":"This article is maintained by","value":"Elsevier"},{"name":"articletitle","label":"Article Title","value":"The association between omega-3 supplementation and cognitive decline in older adults"},{"name":"journaltitle","label":"Journal Title","value":"The Journal of Prevention of Alzheimer's Disease"},{"name":"articlelink","label":"CrossRef DOI link to publisher maintained version","value":"https://doi.org/10.1016/j.tjpad.2026.100569"},{"name":"content_type","label":"Content Type","value":"article"},{"name":"copyright","label":"Copyright","value":"© 2026 The Authors. 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Impairment","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"generic","value":"fish oil","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"generic","value":"omega-3 polyunsaturated fatty acids","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"modality","value":"Omega-3 Fatty Acid Supplementation","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"sample_size","value":"n=819","value_numeric":819},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"study_design","value":"Longitudinal Observational Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"warning","value":"Omega-3 exposure was primarily fish oil; findings may not apply to purified EPA/DHA formulations with lower oxidative risk.","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"warning","value":"The harmful association contradicts most prior RCT evidence; authors acknowledge healthy-user bias and unmeasured confounding may not be fully excluded.","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"warning","value":"The level of evidence is rated 3 (matched cohort), not 1, despite statistically significant findings with mediation analysis.","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"warning","value":"The study population is predominantly White and highly educated, which limits generalizability to other demographic groups.","value_numeric":null},{"paper_doi":"10.1016/j.tjpad.2026.100569","tag_type":"warning","value":"This is an observational study using ADNI data with propensity-score matching — causal inference is not possible; a true randomized design was not used.","value_numeric":null}],"summaries":{"what_studied":"This longitudinal observational study used ADNI data to examine whether omega-3 supplementation (fish oil, flaxseed oil, krill oil) was associated with cognitive decline in 273 users vs. 546 propensity-score-matched non-users (ages 55–90, median follow-up 5 years), and whether core AD pathologies (Aβ-PET, tau-PET, MRI gray matter, FDG-PET) mediated that relationship.","key_result":"Omega-3 supplementation was linked to **faster cognitive deterioration** across all three scales: MMSE (β = −0.266/year, p < 0.001), ADAS-Cog13 (β = +0.823/year, p < 0.001), and CDR-SB (β = +0.205/year, p < 0.001). This was **not mediated** by Aβ, tau, or gray matter atrophy. FDG hypometabolism (synaptic dysfunction) was a significant mediator, explaining 30.8%, 40.8%, and 19.0% of the effect on MMSE, ADAS-Cog13, and CDR-SB, respectively.","limitations":"- **Unmeasured confounding**: despite propensity-score matching, residual confounders (e.g., cardiovascular disease, family history of dementia) could bias results.\n- **Exposure misclassification**: precise dosage and adherence data were unavailable for the full follow-up; formulation type (fish oil vs. other forms) could not be stratified.\n- **Generalizability**: cohort is predominantly White and highly educated; tau-PET data were limited, reducing power for tau-related analyses.","practice_takeaway":"Clinicians should not assume omega-3 supplements are uniformly safe for cognitive protection in older adults — this study raises a safety signal, particularly for long-term use of fish oil formulations. Until dose-, formulation-, and patient-specific evidence is clearer, routine omega-3 supplementation for dementia prevention warrants cautious reassessment."}}],"initialOffset":23,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Cognitive Decline"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Cognitive Decline"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Cognitive Decline"}}}]]

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