APOEResearch Wiki

A living synthesis mined nightly by VaultMiner. Domain: APOE / APOE4 genetics, Alzheimer's risk, cognition and brain-health research (peer-reviewed)

Last updated: 2026-08-03

Genetic Risk Factors

• APOE4 is a well-established genetic risk factor for Alzheimer's disease, with similar risk associations observed across Chinese, Japanese, Filipino, and non-Latino White populations (source: wu-2026-apoe-4-carriership-and-dementia-risk-over-10-years.md)
• The APOE4 allele shows prevalence ranging from 14% in Filipino to 25% in non-Latino White populations (source: wu-2026-apoe-4-carriership-and-dementia-risk-over-10-years.md)
• LILRB1 and SIRPA have been identified as novel immunoregulatory risk genes for Alzheimer's disease through proteome-wide association studies (source: walker-2026-alzheimer-s-disease-proteome-wide-association-study-implicates-adapt.md)
• In American Indian populations, the effect of APOE4 on Alzheimer's disease biomarkers such as p-tau217 and GFAP appears attenuated compared to non-Hispanic White populations, suggesting ancestry-specific differences in risk (source: matheson-2026-lt-i-gt-apoe-4-lt-i-gt-and-alzheimer-s-disease-biomarkers-in-an.md)
• Genetic risks, particularly APOE4, are primarily associated with amyloid-β and Tau pathology, while clinical risks are linked to neurodegeneration and social determinants of health (SDoH) risks are strongly associated with cognition (source: okorie-2026-orthogonal-contributions-of-genetic-clinical-and-social-determinants.md)
• CD33 and clusterin interact biophysically and genetically to modulate Alzheimer's disease risk, with CD33M splice isoform impairing amyloid plaque clearance (source: dodd-2026-cd33-and-clusterin-interact-biophysically-and-genetically-to.md)
• APOE4 and type 2 diabetes cooperatively accelerate amyloid-β and Tau neurodegeneration, with broader amyloid-β deposition in deep cortical areas and tau progression to posterior and frontal cortices in diabetic carriers (source: chen-2026-apolipoprotein-e-4-and-type-2-diabetes-cooperatively.md)
• Neither APOE status nor contemporary Alzheimer's disease polygenic risk scores predict SuperAging status, suggesting that exceptional late-life memory is not simply the inverse of common-variant Alzheimer's disease risk (source: piras-2026-superaging-is-not-the-inverse-of-common-variant-alzheimer-s.md)
• In a pooled analysis of 45,022 participants, APOE ε2/ε3 genotype is associated with lower dementia risk (HR 0.87), while APOE4 homozygosity is associated with dementia onset approximately 8 years earlier, with similar effects across Black and White participants (source: lakomski-2026-the-association-between-lt-i-gt-apoe-lt-i-gt-genotype-race-and-dem.md)
• The strength of the association between APOE4 and dementia differs by modifiable and non-modifiable risk factors. Low educational attainment had the strongest interaction effect, explaining up to 32.1% of the association. In women, high deprivation level, abnormal sleep duration, anxiety, and depression showed interaction effects (5-11.6%). Phenotypic adiposity was associated with increased dementia risk in APOE4 non-carriers but reduced risk in carriers (source: zhang-2026-heterogeneity-in-the-association-between-apoe-4-carrier.md)

Brain Structure and Function

• APOE4 carriers show diagnosis-specific variations in brain asymmetry patterns, challenging conventional aging models (source: hu-2026-variations-of-global-brain-asymmetry-are-associated-with.md)
• Hippocampal asymmetry provides complementary prognostic information to total hippocampal volume for memory decline, particularly in amyloid-β-negative individuals (source: ghanbarian-2026-hippocampal-asymmetry-captures-non-amyloid-related-risk-of-memor.md)
• Mid-life brain traits in medial temporal and frontal regions show genetic covariance with late-life memory performance, mapping to Alzheimer's disease-vulnerable regions (source: yang-2026-genetically-linked-brain-imaging-markers-of-memory-decline.md)
• Among midlife postmenopausal women, APOE4 carriers exhibit decreased activation and hippocampal functional connectivity during verbal encoding tasks, despite no differences in verbal memory performance or Alzheimer's disease biomarker levels (source: wugalter-2026-evidence-of-apoe4-related-brain-vulnerabilities-in-verbal-memory.md)
• Young APOE4 carriers (18-35 years) show no significant differences in spatial navigation or broader cognitive abilities compared to non-carriers, suggesting APOE4-related behavioral differences are minimal in young adulthood (source: graichen-2026-no-effects-of-apoe-4-on-spatial-navigation.md)
• Elevated BrainAGE values, derived from MRI, precede cognitive impairment and improve prediction of future cognitive decline, particularly in APOE4 carriers (source: moradi-2026-elevated-brainage-precedes-cognitive-impairment-and-improves-predict.md)
• Preserved glymphatic system function (high ALPS index) is associated with reduced conversion risk to dementia in APOE4 carriers, suggesting a potential mechanism for clinical resilience (source: saadawy-2026-lt-i-gt-apoe4-lt-i-gt-specific-glymphatic-effects-on-clinical-progr.md)
• Brain age gap (BAG) is moderately heritable, with common variants explaining up to 29% of phenotypic variance, and converges on pathways related to neurodevelopment, cytoskeletal stability, stress responsivity, and cellular maintenance (source: imms-2026-the-genetic-landscape-of-brain-ageing.md)
• Seven genes (PLEKHM1, MAPT, KANSL1, CRHR1, SPPL2C, ARHGAP27, and STH) are consistently associated with brain age across studies (source: imms-2026-the-genetic-landscape-of-brain-ageing.md)
• Middle-aged APOE4 carriers without PICALM risk alleles show subtle cortical thinning in the right temporal pole, though this finding did not survive multiple comparison correction (source: dzianok-2026-subtle-cortical-thinning-in-the-temporal-pole-in.md)
• Longitudinal MRI-derived change measures, combined with risk factors including APOE4 status, improve prediction of future brain atrophy (hippocampal, ventricular, total gray matter) and outperform single-timepoint MRI in identifying progression to mild cognitive impairment and dementia (source: hadji-2026-predicting-future-brain-atrophy-based-on-longitudinal-mri.md)
• In American Indian tribal elders, the effect of APOE4 on white matter microstructure is attenuated compared to non-Hispanic White participants, suggesting ancestry-specific differences in brain health (source: labounek-2026-reduced-effect-of-lt-i-gt-apoe4-lt-i-gt-on-white-matter-microstruc.md)

Biomarkers and Pathology

• Cerebrovascular reactivity impairment is present across Alzheimer's disease genotypes but more strongly linked to pathology in APOE3 carriers (source: di-2026-cerebrovascular-reactivity-and-plasma-p-tau181-in-alzheimer-s-disease.md)
• Glymphatic system dysfunction (measured by ALPS index) associates with regional white matter hyperintensities and plasma amyloid-β burden across the Alzheimer's disease continuum (source: chen-2026-glymphatic-dysfunction-associates-with-regional-white-matter-hyperinte.md)
• Zika virus infection induces persistent Tau phosphorylation in adult mice, associated with memory and social behavior impairments (source: calcagno-2026-zika-virus-infection-induces-a-persistent-accumulation-of.md)
• Plasma GFAP and p-tau217 are dominant predictors for Alzheimer's disease signature ROI thickness and cognitive impairment in amyloid-positive participants (source: kim-2026-relative-importance-of-blood-based-biomarkers-for-alzheimer-s-disease-s.md)
• In individuals with Down syndrome, CSF and plasma Tau biomarkers show differential increases across the Alzheimer's disease continuum, with plasma p-tau217 demonstrating the highest diagnostic accuracy (source: arranz-2026-csf-and-plasma-tau-biomarkers-in-the-down.md)
• Plasma p-tau217 shows utility for ruling out amyloid-β pathology in participants at risk for chronic traumatic encephalopathy, but it is unlikely to be useful for detecting chronic traumatic encephalopathy itself (source: miner-2026-plasma-phosphorylated-tau-217-in-participants-at-risk.md)
• Powassan virus infection induces amyloid-β accumulation and Trem2-ApoE-linked microglial activation in mice, mirroring Alzheimer's disease pathology (source: de-2026-single-cell-analysis-of-powassan-virus-infected-brains-reveals-age-depen.md)
• Six proteins (CXCL10, TTR, APOE, APOD, LGALS3BP, and LYZ) show dysregulation in temporal lobe epilepsy CSF, with CXCL10 and TTR emerging as key diagnostic markers (source: dai-2026-multilayer-validation-reveals-a-glia-associated-secretome-signature-in.md)
• JARID2 has been implicated in cerebral Tau deposition through common and rare variant analyses, suggesting a role in Tau pathology distinct from amyloid-β (source: gunasekaran-2026-common-and-rare-variant-analyses-implicate-lt-i-gt-jarid2-lt-i.md)
• Temporal lobe [[18F]PI-2620 binding is associated with genetic Alzheimer's disease risk, plasma p-tau217, female sex, and episodic memory deficits in cognitively unimpaired older adults (source: maass-2026-associations-of-sup-18-sup-f-pi-2620-binding-with-memory-and-phosphor.md)
• Plasma p-tau217 and p-tau181 are effective biomarkers for distinguishing biologically defined early-onset Alzheimer's disease from early-onset frontotemporal dementia, with discriminative performance further enhanced by incorporating neurofilament light (NfL), GFAP, and APOE4 status (source: kwon-2026-blood-based-multimodal-biomarker-models-for-differentiating-early-onse.md)
• In Parkinson's disease without dementia, plasma p-tau217 shows no significant association with cognitive impairment, suggesting Alzheimer's disease co-pathology is not a major contributor to early cognitive changes (source: kouchache-2026-association-between-plasma-phosphorylated-tau-217-and-cognition-i.md)
• Women with Parkinson's disease dementia exhibit greater amyloid-β plaque pathology burden than men, independent of APOE4 status, highlighting a sex-specific vulnerability to Alzheimer's disease co-pathology (source: dunckley-2026-greater-burden-of-alzheimer-s-co-pathology-in-women-with.md)
• Elevated CSF GAP-43 is associated with reduced cerebral glucose metabolism and cognitive impairment in individuals with mild cognitive impairment, suggesting synaptic dysfunction may contribute to metabolic deficits (source: ahmed-2026-elevated-csf-gap-43-is-associated-with-reduced-cerebral.md)
• LATE-NC (limbic-predominant age-related TDP-43 encephalopathy neuropathologic change) is significantly associated with Alzheimer's disease neuropathologic change, higher amyloid-β and Tau burden, hippocampal sclerosis, cerebral amyloid angiopathy, APOE4, and GRN in a meta-analysis (source: thompson-2026-clinical-genetic-and-neuropathologic-correlates-of-limbic-predomin.md)
• In a C. elegans model, loss of endogenous Tau (PTL-1) suppresses APOE4-induced patterned behavioral decline and axon dysmorphia, suggesting that tau acts downstream of APOE4 to cause progressive neurodegenerative phenotypes (source: cardona-2026-loss-of-endogenous-tau-suppresses-apoe4-induced-patterned-behaviora.md)
• The AlzoSure Predict Assay measures the unfolded conformational variant of p53 (U-p53AZ) in plasma. Higher U-p53AZ levels are independently associated with elevated CSF t-tau and p-tau181 at baseline and follow-up, but show no significant association with FDG-PET SUVR or cognitive scores. Its ability to distinguish cognitively normal individuals from those with mild cognitive impairment is modest (AUC = 0.617) (source: rajabpour-sanati-2026-diagnostic-performance-of-the-alzosure-predict-assay-and.md)

Microglia and Neuroinflammation

• Microglia transition from protective phagocytic phenotypes (M2, DAM1/2) in early Alzheimer's disease to pro-inflammatory and exhausted states (M1, terminal inflammatory microglia [TIM], lipid droplet-accumulating microglia [LDAM]) as pathology advances (source: ma-2026-microglia-in-alzheimer-s-disease-from-homeostatic-guardians-to.md)
• Key pathways including TREM2/SYK phagocytosis, Piezo1 mechanotransduction, TAM receptor signaling, and metabolic regulators (HK2, iron, APOE4-driven lipid metabolism) orchestrate microglial state transitions in Alzheimer's disease (source: ma-2026-microglia-in-alzheimer-s-disease-from-homeostatic-guardians-to.md)
• Microglia interact with astrocytes, T cells, and peripheral immune cells via IL-3, complement C3, MHC-I and MHC-II, forming glial-immune networks that modulate amyloid-β clearance, Tau propagation, and synaptic integrity (source: ma-2026-microglia-in-alzheimer-s-disease-from-homeostatic-guardians-to.md)
• Precisely targeting microglial functional states, rather than broad immunosuppression, is a promising disease-modifying strategy for Alzheimer's disease (source: ma-2026-microglia-in-alzheimer-s-disease-from-homeostatic-guardians-to.md)
• A hypothesis proposes that lipid droplet formation in activated microglia supports the redistribution of plasma membrane lipids required during morphological remodeling, with chronic exposure to amyloid-β reducing microglial branching and surface area, and transcriptomic analyses showing upregulation of genes involved in fatty acid synthesis and activation (source: rebeck-2026-plasma-membrane-remodeling-during-microglial-activation-a-hypothesis.md)
• In HIV-associated neurocognitive disorders (HAND), single-nucleus multiomic analysis reveals immune-metabolic reprogramming consistent with maladaptive trained immunity (TRIM), with microglia showing enrichment of innate immune signaling, upregulation of inflammatory mediators including NLRP3, TLR2, and TLR4, coordinated cholesterol remodeling, and partial glycolytic reprogramming (source: martinez-2026-single-nucleus-multiomic-analysis-reveals-immune-metabolic-reprogr.md)

Diagnostic Tools and AI

• NeuroOmics-Net is a multimodal deep learning framework that integrates structural MRI (sMRI), EEG, and gene expression data for Alzheimer's disease diagnosis and progression prediction, achieving 94.3% classification accuracy and an AUC of 0.975 for distinguishing normal controls, mild cognitive impairment, and Alzheimer's disease, and 93.7% accuracy for predicting conversion from stable to progressive mild cognitive impairment (source: kavitha-2026-neuroomics-net-an-interpretable-multimodal-deep-learning-framework.md)
• Fairness sensitivity analysis of NeuroOmics-Net revealed accuracy ranging from 90.8% (low-education, high-comorbidity proxy subgroup) to 96.1% (low-risk, high-reserve proxy subgroup), with a demographic parity gap of 5.3 percentage points, indicating performance varies across demographic subgroups (source: kavitha-2026-neuroomics-net-an-interpretable-multimodal-deep-learning-framework.md)
• Interpretability analysis of NeuroOmics-Net identified clinically relevant biomarkers including hippocampal and entorhinal atrophy, theta-alpha EEG alterations, and APOE-associated molecular pathways (source: kavitha-2026-neuroomics-net-an-interpretable-multimodal-deep-learning-framework.md)
• Because sMRI, EEG, and gene expression data were sourced from separate, unpaired cohorts, all cross-modal associations in NeuroOmics-Net reflect population-level statistical correspondence rather than within-subject physiological coupling (source: kavitha-2026-neuroomics-net-an-interpretable-multimodal-deep-learning-framework.md)
• A machine learning model (SVM with feature subset selection) using plasma biomarkers, APOE4 status, and CDR can predict cerebral amyloid-β deposition status, achieving an AUC of 0.80 when using a Centiloid threshold of 25 (source: chang-2026-alzheimer-s-disease-related-amyloid-deposition-prediction-based-on-pl.md)

Therapeutic Approaches

• Only 16-32% of memory clinic patients meet eligibility criteria for lecanemab therapy, with exclusions mainly due to negative biomarkers or advanced disease (source: ag-ero-rabes-2026-eligibility-for-lecanemab-therapy-in-a-biomarker-defined.md)
• A navigator-centered model can efficiently deliver amyloid-targeted therapy while supporting safety monitoring, with 13.2% ARIA rate observed (source: brosch-2026-the-indiana-university-brain-health-program-to-deliver.md)
• Carbosilane dendrimer-siRNA nanoplatform shows promise for blood-brain barrier delivery in Alzheimer's disease models (source: zawadzki-2026-tiered-evaluation-of-carbosilane-dendrimer-sirna-nanoplatform-from.md)
• Specialist memory-clinic patients with early symptomatic Alzheimer's disease show high endorsement for lecanemab treatment and EU approval, though support declines in the context of APOE4 homozygosity (source: v-glein-2026-attitudes-of-specialist-memory-clinic-patients-with-early-symptomat.md)
• The KetoFLEX 12/3 diet shows potential for supporting cognitive health through mechanisms targeting insulin signaling, mitochondrial function, and neuroinflammation, though evidence remains preliminary (source: rao-2026-ketoflex-12-3-diet-and-cognitive-health-a-precision-nutrition.md)
• Italian dementia care systems show significant gaps in readiness for anti-Aβ therapies, with specialized centers outperforming primary clinics in diagnostic quality (source: giorelli-2026-preparedness-and-quality-of-dementia-care-in-an.md)
• The traditional Chinese formula Qifuyin improves cognitive performance, lipid metabolism (reducing triglycerides and ApoB, increasing HDL-C), and alters gut microbiota composition in APOE4 transgenic mice, suggesting potential benefits for APOE4-associated cognitive and systemic dysfunction (source: yu-2026-therapeutic-effects-of-the-traditional-chinese-formula-qifuyin.md)
• Lecanemab treatment is associated with greater amyloid-β reduction at the mild cognitive impairment stage than in dementia, with faster amyloid clearance observed in earlier disease stages (source: kim-2026-six-month-real-world-amyloid-pet-outcomes-after-lecanemab-greater.md)
• Leuconostoc mesenteroides lysate shows neuroprotective potential in an Alzheimer's disease model by attenuating amyloid-β-induced oxidative stress and restoring mitochondrial homeostasis, potentially via modulation of APOE expression (source: altves-2026-systems-pharmacology-and-targeted-transcriptional-profiling-suggest.md)
• Anti-amyloid immunotherapies like lecanemab and donanemab show modest cognitive benefits (20-30% slowing of decline) primarily in early-stage Alzheimer's disease with low Tau co-pathology, but face limitations including high ARIA risk in APOE4 carriers, treatment costs, and incomplete recovery (source: mcdiarmid-2026-sustaining-drug-discovery-amid-the-limits-of-alzheimer-s.md)
• In Japanese individuals from the J-ADNI study, baseline Clinical Dementia Rating-Global Score (CDR-GS) and Mini Mental State Examination (MMSE) strongly predict the therapeutic time window for lecanemab and donanemab, with survival probabilities for remaining eligible at 12 and 24 months being 82% and 69% (MCI) versus 51% and 38% (AD) in the lecanemab group, and 92% and 81% (MCI) versus 69% and 52% (AD) in the donanemab group (source: nakashima-2026-therapeutic-time-window-of-disease-modifying-therapy-for-early.md)

Comorbidities and Risk Factors

• Chronic pain combined with APOE4 carriership is associated with greater longitudinal worsening of brain structure and cognitive function (source: bell-2026-chronic-pain-as-a-risk-factor-for-alzheimer-s.md)
• Alcohol use disorder patients show cognitive improvement with prolonged abstinence, associated with normalization of plasma LPS and apolipoprotein levels (source: escudero-2026-longitudinal-cognitive-evolution-in-alcohol-use-disorder-patients.md)
• Lewy body dementia shares genetic risk factors with Alzheimer's disease including APOE and GBA (source: watkins-2026-understanding-the-genetic-imperfections-of-lewy-body-dementia.md)
• Poor oral health is primarily associated with late-onset dementia, particularly among individuals with elevated genetic susceptibility (source: liu-2026-differential-associations-of-oral-health-with-early-and.md)
• The neutrophil-to-lymphocyte ratio (NLR) is associated with cognitive performance in individuals with isolated REM sleep behavior disorder, suggesting a role for peripheral inflammation in early cognitive vulnerability to dementia (source: bortolin-2026-neutrophil-to-lymphocyte-ratio-is-associated-with-cognitive-perfor.md)
• Obstructive sleep apnea is associated with poorer memory and greater dementia risk, irrespective of APOE4 carriage, highlighting the need for early screening (source: abdelmessih-2026-associations-of-self-reported-obstructive-sleep-apnea-with-cogn.md)
• Diabetes and the metabolite ribitol are key predictors of mild cognitive impairment in Hispanic/Latino populations (source: wyss-2026-an-integrated-lifestyle-genetic-and-metabolomics-based-prediction-mode.md)
• Midlife vascular risk factors, including smoking, hypertension, diabetes, and obesity, are associated with late-life depressive symptoms, with higher burden of these factors increasing the odds of depression (source: kanetkar-2026-associations-of-midlife-vascular-risk-factors-with-late-life.md)
• Earlier age at menopause strengthens the associations between APOE4 and key Alzheimer's disease outcomes, including memory decline, brain atrophy, p-tau217 accumulation, and Aβ-PET burden (source: rabin-2026-age-at-menopause-apoe-4-and-alzheimer-s-disease-risk.md)
• Frailty (frailty index scores ≥0.25) is associated with 3.6% younger age at dementia diagnosis (equating to 2-3 years earlier), particularly in individuals with low neuropathologic burden (source: strating-2026-frailty-and-accelerated-dementia-onset-in-genetic-sociodemographic.md)
• Women account for nearly two-thirds of individuals with Alzheimer's disease and demonstrate important biological and clinical differences compared with men, including greater APOE4 risk, earlier Tau accumulation once amyloid pathology is present, and potential delayed diagnosis due to maintained verbal memory performance despite underlying pathology (source: just-2026-considerations-in-alzheimer-s-disease-in-women.md)
• Better cardiovascular health (measured by Life's Simple 7) is associated with lower white matter hyperintensity burden and greater cerebral blood flow over time, primarily benefiting cerebrovascular rather than Alzheimer's disease pathology pathways (source: denier-fields-2026-better-cardiovascular-health-measured-by-life-s-simple-7.md)
• Posttraumatic stress disorder is associated with Alzheimer's disease-relevant molecular alterations in the basolateral amygdala, including increased amyloid-β and pTau231 pathology, gliosis, and synaptic changes (source: seijo-2026-posttraumatic-stress-disorder-is-associated-with-alzheimer-s-disease.md)
• Persistent financial adversity (low household income, financial hardships) is associated with lower processing speed and verbal memory in midlife, followed by slower verbal memory decline attributable to lower baseline scores, and greater ventricular volume in later life, with associations linked to dementia risk (source: liu-2026-persistent-financial-adversity-and-cognitive-aging-a-life.md)
• Associations between financial adversity and brain atrophy are stronger for male participants, those with lower childhood socioeconomic circumstances, and APOE4 carriers (source: liu-2026-persistent-financial-adversity-and-cognitive-aging-a-life.md)

Cognitive Performance and Biomarkers

• VCAM-1 modifies the relationship between GFAP and cognitive performance in cognitively unimpaired Black adults, suggesting interconnected roles of astrocytic injury and endothelial activation in cognitive variability (source: singh-2026-associations-among-cognitive-performance-vcam-1-and-gfap-in.md)
• Instability in depressive symptoms predicts incident mild cognitive impairment and dementia in older adults, independent of APOE4 status (source: rutter-2026-depressive-symptom-instability-predicts-incident-mild-cognitive-impa.md)
• Among participants of European ancestry, there is a significant APOE4 dose-response relationship with Mini Mental State Examination (MMSE) scores, with homozygote carriers scoring lower than heterozygote carriers and non-carriers (source: lopez-2026-curation-of-mini-mental-state-examination-mmse-scores.md)
• Middle-aged adults with faster 15-year epigenetic aging trajectories (measured by DunedinPACE) showed worse processing speed, memory, executive function, and global cognition, as well as lower amyloid-β (Aβ42/Aβ40) levels, compared to typical agers (source: boeriu-2026-epigenetic-clock-trajectories-and-brain-health-in-midlife.md)

Nutritional Strategies

Dietary Quality and Cognitive Frailty

• In the TIGER cohort (n=519, mean age 72.7, 12-year follow-up), four dietary quality trajectories were identified. Compared with a Relatively Lower trajectory, a Relatively Higher dietary quality trajectory was associated with lower odds of traditional cognitive frailty (aOR=0.62) and impaired memory-frailty (aOR=0.48-0.50). Hill-Shaped and Valley-Shaped trajectories were also associated with lower odds of impaired memory-frailty (aOR=0.48-0.60) (source: lee-2026-longitudinal-association-between-dietary-quality-trajectories-and-cogni.md)
• The protective associations between higher dietary quality and cognitive frailty were more evident in participants aged ≥75 years, men, those with normal BMI, APOE4 non-carriers, and those without diabetes or hyperlipidemia, but with hypertension (source: lee-2026-longitudinal-association-between-dietary-quality-trajectories-and-cogni.md)

Specific Nutrients and Strategies

• Omega-3 fatty acids, particularly DHA, show cognitive benefits in mild cognitive impairment populations when administered at higher doses (≥1 g/day) and longer durations (≥6 months) (source: fernando-2026-nutritional-strategies-targeting-glucose-metabolism-to-slow-cognit.md)
• Ketogenic/MCT-based strategies improve cognitive function in mild cognitive impairment and early Alzheimer's disease, with effects tied to plasma ketone levels (source: fernando-2026-nutritional-strategies-targeting-glucose-metabolism-to-slow-cognit.md)
• Anserine/carnosine supplementation may improve verbal memory and executive function, particularly in adults aged ≥70 years and APOE4 carriers (source: fernando-2026-nutritional-strategies-targeting-glucose-metabolism-to-slow-cognit.md)

Shared Genetic Pathways in Neurodegeneration

• Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and frontotemporal dementia share common genetic pathways involving APOE, SNCA, MAPT, TARDBP, LRRK2, and HTT, with shared pathogenic mechanisms including protein misfolding, mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired autophagy (source: pattnaik-2026-exploring-shared-genetic-pathways-and-gene-interplay-in.md)

Sleep and Cognition

• Obstructive sleep apnea (OSA) is associated with a shift toward lighter sleep and reduced slow-wave and REM sleep, which are linked to deficits in attention, memory, and executive functions (source: amicucci-2026-sleep-architecture-impairment-and-cognitive-performance-in-obstruc.md)
• Severe OSA patients report subjective cognitive complaints despite normal objective screening scores, highlighting a critical window for early assessment (source: amicucci-2026-sleep-architecture-impairment-and-cognitive-performance-in-obstruc.md)
• REM-related OSA (REM-OSA) is associated with poorer verbal memory and cognitive vulnerability in APOE4 carriers (source: amicucci-2026-sleep-architecture-impairment-and-cognitive-performance-in-obstruc.md)
• CPAP treatment is associated with improvements in sleep architecture and cognitive performance, although recovery appears incomplete and variable across individuals (source: amicucci-2026-sleep-architecture-impairment-and-cognitive-performance-in-obstruc.md)

Personality and Biomarkers

• Higher neuroticism is associated with higher neurofilament light (NfL), while extraversion, openness, agreeableness, and conscientiousness are associated with lower NfL (source: terracciano-2026-personality-traits-and-blood-based-biomarkers-of-neurodegenerat.md)
• Conscientiousness remains a predictor of lower NfL even after adjusting for demographic, behavioral, and health-related factors (source: terracciano-2026-personality-traits-and-blood-based-biomarkers-of-neurodegenerat.md)
• Personality traits are generally unrelated to GFAP, though conscientiousness shows a marginal inverse association in basic models (source: terracciano-2026-personality-traits-and-blood-based-biomarkers-of-neurodegenerat.md)