Estrella ML, Wagner M, Wilson RS
… +4 more, Barnes LL, Bennett DA, Marquez DX, Lamar M
Alzheimers Dement
· 2026 May · PMID 42168763
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INTRODUCTION: Little is known about whether the cognitive benefits of cognitive activities and resources differ across ethno-racial groups in late-life. METHODS: Participants were 1702 non-Latino White, 766 non-Latino Bl...INTRODUCTION: Little is known about whether the cognitive benefits of cognitive activities and resources differ across ethno-racial groups in late-life. METHODS: Participants were 1702 non-Latino White, 766 non-Latino Black, and 324 Latino adults (≈ 76 years; N = 2792). Linear mixed-effects models tested interaction by ethno-racial group in the associations of lifespan (past and current) cognitive activity and total (past only) cognitive resources, respectively, with change in global cognition (GC) and five cognitive domains (≈ 8 ± 5 years). RESULTS: Significant interactions were observed: higher lifespan cognitive activity predicted slower decline in GC (but not in domains) among non-Latino White participants (estimate = 0.01, standard error [SE] = 0.01) and faster decline in GC (including working memory and perceptual speed domains) among Latino participants (estimate = -0.02, SE = 0.01); no association was observed among non-Latino Black participants. Total cognitive resources did not predict cognitive decline. DISCUSSION: Findings highlight ethno-racial differences in the association between lifespan cognitive activity and decline in global cognition among older adults.
Saeed A, Mckennan C, Clougherty JE
… +16 more, Zhou P, Tripathy S, Kinnee EJ, Duan J, Kip K, Zeng X, Villemagne V, Pascoal T, Mapstone M, Whitsel EA, Lopez OI, Ballantyne C, Karikari TK, Yu B, Reis S, Cohen A
Alzheimers Dement
· 2026 May · PMID 42165338
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INTRODUCTION: We examined the impact of mid-life metabolites on late-life Alzheimer's disease (AD) plasma biomarkers and whether these metabolites mediate air pollution effects. METHODS: In the Heart Strategies Concentra...INTRODUCTION: We examined the impact of mid-life metabolites on late-life Alzheimer's disease (AD) plasma biomarkers and whether these metabolites mediate air pollution effects. METHODS: In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) cohort, we applied high-dimensional regression and meditation models, adjusting for observed and latent confounders, with replication in the Atherosclerosis Risk in Communities (ARIC) study. Exposures included mid-life fine particulate matter (PM), black carbon, metals, and metabolites. Outcomes were: late-life plasma p-tau(181, 217, and 231) and amyloid beta 42/40 (Simoa assays). RESULTS: In the Heart SCORE study, seven lipid- and amnio acid-pathway metabolites measured in mid-life were significantly inversely associated with late-life p-tau181 levels (false discovery rate ≤ 15%) and showed a nominal inverse association with p-tau217 and 231 (P < 0.05). 2-aminobutyrate was associated with mid-life PM concentration (µg/m; β = -0.047; P = 4.0 × 10-4) and mediated the effect of PM on p-tau181 (P = 0.0057). Independent replication in the ARIC study confirmed the inverse association. DISCUSSION: Mid-life metabolite profiles, particularly 2-aminobutyrate, may predict and mediate air pollution-related AD risk. HIGHLIGHTS: Seven mid-life metabolites were inversely linked to late-life plasma phosphorylated tau (p-tau)181. 2-aminobutyrate was tied to fine particulate matter (PM), black carbon, and heavy metal exposure in two independent cohorts. 2-aminobutyrate may link pollution to Alzheimer's disease (AD) via oxidative stress pathways. This effect is specific to p-tau181, a marker of early AD changes. This is the evidence of a metabolic mediator between air pollution and AD risk.
Chatterjee A, Alvarez B, Sharma RU
… +8 more, Jonson C, Wilkins HM, Pa J, Swerdlow RH, Goate A, Yaffe K, Andrews SJ, Alzheimer's Disease Genetics Consortium and the Alzheimer's Disease Neuroimaging Initiative
Alzheimers Dement
· 2026 May · PMID 42163007
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INTRODUCTION: Mitochondrial DNA copy number (mtDNAcn), a measure of mitochondrial genomes per nucleated cell, has an unclear causal relationship with Alzheimer's disease (AD) and Parkinson's disease (PD). We integrated g...INTRODUCTION: Mitochondrial DNA copy number (mtDNAcn), a measure of mitochondrial genomes per nucleated cell, has an unclear causal relationship with Alzheimer's disease (AD) and Parkinson's disease (PD). We integrated genetic correlation, polygenic risk scores (PRSs), and Mendelian randomization (MR) to assess whether mtDNAcn influences the risk of AD and PD, and evaluate how study-specific factors in mtDNAcn genome-wide association studies (GWASs) distort these causal estimates. METHODS: Using GWASs of four mtDNAcn measures, AD, AD/dementia, and PD, we evaluated genetic correlations, generated ancestry-normalized PRS in the Alzheimer's Disease Genetics Consortium (N = 27,383), and applied MR methods including latent heritable confounder-MR (LHC-MR). RESULTS: Across the four mtDNAcn GWASs, only one was consistently associated with AD/dementia and PD, with genetic correlations and PRSs showing negative correlations and MR indicating that higher mtDNAcn reduced AD/dementia and PD risk. DISCUSSION: Higher blood-based mtDNAcn was causally associated with reduced risk of AD/dementia and PD, with limited evidence to suggest a bidirectional effect.
Li ZJ, Yang Z, Zhao D
… +10 more, Qiu YH, Wan WY, Huang ZK, Tian L, Qi RQ, Liu HG, Chen YH, Min DY, Xu XQ, Zhao WD
Alzheimers Dement
· 2026 May · PMID 42162956
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INTRODUCTION: Clearance of cerebral Aβ was primarily mediated by the brain endothelial transporters including LRP1. The regulatory mechanism of LRP1 expression remained unclear. METHODS: LRP1 in brain endothelial cells t...INTRODUCTION: Clearance of cerebral Aβ was primarily mediated by the brain endothelial transporters including LRP1. The regulatory mechanism of LRP1 expression remained unclear. METHODS: LRP1 in brain endothelial cells treated with pro-CTSD were analyzed by western blot. Transgenic mice with high circulatory pro-CTSD (hCTSD) were generated to assess LRP1 levels and brain Aβ deposition by immunostaining and live-imaging. Internalization of pro-CTSD and its co-localization with LRP1 was analyzed using confocal and TIRF microscopy. RESULTS: Circulatory pro-CTSD is increased in the AD models. hCTSD mice exhibited reduced endothelial LRP1 and impaired Aβ clearance. Soluble pro-CTSD bound the Cluster II domain of LRP1, triggering LRP1 endocytosis and lysosomal degradation. Crossing hCTSD mice with AD models increased brain Aβ deposition and exaggerated cognitive deficit. DISCUSSION: Circulatory pro-CTSD triggered degradation of brain endothelial LRP1 to inhibit brain-to-blood Aβ clearance.
Karthivashan G, Wang S, Wu Q
… +6 more, Dahal A, Li X, Galleguillos D, Sipione S, Thinakaran G, Kar S
Alzheimers Dement
· 2026 May · PMID 42162953
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INTRODUCTION: Elevated amyloid beta (Aβ) levels and aggregation contribute to neurotoxicity and development of Alzheimer's disease (AD), the leading cause of dementia in the elderly. While we reported that native poly(D,...INTRODUCTION: Elevated amyloid beta (Aβ) levels and aggregation contribute to neurotoxicity and development of Alzheimer's disease (AD), the leading cause of dementia in the elderly. While we reported that native poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, clinically used in drug delivery, suppress Aβ aggregation/toxicity, their effects in adult 5xFAD mice with advanced Aβ pathology remain unknown. METHODS: We evaluated the effects of native PLGA in 8-month-old male 5xFAD mice via chronic intracerebroventricular (ICV) infusion using mini osmotic pumps. Cognitive function, amyloid level/burden, synaptic integrity, and neurodegenerative events were assessed along with transcript levels in brain tissues using bulk RNA sequencing (RNA-seq). RESULTS: PLGA treatment reversed cognitive deficits, reduced Aβ levels/deposits, and attenuated neurodegenerative events. These effects were associated with modulation of Aβ production, oxidative stress, and lysosomal Aβ clearance. RNA-seq revealed transcriptional changes related to vesicle trafficking, immune activity, and redox regulation. DISCUSSION: Native PLGA, by targeting different facets of the Aβ axis, offer unique therapeutic potential in treating AD-related pathology.
Barbosa-Carvajal JP, García-García M, Gómez Navarro LF
… +8 more, Zubiri V, Gelvez N, López G, Reyes P, García-Cifuentes E, Aguillón D, Acosta-Uribe J, Matallana DL
Alzheimers Dement
· 2026 May · PMID 42162939
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INTRODUCTION: Pathogenic progranulin (GRN) variants are among the main genetic causes of frontotemporal lobar degeneration (FTLD). These variants have been predominantly reported in European cohorts, but their characteri...INTRODUCTION: Pathogenic progranulin (GRN) variants are among the main genetic causes of frontotemporal lobar degeneration (FTLD). These variants have been predominantly reported in European cohorts, but their characterization in Latin America remains scarce. We describe two Colombian cases with novel GRN variants with amnestic and semantic syndromes leading to an initial diagnosis of Alzheimer's disease (AD). METHODS: We conducted clinical, neuropsychological, neuroimaging, and genetic analysis. Biomarkers were included for one case. RESULTS: At 42 years old, Case 1 presented a predominant amnestic profile and carried the GRN c.21G > A (p.Trp7*) variant. Case 2 debuted with a semantic impairment at 62 years old and was a carrier of GRN c.1098T > A (p.Cys366*) variant. Brain imaging revealed asymmetric temporal atrophy, and biomarkers supported diagnosis of FTLD. DISCUSSION: GRN variants can mimic early-onset AD. An integrative approach including serial clinical, genetic, brain imaging, and biomarker analysis are essential for diagnosing Amnestic variants of FTLD in admixed genetic populations.
INTRODUCTION: The degeneration of basal forebrain cholinergic neurons is a key pathophysiological feature of Alzheimer's disease (AD). These cholinergic neurons target cortical neurons including those in the granular ret...INTRODUCTION: The degeneration of basal forebrain cholinergic neurons is a key pathophysiological feature of Alzheimer's disease (AD). These cholinergic neurons target cortical neurons including those in the granular retrosplenial cortex (RSG) to facilitate essential cognitive functions. At the cellular level, acetylcholine supports working memory by inducing persistent firing that outlasts the stimulus, but how such cholinergic-induced persistent firing is altered in AD remains unknown. METHODS: Using multiscale molecular and cellular analyses, we investigated neuron type-specific transcriptomic and physiological impairments of cholinergic persistent signaling in the RSG of 5xFAD mice. RESULTS: Cholinergic inputs to RSG were reduced in 5xFAD mice. Expression of the Chrm1 gene encoding M1 muscarinic receptors was also reduced in RSG neurons, coupled with impaired cellular persistent firing. DISCUSSION: The loss of M1 receptors suggests that allosteric M1 modulators being considered for treatment of AD symptoms may not be as effective on key cell types, necessitating further multiscale investigation.
INTRODUCTION: There is a critical need to identify risk factors of Alzheimer's disease and related dementias (ADRD). METHODS: We included 1227 participants (mean age [standard deviation]: 74.1 [7.9] years) from the Multi...INTRODUCTION: There is a critical need to identify risk factors of Alzheimer's disease and related dementias (ADRD). METHODS: We included 1227 participants (mean age [standard deviation]: 74.1 [7.9] years) from the Multi-Ethnic Study of Atherosclerosis with brain MRI scans. We investigated joint associations of 13 natural, social, and built-environment exposures with gray matter volume (GMV) (n = 1219), white matter fractional anisotropy (WM FA) (n = 1102), and white matter hyperintensity volume (n = 1210) using weighted quantile sum regression. RESULTS: A one-decile increase in all harmful exposures was associated with lower GMV and WM FA; however, associations were null when adjusting for study site. DISCUSSION: Examining the impact of many environmental factors simultaneously may provide insight into important modifiable risk factors for ADRD, capturing concomitant exposures as they are experienced.
INTRODUCTION: Both short and long sleep duration have been associated with Alzheimer's disease (AD) risk, yet the nature of the non-linear associations between sleep quantity and blood-based biomarkers of AD and neurodeg...INTRODUCTION: Both short and long sleep duration have been associated with Alzheimer's disease (AD) risk, yet the nature of the non-linear associations between sleep quantity and blood-based biomarkers of AD and neurodegeneration remains understudied. METHODS: Among 2410 Framingham Heart Study participants (mean age: 70.0 ± 8.45 years; 55.2% female), we examined associations between self-reported sleep duration and plasma phosphorylated tau (p-tau)181, total tau, neurofilament light chain, and glial fibrillary acidic protein using restricted cubic splines (RCS) and categorical comparisons (≤ 6, > 6-< 9 reference; ≥ 9 hours). RESULTS: RCS revealed non-linear associations between sleep duration and p-tau181 (overall p = 0.005; non-linearity p = 0.002), with higher levels at ≥ 8.5 hours, after adjusting for age, sex, apolipoprotein E ε4 genotype, sleep apnea, depression, and kidney function. Categorical comparisons showed no association in adjusted models. DISCUSSION: Sleep duration exhibits robust non-linear associations with p-tau181. Findings underscore the importance of non-linear modeling in relating sleep to blood-based biomarkers. Longitudinal studies are needed to clarify temporal relationships and mechanistic pathways.
Alzheimers Dement
· 2026 May · PMID 42151744
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BACKGROUND: Effects of blood pressure (BP) control on the relationships between arterial stiffness and subsequent cognitive impairment remain unclear. METHODS: The Systolic Blood Pressure Intervention Trial Pulse Wave Ve...BACKGROUND: Effects of blood pressure (BP) control on the relationships between arterial stiffness and subsequent cognitive impairment remain unclear. METHODS: The Systolic Blood Pressure Intervention Trial Pulse Wave Velocity (PWV) substudy evaluated the effect BP control on total (T-PWV, in m/s), structural (S-PWV), and load-dependent (LD-PWV) arterial stiffness over 3 years as they related to time to cognitive impairment over 10 years modeled using multivariable proportional hazard models for baseline stiffness and joint longitudinal survival models for changes in stiffness. RESULTS: Six hundred fourteen participants with stiffness measures had 90 cognitive impairment events over follow-up. Reductions in LD-PWV under intensive BP control were associated with 21% risk reduction for cognitive impairment. T-PWV and S-PWV continued to increase regardless of BP control with each m/s increase in stiffness associated with 11% to 12% increase in risk for cognitive impairment. DISCUSSION: Intensive SBP control reduced LD-PWV over 3 years, which reduced the risk of cognitive impairment over 10 years of follow-up.
Röhr S, Wittmann F, Luppa M
… +28 more, Köhler S, Deckers K, Rosenau C, Betker P, Bohmann P, Brenner H, Flöel A, Heise JK, Karch A, Keil T, Leitzmann M, Lieb W, Meinke-Franze C, Mikolajczyk R, Mons U, Nimptsch K, Övermöhle C, Peters A, Pischon T, Schikowski T, Schulze MB, Tüscher O, Willich SN, Kleineidam L, Wagner M, Berger K, Pabst A, Riedel-Heller SG
Alzheimers Dement
· 2026 May · PMID 42151737
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INTRODUCTION: The Lifestyle for Brain Health (LIBRA) index evaluates modifiable dementia risk, mainly in midlife and older adults. We examined the frequency of LIBRA factors and their individual and combined associations...INTRODUCTION: The Lifestyle for Brain Health (LIBRA) index evaluates modifiable dementia risk, mainly in midlife and older adults. We examined the frequency of LIBRA factors and their individual and combined associations with cognitive functioning across adulthood (20-75 years), considering age, sex, and socioeconomic status (SES). METHODS: Data came from the population-based German National Cohort (NAKO baseline; n = 149,948). We calculated proportions for LIBRA factors, tested frequency trends, and analyzed cross-sectional associations with cognitive functioning using cluster-adjusted regression controlling for confounders. RESULTS: Behavioral and psychosocial risks (smoking, physical inactivity, depression) were more common in younger adults, while cardiovascular risks (hypertension, coronary heart disease, hypercholesterolemia) predominated in older age. Men had higher LIBRA scores. Higher scores were consistently linked to lower cognitive functioning and lower SES across age groups. DISCUSSION: Dementia risk factors were frequent and already associated with poorer cognition in younger adults, underscoring the need for early, targeted, and equity-oriented prevention.
Landau SM, Liu P, Harrison TM
… +18 more, Taggett J, Ward TJ, Murphy A, Lockhart SN, Lovato LC, Koeppe R, Farias ST, Papp KV, Snyder HM, Harvey DJ, Espeland M, Maillard P, DeCarli C, Vemuri P, Weiner M, Baker LD, Jagust WJ, U.S. POINTER Study Group and Alzheimer's Disease Neuroimaging Initiative
Alzheimers Dement
· 2026 May · PMID 42151735
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INTRODUCTION: To examine the generalizability of Alzheimer's disease (AD) biomarker models in real-world older adults, we examined AD biomarker relationships with cognition in two multicenter cohorts that differ with res...INTRODUCTION: To examine the generalizability of Alzheimer's disease (AD) biomarker models in real-world older adults, we examined AD biomarker relationships with cognition in two multicenter cohorts that differ with respect to recruitment approach and health risk factors but were matched on a variety of characteristics. METHODS: We compared harmonized health and demographic data, AD and cerebrovascular biomarkers, and cognitive performance in the community-recruited U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) Imaging substudy and a matched sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) which recruited primarily from academic specialty clinics. RESULTS: Elevated β-amyloid (Aβ) and tau were associated with cognitive performance in ADNI but not U.S. POINTER. Findings were consistent across different cohort matching schemes, and were not explained by discrepancies in vascular risk. DISCUSSION: The role of Aβ and tau in cognitive performance may be reduced in real world samples compared to academic specialty clinics.
Hammers DB, Foster E, Eloyan A
… +38 more, Thangarajah M, Taurone A, Touroutoglou A, La Joie R, Beckett L, Gao S, Vemuri P, Nudelman KN, Kirby K, Dage JL, Aisen P, Atri A, Clark D, Day GS, Duara R, Graff-Radford NR, Grant I, Honig LS, Johnson ECB, Jones DT, Masdeu JC, Mendez MF, Parand L, Womack K, Musiek E, Onyike CU, Riddle M, Rogalski E, Salloway S, Sha SJ, Turner RS, Wingo TS, Wolk DA, Dickerson BC, Rabinovici GD, Carrillo MC, Apostolova LG, LEADS Consortium
Alzheimers Dement
· 2026 May · PMID 42151732
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INTRODUCTION: Research into cognitive dispersion - a cognitive process score measuring the intra-individual variability (IIV) across a single testing session - suggests utility in neurodegenerative populations. Given wid...INTRODUCTION: Research into cognitive dispersion - a cognitive process score measuring the intra-individual variability (IIV) across a single testing session - suggests utility in neurodegenerative populations. Given widespread deficits observed in sporadic early-onset Alzheimer's disease (EOAD), however, it is unclear if examining cognitive dispersion shows benefit in this condition. METHODS: A total of 309 participants (188 amyloid-positive EOAD, 43 amyloid-negative early-onset dementia [EOnonAD], 78 cognitively normal [CN]) completed neuropsychological testing twice over 12 months. Dispersion-related differences among groups were assessed, as was cognitive dispersion's capacity to predict domain-specific cognitive trajectories, and its convergence with imaging biomarkers. RESULTS: EOAD participants displayed higher cognitive dispersion than EOnonAD participants, and associations with EOAD-specific biomarkers. Additionally, cognitive dispersion was associated with 12-month reliable change across several cognitive domains. DISCUSSION: These preliminary results examine cognitive dispersion in sporadic EOAD. When used with baseline cognitive performance, cognitive dispersion measures may enrich future clinical trials in EOAD by enhancing treatment monitoring over time.
Sutherland GT, Chen A, Nguyen-Hao HT
… +5 more, Mundell H, Aladyeva E, Hofer MJ, Harari O, Twigg SM
Alzheimers Dement
· 2026 May · PMID 42151730
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Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both increasing exponentially worldwide. T2D has also been identified as one of 14 modifiable risk factors for dementia, but the mechanism is unknown. T2D could prom...Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both increasing exponentially worldwide. T2D has also been identified as one of 14 modifiable risk factors for dementia, but the mechanism is unknown. T2D could promote dementia via vascular or AD neuropathological changes, and mechanistic hypotheses include central insulin resistance and T2D's peripheral inflammation promoting central inflammation. Here we examine these different hypotheses by reviewing the recent literature in combination with re-analysis of post mortem brain tissue molecular data. Collectively, recent studies and single-cell transcriptomic data suggest that peripheral lipid anomalies and inflammation seen in T2D act together to reduce brain-blood barrier integrity, facilitating aberrant immune signaling between the periphery and the brain. The subsequent promotion of AD-specific microglial subtypes is the most likely mechanism linking T2D and AD. These AD-specific microglial subtypes may be reduced by therapeutic targeting of triggering receptor expressed on myeloid cells 2-apolipoprotein E signaling pathway.
Chong Chie JAK, Persohn SA, Simcox OR
… +4 more, Collins A, Salama P, Territo PR, Alzheimer's Disease Neuroimaging Initiative and MODEL‐AD consortium
Alzheimers Dement
· 2026 May · PMID 42151724
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Historically, imaging diagnostics in Alzheimer's disease (AD) have focused primarily on amyloid and tau accumulation; however, recent work suggests that neurometabolic and vascular dysregulation (MVD) may precede protein...Historically, imaging diagnostics in Alzheimer's disease (AD) have focused primarily on amyloid and tau accumulation; however, recent work suggests that neurometabolic and vascular dysregulation (MVD) may precede protein deposition and persist throughout the disease spectrum, preclinically and clinically. Translating these findings between human patients and preclinical mouse models remains challenging due to cross-species differences. To address this, regional MVD phenotypes were identified using cerebral metabolism and blood flow, and region-set enrichment analysis (RSEA) was conducted to assess brain functional category (BFC) changes based on metabolic variations, facilitating systematic cross-species comparisons. Clinically, MVD showed progressive alterations across the AD spectrum, while mouse models demonstrated similar genotype- and age-dependent changes. Although direct one-to-one regional correspondence is limited, RSEA revealed changes in comparable BFCs. Our findings suggest that imaging-based MVD mapping and RSEAs can bridge species differences, offering a translational framework to support early diagnostics of AD, enhance disease stratification, and enable therapeutic testing.
Hu T, Wang Y, Wang J
… +7 more, Mao X, Ren S, He K, Guan Y, Huang Q, Li B, Xie F
Alzheimers Dement
· 2026 May · PMID 42151723
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INTRODUCTION: We investigated the relationship between metabotropic glutamate receptor subtype 5 (mGluR5) availability and plasma biomarkers in individuals with cognitive impairment. METHODS: Seventy-one subjects were in...INTRODUCTION: We investigated the relationship between metabotropic glutamate receptor subtype 5 (mGluR5) availability and plasma biomarkers in individuals with cognitive impairment. METHODS: Seventy-one subjects were included (17 cognitively unimpaired [CU], 10 early-onset cognitive impairment [EOCI], and 44 late-onset cognitive impairment [LOCI]). Amyloid beta (Aβ) pathology was quantified using F-Florbetapir, and mGluR5 availability by F-PSS232. The associations of mGluR5 availability, plasma biomarkers, and age were explored using partial correlation, mediation, and interaction analyses. RESULTS: In individuals aged over 65 years and the LOCI group, mGluR5 availability was positively associated with plasma glial fibrillar acidic protein (GFAP). This positive relationship of mGluR5 with plasma GFAP in LOCI only survived in the Aβ-positive subgroup (r = 0.475, p = 0.011). DISCUSSION: Increased mGluR5 availability is significantly associated with elevated plasma GFAP levels dependent on age in individuals aged over 65 years and the LOCI group.
Wang Y, Lei B, Jiang K
… +18 more, Chen X, Qu Y, Song X, Dui X, Zhao Q, Zhao X, Zou Y, Ma T, Zhang D, Xiao J, Fan M, Liao J, Long L, Zhang T, Wang C, Li J, Jiang X, Zhang B
Alzheimers Dement
· 2026 May · PMID 42151709
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INTRODUCTION: The American Heart Association's Life's Essential 8 (LE8) framework has been linked to cognitive impairment, but evidence in Chinese older adults remains limited. METHODS: This cross-sectional study include...INTRODUCTION: The American Heart Association's Life's Essential 8 (LE8) framework has been linked to cognitive impairment, but evidence in Chinese older adults remains limited. METHODS: This cross-sectional study included 7469 adults aged ≥60 years from the West China Health and Aging Cohort. Modified Poisson regression with robust error variance was used to examine the associations of LE8 scores and genetic risk, as well as their joint associations, with cognitive impairment. RESULTS: Compared with the low LE8 score group, the high LE8 score group had a prevalence ratio (PR) of 0.65 (95% confidence interval [CI]: 0.56 to 0.76) for cognitive impairment. A joint association was observed between LE8 and genetic risk, with the highest PR of 1.19 (95% CI: 1.12 to 1.27) in the low LE8 and high-genetic-risk group. DISCUSSION: Optimal cardiovascular health was associated with lower cognitive impairment and attenuation of genetic risks among older adults in western China.
Zhang J, Zhang J, Ding J
… +6 more, Zhang X, Wang Y, Wei W, Chai Y, Zhang S, Chen X
Alzheimers Dement
· 2026 May · PMID 42151696
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Neurotoxic protein accumulation is widely recognized as a key feature of Alzheimer's disease (AD), and increasing evidence indicates that impaired brain clearance associated with dysfunction of the meningeal lymphatic an...Neurotoxic protein accumulation is widely recognized as a key feature of Alzheimer's disease (AD), and increasing evidence indicates that impaired brain clearance associated with dysfunction of the meningeal lymphatic and glymphatic may contribute to this process. Disruption of these pathways may weaken homeostatic mechanisms and facilitate amyloid‑β and tau buildup. This review considers lymphatic reconstruction as a potential therapeutic direction aimed at modestly improving clearance efficiency. We summarize current findings from pharmacological approaches targeting aquaporin-4 or vascular endothelial growth factor C signaling, non-invasive methods such as photobiomodulation and focused ultrasound, and emerging surgical or lifestyle interventions designed to enhance drainage. Early clinical attempts, including deep cervical lymphovenous anastomosis (dCLVA), provide preliminary proof of concept but require careful validation. Progress in this field also depends on developing sensitive, non-invasive imaging markers and defining appropriate intervention windows. By situating lymphatic modulation within the broader AD drug-development landscape, we highlight its possible role within multimodal therapeutic strategies.
König A, Tröger J, Mallick E
… +15 more, Linz N, Ritchie C, Gregory S, Hunter M, Johnson K, Benavides GS, Grau-Rivera O, Radoi A, Porta-Mas C, Köhler S, Teipel S, Hansson O, Tideman P, Wuestefeld A, Palmqvist S
Alzheimers Dement
· 2026 May · PMID 42151661
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INTRODUCTION: Early detection of Alzheimer's disease (AD) is critical for timely intervention as disease-modifying treatments emerge. Speech-based digital biomarkers offer scalable options for remotely capturing speech-d...INTRODUCTION: Early detection of Alzheimer's disease (AD) is critical for timely intervention as disease-modifying treatments emerge. Speech-based digital biomarkers offer scalable options for remotely capturing speech-derived functional changes associated with early cognitive decline, but validation across real-world populations remains limited. METHODS: We evaluated the speech biomarker for cognition (SB-C), an automated speech-derived measure associated with cognitive status, in 736 participants across five European cohorts (Barcelonaβeta Brain Research Center's Alzheimer's at-risk cohort, European Prevention of Alzheimer's Dementia Scotland, Dementia Study of Cognitive and Biomarker Dynamics, Longitudinal Cognitive Impairment and Dementia Study, and Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably [BioFINDER-Primary Care]). Participants completed verbal learning and semantic fluency tasks via automated phone or app-based platforms. SB-C performance was compared to Mini-Mental State Examination, Clinical Dementia Rating, Preclinical Alzheimer Cognitive Composite 5, and cerebrospinal fluid amyloid beta and phosphorylated tau181 biomarker status. RESULTS: SB-C significantly differentiated cognitively unimpaired and impaired groups (P < 0.001), correlated with standard cognitive measures, and showed moderate-to-high area under the curve (0.56-0.82) for classifying biomarker positivity, with strongest results in BioFINDER-Primary Care. DISCUSSION: SB-C is a scalable, remote speech-derived marker associated with cognitive status and AD biomarker group differences.