J. Alzheimers Dis. [JOURNAL]
Sun
200 papers
Corrigendum to "Mini-Mental State Examination in Elderly Chinese: A Population-Based Normative Study.".
J Alzheimers Dis · 2026 Jul · PMID 42210671 · Publisher ↗
Abstract loading — click title to view on PubMed.
Mesenchymal stem cell-mediated regulation of neuroinflammation and amyloid-β clearance: A promising therapeutic strategy for Alzheimer's disease.
Wang Y
J Alzheimers Dis · 2026 May · PMID 42199025 · Publisher ↗
Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive decline. Its pathogenesis is complex, involving multiple pathological processes, including amyloid-β (Aβ) deposition, neuroinf...
Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive decline. Its pathogenesis is complex, involving multiple pathological processes, including amyloid-β (Aβ) deposition, neuroinflammation, and synaptic dysfunction. In recent years, the role of mesenchymal stem cells (MSCs) in AD therapy has garnered significant attention. MSCs, through their multi-directional differentiation potential and paracrine effects, exhibit remarkable neuroprotective and anti-inflammatory properties, influencing AD progression. This review summarizes the potential mechanisms and effects of MSCs in AD treatment and explores precision therapeutic strategies based on MSC modulation.
Feasibility, acceptability, and pre- post-program outcome changes of the real-world implementation of an informal caregiver support program via text message.
Perales-Puchalt J, Baker C, Wagle B … +6 more , Godar M, Nieto Gomez S, Johnson H, Drees B, Fracachán-Cabrera M, Ramírez-Mantilla M
J Alzheimers Dis · 2026 Jul · PMID 42199024 · Full text
BackgroundFew dementia caregiver support programs have been tested in real-world settings.ObjectiveWe tested the feasibility and pre- post-program outcome changes (e.g., preparedness for caregiving) of the first short me...
BackgroundFew dementia caregiver support programs have been tested in real-world settings.ObjectiveWe tested the feasibility and pre- post-program outcome changes (e.g., preparedness for caregiving) of the first short message service texting program to support informal caregivers of people with dementia.MethodsWe analyzed observational data from 147 caregivers of people with dementia participating in a service program. This program was a remote, asynchronous, and bidirectional texting program focused on dementia education, skill-building, and community resources that lasted six months. We measured outcomes via surveys and metrics of program usage over six months.ResultsTwo caregivers experienced technical issues during the program, 12.9% unsubscribed, and 68.8% read most texts thoroughly. Most caregivers (64.3-75.9%) reported the two highest levels of acceptability in four four-level items ranging from not at all to a lot/extremely. Levels of preparedness for caregiving and unmet needs improved from pre- to post-program testing in the full sample. We only observed pre- to post-program changes in depressive symptoms and strain when restricting the sample to those with worse baseline levels of those outcomes.ConclusionsAcceptability and pre- to post-program changes in this real-world implementation of a texting caregiver support program were encouraging, though smaller than those observed in efficacy research trials, consistent with findings from other implemented caregiver programs.
Comparison of pre-diagnostic signs and symptoms of young-onset dementia and late-onset dementia in the general practice.
Hibbs C, Hendriks S, Muris J … +4 more , Leijenaar R, Horstkötter D, Köhler S, Vugt M
J Alzheimers Dis · 2026 Jul · PMID 42199021 · Full text
BackgroundDementia can occur in older adults (late-onset dementia; LOD) or before age 65 (young-onset dementia; YOD). YOD often involves more heterogeneous subtypes and atypical early symptoms, making it harder for gener...
BackgroundDementia can occur in older adults (late-onset dementia; LOD) or before age 65 (young-onset dementia; YOD). YOD often involves more heterogeneous subtypes and atypical early symptoms, making it harder for general practitioners (GPs) to recognize YOD early.ObjectiveTo identify differences in pre-diagnostic signs and symptoms between persons with YOD and LOD at the GP, enabling earlier recognition of YOD.MethodsThis case-control study used data from GP records of 88 YOD cases and 174 LOD controls from the Research Network Family Medicine database, matched by sex and GP practice. Persons diagnosed before age 70 were included in the YOD group to account for diagnostic delay. Symptoms up to five years before diagnosis were grouped into eight categories. Differences in symptom presence were analyzed per year using binary logistic regression.ResultsCompared to LOD, YOD cases had significantly higher odds of reporting affective symptoms two (OR = 2.43, 95%CI = 1.30-4.51) and one year (OR = 2.36, 95%CI = 1.35-4.13) before diagnosis. Social indicators were also more common in YOD five (OR = 4.84, 95%CI = 1.09-21.44), four (OR = 3.75, 95%CI = 1.27-11.09), and one (OR = 4.00, 95%CI = 2.33-6.86) year before diagnosis. Gait disturbances were less frequent in YOD at four (OR = 0.33, 95%CI = 0.12-0.89) and two (OR = 0.43, 95%CI = 0.20-0.91) years prior. Surprisingly, no significant differences emerged for cognitive symptoms.ConclusionsYOD differs from LOD in several symptom categories up to five years before diagnosis. These findings provide insight into the pre-diagnostic trajectory of YOD and may support earlier recognition.
Laboratory-based turning performance during walking in people with mild cognitive impairment and dementia.
Mc Ardle R, Kingston A, Del Din S … +5 more , Rehman RZU, Galna B, Thomas AJ, Rochester L, Alcock L
J Alzheimers Dis · 2026 Jul · PMID 42199019 · Full text
BackgroundMobility impairments during straight-line walking show utility in detecting dementia-related cognitive impairment (e.g., Alzheimer's disease). Wearable technologies can now derive mobility outcomes related to t...
BackgroundMobility impairments during straight-line walking show utility in detecting dementia-related cognitive impairment (e.g., Alzheimer's disease). Wearable technologies can now derive mobility outcomes related to turning, considered a more cognitively complex movement. However, it is unclear which turning variables would best detect cognitive impairment.ObjectiveThis study aimed to develop a data-driven model of turning performance relevant to cognitive impairment and compare selected turning variables between people with cognitive impairment and cognitively-intact older adults.Methods77 people with cognitive impairment (31 mild cognitive impairment, 46 dementia) and 28 cognitively-intact older adults. performed six intermittent walking trials with a 180° turn while wearing an inertial measurement unit (APDM Opal) attached to their lower back. 102 spatiotemporal and signal-based turning variables were captured. Following data reduction, 15 variables underwent exploratory factor analysis. One-way ANCOVA, adjusting for age, sex and height, explored between-group differences (Bonferroni correction applied).ResultsThree factors emerged: turn initiation, magnitude and smoothness, accounting for 67% of the total variance in turning performance. The cognitively impaired group demonstrated significant differences in turn initiation (start-phase root mean square (RMS) in vertical direction, start-phase jerk RMS in vertical/mediolateral/anterior-posterior directions) and magnitude (mid-phase RMS in mediolateral direction, mean RMS in vertical direction) domains (p < 0.003) with moderate-large effect sizes (Partial η = 0.09-0.17). Turn initiation and magnitude factor scores were associated with cognitive performance.ConclusionsKey findings suggest that people with cognitive impairment exhibit smaller and slower turning movements specifically during turn initiation and demonstrate lower signal magnitude (RMS) across the turn. Further work should consider use of these variables in predicting incidence of cognitive impairment in at-risk populations.
Status of diagnosis, treatment, and care of Alzheimer's disease continuum in China: A survey-based analysis.
Hao L, Xing Y, Han Y
J Alzheimers Dis · 2026 May · PMID 42199014 · Publisher ↗
BackgroundThe 2018 NIA-AA framework outlines a six-stage continuum from asymptomatic individuals to severe Alzheimer's disease (AD) dementia, but most Chinese research still focuses on dementia or broad diagnostic catego...
BackgroundThe 2018 NIA-AA framework outlines a six-stage continuum from asymptomatic individuals to severe Alzheimer's disease (AD) dementia, but most Chinese research still focuses on dementia or broad diagnostic categories.ObjectiveTo map diagnosis, treatment, and care patterns across all six AD clinical stages in China and identify demographic, clinical, treatment and care-related factors associated with disease stage.MethodsWe conducted a nationwide, open online survey via official media channels targeting patients with clinician-confirmed AD and their caregivers. Data were collected via Questionnaire Star. Descriptive analyses, group comparisons, and ordinal logistic regression were performed to examine factors associated with NIA-AA stage.ResultsA total of 1116 valid responses were analyzed. Most participants were at Stage 2 or higher, with distribution of 0.4%, 9.1%, 16.0%, 24.8%, 26.6%, and 23.0%, across Stage 1-6. Overall, 64.5% had been diagnosed within five years. Neurology (66.4%) and memory clinics (19.2%) were the most frequently visited departments. Donepezil (52.2%) and Memantine (38.8%) were the most common medications, while 34.5% reported engaging in non-pharmacological interventions. Only 1.9% of patients receiving professional dementia institutional care. In logistic regression, disease duration (OR = 0.724, p = 0.006), stage at first outpatient visit (OR= 1.843, p < 0.001), and Donepezil use (OR = 1.394, p = 0.003) were independently associated with current NIA-AA stage.ConclusionsThis study provides the first nationwide, real-world description of diagnosis, treatment, and care across all NIA-AA stages in China. The findings highlight the need for improved primary-care screening, expanded memory-clinic access, and structured caregiver support to promote earlier detection and more equitable, stage-appropriate management of AD.
Early-onset Alzheimer's disease mortality in the United States: A population-based study of trends and disparities, 2015-2024.
Al-Salahat A, Abdul Jabbar AB, Kennedy K … +6 more , Song A, Hackett M, Abualrob MA, Verma H, Singh J, Bernitsas E
J Alzheimers Dis · 2026 May · PMID 42199013 · Publisher ↗
BackgroundPopulation-level data on trends and disparities in early-onset Alzheimer's disease (EOAD) mortality are limited.ObjectiveThis study aimed to examine demographic disparities and trends in mortality from EOAD in...
BackgroundPopulation-level data on trends and disparities in early-onset Alzheimer's disease (EOAD) mortality are limited.ObjectiveThis study aimed to examine demographic disparities and trends in mortality from EOAD in the US from 2015 to 2024.MethodsWe analyzed US mortality data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER), 2015-2024. We examined and identified mortality from EOAD as the underlying cause of death (UCD) using the International Classification of Disease-10-Clinical Modification code, G30.0. Age-adjusted mortality rates (AAMRs) per 1,000,000 population were extracted. Temporal trends were assessed with Joinpoint regression, and demographic disparities were analyzed and compared using rate ratios (RR) of AAMRs. Sensitivity analysis compared EOAD trends with late-onset Alzheimer's disease (G30.1).ResultsAmong 4890 EOAD-related deaths (63.7% female), mortality increased from 0.14 to 2.59 per 1,000,000 between 2015 and 2024 (annual percent change: +19.96%). Females had higher mortality than males (RR = 1.50, 95% CI: 1.40 to 1.59). Non-Hispanic White individuals and residents of the Midwest exhibited the highest mortality rates. The mean age at death was 69.8 years, with the greatest number of deaths occurring between the ages of 65 and 74 years. In comparison, the increase in late-onset Alzheimer's disease mortality was lower than that of EOAD.ConclusionsReported EOAD mortality increased markedly in the US, with significant sex, racial, and regional disparities. These findings highlight persistent inequities in EOAD diagnosis and care and underscore the need for improved recognition and equitable access to specialized dementia care.
Peripheral immune and vascular inflammatory signatures precede Alzheimer's disease onset: A serum proteomic study.
Iga JI, Suzuki J, Matsushita T … +11 more , Yoshino Y, Ozaki T, Tachibana A, Kumon H, Funahashi Y, Ochi S, Kuwahara M, Kawashima A, Takata Y, Ueno SI, Yamashita M
J Alzheimers Dis · 2026 May · PMID 42199011 · Publisher ↗
BackgroundNeuroinflammation plays an important role in the pathogenesis of Alzheimer's disease, but systemic immune alterations preceding clinical onset remain insufficiently characterized. Peripheral immune and vascular...
BackgroundNeuroinflammation plays an important role in the pathogenesis of Alzheimer's disease, but systemic immune alterations preceding clinical onset remain insufficiently characterized. Peripheral immune and vascular inflammatory processes may influence the central nervous system through endothelial dysfunction and blood-brain barrier vulnerability. Serum proteomics offers a minimally invasive approach to identify such early systemic changes.ObjectiveIn this population-based longitudinal cohort study, we analyzed baseline serum proteomic profiles from cognitively normal older adults who were prospectively followed for up to five years for incident Alzheimer's disease.MethodsSerum samples obtained during the preclinical phase were analyzed using a high-throughput affinity-based proteomic platform. Differential protein abundance, pathway enrichment analyses, and regularized machine learning models were applied to identify coordinated biological alterations associated with future disease onset.ResultsAlthough no individual proteins reached false discovery rate-corrected significance, pathway-level analyses revealed biologically coherent patterns. Proteins involved in immune resolution, Fc receptor-mediated phagocytosis, endosomal trafficking, and vascular repair signaling were downregulated, whereas pathways related to neutrophil activation and neutrophil extracellular trap formation were upregulated. Machine learning models using sparse feature selection demonstrated that a small subset of serum proteins could discriminate individuals who later developed Alzheimer's disease, although confidence intervals indicated limited model stability.ConclusionsSystemic immune dysregulation and vascular inflammation are detectable years before the clinical onset of Alzheimer's disease and may contribute to neuroinflammatory vulnerability. Serum proteomics may provide insights into early peripheral processes associated with future disease risk.
The emerging role of oligodendrocytes in Alzheimer's disease: Integrating bibliometric insights with molecular pathogenesis.
Yang X, Gao Y, Zhang M … +3 more , Pan J, Liu H, Fan H
J Alzheimers Dis · 2026 Jul · PMID 42199009 · Publisher ↗
BackgroundOligodendrocytes (OLs) have received relatively limited attention in Alzheimer's disease (AD) research; however, recent studies highlight their significant role in AD pathology, particularly in neuroinflammatio...
BackgroundOligodendrocytes (OLs) have received relatively limited attention in Alzheimer's disease (AD) research; however, recent studies highlight their significant role in AD pathology, particularly in neuroinflammation and myelin integrity.ObjectiveTo bibliometrically analyze oligodendrocyte research in AD.MethodsLiterature was retrieved from Web of Science and Scopus on July 8, 2025. CiteSpace, VOSviewer, and R-based bibliometrix were used for visualization and trend analysis.ResultsA total of 1780 publications from 1981 to 2025 were analyzed. Research output in this field grew significantly, particularly post-2010, following an exponential growth pattern consistent with Price's Law. The USA, China, and Japan were the top contributors, with the USA showing the highest number of publications. The University of California System, Harvard University, and Mayo Clinic emerged as central institutions, while influential authors included George Bartzokis, David A. Bennett, and Patrick L. McGeer. Leading journals, like and have seen a steady increase in research contributions over the years. Keywords analysis showed that terms such as "microbiota", "microglia", "astrocyte", "Alzheimer's disease", "neurodegeneration", "oligodendrocyte" are prominently displayed, Keywords evolution analysis showed that "exosomes", "extracellular vesicles", "white matter injury", "oligodendrocyte precursor cell", "neurodegeneration" "myelination" "machine learning" gradually attracted attention.ConclusionsThe study illustrates a paradigm shift in AD research, from classic pathological markers to a broader understanding that includes neuroglial interactions. This trend emphasizes the role of OLs in neuroinflammation and myelin integrity, presenting new avenues for therapeutic strategies.
Differential associations of core and non-core plasma biomarkers with cognitive performance in Black adults.
Zhu Y, Trani JF, Walker AIB … +3 more , Bekena S, Singh RK, Babulal GM
J Alzheimers Dis · 2026 Jul · PMID 42199003 · Publisher ↗
BackgroundBlack adults experience disproportionately higher rates of Alzheimer's disease and related dementias (ADRD), yet remain underrepresented in blood-based biomarker research. Understanding how plasma biomarkers re...
BackgroundBlack adults experience disproportionately higher rates of Alzheimer's disease and related dementias (ADRD), yet remain underrepresented in blood-based biomarker research. Understanding how plasma biomarkers relate to cognitive performance is essential for equitable detection and monitoring of ADRD.ObjectiveWe examined cross-sectional and longitudinal associations of both core and non-core plasma biomarkers and cognition in a community-based cohort of Black adults.MethodsParticipants from the ARCHES study completed baseline plasma biomarker assessments and neuropsychological testing, including a Preclinical Alzheimer Cognitive Composite (PACC) score and the Montreal Cognitive Assessment (MoCA). Plasma biomarkers reflecting amyloid, tau, neurodegeneration, and astrocytic activation were quantified using immunoprecipitation-mass spectrometry and ultrasensitive immunoassay platforms. Linear regression was used to evaluate cross-sectional associations between biomarkers and cognition. Linear mixed-effects models examined whether baseline biomarker levels were associated with cognitive change over one year, adjusting for age, sex, and education.ResultsThe sample included 334 participants with a mean baseline age of 64.6 years (SD = 10.1; range, 45-92.9). Cross-sectionally, higher brain-derived phosphorylated tau was associated with poorer MoCA score (p = 0.04), and neurofilament light chain (NfL) level was also associated with lower PACC score (p = 0.04). Longitudinally, higher baseline NfL and glial fibrillary acidic protein (GFAP) were associated with faster cognitive decline (p < 0.001 and p = 0.018).ConclusionsNon-core NfL and GFAP biomarkers are associated with both cross-sectional and longitudinal cognitive performance. These findings highlight the importance of inclusive biomarker research and suggest non-core biomarkers may be particularly informative for characterizing cognitive aging and decline in this population.
Hospitalizations and long-term care for older adults with Alzheimer's disease and related dementia: Differences across geographic regions of the United States.
Pilonieta G, Pisu M, Martin RC … +5 more , Shan L, Kennedy RE, Oates GR, Kim YI, Geldmacher DS
J Alzheimers Dis · 2026 May · PMID 42198989 · Full text
BackgroundAlzheimer's disease and related dementia (ADRD) leads to adverse health outcomes, such as higher risk of hospitalizations and long-term institutionalization. However, little is known about differences in ADRD h...
BackgroundAlzheimer's disease and related dementia (ADRD) leads to adverse health outcomes, such as higher risk of hospitalizations and long-term institutionalization. However, little is known about differences in ADRD health outcomes for older adults in the Deep South compared to those in the rest of the United States (non-Deep South).ObjectiveThis study aims to examine the prevalence of hospitalization and long-term use of skilled nursing facilities (SNF) among older adults with ADRD, and factors influencing these healthcare utilization outcomes in the Deep South versus non-Deep South regions.MethodsWe conducted secondary analyses of claims data for 115,879 Medicare beneficiaries with ADRD in 2013-2015. Modified Poisson regression was used to examine the association of outcomes with individual and context-level factors for Deep South and non-Deep South separately.ResultsHospitalization rates were slightly higher in the Deep South. Utilization of long-term SNF was similar across regions. In adjusted analyses, within each region, differences between non-Hispanic Black and White beneficiaries were not significant. Comorbidities, specialist visits, ADRD drug use, and Medicare/Medicaid dual eligibility were associated with more hospitalizations and SNF use for all beneficiaries in the Deep South. For beneficiaries in the non-Deep South region, context-level factors (limited availability of medical resources and poor population health) were significantly associated with healthcare utilization.ConclusionsWe identified differences across regions in the factors associated with hospitalizations and long-term SNF stays, with patient-level factors being relevant in the Deep South region and context-level factors in the non-Deep South region.
Crocin alleviates neuroinflammation and glia-associated synaptic alterations through NRF2 after chronic cerebral hypoperfusion.
Zhang XY, Liu C, Zhou YM … +5 more , Jiang WR, Zhang QN, Wu Y, Song SY, Yao ZH
J Alzheimers Dis · 2026 May · PMID 42198986 · Publisher ↗
BackgroundChronic cerebral hypoperfusion (CCH) is common in vascular dementia, Alzheimer's disease, and related neurodegenerative disorders. It contributes to cognitive dysfunction, with synaptic loss as an important pat...
BackgroundChronic cerebral hypoperfusion (CCH) is common in vascular dementia, Alzheimer's disease, and related neurodegenerative disorders. It contributes to cognitive dysfunction, with synaptic loss as an important pathological event, but the underlying mechanisms remain unclear. Because chronic hypoperfusion, glial activation, and synaptic injury are increasingly implicated in Alzheimer's disease-related neurodegeneration, clarifying the mechanisms of CCH-induced synapse loss may also inform understanding of Alzheimer's disease.ObjectiveTo examine whether CCH promotes glia-associated synaptic marker accumulation and phagocytosis-related activity via damage-associated molecular patterns (DAMPs), and whether crocin can attenuate synaptic injury by suppressing this glial response.MethodsCrocin was evaluated in vascular cognitive impairment patients, in a rat model of CCH, and in oxygen-glucose deprivation-treated glial cells. Cognitive function, neuroinflammation, synaptic injury, phagocytosis-related activity, complement-associated synaptic changes, autophagy-related alterations, lipid droplet accumulation, and NRF2-related mechanisms were assessed.ResultsCrocin improved cognitive function in patients with vascular cognitive impairment and in CCH rats, and reduced neuroinflammation. In experimental models, crocin attenuated microglial- and astrocyte-associated synaptic marker accumulation, suppressed pro-inflammatory activation and phagocytosis-related activity, downregulated MERTK and MEGF10, and reduced complement-associated synaptic vulnerability. Crocin also alleviated autophagy-related imbalance, oxidative stress, and lipid droplet accumulation in an NRF2-related manner.ConclusionsCrocin may alleviate cognitive dysfunction after CCH by suppressing DAMPs-associated glial activation and glia-associated synaptic alterations, supporting its potential relevance to chronic hypoperfusion-related cognitive impairment.
Amygdala microstructural changes in subjective cognitive decline: A diffusion kurtosis and neurite orientation dispersion and density imaging study.
Flaherty R, Sui YV, Masurkar AV … +4 more , Youss ZB, Wisniewski T, Rusinek H, Lazar M
J Alzheimers Dis · 2026 May · PMID 42198982 · Publisher ↗
BackgroundPeople with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease. Prior research has suggested that amygdala volume may be more sensitive than hippocampal volume in detecting differen...
BackgroundPeople with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease. Prior research has suggested that amygdala volume may be more sensitive than hippocampal volume in detecting differences between SCD and age-matched controls, as well as in predicting SCD conversion to mild cognitive impairment. However, the microstructure underlying this volumetric change remains unclear.ObjectiveThis study evaluated amygdala microstructural differences in SCD versus control participants as well as associations between amygdala microstructure and volume, age, memory performance, anxiety, and depression using diffusion imaging.MethodsDiffusion tensor imaging, diffusion kurtosis imaging, and neurite orientation dispersion and density imaging were fit to diffusion MRI images. Group differences and correlations between diffusion metrics, age, memory, anxiety, and depression were assessed in 123 SCD versus 194 age-matched controls over age 55.ResultsIn the left amygdala, SCD participants had significantly lower fractional anisotropy (FA), lower kurtosis fractional anisotropy (KFA), and higher free water fraction (FWF). KFA was lower in the right amygdala in SCD. There were no significant group differences in the amygdala volume. Bilateral KFA negatively correlated with FWF, a marker of neuroinflammation and neurodegeneration. Left FA negatively correlated with orientation dispersion index, a marker of neuritic branching. Right KFA correlated with age only in SCD, while left FA correlated with anxiety only in controls.ConclusionsKFA is sensitive to group differences between SCD and controls in bilateral amygdala. KFA may reflect neuroinflammation and increased sensitivity to aging in the amygdala in SCD.
Enhancing global Alzheimer's disease drug outcomes by comprehensive African data integration.
Isei MO, Okeowo OM, Okoye CN … +1 more , Sobodu TO
J Alzheimers Dis · 2026 May · PMID 42191654 · Publisher ↗
Alzheimer's disease (AD) remains the leading cause of dementia worldwide and continues to pose a substantial therapeutic challenge. Although recent advances in disease-modifying treatments targeting amyloid-β pathology h...
Alzheimer's disease (AD) remains the leading cause of dementia worldwide and continues to pose a substantial therapeutic challenge. Although recent advances in disease-modifying treatments targeting amyloid-β pathology have generated cautious optimism, their translational impact is limited by persistent gaps in population and geographic representation within clinical trials. African populations, the most genetically diverse worldwide, remain markedly underrepresented in AD genomic and therapeutic studies. This gap limits the identification of ancestry-specific genetic risk factors and differential treatment responses and may contribute to the high attrition rates observed across AD drug development pipelines. We examine how the limited inclusion of African cohorts restricts insights into AD pathobiology and reduces the external validity of emerging therapeutic strategies. We highlight opportunities arising from the systematic integration of African population and clinical data, which have the potential to reveal novel biological mechanisms and expand the global relevance of candidate interventions. Persistent barriers, including insufficient research infrastructure and frequent substitution of African American cohorts for indigenous African populations, continue to obscure population-specific variation and hinder the development of a representative evidence base. Advancing the field will require coordinated and context-appropriate recruitment strategies, predictive modeling approaches grounded in region-specific data, and long-term investment in research capacity across the continent. A globally representative scientific framework that captures the full spectrum of human genetic heterogeneity is essential for accelerating progress in AD drug development. Integrating African population and data into clinical research will strengthen scientific rigor, enhance generalizability, and facilitate the development of globally equitable therapeutic strategies.
Nancy Wexler: A personal and scientific memoir.
Talan J
J Alzheimers Dis · 2026 Jul · PMID 42191653 · Publisher ↗
Abstract loading — click title to view on PubMed.
The role of neddylation in mediating radiation-induced neuronal DNA damage and neuroinflammation: Implications for neurodegenerative diseases.
Wang J, Sun F
J Alzheimers Dis · 2026 Jul · PMID 42191647 · Publisher ↗
Neddylation is a post-translational modification that regulates multiple cellular processes, including DNA damage responses and inflammatory signaling. Dysregulation of these pathways has been implicated in neuronal dysf...
Neddylation is a post-translational modification that regulates multiple cellular processes, including DNA damage responses and inflammatory signaling. Dysregulation of these pathways has been implicated in neuronal dysfunction and neurodegeneration. This review summarizes current evidence from the literature regarding the role of neddylation in modulating neuronal responses to ionizing radiation-induced DNA damage, with a focus on mechanisms relevant to genomic instability and neuroinflammation. We reviewed experimental and mechanistic studies investigating neddylation-regulated DNA damage repair, telomere integrity, mitochondrial function, and inflammatory signaling in neuronal and neural-related models, particularly in the context of ionizing radiation exposure. Evidence from the literature indicates that neddylation influences key components of the DNA damage response, including repair pathway choice, telomere stability, and mitochondrial homeostasis, as well as inflammatory signaling cascades. Ionizing radiation serves as an experimental paradigm to investigate these processes under conditions of acute genomic stress. While ionizing radiation does not recapitulate the full complexity of neurodegenerative diseases, radiation-based models provide mechanistic insight into neddylation-regulated pathways that may contribute to neuronal dysfunction. The potential relevance of these mechanisms to Alzheimer's disease and other neurodegenerative disorders warrants cautious interpretation and further investigation.
Gray matter brain age predicts cognitive outcome one year after ischemic stroke.
Tseng WI, Hsieh YC, Hsu YC … +8 more , Huang LK, Fu CK, Chen DY, Chen JH, Hong CT, Lu YH, Chan L, Chiou HY
J Alzheimers Dis · 2026 Jul · PMID 42186374 · Publisher ↗
BackgroundPredicting post-stroke cognitive impairment (PSCI) remains challenging.ObjectiveThis study validated two brain age metrics-Gray Matter Brain Age (GMBA) and Predicted Age Difference (PAD)-as independent predicto...
BackgroundPredicting post-stroke cognitive impairment (PSCI) remains challenging.ObjectiveThis study validated two brain age metrics-Gray Matter Brain Age (GMBA) and Predicted Age Difference (PAD)-as independent predictors of 12-month cognitive decline following ischemic stroke.MethodsWe analyzed 39 patients with ischemic stroke. Brain age was estimated using a machine learning model trained on healthy controls (n = 362). Baseline assessments, including demographics, clinical severity, and thick-sliced (7 mm) 2D T1- and T2-weighted MRI, were performed during acute hospitalization (median 5 days post-stroke). Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) was measured between baseline and 12 months. Multiple linear regression (MLR) and receiver operating characteristic (ROC) analysis identified predictors of CDR-SB.ResultsMLR identified two significant models. In Model 1, PAD (β = 0.109, p = 0.035) and chronological age (β = 0.082, p = 0.038) were independent predictors (Adjusted R = 0.183). In Model 2, GMBA emerged as the sole robust predictor (β = 0.092, p = 0.002; Adjusted R = 0.201). ROC analysis showed GMBA possessed the highest discriminative ability (AUC = 0.717, p = 0.026), followed by PAD (AUC = 0.691, p = 0.050), while chronological age was not significant (AUC = 0.629, p = 0.188).ConclusionsBoth GMBA and PAD are independent predictors of PSCI. Notably, these metrics maintained high predictive utility even when derived from real-world, thick-sliced MRI protocols. Integrating brain age estimation into routine clinical workflows can potentially facilitate early identification of patients at high risk for PSCI.
YWHAG as a novel biomarker in Alzheimer's disease biological research framework.
Zhao QF, Huang LY, Zhu YK … +6 more , Hu HY, Wang HF, Zhang W, Hu H, Tan L, Alzheimer's Disease Neuroimaging Initiative
J Alzheimers Dis · 2026 Jul · PMID 42179099 · Publisher ↗
BackgroundYWHAG has been recognized as a promising biomarker for Alzheimer's disease (AD). However, the precise role of YWHAG within the revised 2024 diagnostic framework for AD remains unclear.ObjectiveOur study aimed t...
BackgroundYWHAG has been recognized as a promising biomarker for Alzheimer's disease (AD). However, the precise role of YWHAG within the revised 2024 diagnostic framework for AD remains unclear.ObjectiveOur study aimed to evaluate YWHAG with established biomarkers to delinea te the role of YWHAG and determine whether it could serve as a complementary biomarker within the 2024 diagnostic criteria.MethodsWe compared YWHAG with established biomarkers among 708 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) across three domains: 1) diagnostic utility, 2) cross-sectional associations with clinical variables and brain structure, and 3) predictive value for clinical progression risk.ResultsOur results demonstrated the accuracy of YWHAG (AUC = 0.856) was comparable to that of FDG-PET (AUC = 0.912) and HVA (AUC = 0.879), but superior to that of T-tau (AUC = 0.796), NFL (AUC = 0.712), and GFAP (AUC = 0.617) in distinguishing AD versus controls. Moreover, YWHAG was consistently among the top three biomarkers most strongly associated with cognitive decline and brain atrophy, alongside HVA and FDG-PET. Furthermore, the YWHAG positive (Y+) group had a significantly higher risk of AD progression (HR = 2.45, 95% CI: 1.75-3.43) compared to the YWHAG negative (Y-) group (p < 0.001).ConclusionsWe identify YWHAG as a novel biomarker predictive of cognitive decline, brain atrophy, and AD progression. The performances of YWHAG are comparable to established biomarkers such as FDG-PET, HVA and T-tau, thereby providing a complement to the current AD diagnostic framework.
Potential biases associated with reported parental history of dementia in the Alzheimer's Disease Research Center cohorts: Implications for secondary data analyses.
Guilliams C, Abner E
J Alzheimers Dis · 2026 Jul · PMID 42179092 · Full text
BackgroundDeterminants of reported parental history of dementia among older adult research volunteers, and its relation to participation in brain aging studies, are incompletely understood.ObjectiveWe aimed to characteri...
BackgroundDeterminants of reported parental history of dementia among older adult research volunteers, and its relation to participation in brain aging studies, are incompletely understood.ObjectiveWe aimed to characterize older adults enrolled in Alzheimer's Disease Research Center (ADRC) cohorts by reported history of parental dementia according to age, ε4 dose, sex, race, Hispanic ethnicity, education, and baseline cognitive status.MethodsData were drawn from the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS). We included all participants who were age ≥ 65 at their most recent visit (N = 34,154). Participants were classified according to reported parental history of dementia (neither parent, mother only, father only, both parents, and unknown). Multinomial regression was used to estimate the adjusted odds ratios for reported parental history of dementia.ResultsDementia in at least one parent was reported by 40% of participants (n = 13,596), 52% (n = 17,881) reported that neither parent had dementia, and 8% (n = 2677) did not know. Participants reporting neither parent had dementia, or reported unknown history, were older, less educated, more likely to be minoritized, and were also most likely to be missing genotype (28% and 37%, respectively) and to be diagnosed with cognitive impairment at baseline (62% and 75%, respectively).ConclusionsADRC participants who report no parental dementia history may represent a meaningfully different group of volunteers, and within this group there is also substantial heterogeneity among all of the characteristics of interest investigated, especially by race. These differences need to be carefully considered during secondary analyses of NACC UDS data.
Uncovering the causal link between cerebral glucose metabolism and cognitive function in Alzheimer's disease.
Tristão-Pereira C, Casquero-Veiga M, Malotaux V … +1 more , Quiroz YT
J Alzheimers Dis · 2026 May · PMID 42179089 · Publisher ↗
Cerebral glucose metabolism is distinctly disrupted in Alzheimer's disease (AD), though its role in downstream cognitive decline remains unclear. Ueda et al. leverage Mendelian Randomization by integrating genetics, imag...
Cerebral glucose metabolism is distinctly disrupted in Alzheimer's disease (AD), though its role in downstream cognitive decline remains unclear. Ueda et al. leverage Mendelian Randomization by integrating genetics, imaging and cognitive data to demonstrate that cerebral glucose metabolism is causally linked to cognitive performance. This approach lays the groundwork for novel therapeutic strategies by suggesting that metabolism-focused interventions may mitigate cognitive impairment in AD. Future studies should further integrate single-cell and multi-omics strategies to elucidate cellular and molecular pathways related to causal effects and explore the influence of co-pathologies and epigenetics on metabolic and cognitive performance.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe