J. Alzheimers Dis. [JOURNAL]
Sun
200 papers
Effects of high-frequency repetitive transcranial magnetic stimulation on memory of post-stroke cognitive impairment patients: A systematic review and meta-analysis.
Liu F, Wang J, Kang Y … +2 more , Su G, Wang X
J Alzheimers Dis · 2026 Jul · PMID 42081190 · Publisher ↗
BackgroundThere is an evident interrelationship between stroke and Alzheimer's disease (AD). Post-stroke cognitive impairment (PSCI) is a frequently encountered and potentially disabling outcome of stroke. Memory impairm...
BackgroundThere is an evident interrelationship between stroke and Alzheimer's disease (AD). Post-stroke cognitive impairment (PSCI) is a frequently encountered and potentially disabling outcome of stroke. Memory impairment is an important component of the post-stroke cognitive syndrome, and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been widely used for memory in patients with PSCI.ObjectiveIn this study, we systematically evaluated the therapeutic effects of HF-rTMS on memory function in patients with PSCI, offering insights that may also inform the treatment of AD.MethodsAll relevant publications in Chinese and English were systematically searched from ten databases up to March 20, 2025. Retrieved articles were carefully screened. The quality of the included studies was assessed using the Cochrane Collaboration's risk of bias tool. The Review Manager 5.4 software was adopted for meta-analysis.ResultsTwenty-one studies of 1746 participants with PSCI were included. Meta-analysis revealed that HF-rTMS ameliorated memory of PSCI patients according to several outcome indicators: Rivermead Behavioural Memory Test [mean difference (MD) = 2.59, 95% confidence interval (CI) (2.08, 3.11), p < 0.00001], forward digit span [MD = 1.79, 95% CI (1.36, 2.22), p < 0.00001] and backward digit span [MD = 1.18, 95% CI (0.77, 1.59), p < 0.00001] of digit span test, Delayed Recall of the Montreal Cognitive Assessment [MD = 0.53, 95% CI (0.47, 0.59), p < 0.00001]; all p < 0.05.ConclusionsThe HF-rTMS might enhance memory in patients with PSCI, with the left dorsolateral prefrontal cortex being the most common stimulation site.
Ketogenic diet enhances cognitive-behavioral function and hippocampal neurogenesis while attenuating amyloid pathology in Tg-SwDI mice.
Pulido-Correa VE, Hernandez AV, Wind EJ … +9 more , Zhu Y, Vogel C, Binu S, Jeneske M, Kuni D, Chiduruppa V, Echeverria B, Rosenberg L, Robison LS
J Alzheimers Dis · 2026 Jun · PMID 42081138 · Publisher ↗
BackgroundThe ketogenic diet (KD), characterized by high-fat, low-carbohydrate, and moderate protein intake, has gained attention for its therapeutic potential in patients with neurodegenerative diseases, including Alzhe...
BackgroundThe ketogenic diet (KD), characterized by high-fat, low-carbohydrate, and moderate protein intake, has gained attention for its therapeutic potential in patients with neurodegenerative diseases, including Alzheimer's disease (AD). Studies in AD rodent models report that KD and/or ketogenic supplements attenuate cognitive-behavioral impairments, neuroinflammation, amyloid-β (Aβ) plaques, and tau pathology. However, it is unknown whether KD can similarly benefit individuals with cerebral amyloid angiopathy (CAA), a prevalent condition in which Aβ accumulates in cerebral vessels. CAA is highly comorbid with AD and, on its own, increases the risk of stroke, cognitive impairment, and dementia, yet no effective treatments currently exist.ObjectiveTo determine whether KD can improve cognitive-behavioral and neuropathological outcomes in a mouse model with CAA.MethodsMale Tg-SwDI mice were fed either a standard chow or KD from 3.5 to 7.5 months of age. Following ∼3 months of dietary intervention, glucose and ketone body levels were assessed, then mice underwent a battery of behavioral tests to evaluate locomotor activity, anxiety-related behaviors, and cognition. Immunohistochemistry was performed to assess amyloid pathology, vascular density, neuroinflammation, white matter integrity, and hippocampal neurogenesis.ResultsIn addition to KD inducing nutritional ketosis and achieving metabolic benefits, mice on KD exhibited increased activity, enhanced spatial learning and memory, and a trend toward improved spatial working memory. These cognitive benefits were accompanied by an attenuation of amyloid pathology and increased hippocampal neurogenesis.ConclusionsThese findings suggest that a KD may be safe and effective in AD and dementia patients with CAA.
Trends in Alzheimer's disease mortality with metabolic syndrome-related conditions among older adults in the United States, 1999-2020.
Alam T, Rajdeep D, Kamal S … +10 more , Osman Abufatima I, Majid M, Siddiqui S, Waheed SA, Nawaz A, Faheem MSB, Burney W, Khatri A, Usman N, Aqeel N
J Alzheimers Dis · 2026 Jun · PMID 42081127 · Publisher ↗
BackgroundAlzheimer's disease (AD) among patients with metabolic syndrome-related conditions is a global threat, contributing significantly to escalating mortality and economic burden. They demonstrate analogous pathophy...
BackgroundAlzheimer's disease (AD) among patients with metabolic syndrome-related conditions is a global threat, contributing significantly to escalating mortality and economic burden. They demonstrate analogous pathophysiologies and risk determinants, highlighting the necessity for addressing this critical issue.ObjectiveThis study analyzed demographic trends and disparities of AD with metabolic syndrome-related conditions among patients aged 75 and above from 1999 to 2020.MethodsThis study examined the death certificates sourced from the CDC-WONDER database from 1999 to 2020, to analyze age-adjusted mortality rates (AAMRs) per 100,000 population. The Joinpoint regression model was used to assess trends in overall demographics, geographic, and place-of-death variables.ResultsThere were 2,355,233 deaths documented with AD listed as the underlying cause of death among older adults (aged ≥75), out of which 444,488 deaths were related to metabolic syndrome-related conditions from 1999 to 2020. The AAMR rose substantially from 36.48 in 1999 to 157.93 in 2020. Women consistently had higher AAMRs than males (females: 107.79, males: 79.02). Non-Hispanic African Americans (121.65) showed the highest mortality rates among all racial groups. However, from 1999 to the early to mid-2000s, all races highlighted a sharp peak in mortality rates. Striking geographical disparities were noted, with Mississippi in the top 90 percentile and Massachusetts in the lower 10 percentile.ConclusionsThis study reveals the demographic and geographic variations in mortality rates, highlighting the modalities of interventions and the need for equitable healthcare access.
Causes of death in patients with dementia: A study in a geriatric hospital in São Paulo, Brazil.
Dieguez Ferreira Y, Braga Moura C, Carneiro Rodrigues A … +3 more , Pereira Da Silva AM, Haddad Santos D, Fernanda Mendes M
J Alzheimers Dis · 2026 Jun · PMID 42081122 · Publisher ↗
BackgroundDementia contributes to morbidity and mortality in aging populations, with infectious diseases as frequent terminal events. In Brazil, data on causes of death in dementia and hospital-based end-of-life care are...
BackgroundDementia contributes to morbidity and mortality in aging populations, with infectious diseases as frequent terminal events. In Brazil, data on causes of death in dementia and hospital-based end-of-life care are limited.ObjectiveTo describe causes of death, clinical characteristics, and pharmacological treatment patterns during the last month of life among patients with dementia hospitalized in a geriatric hospital in São Paulo, Brazil.MethodsThis retrospective observational study included all patients with clinically diagnosed dementia who died between 2015 and 2023 in a specialized geriatric hospital. Demographic, clinical, and pharmacological data were extracted from electronic medical records. Causes of death were classified using ICD-10 codes. Associations between dementia subtypes and infection-related deaths were evaluated using logistic regression adjusted for age, sex, and comorbidities. Statistical analyses were performed using R, with p < 0.05 considered significant.ResultsA total of 122 patients were included (mean age 83.6 ± 7.4 years; 61.5% female). Alzheimer's disease was the most frequent subtype (52.5%), followed by vascular (26.2%) and mixed dementia (21.3%). Infectious diseases accounted for 67.2% of deaths, mainly pneumonia (48.3%) and sepsis (18.9%). Antibiotics were prescribed in 76.2% of cases, and antipsychotics in 58.1%. Palliative care measures were documented in 41.0% of cases.ConclusionsInfectious diseases were the most frequent causes of death among hospitalized patients with dementia, with high antibiotic use and limited palliative care documentation. These findings indicate the need for integrated end-of-life protocols and improved recognition of palliative needs.
Data-driven detection of lucid episodes in advanced dementia: Application of latent class analysis to observational data.
Kottler HC, Gilmore-Bykovskyi A, Cochran A … +1 more , Mueller K
J Alzheimers Dis · 2026 Jun · PMID 42081117 · Full text
BackgroundLucid episodes (LEs) in advanced dementia are significant clinical events yet are challenging to investigate as they are characterized by a transient and unexpected recovery of abilities and present variably ac...
BackgroundLucid episodes (LEs) in advanced dementia are significant clinical events yet are challenging to investigate as they are characterized by a transient and unexpected recovery of abilities and present variably across individuals. Prospective observational studies of LEs in people living with advanced Alzheimer's disease and related dementias currently rely on expert reviewers/informants to detect and confirm LEs, in a process that is arduous and not always feasible.ObjectiveWe seek to examine the utility of data-driven methods for within-person LE detection and determine if such methods need to be individualized.MethodsWe fit multiple latent class analysis (LCA) models to examine longitudinal segments (n = 1283) from video-observations of participants living with advanced dementia (N = 3) who had informant validated LEs using previously established procedures. Fitted models included both individually specified classes and classes constrained to be equal across participants. Estimated classes were compared to the prior informant validations.ResultsModel fit was best with a three-class model, fit separately for each individual. Multiple model fit measures deteriorated when class definitions were constrained to be equal across participants. For each participant, there was a clear candidate lucid class containing the majority of validated LEs.ConclusionsThis report demonstrates the potential for using LCA for data-driven detection of LEs and demonstrates that detection may require participant-level modeling.
Projected burden of Alzheimer's disease and other dementias in the Western Pacific, 2023-2050.
Marzo RR, Li M, Yang Q … +11 more , Chen H, Sam R, Farooqui M, Changmai MC, Bibigul Z, Karlygash A, Respati T, Xu D, Zhang H, Sheferaw W, Wolde ZM
J Alzheimers Dis · 2026 Jun · PMID 42081116 · Publisher ↗
BackgroundAlzheimer's disease and other dementias (ADODs) are increasing rapidly with population aging, yet region-specific projections for the Western Pacific remain limited.ObjectiveTo project ADOD disability-adjusted...
BackgroundAlzheimer's disease and other dementias (ADODs) are increasing rapidly with population aging, yet region-specific projections for the Western Pacific remain limited.ObjectiveTo project ADOD disability-adjusted life-years (DALYs) and deaths in the Western Pacific to 2050 and evaluate how modifying key risk factors could inform policy and planning.MethodsUsing the Global Burden of Disease 2021 scenario framework, we modeled ADOD burden for 37 Western Pacific countries/areas (2023-2050), stratified by age and sex. Primary outcomes were all-age DALY and death rates per 100,000. Projections included a reference and four counterfactual scenarios. Uncertainty was estimated using 1000 Monte Carlo draws, summarized with 95% uncertainty intervals (UIs).ResultsRegional DALY rates rise from 777.6 (95% UI 375.5-1714.8) in 2023 to 1980.9 (964.7-4176.9) in 2050 (+154.7%), while death rates increase from 41.1 (10.5-110.2) to 119.7 (30.5-302.8) (+191.3%). Female rates exceed male rates throughout, widening absolute sex gaps. By 2050, ages 80-94 account for ∼62% of DALYs and ∼69% of deaths; ≥95 contribute ∼10% and ∼17%. Japan remains highest, while the Republic of Korea approaches comparable levels. China and Singapore show the steepest absolute increases. Scenario curves remain similar until the 2040s; small differences by 2050 reflect survival-driven cohort expansion at high-risk ages.ConclusionsDemographic aging will dominate Western Pacific dementia burden through mid-century. Prevention remains critical to delay onset, compress disability, and improve overall healthy aging, but demographic aging will still drive substantial growth in service needs. Health systems must scale dementia-capable primary care, long-term and palliative services, caregiver support, and gender-responsive planning.
Validation of longitudinal change in proper name recall with pTau217 as a marker of early cognitive decline in cognitively unimpaired adults at risk for Alzheimer's disease dementia.
Basche K, He D, Langhough R … +7 more , Jonaitis E, Du L, Bruno D, Wilson R, Hermann B, Johnson S, Mueller K
J Alzheimers Dis · 2026 Jun · PMID 42081092 · Publisher ↗
BackgroundPrevious work has shown that proper name recall from the Logical Memory (LM) task is sensitive to PET and cerebrospinal fluid biomarkers of Alzheimer's disease (AD) in older adult populations. These findings in...
BackgroundPrevious work has shown that proper name recall from the Logical Memory (LM) task is sensitive to PET and cerebrospinal fluid biomarkers of Alzheimer's disease (AD) in older adult populations. These findings indicate potential utility in identifying preclinical AD.ObjectiveThe purpose of this study is to validate previous findings of the association of proper name recall and blood-based plasma pTau217.MethodsParticipants came from the Wisconsin Registry for Alzheimer's Prevention study. We fit linear mixed effects models of longitudinal LM and proper name recall as a function of most recent pTau217 values. Follow-up analyses added interaction terms to models for group differences in sex and ε4 allele carriage. As an exploratory aim, logistic regression models were used to examine if proper name recall aided in predicting clinical diagnosis.ResultsParticipants with higher concentrations of pTau217 showed a steeper decline on conventional LM and proper name recall. ε4 allele carriers with higher concentrations of pTau217 showed a greater decline in longitudinal task performance, while there was no significant interaction for sex, indicating that men and women with high pTau217 show similar rates of decline.ConclusionsOur findings validate that proper name recall is sensitive to blood-based pTau217. Measuring proper name recall may be an efficient marker assessing early cognitive change that could be leveraged when designing future cognitive tests.
Update on the current state of speech and language testing in Alzheimer's disease.
Dhareshwar S, Kane M, Lewis C … +7 more , Mineur R, Yao K, Snyder PJ, Alber J, Robb C, Lim YY, Vogel AP
J Alzheimers Dis · 2026 Jul · PMID 42081089 · Publisher ↗
Alzheimer's disease (AD) causes alterations in speech and language across multiple domains, including semantic content, pragmatics, prosody, morphosyntax, phonology and timing/fluency, with some of these changes detectab...
Alzheimer's disease (AD) causes alterations in speech and language across multiple domains, including semantic content, pragmatics, prosody, morphosyntax, phonology and timing/fluency, with some of these changes detectable early in the disease course. Definitive biomarker assessments of AD are often invasive or resource-intensive; there is a need for scalable measures in screening and monitoring AD. Advances in natural language processing and automated transcription can quantify speech and language features from structured tasks and natural conversations. This review summarizes domain-specific changes across the AD continuum, evaluates evidence linking these features to biomarkers of AD pathology (amyloid and tau), and discusses opportunities and limitations for future work. We conclude by identifying priorities for the field, namely, domain-aware task design, demographic and language-sensitive norms and standardized, biomarker-validated datasets.
Donepezil increases angiogenic potential in patients with Alzheimer's disease.
Lee M, Kim M
J Alzheimers Dis · 2026 Jun · PMID 42057407 · Publisher ↗
BackgroundAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Acetylcholinesterase inhibitors are the mainstay of symptomatic treatment, and vascular dysfunction is increasingly recognized as a key...
BackgroundAlzheimer's disease (AD) is the leading cause of dementia in the elderly. Acetylcholinesterase inhibitors are the mainstay of symptomatic treatment, and vascular dysfunction is increasingly recognized as a key contributor to AD pathophysiology. While donepezil is a standard AD treatment, its effects on the vascular system remain poorly understood despite known neurovascular interactions.ObjectiveTo investigate whether donepezil treatment influences endothelial progenitor cell (EPC) populations and differentiation capacity in patients with AD.MethodsEPCs were evaluated in healthy controls and patients with AD (n = 20 per group; N = 80 total): controls (Ctrl), patients initiating donepezil 5 mg (Dp_Start), patients receiving donepezil 5 mg for ≥6 months (Dp_5 mg), and patients escalated to 10 mg after ≥6 months of 5 mg treatment (Dp_10 mg). Peripheral blood samples were collected at baseline, 12 weeks, and 24 weeks. Circulating EPCs were quantified by flow cytometry, and EPC differentiation capacity was assessed by counting early and late EPC colony-forming units (CFUs).ResultsAt baseline, EPC differentiation capacity was reduced in AD patients compared with controls. Circulating EPC levels did not show significant changes across groups or treatment durations. In contrast, both early and late EPC CFU counts were significantly increased in AD patients receiving donepezil, particularly during the first 12 weeks of treatment. This effect was pronounced in patients initiating donepezil therapy.ConclusionsDonepezil enhanced EPC differentiation into early and late populations without altering circulating EPC levels. These findings suggest that donepezil improves EPC functional competence and vascular regenerative capacity beyond its established cognitive effects.
Associations of circulating resistin with Alzheimer's disease biomarkers and cognitive function in the preclinical stage of Alzheimer's disease.
Eruysal E, Ravdin L, Iadecola C … +1 more , Ishii M
J Alzheimers Dis · 2026 Jun · PMID 42047539 · Full text
BackgroundResistin is a circulating protein linked to systemic metabolic disorders and inflammation, both of which can contribute to the pathogenesis of Alzheimer's disease (AD). However, the role of resistin during the...
BackgroundResistin is a circulating protein linked to systemic metabolic disorders and inflammation, both of which can contribute to the pathogenesis of Alzheimer's disease (AD). However, the role of resistin during the preclinical stage of AD and its associations with amyloid-β and tau pathology have not been established.ObjectiveTo measure plasma resistin concentrations in cognitively normal older adults and examine its association with cerebrospinal fluid (CSF) AD biomarkers and neuropsychological measures.Methods155 (64 men and 91 women) cognitively normal (Clinical Dementia Rating 0) volunteers met all study criteria with 55 (29 men and 26 women) categorized as preclinical AD based on established CSF criteria. Plasma resistin concentrations were measured by immunoassay.ResultsSince plasma resistin concentrations were higher in men compared to women, all analyses were sex stratified. In men, plasma resistin concentrations were significantly higher in preclinical AD compared to biomarker negative controls and were associated with CSF concentrations of tau and p-tau; however, after correcting for multiple comparisons, there were no significant associations with any AD biomarkers. Furthermore, plasma resistin concentrations were significantly associated with semantic fluency but not with episodic memory or executive function. In women, plasma resistin concentrations were similar between preclinical AD and controls, and there were no significant associations with CSF AD biomarkers and cognitive measures.ConclusionsThese findings raise the possibility that, in men, alterations in peripheral resistin signaling occur during the earliest stages of AD and could represent an early link between systemic metabolic and inflammation dysregulation in AD.
Age-related macular degeneration and dementia: Association through pathogenesis or visual impairment?
Gu X, Terebuh P, Xu R … +2 more , Kaelber DC, Davis PB
J Alzheimers Dis · 2026 Jun · PMID 42033410 · Publisher ↗
BackgroundStudies suggest a link between blindness, age-related macular degeneration (AMD), and dementia risk, but whether this stems from AMD pathology or blindness remains unclear. This study examines the relationship...
BackgroundStudies suggest a link between blindness, age-related macular degeneration (AMD), and dementia risk, but whether this stems from AMD pathology or blindness remains unclear. This study examines the relationship between AMD and dementia.ObjectiveTo evaluate the association between AMD and 5-year dementia risk in non-blind patients.MethodsThis retrospective cohort study used TriNetX to compare non-blind patients with exudative AMD (n = 35,021) and non-exudative AMD (n = 96,809) to those without AMD (n = 1,801,879) for five-year dementia risk. Blind (n = 90,615) and non-blind (n = 800,737) patients were compared. Cohorts were propensity-matched for confounding factors.ResultsNon-blind AMD patients had decreased Alzheimer's disease risk, while blindness showed a strong positive association. Exudative AMD had HR of 0.84 (95% CI = [0.72, 0.97]), non-exudative AMD had HR of 0.95 (95% CI = [0.87, 1.04]), but blindness increased Alzheimer's disease risk (95% HR = 1.29, CI = [1.17, 1.41]).ConclusionsThese findings suggest that previously reported associations between AMD and dementia may be partially mediated by visual impairment. The modest reduction in dementia risk in non-blind AMD patients may reflect differences in healthcare utilization or treatment exposure among AMD patients.
Plasma phosphorylated tau 181, vascular risk factors, and cognition in elderly Hispanics.
Bahl A, Honig LS, Kang MS … +8 more , Sanchez D, Reyes-Dumeyer D, Manly JJ, Lantigua RA, Brickman AM, Vardarajan BN, Mayeux R, Gu Y
J Alzheimers Dis · 2026 Jun · PMID 42033409 · Full text
BackgroundCerebrovascular risk factors, a group of conditions that reduce or disrupt blood flow to the brain, often occur with Alzheimer's disease (AD) and may contribute to the pathogenesis and cognitive decline. Hispan...
BackgroundCerebrovascular risk factors, a group of conditions that reduce or disrupt blood flow to the brain, often occur with Alzheimer's disease (AD) and may contribute to the pathogenesis and cognitive decline. Hispanic individuals are at increased risk of vascular risk factors compared to non-Hispanic white counterparts.ObjectiveWe examined associations among vascular risk factors, including hypertension, diabetes, history of heart disease, and history of stroke, with plasma phosphorylated tau-181 (P-tau181) and cognition.MethodsWe pooled data from 2159 two cohorts of older Hispanic adults. Vascular risk factors were self-reported. Plasma P-tau181 was measured using standardized protocols. Linear regression and mediation models assessed associations among vascular risk, P-tau181, and global cognition, stratified by cognitive status.ResultsOverall, P-tau181 was significantly associated with vascular risk factors and inversely associated with cognitive function. However, vascular risk factors were not independently associated with cognition. Among cognitively unimpaired individuals, vascular risk factors mediated the association between P-tau181 and cognition, while in cognitively impaired individuals, P-tau181 was strongly and independently associated with cognition, without mediation by vascular risk factors.ConclusionsAmong elderly without dementia, vascular risk factors mediate the association between P-tau181 and cognition. However, among individuals with dementia there is no mediation, suggesting that the association between P-tau181 with dementia is independent of cerebrovascular pathology.
Dietary intervention and cognition across Alzheimer's disease biomarker levels: The MIND clinical trial.
Dhana K, Aggarwal NT, Arfanakis K … +2 more , Sacks FM, Barnes LL
J Alzheimers Dis · 2026 Jun · PMID 42033408 · Publisher ↗
BackgroundThe cognitive response to dietary interventions may differ according to levels of Alzheimer's disease-related plasma biomarkers.ObjectiveUsing data from the MIND clinical trial, we examined whether baseline bio...
BackgroundThe cognitive response to dietary interventions may differ according to levels of Alzheimer's disease-related plasma biomarkers.ObjectiveUsing data from the MIND clinical trial, we examined whether baseline biomarkers, including Aβ, the Aβ ratio, and p-tau181, modified the association between the MIND diet and longitudinal change in global cognition.MethodsThe MIND randomized clinical trial enrolled 604 community-dwelling adults aged 65-84 years without cognitive impairment at baseline. Recruitment occurred from January 2017 to April 2018, with data collection continuing through June 2021. Participants were randomized in a 1:1 ratio to the MIND or control diet for 3 years, with counseling on diet adherence and weight loss support provided at the same frequency throughout the intervention. Annual change from baseline in a global cognitive composite z-score was derived from a 12-test battery, with higher scores indicating better cognitive performance.ResultsOf the 602 individuals included in the analysis, 391 (65%) were female, and the mean baseline age was 70.4 (SD = 4.2) years. Baseline levels of Aβ and p-tau181 modified the association between MIND assignment and longitudinal change in global cognition, with significant between-group differences in biomarker-related annual cognitive slopes for Aβ (β=0.027, 95%CI 0.006-0.048) and p-tau181 (β=0.023, 95%CI 0.002-0.043), but not for the Aβ ratio.ConclusionsThe association between the MIND diet intervention and cognition varied by baseline levels of Aβ and p-tau181, with greater improvement in cognitive scores in the MIND group than in the control group among individuals with higher biomarker levels. ClinicalTrials.gov Identifier: NCT02817074.
Dementia screening with the Rivermead Behavioural Memory Test: A machine learning analysis.
Fujiwara Y, Toyoda K, Maruyama S … +3 more , Kitano M, Toda H, Kanazawa T
J Alzheimers Dis · 2026 Jun · PMID 42033406 · Publisher ↗
BackgroundWith the advent of anti-amyloid-β monoclonal antibody therapies and the growing societal burden of dementia, early identification of Alzheimer's disease and related dementias has become a clinical priority.Obje...
BackgroundWith the advent of anti-amyloid-β monoclonal antibody therapies and the growing societal burden of dementia, early identification of Alzheimer's disease and related dementias has become a clinical priority.ObjectiveTo evaluate the diagnostic accuracy of a machine learning model using a neuropsychological battery to classify individuals as Healthy controls, mild cognitive impairment (MCI), or Dementia, and to identify neuropsychological tests and cognitive domains that contributed most to classification accuracy, determining optimal tests for dementia screening.MethodsIn this retrospective cross-sectional single-center study, we analyzed 590 participants evaluated for suspected dementia. The final sample comprised 74 Healthy controls, 190 individuals with MCI, and 326 with Dementia (including 269 with Alzheimer's disease). Scores from the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Japanese version (MoCA-J), Rivermead Behavioural Memory Test (RBMT), Japanese Adult Reading Test (JART), and Wechsler Adult Intelligence Scale-III were input into a random forest machine learning model. Model performance was assessed using the area under the ROC curve (AUC). A variable importance analysis determined each test's relative contribution to classification.ResultsThe multiclass model achieved an AUC of 0.898. RBMT was the strongest contributor, exceeding MMSE and MoCA-J. In borderline MMSE/MoCA-J subsets, adding RBMT improved classification performance for both Healthy versus MCI and MCI versus Dementia decisions.ConclusionsRBMT provides substantial incremental value for dementia-related diagnostic discrimination, particularly as a second-line assessment when brief screening results are borderline. However, its administration time may limit its role as a universal first-line screening tool.
Examining the effects of alcohol use on verbal memory processes in older adults with mild cognitive impairment.
Cuperfain AB, Pishdadian S, Binns MA … +12 more , Black SE, Chertkow H, Freedman M, Louis J, Ma C, Masellis M, Mclaughlin PM, Ramirez J, Tang-Wai DF, Tartaglia MC, Kumar S, CCNA COMPASS-ND Group, and on behalf of the ONDRI Group
J Alzheimers Dis · 2026 Jun · PMID 42033405 · Publisher ↗
BackgroundExcessive alcohol use is associated with memory impairment due to its effects on encoding and retrieval of information. However, the underlying mechanisms in those with neurodegenerative disorders is not well u...
BackgroundExcessive alcohol use is associated with memory impairment due to its effects on encoding and retrieval of information. However, the underlying mechanisms in those with neurodegenerative disorders is not well understood.ObjectiveWe evaluated the effects of alcohol on verbal memory processes in those with mild cognitive impairment (MCI).MethodsData came from two cohorts, the Comprehensive Assessment of Neurodegeneration and Dementia and the Ontario Neurodegenerative Disease Research Initiative. Participants were diagnosed with MCI due to Alzheimer's disease or cerebrovascular disease, and categorized into "zero", "low-medium", or "high" alcohol use groups. We compared occurrence of any intrusion, total intrusions, change in intrusions post-interference, and intrusion subtypes on the Rey Auditory Verbal Learning Test across groups.ResultsWe analyzed 521 participants with high (n = 79), low-medium (n = 304), and zero (n = 138) alcohol use. Mean (SD) age was 71.6 (7.4) years and did not differ between groups. The high alcohol use group had higher occurrence of any intrusions (96.2%) compared to the low-medium (87.2%), and zero (92.8%) alcohol use groups (p = 0.027). Alcohol use was associated with increased post-interference intrusions, with the high group adjusted mean (M), standard error (SE) = 1.7 (0.3), low-medium group M(SE) = 1.0 (0.2), and zero group M(SE) = 0.9 (0.2), (p = 0.027). Other intrusion subtypes did not differ between groups.ConclusionsIndividuals with MCI and excessive alcohol use are more susceptible to interference from recently learned task-irrelevant information. Findings may inform future research regarding mechanisms of alcohol related memory impairment.
Underweight is associated with increased risk of all-cause dementia in older adults with vascular risk factors, independent of brain atrophy and small vessel disease.
Kitagawa K, Toi S, Yoshizawa H … +1 more , Todo K
J Alzheimers Dis · 2026 Jun · PMID 42024130 · Publisher ↗
BackgroundUnderweight, defined as a body mass index (BMI) < 18.5 kg/m2, has been associated with increased risk of dementia in older adults. However, whether this association reflects a causal relationship remains unclea...
BackgroundUnderweight, defined as a body mass index (BMI) < 18.5 kg/m2, has been associated with increased risk of dementia in older adults. However, whether this association reflects a causal relationship remains unclear.ObjectiveTo examine the association between low BMI and dementia, independent of brain magnetic resonance imaging findings.MethodsWe analyzed data from patients aged ≥ 65 years with vascular risk factors enrolled in a Japanese observational registry. Patients were categorized by BMI as underweight (<18.5 kg/m), normal weight (18.5-24.9 kg/m), or overweight (≥25.0 kg/m). The outcomes were all-cause dementia and Alzheimer's disease (AD) dementia.ResultsA total of 607 patients (median age, 74 years) were included: 58 underweight, 389 normal weight, and 160 overweight. During a median follow-up of 4.7 years, 39 patients developed dementia and 30 developed AD dementia. Kaplan-Meier analysis showed that underweight group had a significantly higher incidence of all-cause dementia (p = 0.002) and AD dementia (p = 0.009) compared with the other groups. Cox regression hazard analysis adjusted for age and sex revealed that underweight had a higher risk of all-cause dementia (hazard ratio, 3.38; 95% confidence interval, 1.49-7.67) compared with normal weight. In exploratory analysis, the association between underweight and all-cause dementia remained significant after adjustment for additional confounders, medial temporal atrophy, and white matter hyperintensities.ConclusionsUnderweight in older adults was associated with increased risk of all-cause dementia independent of age, sex, confounding factors, brain atrophy and white matter hyperintensities. These findings warrant confirmation in larger cohorts.Clinical Trial RegistrationUMIN000026671.
Alterations in choroid plexus volume associated with butylphthalide treatment in mild cognitive impairment: Data from a randomized, placebo-controlled study.
Shan A, Xu C, Chen R … +17 more , Han X, Sun W, Yao Q, Wang X, Luan H, Li S, Wen B, Cui T, Guo J, Lian Q, Sun Y, Li C, Jia H, Ma H, Lv S, Sun Q, Wei C
J Alzheimers Dis · 2026 Jun · PMID 42024119 · Publisher ↗
BackgroundThe choroid plexus (ChP) is increasingly recognized as an essential component in the pathogenesis of cognitive impairment associated with Alzheimer's disease. DL-3-n-butylphthalide (NBP) has been confirmed to e...
BackgroundThe choroid plexus (ChP) is increasingly recognized as an essential component in the pathogenesis of cognitive impairment associated with Alzheimer's disease. DL-3-n-butylphthalide (NBP) has been confirmed to exert neuroprotective effects through multiple pathways and thereby enhance cognitive function. However, the role of NBP in the ChP volume remains unclear at present.ObjectiveThis trial aimed to explore the clinical efficacy of NBP in patients with mild cognitive impairment (MCI) and its corresponding ChP imaging characteristics.MethodsThis randomized, double-masked, placebo-controlled study included 270 MCI patients, randomly assigned in a 1:1 ratio to receive either NBP or placebo. Concurrently, all participants received clinical cognitive evaluations and 3D T1-weighted magnetic resonance imaging scans at both baseline and post-treatment phases. The objective was to evaluate the efficacy of 12-month NBP treatment on cognitive impairment and investigate the neuroimaging correlates of NBP therapy, focusing specifically on longitudinal alterations in ChP.ResultsThe NBP treatment significantly improved the cognitive symptoms of MCI patients, which was strongly correlated with the decrease in ChP volume in the drug group. Moreover, subgroup analysis indicated that cognitive enhancement was closely related to changes in ChP volume in the effective group. Mediation effect analysis revealed that ChP volume partially mediated the enhancement of cognitive symptoms in MCI patients undergoing NBP treatment.ConclusionsThis research provided evidence that NBP may improve cognitive symptoms in MCI patients by regulating changes in ChP volume, as well as offered insight into identifying early neuroimaging markers of MCI and drug targets for NBP.Clinical trial registry nameEfficacy and safety of butylphthalide on patients with mild cognitive impairment; Registration number: ChiCTR1800018362.
Dysbiosis of gut microbiota synergizes with the activation of enteric glial cells to promote Alzheimer's disease.
Sun Q, Li Y, Wang Y … +4 more , Tao SS, Huan X, Li YQ, Zhang H
J Alzheimers Dis · 2026 Jun · PMID 42024118 · Publisher ↗
BackgroundThe microbiota-gut-brain axis (MGBA) plays a crucial role in the onset and progression of Alzheimer's disease (AD). Enteric glial cells (EGCs) represent a fundamental cellular constituent that upholds the struc...
BackgroundThe microbiota-gut-brain axis (MGBA) plays a crucial role in the onset and progression of Alzheimer's disease (AD). Enteric glial cells (EGCs) represent a fundamental cellular constituent that upholds the structural and functional integrity of the MGBA. However, the specific mechanistic role of EGCs in the pathogenesis of AD remains unclear.ObjectiveThe present study aimed to investigate the synergistic interaction between gut microbiota (GM) dysbiosis and EGCs activation in a mouse of AD.MethodsAmyloid precursor protein (APP)/presenilin 1 (PS1) transgenic AD mice were utilized as the experimental model. Behavioral experiments, 16S rRNA sequencing, Nissl staining, and immunofluorescence staining were used to evaluate the related changes of AD in cognitive function, neuropathology, GM, and EGCs, respectively.ResultsAD mice exhibited significant cognitive dysfunction, with obvious neuronal damage and Aβ plaques formation in the hippocampus and primary somatosensory cortex. The GM composition of AD mice was significantly altered, -diversity decreased, and the dominant bacterial population was significantly different from the control group. Morphologically, EGCs in the myenteric plexus (MP) and submucosal plexus (SP) of AD mice were markedly activated, concomitant with a reduction in neuronal count. This alteration in EGCs-neuron interactions was shown to be region-specific in MP and SP.ConclusionsThis study confirms characteristic alterations in GM and abnormal EGCs activation in AD mice, while also uncovering regional specificity of these changes within the enteric nervous system. These findings may provide experimental evidence for the development of targeted intervention strategies for AD based on GM and EGCs.
A metabolic-glial plasma signature defines early Alzheimer's disease: Insights from an understudied cohort.
Santos LTR, Costa FL, Rosa ID … +16 more , Frota AF, Bezerra JR, Soares MVR, Barbosa CSN, Farias JWF, da Silva LRAM, Gonçalves PVS, Carvalho LEM, Carlos LMB, Coelho Filho JM, Lôbo RR, Gallo MBC, Teixeira AL, Diniz BS, Peixoto Junior AA, Macedo DS
J Alzheimers Dis · 2026 Jun · PMID 42024117 · Publisher ↗
BackgroundEarly detection and staging of Alzheimer's disease (AD) remain challenging in low-resource settings where cerebrospinal fluid analysis and neuroimaging are not routinely accessible. Blood-based biomarkers such...
BackgroundEarly detection and staging of Alzheimer's disease (AD) remain challenging in low-resource settings where cerebrospinal fluid analysis and neuroimaging are not routinely accessible. Blood-based biomarkers such as phosphorylated tau at threonine 181 (p-tau181), glial fibrillary acidic protein (GFAP), and amyloid-tau ratios have improved diagnostic performance; however, their integration with systemic metabolic markers remains insufficiently investigated.ObjectiveTo characterize metabolic-neuroglial plasma signatures across the cognitive continuum and identify biomarkers capable of discriminating mild cognitive impairment (MCI) from mild AD and cognitively unimpaired (CU) individuals.MethodsSeventy adults classified as CU, MCI, or mild AD underwent plasma quantification of Aβ, Aβ, p-tau181, and GFAP alongside metabolic markers, including glycated hemoglobin, calcium, vitamin D, homocysteine, thyroid-stimulating hormone, C-reactive protein, and platelet count. Group comparisons were conducted using non-parametric tests. Multivariate approaches, principal component analysis, partial least squares discriminant analysis, and Random Forest (RF), were applied to detect discriminative biomarker patterns, incorporating automatically generated ratios.ResultsMCI participants showed higher plasma homocysteine and Aβ than CU. Mild AD was characterized by elevated p-tau181 and GFAP and a reduced amyloid-tau balance captured by Aβ-based ratios. CU was distinguishable from both clinical groups using univariate markers and ratios, whereas separation between MCI and mild AD required multivariate integration. A six-biomarker RF signature robustly discriminated MCI from mild AD (AUC = 0.854; permutation p = 0.0044).ConclusionsIntegrated plasma panels combining neurodegenerative and metabolic markers improve staging across the AD continuum and may support clinical decision-making where advanced diagnostics are limited.
Systematic review and meta-analysis of associations between neuropsychiatric symptoms and amyloid, tau, neuronal, and glial biomarkers in young-onset dementias.
Chiu WH, Kang MJY, Goh AMY … +2 more , Velakoulis D, Loi SM
J Alzheimers Dis · 2026 Jun · PMID 42024116 · Publisher ↗
BackgroundNeuropsychiatric symptoms (NPS) are highly prevalent in dementia. While biomarkers reflecting amyloid, tau, neuronal injury, and glial activation are increasingly used in dementia research, their association wi...
BackgroundNeuropsychiatric symptoms (NPS) are highly prevalent in dementia. While biomarkers reflecting amyloid, tau, neuronal injury, and glial activation are increasingly used in dementia research, their association with NPS remains unclear.ObjectiveTo identify and characterise associations between biomarkers and NPS in people with young-onset dementia (YOD).MethodsWe conducted a systematic review and meta-analysis of studies examining associations between validated biomarkers and NPS in individuals with Alzheimer's disease (AD), frontotemporal dementia (FTD), Huntington's disease (HD), and vascular dementia (VaD), published between 2010 and 2024. The review followed PRISMA guidelines and was prospectively registered (PROSPERO; CRD42022314243).ResultsPrinciple meta-analyses identified no consistent evidence for associations between NPS and amyloid, tau, and neuronal biomarkers in AD, with limited data available for glial biomarkers. There was a scarcity of studies investigating the relationship between biomarkers and NPS in HD, VaD, and FTD.ConclusionsThe absence of consistent associations likely reflects substantial heterogeneity in pathology, clinical presentation, and methodological approaches, particularly within YOD populations, rather than a true lack of biological linkage. NPS in dementia may emerge from complex bio-psycho-social interactions that transcend classical biomarker models. Longitudinal, multimodal studies are needed to better delineate these relationships.
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