Abstract Objective This study examined how cognitive difficulties, an early marker of memory impairment and a potential precursor to Alzheimer’s disease and related dementias, vary across U.S. states among Latinos aged 45 and older. Methods Using data from the 2008–2019 American Community Survey, we estimated logistic regression models to examine state-level differences in cognitive difficulties among Latinos aged 45 and older. We analyzed patterns within the pan-ethnic Latino population, stratified by nativity, Latino heritage, and country or region of origin. Results We observed substantial heterogeneity in the prevalence of cognitive difficulties among Latino populations across states and subgroups. Pan-ethnic Latino populations in Pennsylvania, Massachusetts, Michigan, Ohio, and New Mexico exhibited notably higher rates of cognitive difficulties. When disaggregated by nativity, U.S.-born Latino populations consistently reported higher levels of cognitive difficulties compared to their foreign-born counterparts. Among these, Puerto Ricans, Dominicans, and Cubans showed the highest prevalence in several states. Our findings also highlight that the intersection of nativity, heritage, and state-level context shapes distinct cognitive risk profiles within the Latino population. Discussion This study contributes to gerontological research by illuminating how structural, cultural, and geographic factors intersect to shape cognitive aging among diverse Latino populations. These findings underscore the importance of moving beyond pan-ethnic categorizations to understand cognitive health disparities within the Latino population. They also highlight the role of state-level sociopolitical environments in shaping cognitive health outcomes. Public health strategies should prioritize culturally and geographically tailored interventions, particularly in high-risk states, to improve access to cognitive screening and early diagnosis.

Treatment patterns of symptomatic treatments for Alzheimer's disease and related dementias.

Hospitalization Experiences Among Nursing Home Residents With Dementia.

Anosognosia, the lack of awareness of memory decline, and Neuropsychiatric Symptoms (NPS) are prevalent and debilitating symptoms in Alzheimer's disease (AD) dementia. Understanding the coexistence of these symptoms may help guide clinical interventions and treatment strategies. This study aimed to compare NPS prevalence in patients with and without anosognosia at baseline and to assess the association between anosognosia and NPS over time. We examined patients with AD dementia enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To be included in the current study, patients had to have undergone baseline assessments and at least one subsequent follow-up evaluation. Furthermore, all patients had to have amyloid (as assessed using Positron Emission Tomography, PET), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), and Everyday Cognition (ECog) variables available throughout the study. Anosognosia, our exposure of interest, was determined using Ecog scores from patients and study partners. Study partners evaluated the presence or absence of 12 NPS (our outcomes of interest) using the NPI. Cox proportional hazards models, excluding patients who had any symptoms of NPS at baseline, were used to evaluate NPS onset by group (anosognosia/no anosognosia) while adjusting for age, sex, years of education, and MMSE. 112 patients with follow-up data (mean = 1 year) were included in this study. Of these, 47.3% (n = 53) had anosognosia, while 52.7% (n = 59) did not. In those with anosognosia at baseline, we observed a trend toward greater prevalence of agitation and motor symptoms. Exploratory time-to-event analysis demonstrated that the patients with anosognosia had a faster onset of apathy (HR: 2.78, 95% CI: 1.37-5.62, p = 0.01) compared to the patients without anosognosia. In this exploratory study, while there were no significant differences in frequency of NPS at baseline between the groups, patients with anosognosia demonstrated faster onset of apathy as compared to patients without anosognosia. These findings underscore the importance of longitudinal assessments and tailored interventions targeting the management of NPS in AD dementia patients with anosognosia. Further research is warranted to explain the underlying mechanisms driving these associations and to inform the development of targeted therapeutic strategies aimed at improving patient outcomes in this population.

High-Frequency Oscillations >250 Hz in People with Down Syndrome and Associated Alzheimer's Disease Dementia Lisgaras CP, Giménez S, Carmona-Iragui M, Maure-Blesa L, Blessing E, Fortea J, Osorio RS. Alzheimers Dement . 2025;21(7):e70386. https://doi.org/10.1002/alz.70386 Introduction: Alzheimer's disease (AD) dementia has near full penetrance in adults with Down syndrome (DS) and is strongly linked to late-onset myoclonic epilepsy in Down syndrome (LOMEDS). However, promising biomarkers of epileptogenicity, such as high-frequency oscillations (HFOs >250 Hz), have not been studied. This study is the first to use wideband polysomnography in DS to investigate if HFOs occurred and preceded AD dementia and LOMEDS. Methods: Wideband (0.1 to 500 Hz, 2048 Hz) polysomnography was performed using the international 10–20 system. HFOs were automatically detected during slow-wave sleep, followed by manual review. Results: Fourteen individuals with DS and five age-matched euploid controls were studied, with all DS cases showing HFOs. HFOs emerged before AD dementia and LOMEDS and showed hemispheric lateralization in asymptomatic but not symptomatic AD dementia cases. A trend toward increasing HFO rates with age in DS warrants further confirmation. Discussion: HFOs are promising biomarkers that may predict symptomatic AD dementia in adults with DS.

Abstract Background and Objectives While early detection of Alzheimer’s disease and related dementias (ADRD) can help delay progression and improve outcomes, limited research is available on dementia-related health behavior, such as screening intention among American Indian/Alaska Native communities. Guided by the Theory of Reasoned Action, the Theory of Planned Behavior, and the Health Belief Model, this study examines whether self-efficacy mediates the association between dementia knowledge and intention to seek ADRD screening among American Indian adults. Research Design and Methods Using a community-based participatory research approach, a cross-sectional survey was conducted with 248 American Indian adults (18 years and over) from a partner tribal community in the Northern Plains region in 2024. Measures included dementia knowledge, self-efficacy, screening intention, perceived susceptibility, stigma, and demographic factors. Mediation was tested using the Baron and Kenny framework and Sobel-Goodman tests. Results Dementia knowledge significantly predicted both ADRD screening intention and self-efficacy. Self-efficacy also significantly predicted screening intention and partially mediated the relationship between knowledge and intention. Approximately 32% of the effect of dementia knowledge on screening intention was mediated by self-efficacy. Discussion and Implications Findings underscore self-efficacy as a critical mechanism through which dementia knowledge translates into ADRD screening intention in American Indian communities. Interventions to promote early ADRD detection could enhance both knowledge and individual confidence. Future research should include more diverse groups within American Indian communities to identify common and unique dynamics among knowledge, self-efficacy, and screening intention, informing effective intervention strategies to reduce stigma and confidence in seeking timely ADRD screening.

BackgroundDepression is a common comorbidity in Parkinson’s disease (PD) and Lewy body dementia (LBD). However, studies examining the rate of incident depression in the period preceding and following the diagnosis of PD and LBD are lacking in the literature.AimsTo quantify the incidence of depression in the period preceding and following the diagnosis of PD and LBD.MethodsWe conducted a retrospective case-control study. Specifically, we used Danish registers to identify all patients with a diagnosis of PD or LBD in the period from 2007 to 2019. These patients were matched by age, calendar year of diagnosis and sex with up to three patients diagnosed with rheumatoid arthritis (RA), chronic kidney disease (CKD) or osteoporosis, respectively. The outcome was incident depression. The incidence of depression was assessed for up to 10 years before and up to 10 years after the diagnosis of PD or LBD. Hazard rates of incident depression for patients with PD or LBD, both before and after diagnosis, were compared with those for patients with RA, CKD or osteoporosis using a Cox-proportional hazards model.ResultsWe identified 17 711 patients with PD or LBD. Their median age was 74.98 (68.10–80.85) years, and 39.92% were females. These patients were matched to 19 556, 40 842 and 47 809 patients with RA, CKD and osteoporosis, respectively. From 7 to 8 years before diagnosis to 5 years after diagnosis, patients with PD and LBD consistently had higher hazard rates of incident depression than all comparator groups.ConclusionsThese findings are compatible with depression being an early manifestation of the neurodegenerative changes eventually leading to PD and LBD and imply that incident depression at a late age should raise awareness of potential PD and LBD.

Changes in the public IgM repertoire and its idiotypic connectivity in Alzheimer's disease and frontotemporal dementia.

Platelet-derived growth factor is increased with cognitive fluctuations and hallucinations in Lewy Body disease.

CCR5 as a key modulator in neurocognitive disorders.

Nil per os on Admission and Dehydration Are Risk Factors for Delirium in Hospitalized Older Adults With Dementia and Dysphagia.

Creating zines about Alzheimer's disease and related dementias for American Indian and Alaska Native youth caregivers

Alternative splicing and the aging brain in AfrAbia: New frontiers in dementia research.

Effectiveness of Cognitive Behavioral Therapy and Aerobic Exercise in Parkinson Disease Dementia: A Pilot Study

The effect of shingles vaccination at different stages of the dementia disease course.

Keeping current with the burden and risk factors of Alzheimer disease and other dementias (ADOD) from global to national levels is critical for healthcare planning, prevention strategies, and the allocation of resources. In this descriptive epidemiological analysis, we conducted a secondary analysis of global burden of disease data to examine the epidemiological burden of ADOD from 1990 to 2021 across global, regional and national levels. The study assessed age-standardized rates of incidence, prevalence, mortality, disability-adjusted life years, years lived with disability, and years of life lost. In 2021, global ADOD burden showed notable geographical disparities across all metrics. The highest incidence and prevalence rates were reported in China, while Gabon recorded the highest death rates. The Democratic Republic of the Congo observed the highest DALYs rates. From 1990 to 2021, age-standardized ADOD rates increased globally. Notably, China saw significant increases in incidence, prevalence, and years lived with disability, while Indonesia and Eritrea reported the highest rises in deaths and years of life lost, respectively. The burden growth was most pronounced in high-middle and middle socio-demographic index regions. The study also highlighted the impact of metabolic risk factors on the ADOD-related disability-adjusted life years across regions and sexes. Based on the findings of significant geographical heterogeneity in the escalating global burden of ADOD and its close association with specific risk factors, public health intervention strategies must be both geographically targeted and closely aligned with the predominant risk factors in each region to optimize resource allocation and maximize prevention and control efficiency.

Background/Objectives: This systematic review aimed to determine the effects of resistance training on cognitive and motor function in older adults diagnosed with Alzheimer’s disease (AD). Methods: The review followed PRISMA guidelines. A comprehensive search strategy was applied across MEDLINE (OVID), SCOPUS, Web of Science, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL). The included studies were experimental, quasi-experimental, cohort, case–control, and cross-sectional designs. Exclusion criteria included studies in animals, pediatric populations, individuals with other types of dementia, Down syndrome, or other neurodegenerative diseases. Conclusions: Resistance training appears to exert beneficial effects on both motor and cognitive functions in older adults with AD. However, the development of standardized, individualized exercise protocols is essential to optimize therapeutic outcomes

Lewy body dementia (LBD), which includes Parkinson's disease dementia and dementia with Lewy bodies, is characterized by progressive cognitive decline, α-synuclein (α-Syn) aggregation, and concurrent microglial activation and neuroinflammation. The nucleus basalis of Meynert (NBM), the primary source of cortical cholinergic input, plays a key role in cognitive function and is particularly affected in LBD. Cholinergic neurons within the NBM are highly vulnerable to Lewy body pathology, yet the underlying mechanisms remain poorly understood. In this study, we employed a mouse model with PFF injections into the NBM to investigate how microglia and their exosomes influence α-Syn pathology. We found that exosomes derived from activated microglia exacerbate α-Syn deposition and cognitive deficits, whereas microglial depletion mitigates these pathological changes. In vitro, activated microglial exosomes enhanced the uptake of exogenous α-Syn by cholinergic neurons. Mechanistically, we discovered that microglial exosomes can transfer bioactive membrane receptors to neurons. Focusing on lymphocyte-activation gene 3 (LAG3), a receptor critical for α-Syn internalization, we demonstrated that LAG3 is abundant in exosomes from activated-but not resting-microglia. These exosomes deliver LAG3 to neuronal membranes via an endosomal recycling pathway, a process facilitated by elevated cholesterol content, thereby promoting α-Syn uptake. Together, these findings indicate that microglial exosomes function not only as carriers of signaling molecules but also as vectors for receptor transfer, reshaping neuronal membrane composition. Our results provide a mechanistic explanation for the heightened vulnerability of NBM cholinergic neurons in LBD and reveal a novel pathway in which LAG3-rich microglial exosomes drive neuronal α-Syn internalization, advancing our understanding of neurodegeneration and identifying potential therapeutic targets.

The degradation of aggregation-prone tau is regulated by the ubiquitin-proteasome system and autophagy, which are impaired in Alzheimer's disease (AD) and related dementias (ADRD), causing tau aggregation. Protein ubiquitination, with its linkage specificity determines the fate of proteins, which can be either protein degradative or stabilizing signals. While the linear M1-linked ubiquitination on protein aggregates serves as a signaling hub that recruits various ubiquitin-binding proteins for the coordinated actions of protein aggregate turnover and inflammatory nuclear factor-kappa B (NF-κB) activation, the deubiquitinase OTULIN counteracts the M1-linked ubiquitin signaling. However, the exact role of OTULIN in neurons and tau aggregates clearance in AD are unknown. Based on our quantitative bulk RNA sequencing analysis of human inducible pluripotent stem cell–derived neurons (iPSNs) from an individual with late-onset sporadic AD (sAD2.1), a downregulation of the ubiquitin ligase activating factors (MAGE-A2/A2B/H1) and OTULIN long noncoding RNA (OTULIN lncRNA) was observed compared to healthy control WTC11 iPSNs. The downregulated OTULIN lncRNA is concurrently associated with increased levels of OTULIN protein and phosphorylated tau at p-S202/p-T205 (AT8), p-T231 (AT180), and p-S396/p-S404 (PHF-1) in sAD2.1 iPSNs. Inhibiting the deubiquitinase activity of OTULIN with a small molecule, UC495 reduced the phosphorylated tau in iPSNs and SH-SY5Y cells, whereas the CRISPR-Cas9–mediated OTULIN gene knockout (KO) in sAD2.1 iPSNs decreased both the total and phosphorylated tau levels. CRISPR-Cas9–mediated OTULIN KO in SH-SY5Y resulted in a complete loss of tau at both mRNA and protein levels, and increased levels of polyubiquitinated proteins, which are being degraded by the proteasome as confirmed with an inhibitor, Lactacystin. In addition, SH-SY5Y OTULIN KO cells showed downregulation of various genes associated with inflammation, autophagy, ubiquitin-proteasome system, and the linear ubiquitin assembly complex that consequently may prevent development of an autoinflammation in the absence of OTULIN gene in neurons. Together, our results suggest, for the first time, a noncanonical role for OTULIN in regulating the gene expression and RNA metabolism, which may have a significant pathogenic role in exacerbating tau aggregation in neurons. Thus, OTULIN could be a novel potential therapeutic target for AD and ADRD.

Vascular dysfunction contributes to Alzheimer disease (AD) and related dementias (ADRDs), but the underlying mechanisms remain unclear. Previous studies link midlife hemostasis and platelet aggregation measures to late-life dementia risk. We aimed to determine whether platelet aggregation in midlife is associated with imaging markers of AD pathology. In a cross-sectional study, we evaluated associations between platelet aggregation, measured by light transmission aggregometry, and amyloid (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET uptake in dementia-free, middle-aged adults from the Framingham Heart Study. Co-primary outcomes included amyloid and tau uptake in AD-vulnerable regions. We also examined an MRI-based cortical thickness signature of AD risk as a secondary outcome. We used multivariable regression models adjusted for demographic and clinical factors, considering potential nonlinear associations. Platelet aggregation response was evaluated in 382 participants (mean age 56 ± 8 years, 53% female) approximately 1.2-1.5 years before amyloid and tau PET imaging. MRI data used for the AD signature were acquired together with PET imaging or within several months. The aggregation response exhibited a nonlinear association with AD pathology. Among those in the lowest tertile of adenosine diphosphate (ADP) response, platelet aggregation response was positively associated with increased amyloid in the precuneus (β = 0.047, p = 0.020) and tau in the rhinal (β = 0.077, p = 0.012), entorhinal (β = 0.066, p < 0.020), temporal global (β = 0.063, p = 0.031), and cortical (β = 0.064, p = 0.028) regions. For the secondary outcome analysis (n = 256), platelet aggregation response was negatively associated with the MRI-based cortical thickness signature of AD risk (β = -0.002, p < 0.035), consistent with a neurodegenerative pattern. Our findings indicate that platelet aggregation is linked to PET and MRI markers of AD pathology as early as midlife. These findings support further investigation of platelet-mediated mechanisms in AD pathogenesis.