Subjective cognitive decline (SCD) is a well-recognized risk state for developing mild cognitive impairment (MCI) and dementia. Optimal risk stratification for early interventions and clinical trial selection remains challenging. This study evaluates progression risk across multimodal biomarker profiles in SCD. We conducted a longitudinal observational study including participants from the BioFINDER-1 and BioFINDER-2 cohorts with a baseline diagnosis of SCD, at least 1 follow-up visit, and available information on dementia progression. Baseline predictors included cognitive performance, APOE4 status, plasma phosphorylated tau (p-tau) 217, "AD-signature" cortical thickness, hippocampal volume, and white matter hyperintensities (WMHs) measured by the Fazekas scale. Missing data were handled using multiple imputation. Predictors were evaluated individually and then combined in progressively complex Cox regression models to predict progression to all-cause dementia, Alzheimer disease (AD) dementia, and MCI (BioFINDER-2 only). Model performance was assessed using the Harrell C-index, and Akaike information criterion was used for comparing model fit. A total of 469 participants with SCD (mean age 69.1 ± 7.1 years, 51.4% female) were included in the main sample. Eighty-four individuals progressed to dementia over 4.0 ± 2.1 years (66.7% AD dementia). Progressors were older and more frequently APOE4 carriers and showed worse baseline cognition, higher plasma p-tau217, and greater atrophy and WMH burden. Plasma p-tau217 was the strongest individual predictor for AD dementia (C-index = 0.86 ± 0.012), but multivariable models outperformed single-biomarker models. The best model for all-cause dementia included all variables and achieved a C-index of 0.89 ± 0.003. For AD dementia, a more parsimonious model combining plasma p-tau217, cognitive scores, and APOE4 status showed excellent predictive ability (C-index = 0.91 ± 0.009), with only marginal improvement when MRI markers were added. Among 249 individuals from BioFINDER-2, 84 progressed to MCI within 2.3 ± 1.2 years. For MCI prediction, model performance was generally lower and similar between the plasma model and the model including all variables (C-index = 0.83 ± 0.009). A clinically feasible multimodal approach combining cognitive assessment, plasma p-tau217, and APOE4 status accurately predicts AD dementia risk in individuals with SCD. Adding MRI measures of brain atrophy and WMHs further improves prediction for all-cause dementia. These findings underscore the clinical value of plasma p-tau217 in refining risk assessment in SCD and support its potential implementation in memory clinic settings alongside other widely available biomarkers.
Objective: To examine the association between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) and the occurrence of dementia in patients undergoing maintenance hemodialysis (MHD). Methods: A multicenter cross-sectional study was conducted, involving MHD patients from 10 hemodialysis centers in Guizhou Province between May 2019 and November 2023. Cognitive function was assessed using the mini-mental state examination (MMSE), and the presence of dementia was determined according to the corresponding criteria based on the patient's educational level. NHHR was used as a marker of lipid metabolism. Patients were categorized into four groups (Q1-Q4) according to NHHR quartiles: Q1 group (NHHR<1.89), Q2 group (NHHR 1.89-<2.55), Q3 group (NHHR 2.55-<3.42), and Q4 group (NHHR≥3.42). The association between NHHR and the risk of dementia was assessed through multivariate logistic regression, multiple linear regression, restricted cubic splines (RCS), subgroup analysis, and interaction testing. Results: A total of 2 279 MHD patients (1 385 males and 894 females) aged 58 (49, 68) years were included in the study. Among these patients, 179 cases (7.9%) (103 males and 76 females) were diagnosed with dementia, with the age of 69 (60, 77) years. Multivariate logistic regression analysis revealed that, after adjusting for relevant confounding factors, the risk of dementia in the Q3 group was 1.98 times greater than that in the Q1 group (OR=1.98, 95%CI: 1.20-3.27, P=0.007). Furthermore, the risk of dementia in the Q4 group was 2.56 times that of the Q1 group (OR=2.56, 95%CI: 1.56-4.20, P<0.001). Multiple linear regression analysis indicated a negative correlation between NHHR and the total MMSE score (β=-0.25, 95%CI:-0.38--0.12, P<0.001). Subgroup analysis demonstrated an interaction between gender and NHHR (Pinteraction=0.005). Among female MHD patients, the risk of dementia in the NHHR Q4 group was 6.04 times that of the Q1 group (OR=6.04, 95%CI: 2.59-16.54), whereas no significant correlation was observed between NHHR and dementia in male MHD patients (all P>0.05). Restricted cubic splines analysis indicated a linear relationship between NHHR and the risk of dementia (Pnonlinearity=0.240). Conclusion: Elevated NHHR levels areassociated with an increased risk of dementia in MHD patients, with a more pronounced effect observed in female patients. 目的： 探讨非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值（NHHR）和维持性血液透析（MHD）患者发生痴呆的相关性。 方法： 采用多中心横断面研究，纳入2019年5月至2023年11月贵州省10家血液透析中心的MHD患者，使用简易精神状态检查（MMSE）量表评估认知功能，并根据患者文化程度，采用相应标准判定是否存在痴呆。以NHHR作为反映脂质代谢的指标，根据NHHR四分位数将患者分为4组（Q1~Q4组），其中，Q1组NHHR<1.89，Q2组NHHR 1.89~<2.55，Q3组NHHR 2.55~<3.42，Q4组NHHR≥3.42。采用多因素logistic回归模型、多重线性回归模型、限制立方样条（RCS）、亚组分析及交互作用检验等方法分析NHHR与痴呆风险的关系。 结果： 共纳入2 279例MHD患者，男1 385例，女894例，年龄58（49，68）岁。179例（7.9%）存在痴呆，男103例，女76例，年龄69（60，77）岁。多因素logistic回归分析结果显示，在调整相关混杂因素后，Q3组患者发生痴呆的风险为Q1组的1.98倍（OR=1.98，95%CI：1.20~3.27，P=0.007），Q4组患者发生痴呆的风险为Q1组的2.56倍（OR=2.56，95%CI：1.56~4.20，P<0.001）。多重线性回归分析结果显示，NHHR与MMSE总分呈负相关（β=-0.25，95%CI：-0.38~-0.12，P<0.001）。亚组分析结果显示，性别与NHHR存在交互作用（P交互=0.005），女性MHD患者中NHHR Q4组痴呆风险是Q1组的6.04倍（OR=6.04，95%CI：2.59~16.54），而男性MHD患者中NHHR 与痴呆无明显相关性（均P>0.05）；RCS分析显示NHHR与痴呆风险呈线性关系（P非线性=0.240）。 结论： NHHR水平升高与MHD患者痴呆风险增加相关，且在女性患者中更加明显。.
Studies and settings designed to identify incident cases of dementia can take advantage of imaging, biomarkers, and specialist clinicians to aid in diagnosis. This is not always feasible for large cohort studies. The Successful AGing after Elective Surgery (SAGES) study is a long-term, observational study of 560 community-dwelling adults aged ≥70, with serial neuropsychological assessments completed up to 72 months postsurgery. Mild cognitive impairment (MCI) and dementia diagnoses were determined retrospectively using a rigorous multimodal approach with nested subsamples. This included 1) an expert panel consensus based on serial neuropsychological testing in all participants; 2) diagnosis based on chart review in a subsample of participants; and 3) an in-person neurologist examination in a subsample. An expert adjudication panel then used a Delphi approach to assign research diagnoses incorporating information from all available modalities. During 72 months of follow-up, 63 incident cases of MCI (11.3%) and four cases of dementia (0.7%) were identified. The most frequent multimodal approach involved combined expert panel consensus and chart review in 41% of MCI (n = 26) diagnoses. Twelve MCI (19%) and three dementia (75%) diagnoses used all three modalities. Eight cases (12%) were diagnosed by a single modality. Diagnostic confidence considered both number and type of information sources used, for example, if agreement by more than one source, or diagnosis only by an in-person exam with a neurologist. Of the 63 MCI and four dementia diagnoses, the expert panel rated their confidence as moderate in four cases (all were MCI) and high in the remaining 63 cases (4 dementia and 59 MCI). A novel approach that integrates multiple sources of information and a robust adjudication process to determine incident MCI and dementia in a long-term cohort study may be useful for research applications. Such an approach may be useful when access to expert specialists, biomarkers, advanced neuroimaging and other diagnostic tests may be limited.
Dementia is projected to rise steepest in racially minoritised communities; nearly six times the UK average. Understanding of disparities is limited due to research under-representation, however evidence suggests racially minoritised people experience delayed diagnoses, more often in crisis situations, and die younger. To explore cultural understandings of ageing and dementia, and barriers/enablers to healthcare access for family-carers of racially minoritised people with memory problems. Generate community-led intervention ideas to improve access/uptake. Scoping review of UK literature 2) Qualitative Photovoice (participatory action research) focus groups with family-carers of people with memory concerns from Chinese, Caribbean and South Asian communities in Sheffield 3) Co-design workshops with community leaders on intervention prototypes. Scoping review of barriers/enablers and existing interventions. Photovoice methodology: purposive recruitment of 24 family-carers (8/community) supporting those aged≥65 with memory concerns; diverse in gender, age and language. Eight-week data collection culminating in focus groups co-facilitated and interpreted by bilingual community research link workers, transcribed verbatim, and independently thematically analysed. Photo-exhibition for public and policy-makers. Stakeholder workshop with community leaders to co-design intervention prototypes. Despite steeply rising dementia rates in racially minoritised communities, inequity persists in service access/uptake. Little is understood about cultural influences effecting engagement with dementia care and no formal intervention development tackling racial inequity has been published. This work will increase knowledge on cultural nuances and structural discrimination impacting families living with dementia and consider new approaches.
People with dementia manage complex medication regimens and face a heightened risk of medication-related harm. Co-design approaches are increasingly being used to develop interventions/tools to improve medication safety in this population. To describe how co-design has been applied in developing interventions or tools related to medication safety involving people with dementia and/or carers. We conducted a scoping review across seven electronic databases (MEDLINE, CINAHL, PsycINFO, Embase, Scopus, Association for Computing Machinery and Cochrane Library) to identify studies that adopted co-design. We evaluated which co-design phases (pre-design, generative, evaluative and post-design) were applied in each study. Eight studies met the inclusion criteria. Two studies involved people with dementia and/or carers across all co-design phases. Studies adopted co-design approaches to inform intervention content, identify areas of improvement and/or increase their implementation in practice. Most studies involved people with dementia and/or carers in two phases of co-design (n = 4), the generative and evaluative phases. The evaluative phase was the most frequently used (n = 7), followed by the generative phase (n = 5) and lastly the pre-design (n = 3) and post-design phases (n = 3). Interventions addressed deprescribing (n = 4), medication management (n = 3 and prescribing cascades (n = 1). Reported benefits included improved relevance, accessibility and usability of interventions through stakeholder input. Co-design in medication safety for dementia care remains inconsistently applied and reported. Greater emphasis on meaningful involvement across all phases is needed to ensure interventions reflect lived experience. The utilisation of co-design frameworks may improve the reporting of co-design approaches in medication safety studies.
Young-onset dementia (YOD), defined by symptom onset before the age of 65, profoundly impacts personal identity, work, and family life. Despite growing interest in the psychosocial dimensions of YOD, the direct voices of people living with the condition remain underrepresented. Existing qualitative research has mainly relied on structured interviews, which can constrain spontaneity and the emergence of authentic meanings. This study adopts an innovative approach by analyzing spontaneous conversations as a naturalistic form of data, enabling a more ecological understanding of living experience. An exploratory qualitative study was conducted at an Italian Meeting Center for people with YOD. Eleven participants (aged 55-68) took part in 14 naturally occurring group conversations, recorded between October 2024 and February 2025. Transcripts were analyzed using the General Inductive Approach. Themes were co-developed through iterative coding and later validated in a participatory feedback session involving all participants. Four overarching themes were identified: (1) Living with Alzheimer's: between awareness and "broad shoulders"-redefining identity and meaning in everyday life; (2) Significant relationships: between closeness, misunderstanding, and new balances-navigating relational change and finding belonging in peer groups; (3) The struggle to be believed: between invisible illness and judging gazes-confronting stigma, disbelief, and social invisibility; (4) Support that makes a difference: between resources and ideas for living better-valuing respectful, personalized, and co-designed support. Participants collectively emphasized the need to move from a "for" to a "with" logic in dementia care and research:"It is not enough to do something for us. We need to build it together." Spontaneous conversations offer a powerful lens to capture the nuanced, relational, and participatory aspects of living with young-onset dementia. This approach complements traditional qualitative methods by restoring authenticity to the voices of people with dementia, fostering inclusion, and informing the co-construction of more responsive psychosocial and community interventions.
Behavioral and psychological symptoms of dementia (BPSD) are a major risk factor for depressive symptoms in family caregivers of people with dementia, yet the mechanisms linking BPSD to caregiver depression remain insufficiently understood. This study adopted a symptom-specific perspective to examine associations between BPSD and individual depressive symptoms in caregivers. We analyzed an integrative cross-sectional dataset from three randomized controlled trials including family caregivers of people with dementia (N = 440). Associations between global and domain-specific BPSD (BEHAVE-AD) and caregivers' depressive symptoms (CES-D) were examined using regularized Gaussian graphical network models. Global BPSD were primarily linked to caregivers' sense of failure and fatigue, with a smaller association with depressed mood. When individual BPSD domains were considered simultaneously, most domains did not show unique associations with depressive symptoms, suggesting that associations between BPSD and caregiver depressive symptoms are partly shared across domains. Nevertheless, some domain-specific associations were observed: aggressiveness was uniquely associated with sense of failure and depressed mood, whereas diurnal rhythm disturbances and activity disturbances showed specific associations with fatigue. These findings provide initial evidence for symptom-level associations between BPSD and caregiver depressive symptoms, particularly involving sense of failure and fatigue. They further suggest that different BPSD domains may show somewhat different patterns of association with these depressive symptoms. A symptom-specific perspective may contribute to a more nuanced understanding of how care-recipient symptoms relate to caregiver mental health and may help inform more targeted intervention approaches.
BackgroundConverging evidence supports a bidirectional link between epilepsy and Alzheimer's disease (AD). Limited data are available regarding the association of epilepsy with frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB).ObjectiveTo estimate the bidirectional association between epilepsy and AD, FTD, and DLB in the UK Biobank, a large, multi-source healthcare dataset.MethodsEpilepsy, AD, FTD, and DLB cohorts were extracted. Cox proportional-hazard models were used to compare the AD risk in the epilepsy cohort against matched controls, and the epilepsy risk in the AD cohort against matched controls. Prevalent association of epilepsy with FTD and DLB was assessed using Chi-squared/Fisher test.ResultsHazard-ratio (HR) for AD in the epilepsy population versus controls was 2.5 (1.8-3.4, p < 0.001); HR increased when epilepsy was diagnosed in the sixth-seventh decade and in individuals with epilepsy carrying the APOE ε4 allele. Conversely, HR for epilepsy in AD versus controls was 14.8 (9.7-22.5, p < 0.001). Epilepsy prevalence was higher in the FTD population compared to controls, with prevalence ratio (PR) of 5.3 (2.4-11.8, p = 0.001). Epilepsy PR in DLB versus controls approached but did not achieve statistical significance (2.4, 1.0-5.7, p = 0.068).ConclusionsOur findings reinforce the notion of a bidirectional association between epilepsy and AD, providing proof-of-concept that epilepsy, especially late-onset, may be successfully integrated into AD risk frameworks. Furthermore, we found a high prevalence of epilepsy in the FTD population. Careful stratification of individuals with epilepsy could offer an opportunity to identify those at higher risk of future or covert AD and neurodegeneration.
Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Puerarin (PUE) is a natural compound isolated from Puerariae Lobatae Radix, plays an important role in treating neurodegenerative and neurovascular diseases. Studies have confirmed that Puerarin can reduce neuroinflammation and protect the blood-brain barrier (BBB). However, the precise mechanism by which PUE treats VaD remains to be elucidated. To investigate the therapeutic effect of Puerarin on VaD and its underlying molecular mechanisms. Cognitive performance was assessed using the behavioral testing. Hematoxylin and Eosin staining (H&E) and Nissl staining were employed to assess neuronal morphology in the hippocampus. Additionally, network pharmacology (NP) was used to identify putative bioactive compounds in PUE and candidate targets associated with VaD. Transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR), and Western blotting were used for experimental validation. To further interrogate pathway involvement, lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist, was administered, followed by repeated behavioral testing and molecular analyses. Behavioral testing showed that PUE mitigated two-vessel occlusion (2VO)-induced cognitive deficits and reduced hippocampal neuronal injury. NP identified 17 putative active compounds and 100 overlapping targets between PUE and VaD. GO and KEGG enrichment analyses indicated that these targets were enriched in Toll-like receptor and NF-κB signaling, implicating an anti-neuroinflammatory mechanism. Experimental assays showed that PUE reduced TLR4 and myeloid differentiation primary response 88 (MyD88) expression, decreased nuclear factor-kappa-B p65 (NF-κB p65) phosphorylation, and lowered pro-inflammatory mediator levels. Importantly, the administration of the TLR4 agonist LPS effectively counteracted the therapeutic effects of Puerarin. Puerarin improves learning and cognitive abilities in VaD rats by inhibiting the TLR4/MyD88/NF-κB signaling pathway, thereby attenuating pathological alterations in the hippocampus, protecting the BBB integrity from cerebral ischemic damage, and exerting anti-neuroinflammatory effects.
People living with dementia (PLWD) often have high symptom burden, exacerbated by comorbidities and experience unplanned hospital admissions that increase towards the end of life. Unmanaged symptoms and unplanned hospital admissions are distressing for the person living with dementia and family carers and expensive for the healthcare system. To explore the relationship between unmanaged symptoms of PLWD following an unplanned hospital admission and carer health and wellbeing outcomes over time. Prospective longitudinal cohort study. Physical, psychosocial and spiritual symptoms of the PLWD and carer burden, distress and pre-death grief were assessed over 12 months following an unplanned hospital admission. Descriptive statistics and multilevel linear regression analyses were used to examine the relationships between PLWD unmanaged symptoms and carer outcomes. A total of 51 carers of PLWD with a mean age of 59.6 participated. Carer burden was significantly associated with increasing PLWD unmanaged symptoms (coefficient = 0.07, 95% CI [0.03, 0.12], p = 0.002) and agitation (coefficient = 0.08, 95%CI [0.02, 0.14], p = 0.009). Carer psychological distress showed a positive trend in its association with increasing PLWD unmanaged symptoms (coefficient = 0.07, 95% CI [-0.00, 0.13], p = 0.059) and agitation (coefficient = 0.06, 95% CI [-0.01, 0.14], p = 0.090), but both analyses did not reach statistical significance. Carer pre-death grief was not associated with PLWD symptoms or agitation. Identifying and addressing symptoms in PLWD following an unplanned hospital admission is essential in enhancing the wellbeing of PLWD and carers. Hospital discharge planning should incorporate carer perspectives, provide support for carer burden and distress, and ensure continuity of care to reduce symptoms and improve outcomes for both PLWD and their carers.
Electroencephalography (EEG) offers a non-invasive window into brain function, often revealing abnormalities long before cognitive symptoms or neurodegeneration emerge. This review examines the expanding role of EEG in neurodegenerative disease and comorbid conditions that contribute to abnormal EEG. We review emerging EEG technologies that uncover previously underappreciated EEG abnormalities and outline future steps needed to advance EEG as a practical tool in clinical and research settings for dementia.
Growing awareness of "copathology" inspires nuanced testing and treatment strategies.
暂无摘要（点击查看详情）
Progression from Parkinson's disease (PD) to Lewy body dementia is a major clinical concern. Although several progression-associated loci have been identified, their cumulative effects on cognitive decline have not been systematically evaluated. To assess the dose-dependent effect of five candidate progression loci linked to synaptic vulnerability (RIMS2, TMEM108, GBA1) and amyloid-tau pathology (APOE, WWOX), we analyzed 7745 participants from 24 cohorts with 28,737 longitudinal visits over 15 years using random-effects meta-analyses of cohort-specific Cox proportional hazards models. Dementia risk increased monotonically with the number of progression loci (0, 1, 2, or ≥3). A single locus conferred a 1.56-fold increase in risk (hazard ratio (HR) = 1.56, 95% CI: 1.28-1.89), rising to 3.21-fold for two loci (HR = 3.21, 95% CI: 2.19-4.70) and 7.49-fold for three or more loci (HR = 7.49, 95% CI: 4.98-11.28). Individually, GBA1 (HR = 2.09), APOE ε4 (HR = 1.71), RIMS2 (HR = 1.90), TMEM108 (HR = 2.05), and WWOX (HR = 1.56) were associated with dementia risk, but there was heterogeneity between clinical trials, biomarkers, and population-based cohorts. Multi-locus dosage increases dementia risk in a monotonic manner and may improve stratification and clinical trial design in PD.
Age-related disorders known as neurodegenerative illnesses are defined by uncontrolled neuronal loss that gradually impairs brain function. The majority of age-related neurodegenerative disorders are caused by dementias, in particular. Nowadays, the neurodegenerative disorders are not limited to age and are reported in all age groups. The drug delivery to treat the neurodegenerative disorders is challenging due to the presence of the blood-brain barrier (BBB). A critical literature review has been conducted across databases such as Scopus, Embase, Cochrane, and PubMed. Blood-brain barrier, neurodegenerative disorders, novel drug delivery system, and targeted drug therapy were the search terms. Neurodegenerative Diseases (NDD) impact the peripheral nervous system, nerve cells, muscles, and the nerve-muscle junction. This term broadly encompasses cognitive disorders, such as Alzheimer's disease, Lewy body dementia, frontotemporal dementia, and vascular dementia. Additionally, other neurodegenerative conditions such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and spinocerebellar ataxias predominantly impair motor system function and nerves in the limbs. The existing therapeutic approaches to treat neurological diseases exhibit limited efficacy due to the BBB. This highly selective semipermeable membrane permits vital nutrients to enter the brain while blocking the potentially harmful toxins. It makes it very challenging to get medications into the brain. There are several effective approaches to deliver drugs to the brain (nanocarrier systems, intranasal administration, and focused ultrasound) to address the limitations of conventional treatments. This review discusses neurodegenerative disorders, brain anatomy/physiology, barriers to drug delivery, and strategies to overcome these limitations.
In Israel, several policies have supported the growth of home-based hospice through a unique public-private care delivery and financing system. Yet, little is known about trends in home hospice use in Israel. To describe 10-year trends in diagnosis, length of stay (LOS), and discharge patterns among home hospice patients in Israel. We conducted a retrospective cohort study of all patients admitted to Sabar Health's home hospice program between 2014 and 2023. Demographic and clinical data were analyzed by primary diagnosis: Cancer, dementia, end-organ failure, frailty, and neurodegenerative disease. Trends in enrollment, LOS, and live discharge rates were assessed over time. Among 25,673 patients, the proportion with cancer annually declined from 88.6% in 2014 to 57.8% in 2023, while admissions for dementia rose from 0% in 2014 to 19.6% in 2023. Median LOS increased from 20 to 35 days, with the longest durations observed among patients with dementia and neurodegenerative disease. Live discharge rates also rose, particularly in the dementia group from 12.2% to 20% over the observed period, with a growing share occurring after ≥180 days. Home hospice care in Israel has evolved significantly over the past decade, with increasing enrollment of patients with prolonged and uncertain illness trajectories. These trends emphasize the need for more adaptable eligibility frameworks, improved prognostic tools, and expanded caregiver support to meet the needs of a diversifying hospice population.
Atherosclerosis has been increasingly recognized as a contributor to cognitive decline through mechanisms such as cerebral hypoperfusion, oxidative stress, and chronic inflammation. These mechanisms include cerebral hypoperfusion, which limits oxygen and nutrient supply to the brain; microvascular damage, which impairs small vessel function and blood-brain barrier integrity; chronic inflammation, which promotes neurodegeneration through sustained immune activation; and oxidative stress, which accelerates neuronal aging via mitochondrial dysfunction. This narrative review synthesizes findings from epidemiological studies, mechanistic research, and clinical trials to examine the interplay between atherosclerotic diseases and cognitive impairment. Shared risk factors, including hypertension, diabetes, hyperlipidemia, and smoking, accelerate neurovascular dysfunction and increase susceptibility to dementia. Advances in neuroimaging and biomarker research offer improved diagnostic precision, facilitating early detection and intervention. Preventive strategies, including lifestyle modifications, pharmacological therapies such as statins and antihypertensives, and cognitive rehabilitation, have the potential to mitigate cognitive deterioration associated with atherosclerosis. Despite accumulating evidence, vascular contributions to dementia remain underdiagnosed in clinical settings, highlighting the need for a multidisciplinary approach that integrates cardiovascular and neurological care. A comprehensive strategy encompassing risk stratification, early therapeutic intervention, and long-term monitoring is essential for improving cognitive outcomes in at-risk populations. Future research should focus on refining diagnostic methodologies, optimizing prevention and treatment protocols, and identifying high-risk individuals for targeted interventions. Given the rising global burden of both cardiovascular disease and dementia, a proactive approach addressing modifiable risk factors is critical to reducing morbidity and enhancing quality of life.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose molecular mechanisms involve multiple biological pathways. Longitudinal blood-based omics data, such as lipidomics and metabolomics profiles, offer promising noninvasive biomarkers for early detection and prognosis, yet they are high-dimensional, sparse, and exhibit complex temporal and cross-feature correlations. The primary goal of this study is to identify which omics data types are most strongly associated with time to dementia onset in patients with mild cognitive impairment (MCI) at baseline. To address this, we propose a longitudinal sparse single-omics factor analysis (LS-SOFA) framework that models each omics view through view-specific latent factors and feature-weight matrices, with temporal dynamics captured by functional principal component analysis (FPCA). The resulting functional principal component (FPC) scores are incorporated into a survival model to test whether each omics view is associated with time to dementia onset. An efficient covariance-based estimation algorithm substantially reduces computational and memory cost, enabling large-scale application in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. In simulations, LS-SOFA achieves higher longitudinal estimation accuracy and more stable hypothesis testing than competing methods. Applied to five blood-based omics views from ADNI, LS-SOFA identified plasma lipidomics and serum metabolomics from FIA and UPLC as significantly associated with dementia risk after FDR adjustment, with nominal evidence of association for gut microbial metabolomics from serum. The top features within each omics view reveal biologically interpretable metabolic pathways that may serve as blood-based biomarkers for AD progression.
Prediction models based on administrative data may present a scalable opportunity to identify risk of cognitive impairment, but their accuracy relative to models using richer information is uncertain. We developed and validated models to identify the likelihood of mild cognitive impairment (MCI) and dementia using the Health and Retirement Study linked to Medicare data from 2000 to 2016 (N = 63,740). Predictors covered most risk factors identified by the 2024 Lancet Commission. Model performance was assessed using multiple metrics, including the area under the receiver operating characteristic curve (AUC). Probit models with demographics and chronic conditions yielded high AUCs of 71.3% (MCI) and 82.1% (dementia). Adding individual level education provided the largest improvement in AUCs, whereas dual eligibility status offered smaller gains (p  <  0.001). Air pollution exposure, obesity, and interaction terms did not enhance prediction. Predictors in administrative data can be used to generate reasonably accurate, well calibrated models predicting likelihood of cognitive impairment.
DNA methylation (DNAm)-based epigenetic clocks are emerging biomarkers of biological aging and have been linked to cognitive decline and dementia, but their relationship with blood-based neurodegenerative biomarkers remains understudied in low- and middle-income countries (LMIC). Using the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD), we examined whether epigenetic aging was associated with levels and changes in neurodegenerative biomarkers among adults aged ≥60 years. Seven epigenetic clocks were derived from DNAm data and related to plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), phosphorylated tau 181 (pTau181), total tau, Amyloid-β (Aβ)42, Aβ40 and Aβ42/Aβ40 measured at two time points. Baseline accelerated epigenetic aging was associated with higher levels of neurodegenerative biomarkers, including pTau181, GFAP, and NfL, with more consistent associations with increases in GFAP and NfL for morbidity- and mortality-trained clocks. These findings support the utility of epigenetic clocks as scalable tools for identifying risk of neurodegeneration in LMIC settings.